Which is better for nail fungus, fluconazole or terbinafine? Clinical evaluation of the effectiveness of the combined use of fluconazole and terbinafine in the treatment of onychomycosis

Itraconazole and terbinafine are the most popular antifungal drugs. They are best suited for the treatment of onychomycosis. Onychomycosis general fungal infection nails Itraconazole and terbinafine are also associated with a number of potentially dangerous drug interactions.

Itraconazole capsules require an acidic stomach environment, so it is recommended to take it with food for better absorption, as foods stimulate the production of of hydrochloric acid it is responsible for the acidity of the environment in the stomach. If you are taking other drugs such as inhibitors proton pump, H-2 antagonists, antacids, etc., which can reduce acidity in the stomach, then you should space the intake of itraconazole by one to two hours. Unlike Itraconazole capsules, Itraconazole in the mixture does not require acidity gastric juice for absorption, so it does not need to be taken with food. Itraconazole remains in the nails for six to nine months after stopping therapy. Drugs that may increase itraconazole concentrations include macrolides (clarithromycin), antibiotics (erythromycin) and inhibitors such as ritonavir. Itraconazole should not be used with the following drugs:

Antiarrhythmic drugs, such as digoxin, quinidine

Anticonvulsants such as carbamazepine

Rifabutin

Antineoplastic like busulfan, docetaxel, vinca alkaloids

Neuroleptics (pimozide)

Benzodiazepines such as alprazolam, diazepam, midazolam, triazolam

Calcium channel blockers: dihydropyridines, verapamil

Gastrointestinal motility agents (cisapride) and HMG-CoA reductases such as atorvastatin, lovastatin, simvastatin.

Complications such as torsade de pointes, ventricular fibrillation, cardiac arrest, and/or sudden death may occur if the above drugs and itraconazole are taken simultaneously. Research has shown increased risk acute necrosis skeletal muscles at simultaneous use itraconazole and HMG-CoA reductases. Itraconazole increases plasma concentrations of benzodiazepines and causes sedative and hypnotic effects.

On the other hand, Terbinafine is well absorbed in 70% of cases after oral administration; the acidity of gastric juice does not affect absorption.
rbinafine is lipophilic - meaning that it has a high affinity for reacting species to combine with lipids. After oral administration, the drug is found in adipose tissue, stratum corneum, skin, epidermis and nails; terbinafine is 99% protein bound. It is not metabolized by the cytochrome P450 system, unlike itraconazole. Terbinafine remains in the nails for up to nine months after stopping therapy. Medicines that may reduce Terbinafine concentrations: anticonvulsants(carbamazepine, phenobarbital, phenytoin), antimicrobials (isoniazid, rifabutin, rifampicin), gastric acid suppressors/neutralizers and nevirapine. You should take Terbinafine with caution if you are taking warfarin because studies show that terbinafine interacts with warfarin. There are studies showing the interaction of the drug with contraceptives and hormonal drugs, theophylline, phenytoin, thiazide drugs, diuretics, beta blockers and calcium channel blockers.

Basic information:

1. Itraconazole and terbinafine antifungal drugs. Best suited for the treatment of onychomycosis.

2. Itraconazole capsules require an acidic gastric environment and are recommended to be taken with meals for better absorption.

3.Drugs such as proton pump inhibitors, H-2 antagonists, antacids, etc., which can reduce stomach acidity should not be taken with Itraconazole. The composition of Itraconazole does not require gastric acidity.

4. The acidity of gastric juice does not affect the absorption of Terbinafine.

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Systemic therapy is the most effective and reliable treatment onychomycosis. Systemic therapy is used when treatment local means turns out to be ineffective.

INDICATIONS FOR SYSTEMIC THERAPY

Clinical characteristics of onychomycosis:

clinical form:

distal-lateral (late stages),

proximal,

total;

damage to more than half of the nail;

involvement of the matrix in the process;

pronounced changes in the nail (hyperkeratosis, onycholysis);

damage to more than 2-3 nails

Inefficiency local therapy

Combination of onychomycosis with widespread skin or hair lesions

Although systemic therapy most often cures onychomycosis, its use is associated with a number of difficulties. When administered systemically, the drug does not enter the nails immediately, but first overcomes numerous obstacles. Its concentration in nails is much less than when applied topically. For this concentration to become effective, i.e. destroyed fungi or suppressed their growth, you can, firstly, increase the concentration as a result of increasing the dose of the drug. However, increasing the dose will increase the risk of side effects and toxic effects. To overcome these difficulties, new drugs are used that accumulate in the nail when administered repeatedly. Secondly, you can choose a drug that is effective in low concentrations. Modern drugs with very low MICs for onychomycosis pathogens meet this requirement.

Systemic antifungal drugs

There are only 8 systemic antimycotics. Of these, griseofulvin, terbinafine, ketoconazole and itraconazole are widely used in the treatment of onychomycosis, and fluconazole is currently being introduced into therapy. All these drugs are prescribed orally.

The main criteria that determine the effectiveness of a systemic antifungal drug for onychomycosis:

— antifungal activity and spectrum of action;

- pharmacokinetics (the ability to quickly penetrate the nails, accumulate and linger in them);

- safety.

Not all systemic therapies meet each of these criteria. When prescribing them, one should take into account the characteristics of each case of onychomycosis, the patient’s condition, concomitant diseases and their therapy. Below we present the main characteristics of each drug.

Griseofulvin

The antifungal antibiotic griseofulvin is the first systemic drug for the treatment of dermatophyte infections. Griseofulvin has been used in the treatment of onychomycosis for more than 30 years.

Griseofulvin acts only on dermatophytes; the MIC for them is in the range of 0.1-5 mg/l.

Griseofulvin is not completely absorbed from the gastrointestinal tract; absorption improves when taken with food. In order to improve absorption, micronized (finely divided) and ultramicronized forms have been developed. Taking 500 mg of griseofulvin provides maximum concentrations of 0.5-2.0 mg/l, which does not always exceed the MIC. Treatment of onychomycosis is usually carried out with griseofulvin at a dose of 1000 mg/day.

In the blood, griseofulvin is partially bound to plasma proteins. Metabolism occurs in the liver, more than a third of the drug is excreted in the feces.

Although griseofulvin is a lipophilic substance that can accumulate in tissues, its affinity for keratin is rather low. 48-72 hours after discontinuation of the drug, it is no longer found in the stratum corneum, so treatment of onychomycosis with griseofulvin is carried out continuously, until a healthy nail plate grows. In general, the kinetics of griseofulvin in the nail has been poorly studied.

Griseofulvin for oral administration is available in tablets and in the form of an oral suspension. Tablets contain 125 or 500 mg of griseofulvin, in a package of 25 or 1000 tablets of 125 mg, 25 or 250 tablets of 500 mg. 1 ml of suspension contains 0.1 g of griseofulvin.

Enhanced absorption formulations include micronized griseofulvin (griseofulvin forte), available in 125, 250, or 500 mg tablets, and ultramicronized griseofulvin in 125 mg tablets. IN last decades Micronized forms are most widely used.

The dose of griseofulvin is determined in accordance with the age and body weight of the patient. The daily dose for adults of the micronized form of griseofulvin for onychomycosis is from 500 to 1000 mg (in 2-4 doses), but not less than 10 mg/kg. The duration of treatment for fingernails is about 4-6 months, for toenails - from 9 to 12, sometimes up to 18 months.

For children weighing less than 25 kg, the daily dose is prescribed at the rate of 10 mg/kg (or in 2 doses of 5 mg/kg), children weighing more than 25 kg are given 250-500 mg/day. In general, it is not recommended to prescribe griseofulvin for the treatment of onychomycosis in children.

When treating with ultramicronized griseofulvin, the dose is reduced by a third or even half.

When prescribing griseofulvin with other drugs, their possible interactions should be taken into account. Barbiturates reduce the absorption of griseofulvin. Griseofulvin weakens the effect indirect anticoagulants, reduces cyclosporine concentrations. It should be remembered that griseofulvin can significantly weaken the effect of hormonal contraceptives.

Most common side effects when taking griseofulvin - nausea, sometimes vomiting, discomfort in the epigastrium, headache and dizziness. In addition, griseofulvin has photosensitizing properties. Toxic effects include effects on the liver, as well as rare cases of agranulocytosis. Griseofulvin is not prescribed to pregnant and nursing mothers.

Terbinafine (Lamisil)

Terbinafine - synthetic drug from the class of allylamines, has been used in the treatment of onychomycosis since the early 90s.

The average MIC of terbinafine for dermatophytes does not exceed 0.06 mg/l. In addition, terbinafine acts in vitro against many other molds. The effectiveness of terbinafine for non-dermatophyte mold infections is unknown. Many yeast mushrooms, in particular Candida albicans, are resistant to terbinafine in MICs up to 128 mg/l.

Terbinafine is well absorbed from the gastrointestinal tract; food intake does not affect absorption. Peak plasma concentrations at doses of 250 and 500 mg are about 0.9 and 1.7-2 mg/l, respectively. This is much higher than the MIC for sensitive fungi. Concentrations are directly dependent on the dose and increase with its increase and with repeated administration of the drug. In the blood, terbinafine binds to proteins of all plasma fractions and to formed elements.

Terbinafine is metabolized in the liver. There are 15 known metabolites, all of them inactive. About 80% of the drug is excreted in the urine. Insufficient liver or kidney function slows elimination.

Terbinafine appears on the distal edges of the nails on average at 8 weeks from the start of treatment. Terbinafine penetrates the nail plate primarily through the matrix, but also through the nail bed. After discontinuation of treatment, terbinafine in effective concentrations remains in the nails for 4-6 weeks.

Terbinafine hydrochloride for oral administration is available in tablets of 125 and 250 mg, in a package of 14 or 28 tablets.

In the treatment of onychomycosis caused by dermatophytes, terbinafine is used at a dose of 250 mg/day. IN last years Terbinafine is prescribed in short courses: for infections of the fingernails for a period of 6 weeks (1.5 months), for infections of the toenails for a period of 12 weeks (3 months). The effectiveness of terbinafine at a dose of 500 mg per day for 3 months for nail candidiasis was studied. Pulse therapy with terbinafine is possible at a dose of 500 mg/day in one-week courses for 3-4 months.

Doses for children are 62.25 mg for body weight up to 20 kg (half a tablet is 125 mg), up to 40 kg - 125 mg, children weighing more than 40 kg are given the full dose. Experience in treating children with terbinafine is limited.

When prescribing terbinafine, its possible interaction with drugs metabolized by the liver should be taken into account. Rifampicin reduces, and cimetidine and terfenadine increase, concentrations of terbinafine.

The most common side effects with terbinafine include nausea, a feeling of fullness or abdominal pain, and sometimes decreased appetite. Loss or changes in taste have been reported during treatment. In addition to dyspeptic symptoms, urticaria may develop during treatment with terbinafine. Toxic effects - hepatotoxicity, agranulocytosis, damage to the organ of vision and some others are very rare. Terbinafine should not be prescribed to persons with liver disease. In case of renal failure, the dose of terbinafine should be reduced by half if the creatinine clearance exceeds 50 ml/min. Terbinafine is not prescribed to pregnant and nursing mothers.

Ketoconazole (nizoral, oronazole)

This synthetic drug from the azole class has been used in the treatment of mycoses since the late 70s.

Ketoconazole has wide range actions. The average MIC for dermatophytes is about 0.1-0.2 mg/l, for Candida albicans - about 0.5 mg/l. Many molds that cause nondermatophytic onychomycosis are resistant to ketoconazole.

Ketoconazole is not completely absorbed from the gastrointestinal tract. Absorption is worse with reduced acidity and improves when taken with food. Taking 200 mg of ketoconazole leads to a peak plasma concentration of about 3 mg/l, taking 400 mg - 5-6 mg/l. These concentrations exceed the MIC for sensitive pathogens.

In the blood, ketoconazole is almost completely bound to plasma proteins and is intensively metabolized in the liver. Metabolites are inactive, most of them are excreted in feces.

Ketoconazole has a high affinity for keratin. The drug enters the nails through the matrix and nail bed; it can be detected on the 11th day from the start of treatment. Although ketoconazole appears to be retained in the nail for some time after treatment is stopped, the kinetics of the drug in the nail have not been well studied.

Ketoconazole for oral administration is available in tablets of 200 mg, in a package of 10, 20 or 30 tablets.

For onychomycosis, ketoconazole is prescribed at a dose of 200 mg/day. It is better to take the drug with food. Treatment takes 4-6 months for onychomycosis of the hands and 8-12 months for onychomycosis of the feet.

For children weighing from 15 to 30 kg, ketoconazole is prescribed 100 mg (half a tablet). Children with greater body weight are given the full dose. In general, ketoconazole should not be used to treat onychomycosis in children.

When prescribing ketoconazole, it is necessary to take into account its possible interaction with many drugs. Antacids and agents that reduce gastric secretion interfere with the absorption of ketoconazole. Ketoconazole increases half-life antihistamines terfenadine, astemizole, and cisapride; the combined use of these drugs may lead to the development of arrhythmia. Ketoconazole increases the half-life of midazolam, triazolam, cyclosporine and potentiates the effect of indirect anticoagulants. Concentrations of ketoconazole are reduced when administered with rifampicin and isoniazid and change when used with phenytoin.

Common side effects of ketoconazole include nausea, less commonly vomiting, and decreased appetite. By taking the drug with meals or at night, you can avoid these phenomena.

The main toxic effect of ketoconazole is its effect on the liver. An increase in the concentration of liver transaminases during treatment is observed in 5-10% of patients taking ketoconazole. If these phenomena become permanent or intensify, the drug should be discontinued. Severe liver damage is rare, but long-term treatment onychomycosis their likelihood increases. The effect of ketoconazole on steroid metabolism in humans may cause changes in cholesterol levels and steroid hormones in the blood, but these changes do not manifest themselves clinically. Ketoconazole should not be prescribed to pregnant and nursing mothers.

Itraconazole (orungal)

This synthetic drug from the azole class has been used in the treatment of onychomycosis since the early 90s.

The spectrum of action of itraconazole is the widest among all antifungal agents for oral administration. Itraconazole acts on dermatophytes (with an average MIC of about 0.1 mg/l), different types Candida (with MIC in the range of 0.1-1 mg/l) and many molds found in onychomycosis.

Itraconazole is not completely absorbed from the gastrointestinal tract. Absorption of the drug is worse at low acidity, but significantly improves when taken with food. After taking 100 mg of the drug, maximum plasma concentrations are 0.1-0.2 mg/l, increasing to 1 mg/l when taking 200 mg and up to 2 mg/l when taking 400 mg. This exceeds the MIC for most pathogenic fungi.

In the blood, Itraconazole is almost completely bound to plasma proteins and is intensively metabolized in the liver. The main metabolite is hydroxyItraconazole, which is not inferior in activity to itraconazole. Most of the metabolites are excreted in the feces.

The keratophilicity of itraconazole ensures its high concentrations in the skin and nails, 4 times higher than plasma levels. At the distal ends of the nail plates, itraconazole can be detected after 1 week of treatment. Itraconazole penetrates into the nail plate both through the matrix and directly through the nail bed. The drug accumulates in the matrix and is released only when a new nail plate grows, therefore effective concentration after its discontinuation, the drug is maintained in the fingernails for another 3 months, and in the toenails for 6-9 months with a 3-month course of treatment.

Itraconazole for oral administration is available in capsules containing 100 mg of the drug, in a package of 4 or 15 capsules.

It is possible to treat onychomycosis with short courses of 200 mg of itraconazole every day for 3 months. In recent years, the pulse therapy technique has gained greater recognition, when itraconazole is prescribed at a dose of 400 mg/day (in 2 doses) for 1 week. When treating infections on the hands, 2 courses of pulse therapy are prescribed in a one-week course every month. When treating leg infections, 3 or 4 courses are prescribed depending on the shape and severity of the lesion. Itraconazole should be taken with food, no more than 200 mg (2 capsules) per dose. Since experience with the use of itraconazole in pediatrics is limited, recommendations for the dosage of the drug in children have not been developed.

When prescribing itraconazole, the risk of interaction with other drugs is taken into account. Antacids and gastric depressants interfere with the absorption of itraconazole. Itraconazole should not be co-administered with astemizole, terfenadine or cisapride due to the potential for arrhythmia. Itraconazole also increases the half-life of midazolam and triazolam, digoxin, cyclosporine, and potentiates the effect of indirect anticoagulants. Rifampicin and phenytoin reduce itraconazole concentrations.

The most common side effects are nausea, epigastric discomfort and abdominal pain, and constipation. A small proportion of patients experience a transient increase in the concentration of hepatic transaminases. If it does not decrease or symptoms of hepatitis appear, then treatment is stopped. Itraconazole should not be prescribed to patients with liver disease. At the indicated doses, itraconazole has no effect on the metabolism of steroid hormones. Pregnant and nursing mothers are not treated with itraconazole for onychomycosis.

Fluconazole (Diflucan)

Fluconazole is a drug from the azole class, was obtained in 1982. It began to be used for onychomycosis in recent years.

The spectrum of action of fluconazole is wide. The MIC for dermatophytes is up to 1 mg/l, for Candida albicans - 0.25 mg/l. The activity of fluconazole against various molds, apparently less than for yeast.

Fluconazole is almost completely absorbed from the gastrointestinal tract. When 50 mg of the drug is taken orally, the maximum concentration in plasma is about 1 mg/l, with repeated administration it reaches 2-3 mg/l. This exceeds the MIC for many sensitive fungi.

In blood plasma, no more than 12% of the drug is bound to proteins, the main amount is in free form. Fluconazole is very poorly metabolized by the liver and is excreted by the kidneys mainly unchanged. Excretion of the drug depends on the glomerular filtration rate.

High concentrations of fluconazole are created in the skin and nails. The hydrophilicity of fluconazole, which is in free form, allows it to quickly penetrate into the nail plate through the nail bed. Fluconazole can be detected in the nail plate just a few hours after administration. Fluconazole has some keratinophilicity and is cleared from the stratum corneum more slowly than from plasma.

For oral administration, the drug is available in the form of gelatin-coated capsules of 50, 100, 150 or 200 mg, in a package of 1, 7 or 10 capsules.

In the treatment of onychomycosis, fluconazole is used according to a pulse therapy regimen, prescribing 150 mg (once) per week. The duration of such therapy depends on the form and localization of onychomycosis: about 6 months for damage to fingernails, up to 12 months for toenails. Abroad, a pulse therapy regimen is used with the prescription of 300 mg per week (2 capsules of 150 mg each) for 9 months. Doses for children should not exceed 3-5 mg/kg per week.

The possible interaction of fluconazole with other drugs should be taken into account. Fluconazole should not be co-administered with cisapride. Fluconazole increases the half-life of hypoglycemic agents - glibenclamide, chlorpropamide, tolbutamide, potentiates the effect of indirect anticoagulants, increases the concentrations of phenytoin and cyclosporine. Rifampicin reduces fluconazole concentrations.

When prescribing fluconazole for long courses in large doses, the state of renal function is taken into account.

Side effects include nausea and abdominal discomfort. Treatment of onychomycosis with small doses of fluconazole once a week is usually not accompanied by any side effects or toxic effects.

Choice of drug

When choosing a drug for the systemic treatment of onychomycosis, you need to remember that each drug can provide a cure if given a reasonable and reasonable prescription.

We consider the spectrum of its action to be the main criterion determining the choice of a systemic drug. The spectrum should include fungi isolated from affected nails. In this regard, the etiology of onychomycosis, according to cultural studies, should be known to the doctor. If the etiology is unknown or several fungi have been isolated, a broad-spectrum drug is prescribed, including dermatophytes, fungi of the genus Candida, and non-dermatophyte mold fungi (Table 4.2.1).

Table 4.2.1

With a known etiology, the choice of drug is determined by the type of fungus isolated in the culture. For onychomycosis caused only by dermatophytes, terbinafine or griseofulvin is prescribed. For onychomycosis caused by Candida mushrooms, and for candidal paronychia, itraconazole, ketoconazole or fluconazole are indicated. For onychomycosis caused by molds- non-dermatophytes, use itraconazole.

We consider the second criterion clinical form onychomycosis, severity and localization of the lesion. When treating fungal infections affecting toenails with severe hyperkeratosis and matrix involvement, it is required long-term treatment. In these cases, griseofulvin or ketoconazole are often ineffective and unsafe in terms of side and toxic effects. For onychomycosis of the toes, the drugs of choice are itraconazole and terbinafine.

If you still have to prescribe griseofulvin and ketoconazole, then systemic treatment They are best combined with local therapy with antifungal agents and removal of the affected nail plate. This increases the effectiveness of treatment and helps reduce its duration.

The third criterion is the safety of treatment, the risk of side and toxic effects. Security issues are discussed below.

Duration of treatment

The duration of treatment for onychomycosis depends on the rate of nail growth. The growth rate is determined by location (toenails grow more slowly), the age of the patient and concomitant diseases- in elderly and weakened patients, people with chronic systemic diseases or previous nail pathology, they grow more slowly.

Average healthy nails on the hands they grow back in 4-6 months, on the legs - in 12-18 months. These periods determine the duration of treatment with griseofulvin and ketoconazole, as well as fluconazole.

Terbinafine and, to a greater extent, itraconazole can accumulate in the nail and remain there for a long time after treatment is discontinued. This allows you to shorten the treatment period by using short courses, intermittent therapy and pulse therapy. However, the recommended duration of treatment for such regimens is only approximate; in some cases, when toenails are affected with severe hyperkeratosis or degenerative phenomena, treatment must be extended.

Methods of prescribing drugs

There are 4 assignment schemes systemic drugs with onychomycosis.

1. Standard regimen, providing for daily administration of the usual dose of the drug throughout the entire treatment period. The duration of treatment corresponds to the time of growth of the nail plate. Any systemic drug can be prescribed according to this regimen.

2. A shortened scheme, in which the treatment period is shorter than the time of nail regrowth. Treatment is carried out with regular or increased doses. This regimen can be used with itraconazole and terbinafine, which can for a long time linger in the nails after stopping treatment.

3. An intermittent, or intermittent, regimen involves prescribing a regular or increased dose of the drug in several short courses. The intervals between these courses are equal to the duration of the courses themselves, for example a weekly course with a weekly interval. According to this scheme, you can use itraconazole and terbinafine, which accumulate and linger in the nails for a long time, and, in principle, all lipophilic drugs. The intermittent circuit has not yet received widespread acceptance.

4. Pulse therapy scheme. According to this scheme, an increased dose of the drug is prescribed in short courses at intervals exceeding the duration of the courses themselves. Treatment can be short, as with itraconazole, or as long as the nail plate grows out, as with fluconazole.

The most common drug prescription regimens used throughout the world are shown in Table. 4.2.2.

Table 4.2.2

* In the practice of domestic dermatologists, it is customary to change the regimen during treatment with griseofulvin: in the 1st month, 1000 mg of the drug is prescribed every day, in the 2nd month - every other day, in the 3rd and the rest - once every 3 days.

The advantages of short, intermittent and pulse therapy regimens are their safety in terms of side and toxic effects and the convenience for the patient while maintaining high efficiency. However, the standard treatment regimen with any drug gives statistically better cure rates.

Treatment safety

Security, i.e. the absence of serious side and toxic effects of the drug is one of the main requirements for any systemic therapy. First of all, it should be said that none of the antifungal agents used is free from side effects and toxic effect. In general, with reasonable prescription of drugs, all these side effects are transient, do not pose a threat to the life and health of the patient, and are almost always easily tolerated. Severe disorders complicating treatment with systemic drugs are very rare and are either anaphylaxis or idiosyncrasy.

According to the pharmacokinetic properties that determine the distribution and metabolism of the drug in the patient’s body, and therefore the possibility of certain side effects, all are presented in Table. 4.2.2 drugs can be divided into 2 groups. One group includes lipophilic drugs: griseofulvin, terbinafine, ketoconazole and itraconazole. They are not completely absorbed in the intestine; they are present in the blood predominantly in the form bound to plasma proteins, accumulate in tissues, undergo intensive metabolism in the liver, and are excreted in an altered form. The only representative of the other group is hydrophilic drug fluconazole.

General pharmacokinetic properties cause some side effects common to all of these drugs.

So, suction in digestive tract All 4 lipophilic drugs may be complicated by dyspeptic symptoms: nausea, abdominal discomfort, sometimes pain, vomiting. Intensive metabolism in the liver determines the possibility of hepatotoxic effects, manifested by an increase in the concentration of liver transaminases, alkaline phosphatase. All these effects can be prevented by prescribing therapeutic doses of drugs strictly according to indications in compliance with the recommended method of use.

Fluconazole - relatively safe drug, as evidenced by great experience its use in deep mycoses. The side effects of fluconazole are also similar to those of other drugs - dyspeptic symptoms and very rare cases toxic hepatitis. Features of the side and toxic effects of each of those included in the table. 4.2.2 antifungal agents are shown above in the description of these drugs.

It should be recognized that the risk of toxicity depends on the effectiveness of the drug. The less effective the drug is, the larger its doses have to be prescribed. The likelihood of toxic effects also depends on the characteristics of pharmacokinetics. Drugs with a high affinity for keratin, which accumulate in the nails, can be prescribed in shorter courses. The shorter the treatment period, the less likely unwanted effects.

The least dangerous regimens are pulse therapy, intermittent and shortened regimens;

the prescription of the drug must be etiologically justified. If the spectrum of action of the drug does not include the isolated pathogen, it should not be prescribed even in large doses;

duration of treatment traditional means can be reduced using combination therapy or intermittent regimen;

interactions with other drugs should be taken into account; no systemic drug should be prescribed to patients with liver disease;

No systemic drug should be prescribed during pregnancy and lactation.

Low efficiency and relatively low ability to accumulate in nails lead to a greater risk of using traditional systemic agents griseofulvin and ketoconazole. These drugs are prescribed according to standard scheme for up to 1 year, sometimes longer. The frequency of side effects and toxic effects is greatest when using griseofulvin and ketoconazole. With the advent of modern antifungal agents, neither griseofulvin nor ketoconazole is recommended for use as monotherapy for onychomycosis.

If the doctor does not have drugs other than griseofulvin or ketoconazole in his arsenal, he should consider how to make treatment with these drugs safe while maintaining effectiveness. There are two solutions to the problem. Firstly, it is possible to shorten the duration of treatment, and at the same time increase its effectiveness by combination therapy using local antifungal drugs And aids. Secondly, you can use an intermittent regimen, periodically (no longer than 1 week) allowing the patient’s body to rest and also combining systemic therapy with active local treatment.

The possibility of interaction of antifungal agents with other systemic drugs should always be considered. When prescribing a drug, you should carefully read the instructions or refer to this section of our book.

The main contraindications to systemic therapy for onychomycosis are liver disease and pregnancy. None of the systemic antifungal drugs should be prescribed to patients with liver disease or a history of hepatotoxic reactions. If persistent clinical or laboratory signs liver dysfunction, treatment is stopped.

When prescribing any drug daily for a period of more than 1 month, liver function indicators should be regularly determined - the content of aminotransferases and alkaline phosphatase (Table 4.2.3), starting with a control study before starting therapy.

If renal function is impaired or the glomerular filtration rate decreases, a dose adjustment of terbinafine may be required, since this drug is excreted primarily by the kidneys. No dose adjustment of fluconazole is required because it is prescribed in a relatively small dose only once a week.

Drug allergies, for example to penicillin antibiotics Many authors consider griseofulvin to be a contraindication.

Table 4.2.3

* When prescribing any drug, the individual characteristics of the patient, in particular his attitude to alcohol, should be taken into account. In people who regularly use alcoholic drinks, the level of liver aminotransferases is recommended to be determined after 1 week of treatment with any drug.

None of the 5 systemic drugs are recommended for pregnant women. With onychomycosis, the therapeutic benefit does not exceed the risk to the fetus. Because everything system tools excreted or can be excreted in milk, they should not be prescribed during lactation.

Drugs from the azole group can affect the metabolism of steroids in the human body. However clinical manifestations such interactions are not observed when using therapeutic doses. Doses, regimens and treatment periods used in the treatment of onychomycosis are much less than the maximum safe doses and timing recommended for azole drugs. Treatment of onychomycosis with azole drugs does not pose any risk of disrupting the patient's steroid hormone metabolism.

Reasons for failure of systemic therapy

When considering cases of unsuccessful treatment of onychomycosis with systemic antifungal drugs, it is worth paying attention to both the shortcomings of the drugs themselves, as well as their incorrect prescription by the doctor and the patient’s non-compliance with the prescribed dosage regimen.

Treatment with griseofulvin and ketoconazole is the least effective and most likely to cause side effects. Even with a treatment period of 1 year, the clinical and mycological effectiveness of treatment barely reaches 50%, and the relapse rate is 30-40%. Failure of treatment with griseofulvin or ketoconazole alone without the use of topical therapy can be considered common.

Doctor errors include prescribing potentially highly effective antifungal drugs without taking into account the clinical picture and etiology of onychomycosis, using inadequate doses and timing of treatment, ignorance individual characteristics patient (Table 4.2.4).

Failure of a patient to comply with the prescribed regimen of taking the drug is partly a mistake of the doctor, who did not explain to the patient the importance of strict adherence to this regimen and does not monitor the implementation of his recommendations.

There are cases when, even with a fully justified prescription, and the doctor and patient comply with all the rules and recommendations, it is not possible to cure onychomycosis or achieve removal of the fungus from the affected nails. In these cases, the treatment period is extended, the drug is replaced (for example, terbinafine is replaced with itraconazole and vice versa), and treatment with local antifungal agents is added to systemic therapy. In addition to prescribing antifungal agents, in the treatment of onychomycosis it is necessary to remove the affected parts of the nail different ways(removal of the nail plate, keratolytics, cleaning of the nail bed).

Table 4.2.4

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Terbinafine is a broad-spectrum fungicidal antifungal drug from the allylamine class, effective against dermatophytes, yeasts and molds. Available in tablets of 250 mᴦ. The daily dose for adults is 250 mᴦ. For children daily dose is calculated depending on the child’s body weight and is for body weight up to 20 kg – 62.5 mg/day, from 20 to 40 kg – 125 mg/day, over 40 kg – 250 mg/day. Terbinafine is prescribed once a day; food intake and the acidity of gastric juice do not affect its absorption. The average duration of treatment is 6 weeks for fingernails and 12 weeks for feet. In patients young with a normal rate of nail growth, it is possible to reduce the duration of therapy, and vice versa, with poor nail growth, terbinafine therapy is indicated for more than 3 months. Terbinafine has the highest activity among systemic antimycotics against dermatophytes, which cause the majority (up to 94%) of cases of dermatomycosis. Fungicidal concentrations of the drug remain in the skin and nail plates for 30 - 36 weeks after the end of treatment, ᴛ.ᴇ. the effect of the drug in the nail remains for up to 9 months, which significantly increases the percentage complete cure. Side effects in the form of a feeling of discomfort in the epigastrium, nausea, loss of taste, itching of the skin are short-term in nature and do not require cessation of treatment. In general, terbinafine is well tolerated.

Terbinafine, unlike other systemic antimycotics, does not affect the cytochrome P 450 system and therefore does not interact with other drugs (antihistamines, oral hypoglycemic drugs, oral contraceptives). Thanks to this, terbinafine can be used in the treatment of onychomycosis in the elderly, if concomitant pathology and taking other medications for chronic compensated liver and kidney diseases. Terbinafine can be used in the treatment of onychomycosis in children (officially approved for use in pediatric practice).

Itraconazole is a broad-spectrum azole antifungal drug. It is prescribed to patients with onychomycosis caused by dermatophytes, yeast and mold fungi. Itraconazole is most effective when prescribed using the pulse therapy method, ᴛ.ᴇ. take 2 capsules of 100 mg in the morning and evening (400 mg/day) for 7 days, then after a three-week break the course is repeated. When nails are affected on the fingers, patients receive two courses of therapy, on the toes - 3-4 courses, depending on the type, shape, area of ​​the lesion, and the rate of nail growth. After cessation of treatment, the effective concentration of the drug in the nails on the hands remains for 3 months, on the feet after 3 courses - 6-9 months, after 4 courses - up to 1 year. Tolerability of the drug is satisfactory. Side effects in the form of dysfunction gastrointestinal tract͵ headache, skin itching short-term and do not require a break in treatment.

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What types of treatment are carried out against nail fungus

Severe damage to the nail plate, when it is completely deformed, is called hypercarotic form. In this case, self-medication is unacceptable. In other cases, you can get by with ointments, creams and sprays based on some multifungal active ingredient.

Most often, therapy includes:

• Oral antifungal medications plus application similar drug to the site of the lesion.
• Removal of the affected part of the nail plate using keratolytic plasters Ureaplast, Microspora, Onychoplast, followed by treatment with antifungal drugs. Removing part or all of the plate speeds up the process of treatment and restoration of the nail.
• Application of antifungal varnishes. Helps in complex treatment, as prophylactic or on the initial stage diseases. Trade names varnishes: Amorolfine (Amorolfine), Lotseril ( active substance amorolfine), Ciclopirox, Batrafen (on ciclopirox), Omorolfine.
• Application of creams, ointments, solutions and sprays based on terbinafine.
• Prescription of oral systemic antifungal drugs - Griseofulvin, Grimelan, Ketoconazole, Itraconazole, Irunin, Terbinafine, Fluconazole and others. At the same time as the tablets, external agents are prescribed depending on the nature of the disease.
• In severe cases of the disease, medications are prescribed that contain not only antifungal substances, but also antibacterial or corticosteroid components. For example, Travocort contains isoconazole for fungi and diflucortolone valerate (corticosteroid), which relieves itching and allergies. Pimafucort is also a good drug, which contains a broad-spectrum antibiotic, an antifungal drug and a corticosteroid.
• As maintenance therapy, lotions with Dimexide are prescribed - it relieves inflammatory processes, drops and ointments with zinc, copper - accelerate the restoration of skin and nails.

One of the most affordable means for oral, that is, external, administration for nail fungus- Terbinafine. The name of the drug and the active substance are the same. Also suitable for treating skin, hair, mucous membranes. It is available in the form of ointments, creams, tablets, sprays, and solutions. It is rarely prescribed systemically; in most cases, local application is indicated. Belongs to the group of allylamines.

Terbinafine has a strong fungicidal effect on different kinds dermatophytes and other fungi and yeasts. It destroys intercellular membranes, and over time the fungi die. This drug is prescribed for a number of diseases: nail fungus, microsporia, mycoses caused by the fungus rubrum, trichophytosis, candidiasis of the mucous membranes and skin.

For local treatment fungus Terbinafine cream, ointment or spray is prescribed 1 time per day. The approximate duration of the course is 1 week. You cannot interrupt the course, despite the fact that improvement will occur after the second or third use of the drug. Main contraindications for use medicines with this active substance are hepatic and renal failure, as well as tumors of different nature, psoriasis, endocrine diseases.

It is most convenient to use sprays from different manufacturers. Alcohol solutions terbinafine are quickly absorbed into the nail plate, practically do not enter the blood (less than 5%), and dry instantly. So you can put on socks and shoes almost immediately after application.

Preparations for the treatment of mycoses with this active ingredient:

• Lamisil.
• Binafin.
• Thermikon.
• Terbasil.
• Fungoterbin.
• Exifin.
• Atifin and others.

They all have the same active ingredient, the same concentration for specific forms. The only difference is Excipients, responsible for softening the plate and transporting active substances into the nail. It is worth choosing based on individual tolerance and price.

This is another drug for the treatment of fungus with a broad spectrum of action. Belongs to the group of triazoles. Itraconazole has also been used successfully to treat lesions of the nail plate, as has Terbinafine. However, it is prescribed with caution to patients with liver and kidney disease.

Names of drugs based on Itraconazole:

• Irunin.
• Orungal.
• Tecnazole.
• Orungamin.
• Orunite.
• Rumicosis and others.

The most affordable are Irunin capsules. The duration and course of treatment (with intervals between doses) are prescribed by the doctor strictly individually.

It also belongs to the triazole series of drugs, that is, it acts similarly to Itraconazole. Its advantage over related drugs is that it has virtually no effect on human pathogenic microflora, that is, beneficial fungi in our body.

This is a relatively expensive drug that is prescribed in in rare cases when the patient has difficulties with immune system. So, he can be prescribed if there are tumors, immune depression, if the patient will have to undergo surgery in the near future, radiation therapy. In common cases of nail fungus, Fluconazole is not recommended. It is worth noting that this drug has a number of unpleasant adverse reactions, which are not characteristic of other antifungal agents.

Analogues:

• Diflucan.
• Mikosist.
• Flucostat.

All these capsule preparations are focused mainly on the systemic treatment of fungal diseases associated with genitourinary system person.

A fairly active antifungal drug that is most effective in the treatment of systemic lesions. There are practically no contraindications - only intolerance, pregnancy, lactation, serious illnesses liver, however, it can cause a number of side effects.

Medicines containing Ketoconazole:

• Mycozoral.
• Fungikok.
• Oronazole.
• Dermazol.

This active substance is also often used in the production of medicinal and cosmetic shampoos and ointments. For example, it is found in Nizoral shampoo and Perhotal.

Video: Antifungal drugs

Let's summarize the main drugs for nail fungus

Modern pharmacology can offer a number of antifungal drugs that affect many types of microfungi. Some of the drugs can be classified as specialized for treatment certain groups diseases. So, for example, they act medications based on Ketoconazole or Fluconazole.

Most often, mycologists prescribe products based on Terbinafine or Itraconazole to treat nail fungus. Some of the drugs based on them are widely advertised and are quite expensive. At the same time, the effect of such popular drugs has been well studied, which allows doctors to recommend these particular drugs.

If the problem has not gone too far, you can try to self-medicate. To do this, you need to soften the damaged part of the plate using special patches and remove it. Then choose an ointment, cream or spray for local application based on Terbinafine or Itraconazole and use according to the instructions.

For elimination discomfort Ointments with corticosteroids are suitable. Zinc and copper ointments will contribute to skin restoration. If therapy does not produce results, contacting a doctor is necessary. Not only loss of the nail is possible, but also systemic damage to the body by fungi.

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For systemic therapy of onychomycosis, terbinafine (Lamisil) from the group of allylamines, which has a fungicidal effect, and itraconazole (Orungal), which belongs to the triazoles and has a fungistatic effect, are currently used. Treatment with terbinafine is usually carried out continuously for 12 weeks, itraconazole is used continuously (at the same time) or for 1 week of every month for 3-4 months (pulse therapy), and a number of authors consider pulse therapy to be as effective as and continuous treatment with itraconazole or terbinafine. A prospective multicenter, double-blind, randomized study examined the effectiveness and safety of continuous treatment with terbinafine compared with pulse therapy with itraconazole in patients with onychomycosis of the feet. The study, conducted over 72 weeks, involved 35 centers in 6 European countries. The study group consisted of 496 patients aged 18 to 75 years with clinically and mycologically confirmed onychomycosis of the feet caused by dermatophytes. Patients were randomized into 4 parallel groups and received treatment with terbinafine 250 mg/day for 12 (group T12) or 16 weeks (T16) or itraconazole 400 mg/day (4 capsules of 100 mg) for 1 week of each month for 3 or 4 months (groups I3 and I4).

The primary outcome measure was the mycological cure rate, determined based on negative results microscopic and cultural studies of material taken from target affected nails (nail thumb feet). Mycological cure rates were assessed after 72 weeks of follow-up. Secondary efficacy criteria were the frequency of clinical cure (100% cleansing of the nail), the frequency of complete cure (mycological and clinical), clinical effectiveness(mycological cure, growth of at least 5 mm of a new nail not affected by mycosis) and overall rating given by the doctor and the patient.

The causative agents were: Trychophyton rubrum (89,3%), T.mentagrophytes (8,5%), T.rubrum+ non-dermatophyte molds (1.6%), T.rubrum + T.mentagrophytes (0,6%).

The mycological cure rate after 72 weeks was: 75.7% and 80.8% in groups T12 and T16, 38.3% and 49.1% in groups I3 and I4 (see figure). The clinical cure rate was significantly higher with any of the terbinafine treatment regimens compared with pulse itraconazole therapy (p<0,0022). На протяжении всего исследования (вплоть до 72-й недели) частота микологического и клинического излечения в обеих группах тербинафина продолжала повышаться, тогда как в группах итраконазола она не менялась.

Rice. Mycological cure rate (%)

The complete cure rate and clinical efficacy were significantly higher in the terbinafine groups compared with the itraconazole groups (p<0,005). Общая оценка результатов лечения выявила достоверное преимущество непрерывного лечения тербинафином по сравнению с пульс-терапией итраконазолом (р<0,0001).

236 patients reported adverse events (55, 61, 60 and 60 in groups T16, T12, I3, I4, respectively). The characteristics of adverse events for all 4 groups did not differ significantly and were within the known safety profiles of both drugs.

Treatment results were rated as good or very good by 79-85% of doctors and patients in the terbinafine groups and only 44-55% in the itraconazole groups.

The study showed that treatment with terbinafine 250 mg/day for 12 or 16 weeks provides a higher rate of mycological and clinical cure compared with pulse therapy with itraconazole after 72 weeks of follow-up.

One possible explanation for the higher efficacy of terbinafine in this study is the differences in fungicidal and fungistatic concentrations of both drugs described in the literature. Terbinafine has a fungicidal effect against dermatophytes, and its minimum fungicidal concentration (MFC) is approximately 0.004 μg/ml. Itraconazole has a fungistatic effect, and its average MPA against dermatophytes is approximately 0.6 μg/ml. When treating with terbinafine, drug concentrations are created in the nail that are 100 times higher than its MPA, while when using itraconazole, the drug concentration in the nail is only on the border between fungistatic and fungicidal concentrations. Fluctuations in itraconazole concentrations observed in different patients can worsen treatment results, while the use of terbinafine, despite significant fluctuations in concentrations, ensures the destruction of the pathogen. The therapeutic advantage of terbinafine was more clearly demonstrated in this study, since it included patients who had severe onychomycosis with a relatively large extent of lesions and a long course of the disease.

Literature:
Based on materials from: E.G.V. Evans, B. Sigurgeirsson. Double blind, randomized study of continuous terbinafine compared with intermittent itraconazole in the treatment of toenail onychomycosis. // British Medical Journal, 1999; 318: 1031-1035.

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Terbinafine is a broad-spectrum fungicidal antifungal drug from the allylamine class, effective against dermatophytes, yeasts and molds. Available in 250 mg tablets. The daily dose for adults is 250 mg. For children, the daily dose is calculated depending on the child’s body weight and is for body weight up to 20 kg - 62.5 mg/day, from 20 to 40 kg - 125 mg/day, over 40 kg - 250 mg/day. Terbinafine is prescribed once a day; food intake and the acidity of gastric juice do not affect its absorption. The average duration of treatment is 6 weeks for fingernails and 12 weeks for feet. In young patients with a normal rate of nail growth, it is possible to reduce the duration of therapy, and vice versa; in case of poor nail growth, terbinafine therapy is indicated for more than 3 months. Terbinafine has the highest activity among systemic antimycotics against dermatophytes, which cause the majority (up to 94%) of cases of dermatomycosis. Fungicidal concentrations of the drug remain in the skin and nail plates for 30–36 weeks after the end of treatment, i.e. The effect of the drug in the nail remains for up to 9 months, which significantly increases the percentage of complete cure. Side effects such as discomfort in the epigastrium, nausea, loss of taste, itching of the skin are short-term and do not require cessation of treatment. In general, terbinafine is well tolerated.

Terbinafine, unlike other systemic antimycotics, does not affect the cytochrome P 450 system and therefore does not interact with other drugs (antihistamines, oral hypoglycemic drugs, oral contraceptives). Thanks to this, terbinafine can be used in the treatment of onychomycosis in the elderly, in the presence of concomitant pathology and taking other medications, in chronic compensated diseases of the liver and kidneys. Terbinafine can be used in the treatment of onychomycosis in children (officially approved for use in pediatric practice).

Due to its fungicidal effect, short course of treatment and high percentage of complete cure (93-96%), terbinafine is considered the drug of choice for the treatment of onychomycosis.

Itraconazole is a broad-spectrum azole antifungal drug. It is prescribed to patients with onychomycosis caused by dermatophytes, yeast and mold fungi. Itraconazole is most effective when prescribed using the pulse therapy method, i.e. take 2 capsules of 100 mg in the morning and evening (400 mg/day) for 7 days, then after a three-week break the course is repeated. When nails are affected on the fingers, patients receive two courses of therapy, on the toes - 3-4 courses, depending on the type, shape, area of ​​the lesion, and the rate of nail growth. After cessation of treatment, the effective concentration of the drug in the nails on the hands remains for 3 months, on the feet after 3 courses - 6-9 months, after 4 courses - up to 1 year. Tolerability of the drug is satisfactory. Side effects such as gastrointestinal dysfunction, headache, skin itching are short-lived and do not require a break in treatment.

studopedia.su

Terbinafine and clotrimazole - what is the difference

After analyzing the medication instructions, we identified the advantage of Clotrimazole over Terbinafine. If Terbinafine ointment can only be used by children from 12 years of age, then Clotrimazole can be used from two years of age.

Having carried out a complete comparison of them, we came to the conclusion that the medications are equally good in their intended use. It’s another matter when you need an answer to the question with what effectiveness a particular drug treats your specific disease. We recommend that you contact your Dermatologist with this question.

A specialist with extensive professional experience will prescribe you the best treatment option for a particular ailment. This will be the most correct decision in your situation.

Video: Everything you need to know about Terbinafine

Systemic antifungals

V.S. Mitrofanov

Antifungal drugs can be classified according to the targets of their action in/on the fungal cell. Such classes include: polyene antibiotics, nucleoside analogues (fluorinated pyrimidines), azoles, pneumocandins-echinocandins, pradimycins-benanomycins, nikkomycins, allylamines and thiocarbamates, sordarins and others (Table 1).

Table 1.

Mechanisms of action of antifungal drugs.
(Vanden Bossche H, Marichal P. and Odds F. (1994)).

* Preparations for external use.

Polyene antibiotics.

Polyene antibiotics form complexes with ergosterol and disrupt the plasma membrane of fungal cells, which leads to an increase in its permeability, leakage of plasma contents and, as a consequence, the death of the fungal cell. Thus, polyenes are fungicidal agents and have the widest spectrum of antifungal activity. The affinity of polyenes for ergosterol in fungal cells is significantly higher than for cholesterol in mammalian cells, which makes their use in humans possible.

Nystatin.

Nystatin was discovered by Brown and Hazen in 1949 in soil samples containing actinomycetes Streptomyces noursei. It has been used in medicine since 1951. The name Nystatin stands for the abbreviation N-Y-State (New York State). The drug is poorly absorbed from the intestine after administration per os and it is not administered parenterally. As a result, the range of its use is quite narrow: local therapy for oropharyngeal candidiasis, superficial esophageal candidiasis, non-invasive intestinal candidiasis.

Amphotericin-B.

Amphotericin B (Amph-B) was obtained in 1953. from Streptomyces nodosus, isolated by W. Gold et al. from a soil sample on the Orinoco River in Venezuela. Amph-B is a broad-spectrum antifungal drug against fungi. It has a detrimental effect on Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporotrix spp. And Candida glabrata. It is also highly active against C. albicans and other types Candida, excluding C. lusitaniae.

At the same time, Amph-B is variably active against Aspergillus spp. and zygomycetes ( Mucor spp.), whereas Fusarium, Trichosporon spp. and Pseudoallescheria boydii are often resistant to Amph-B. Intravenous administration of Amph-B remains the main therapy for invasive mycoses: blastomycosis, coccidioidomycosis, paracoccidioidomycosis, histoplasmosis, fusarium, cryptococcal meningitis (severe and moderate), candidiasis, all forms of invasive aspergillosis and mucormycosis. The drug practically does not penetrate into the cerebrospinal fluid.

Nephrotoxicity is the most serious side effect of Amph-B. All patients receiving Amph-B have impaired renal function to varying degrees. The use of Amph-B should be accompanied by monitoring the level of creatinine and potassium in the blood serum. Typically, when the creatinine level exceeds 3.0-3.5 mg% (265-310 µmol/l), it is recommended to interrupt the administration of Amph-B for several days and then continue at a reduced dosage. Adverse reactions to Amph-B can be dose-dependent (nephrotoxicity, normochromic anemia), idiosyncratic (redness, rash, acute liver damage, thrombocytopenia, general pain, convulsions, ventricular fibrillation, cardiac arrest, fever and chills). It should be noted that fever and chills are observed in almost all patients, while other adverse reactions to the administration of Amph-B can occur unpredictably.

To reduce the phenomenon of fever during treatment, Amph-B is sometimes prescribed per os acetaminophen (paracetamol) 650 mg every 4 hours or diphenhydramine (diphenhydramine) 100 mg. Sometimes these drugs are given together half an hour before the start of Amph-B administration. Intravenous administration of prednisolone or hydrocortisone (25-50 mg) before the administration of Amph-B also reduces toxic reactions. These activities are called "premedication". In order to minimize the toxicity of Amph-B, an infusion of 1 liter of 0.9% sodium chloride solution was also used immediately before the administration of Amph-B. The most effective method to reduce the toxicity of Amph-B is the use of its liposomal forms.

Lipid-associated forms of Amphotericin B.

Lipid-associated forms of Amph-B have been developed to reduce the nephrotoxicity of traditional Amph-B. Amph-B in lipid complexes or liposomes has antifungal activity comparable to traditional Amph-B, but differs in pharmacological and toxicological properties. Lipid complexes of Amph-B (Abelset, AbelcetФ) are built like a double-sided membrane in the form of ribbons, the colloidal dispersion of Amph-B (Amphotec, AmphotecФ, Amfocil, AmphocilD) is complexes of cholesterol sulfate with Amph-B in the form of disks, and true liposomal Amph -B (Ambisome, AmbisomeФ) - compounds in the form of microspheres (Table 2).

Table 2.

Characteristics of lipid-associated forms of amphotericin B

New polyene antibiotics.

These, first of all, include the liposomal form of nystatin (Nyotran, Nyotran - produced by Aronex), which in the experiment showed high activity against invasive candidiasis and aspergillosis. The effective dose ranged from 2 to 8 mg/kg. The main advantage of niotran is its activity against all yeasts that are resistant in vitro to fluconazole, itraconazole and lipid-associated Amph-B complexes. Available in bottles of 50 mg (in 50 ml) and 100 mg (in 100 ml), the infusion rate is 2 ml/min. Minimum inhibitory concentration (MIC) in vitro is 1 µg/ml. Therapeutic blood concentrations were obtained after a single infusion of liposomal nystatin at a dose of 2 mg/kg.

The new polyene SPA-S-843 (developed by Societa Prodotti Antibiotici) showed high activity in vitro against Candida spp., Cryptococcus spp. And Saccharomyces spp. and less toxic than regular Amph-B. Also inhibitory activity in vitro SPA-S-843 vs. Aspergillus spp..was higher than that of Amph-V, and corresponded to Amph-V against R. orizae, P. variotii, Penicillium spp.. And S. shenkii, but was lower than Amph-B in relation to Mucor, Microsporium and Trichophyton spp.

Nucleoside analogues (fluorinated pyrimidines).

5-fluorocytosine (flucytosine, ancotyl), a synthetic analogue of cytosine, was specifically synthesized in 1957 for the treatment of leukemia, but due to the lack of cytotoxicity it was not used for these purposes. The antifungal activity of 5-fluorocytosine was discovered later and first proven in 1963 in experimental models of candidiasis. 5-fluorocytosine inhibits pyrimidine metabolism, which is necessary for the synthesis of RNA and protein in fungal cells.

Although fluorocytosine is active in vitro against Candida spp.. (including C. glabrata), Cr. neoformans and Aspergillus spp., in the clinic it was usually used only for the treatment of candidiasis and cryptococcosis, which was associated with weak therapeutic activity in monotherapy and the rapid development of pathogen resistance in both candidiasis and cryptococcosis. Despite the fact that flucytosine (mainly in combination with Amph-B) was used to treat candidal endophthalmitis and meningitis, cryptococcal meningitis and invasive aspergillosis, due to the advent of new antifungal drugs, it is now practically not used.

Azole derivatives.

Initially, azole derivatives included imidazoles (clotrimazole, miconazole and ketoconazole), followed by 1st generation triazoles (fluconazole and itraconazole) and then 2nd generation fluconazole derivatives (voriconazole, ravuconazole) and itraconazole (posaconazole).

Azoles inhibit the C14-a enzyme in fungi, a demethylase of the cytochrome P450 system, which is responsible for the conversion of lanosterol to ergosterol. This leads to depletion of ergosterol in the fungal cell membrane and its death. Activity in vitro for azoles varies and may not always coincide with clinical activity. Azoles are active against C. albicans, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, Paraccoccidioides brasiliensis; usually resistant to azoles Candida glabrata, Aspergillus spp., Fusarium spp. and zygomycetes (Table 3).

Table 3.

Spectrum of activity of antifungal azoles

(Using data from Graybill J.R., 1989)

The oldest (early) azoles.

Clotrimazole and miconazaol, discovered in 1969, are poorly absorbed when taken per os, However, clotrimazole cannot be administered parenterally and is used almost exclusively for local treatment of oral and vaginal candidiasis. At one time, miconazole preparations for intravenous use (Daktarin) were produced, but their effect was assessed as not quite optimal, and miconazole is used mainly for the treatment of superficial mycoses.

The azoles currently used for systemic use, including voriconazole, which will enter widespread clinical practice in the near future, are presented in Table 4

Table 4

Comparative pharmacokinetics of azoles

*Note. The pharmacokinetics of voriconazole is nonlinear after dosing per os, is linear up to 4 mg/kg when administered intravenously, but after 4 mg/kg it becomes nonlinear (increases disproportionately).

Ketoconazole (nizoral) )

Ketoconazole, discovered in 1978, has good oral absorption, a broad spectrum of activity and low toxicity, but can be hepatotoxic and cause certain dyshormonal disorders, such as a decrease in testosterone levels and ACTH synthesis. There is no dosage form of ketoconazole for intravenous administration. Oral ketoconazole is effective in patients with candidiasis, coccidioidomycosis, blastomycosis, histoplasmosis, paracoccidioidomycosis and dermatophytosis. Ketoconazole is protein bound, has poor penetration through the blood-brain barrier, and is not used to treat CNS lesions. Ketoconazole causes hepatitis in approximately 5% of cases.The dose of ketoconazole - 200-400 mg per day for 5-7 days does not affect the pharmacokinetics of aminophylline, however, in other studies, an increase in theophylline content by 22% was noted. Currently, it is being replaced from clinical practice by second-generation azoles. Ketoconazole is taken with food, which ensures its maximum absorption. The drug can be washed down with Coca-Cola or seltzer water, and in some cases it is dissolved in hydrochloric acid, gastric juice or together with acidin-pepsin and drunk through a straw so as not to damage the teeth with acid.

Fluconazole (Diflucan) ) .

Fluconazole was discovered in 1981. It is a metabolically stable, water-soluble, low-lipophilic bistriazole that binds poorly to plasma proteins. The drug is active both orally and intravenously, and the two routes have identical pharmacokinetics. For example, once daily administration of fluconazole results in high concentrations and rapid equilibration of the drug in body tissues with good tissue availability, including penetration into the cerebrospinal fluid, e.g. 100 mg per day serum concentration is 4.5-8 mcg/ml c 89% penetration into the cerebrospinal fluid. Fluconazole is well tolerated, has a very low level of side effects and a wide range of antifungal activity, excluding fungi of the genusAspergillus spp.. It should be noted that there are significant differences in the activity of the drug against fungi in the modelsin vivo And in vitro, which must be kept in mind when selecting antifungal therapy taking into account sensitivity. Comparative Activity Datain vitro And in vivo against Candida albicansfor azoles and Amph-B are presented in the table 5.

Table 5.

Comparative data on the activity of antifungal drugs in vitro(MIC) and in vivo(minimum effective concentration mg/kgd 4) .

The absorption of fluconazole is independent of gastric pH and food intake. It is highly soluble in water, which is why it is formulated for intravenous administration. Fluconazole is unique among known antifungal agents in that it is excreted through the kidneys predominantly unchanged (69-90%) and only about 4% in the urine as a metabolite. Fluconazole metabolites active against fungi are unknown. The drug accumulates in tissues for up to 2 weeks. Fluconazole is freely secreted by saliva and food liquids, which is proven by eradication Candida spp. from the intestines with intravenous administration. Resistant to fluconazole C. krusei And C. glabrata.

Fluconazole has been shown to interact with CYP2C9 and CYP3A4 of the cytochrome P450 system, but it is a significantly weaker inhibitor of CYP3A4 than other azoles, as was shown in experiments with cyclosporine. Meanwhile, it still reduces the clearance of cyclosporine and warfarin, which should be taken into account when using them together. No clinically significant inhibitors of fluconazole metabolism have been identified in humans, but its level may be affected by drugs excreted through the kidneys and affecting renal clearance. On the other hand, cimetidine, being a cytochrome P450 inhibitor, reduces the plasma concentration of fluconazole by 20%, which is likely due to decreased absorption. Relapses of mycotic infection and a decrease in AUC (area under the curve) of fluconazole when taken together with rifampicin and fluconazole have been described.

Currently, fluconazole is one of the most effective drugs for the treatment of oropharyngeal, esophageal and vaginal candidiasis, especially in patients with HIV infections or cancer. It is also effective for peritonitis, candidemia or disseminated candidiasis (including processes in patients with neutropenia), hepatosplenic candidiasis; and is the main drug for candiduria and other lesions of the urinary system. Long-term oral administration of fluconazole after Amph-B therapy prevents relapses of candidal endocarditis. Fluconazole has been successfully used to treat pulmonary and disseminated cryptococcosis, especially in patients with HIV infection. Fluconazole 200 mg three times weekly in HIV-infected patients with a CD4 count below 100 was effective for the primary prevention of cryptococcal infection. Fluconazole is well tolerated, even at very high dosages such as 2000 mg per day.

Itraconazole (Orungal)

Itraconazole, discovered in 1986, is a triazole with a broad spectrum of antifungal activity, including fungi of the genus Aspergillus. It is poorly soluble in water and is currently available only for oral administration. The drug can be given once a day. However, high doses (more than 400 mg/day), which are used for severe mycotic processes and pulse therapy, are prescribed in two doses. Due to the lipophilicity of itraconazole, its concentration in the skin can be 10, and in the liver - 10-20 times higher than in blood plasma. The bioavailability of itraconazole can vary significantly and is greatest when the drug is given with food. Taking grapefruit juice, which is a dietary inhibitor of cytochrome C450, does not affect the pharmacokinetics of itraconazole. Itraconazole is extensively metabolized in humans: no unchanged drug was found in urine and less than 20% was found in feces. Typically, itraconazole is metabolized to the active metabolite p-hydroxyitraconazole, which is an important metabolite due to its antifungal activity, although less than that of itraconazole, as well as -due to the tendency to accumulate in the blood serum in high concentrations.

The AUC of itraconazole after a 200 mg dose was approximately ten times higher than after a 50 mg dose. The main metabolism of itraconazole occurs through the CYP3A4 isoenzyme. However, many of the drugs affected by itraconazole are substrates of P-glycoprotein, which mediates drug transport in the small intestine, since itraconazole is an inhibitor of P-glycoprotein activity. Cimetidine reduces the half-life of itraconazole by 40%. Itraconazole should not be prescribed simultaneously with antacids, anticholinergic drugs, histamine H2 receptor blockers, omeprazole, because an increase in gastric pH leads to decreased absorption of itraconazole. The above applies to itraconazole, produced in capsules. The use of itraconazole in a mixture with b-hydroxycyclodextrin made it possible to create forms for intravenous administration and at the same time achieve absorption of more than 60% when taken per os Currently, itraconazole is produced in an oral solution (10 mg per ml, 200 mg per vial). The usual dose is 10 ml (100 mg) on ​​an empty stomach. Intravenous formulations of itraconazole are undergoing clinical trials.

Absorption of itraconazole is reduced in patients with acute leukemia and HIV infection. Although there is no clear correlation between clinical response and serum concentrations of itraconazole, monitoring serum concentrations in severely ill patients is necessary to monitor oral absorption. The feasibility of prescribing so-called “saturation doses” (300 mg twice a day - 3 days) is possible for certain groups of patients. Concentrations of itraconazole in the cerebrospinal fluid, eye and saliva are negligible.

Taking with astemizole, cisapride, terbenafine is dangerous due to the possibility of cardiac arrhythmias. If it is necessary to prescribe antihistamines, it is advisable to use the active metabolites of terfenadine (texofenadine) and hydrocysine (cetirizine).

Metabolism and drug interactions of antifungal azoles.

All antifungal azoles are metabolized using the cytochrome P450 system. The cytochrome P450 system refers to a group of heme-containing isoenzymes (CYP) located on the membrane of the smooth endoplasmic reticulum, mainly in the liver and small intestine.

The cytochrome P450 isoenzyme system plays an important role in the metabolism of many endogenous substances (steroids, hormones, prostaglandins, lipids and fatty acids) and in the detoxification of endogenous components (especially after oral administration). All drugs can be divided into three groups in relation to the cytochrome P450 system: substrates, inducers and inhibitors of this system.

Substrates are drugs that are metabolized by the catalytic action of enzymes of the cytochrome P540 system. Most drugs are metabolized predominantly by a single P450 enzyme. Ketoconazole and itraconazole are substrates of the cytochrome P450 system.

What are P450 inhibitors? These are drugs that suppress the metabolism of P450 substrates; the process is competitive and reversible - as soon as the inhibitor is withdrawn, metabolism returns to normal. Drugs may not be substrates and may be P450 inhibitors. For example, fluconazole is a weak P450 inhibitor, but it is not a P450 substrate and is excreted primarily through the kidneys. Ketoconazole and itraconazole, on the contrary, are pronounced inhibitors of the cytochrome P450 system.

What are P450 inductors? Inducer drugs increase the number of P450 isoenzymes in vivo. This process is associated with the activation of enzyme synthesis. Unlike the action of inhibitors, induction lasts several days even after discontinuation of the inducing drug. Rifampicin and phenobarbital are the two most powerful inducers of P450 enzyme synthesis. Of the antifungal drugs, griseofulvin is a P450 inducer.

Most drugs are eliminated from the body through the liver and kidneys. Only a small number of them are excreted in another way. Very large macromolecules, such as heparin and Amph-B, are taken up by phagocytic cells such as liver Kupffer cells. This pathway is called reticuloendothelial clearance.

All three azoles (ketoconazole, fluconazole and itraconazole) used in antifungal therapy can block the metabolism of drugs that use the CYP3A4 isoenzyme as a substrate for metabolism (i.e. astemizole, terfenadine, loratadine, cisapride, cyclosporine, erythromycin, clarithromycin, omeprazole) . For example, 99% of terfenadine entering the body is metabolized by the CYP3A4 isoenzyme. This isoenzyme has significant variability in expression and is responsible for 10-60% of the total cytochrome P450 activity in the liver. Ketoconazole and itraconazole may cause ECG QT prolongation when used with astemizole and terfenadine. Loratadine is also metabolized by the hepatic cytochrome P450 system CYP3A4, but in the presence of CYP3A4 inhibitors it may be metabolized via an alternative pathway via CYP2D6. Ketoconazole (200 mg 2 times a day for 5 days) inhibited the metabolism of loratadine in apparently healthy people. There are also reports of a possible connection between the use of loratadine and the occurrence of cardiac arrhythmias. The safest combination when using antifungal azoles together with antihistamines is the use of texofenadine (Telfast) or cetirizine (Zyrtec). All azole antifungals may potentiate cardiotoxicity when used with cisapride (although fluconazole did not contribute to cardiotoxicity when administered with astemizole and terfenadine). Antifungal azoles may enhance the effect of warfarin and significantly increase cyclosporine levels, so the combination of cyclosporine with these three drugs requires monitoring of its serum concentrations.

Since triazoles inhibit CYP3A4, one of the enzymes responsible for the metabolism of theophylline, coadministration may cause an increase in theophylline levels. Significant theophylline toxicity may occur during treatment with fluconazole. Theophylline levels may increase, decrease, or show no significant change when taking ketoconazole, probably because theophylline is metabolized by multiple P450 isoenzymes, so theophylline levels should be monitored during treatment with ketoconazole.

In the above situations, terbinafine is a safe alternative and can be used to replace ketoconazole, fluconazole or itraconazole. If drug replacement cannot be used, it is necessary to monitor their toxicity. The main drug interactions of azoles are presented in Table 6.

Table 6

Drug interactions of antifungal azoles
(Lasar J.D. et al. (1990); Como J.A. et al. (1994).

Note:

Very pronounced effect on drug concentration (the combination is ineffective)

Pronounced influence (high likelihood of side effects)

Significant impact (possible side effects)

Low impact (to be considered)

0 - no interaction

No information on drug interactions

Promising developments of azoles.

There is a lot of development of antifungal azoles, of which only voriconazole is currently being introduced into clinical practice.

Voriconazole.

Voriconazole, created in 1995, is a derivative of fluconazole. It is ten times more active than fluconazole when acting against Aspergillus spp ., Cryptococcus spp . And Candida spp., including C. krusei And S. glabrata resistant to fluconazole. Moreover, voriconazole showed not only fungistatic, but also fungicidal activity against Aspergillus spp. at concentrations approximately twice the MIC. Activity in vitro established for endemic pathogens ( Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis And Histoplasma capsulatum), as well as potential pathogens, including Fusarium spp., Acremonium kilensii, Scedosporium infatum, Trichosporon spp. And Pseudallescheria boydii resistant to fluconazole, itraconazole and Amph-B. Voriconazole is produced in dosage forms for oral and intravenous use, penetrates well into body tissues, including the brain and cerebrospinal fluid, and has a low level of side effects. The bioavailability of voriconazole is more than 80%, however, it should be borne in mind that taking the drug within an hour after a meal reduces it. When entering the body, 60% of the active substance binds to blood serum proteins. Metabolism occurs through the cytochrome P450 system: isoenzymes CYP2C9, CYP3A4 and CYP 2C19. Voriconazole may inhibit the activity of CYP2C9, CYP2C19 and, to a lesser extent, CYP3A4.

Posaconazole

Posaconazole (SCH -56592) is a second generation triazole and a structural analogue of itraconazole. The drug has low solubility in water (less than 2 mg/ml); it is produced only for oral use (in 100 mg tablets and oral suspension). Level of inhibition of C14a - demethylase in A. flavus And A. fumigatus for posaconazole is 10 times higher than for itraconazole. The half-life ranged from 15 to 25 hours and was dose dependent. The drug penetrates poorly into the cerebrospinal fluid, however, some positive effects have been noted for lesions of the central nervous system. Experimental models have shown high effectiveness against Coccidioides immitis. Animal studies have shown that achieving posaconazole plasma concentrations of 1-2 mcg/ml was effective in eradicating most lethal systemic fungal infections. Side effects include dizziness, headache, and drowsiness.

Ravuconazole.

Ravuconazole (BMS-207147), a derivative of fluconazole, showed high activity in vitro and high efficacy in experimental models of invasive aspergillosis, which were comparable to Amph-B, as well as higher activity than itraconazole and fluconazole against Candida spp . (including C. krusei), Coccidioides, Histoplasma, Fusarium And Blastomyces compared to itraconazole and fluconazole, maintaining fungicidal concentrations close to the MIC. It was also superior to fluconazole in models in vivo with cryptococcosis and candidiasis of the gastrointestinal tract. The half-life was very long, ranging from 5 to 8 days, with good bioavailability and tolerability. It is the long half-life that requires study in terms of such effects and drug interactions, since, according to other data, in experimental invasive aspergillosis in rabbits, the half-life was 13 hours, and no accumulation of the drug was noted 6 days after cessation of treatment.

Echinocandins and pneumocandins

Echinocandins are cyclic lipoprotein fungicidal agents that interfere with cell wall synthesis due to noncompetitive inhibition of the synthesis of 1,3-b-D-glucan, an enzyme absent in mammals. This inhibition is highly specific and even a short exposure of the drug leads to the death of the fungal cell. The disadvantage of echinocandins is their low activity against cryptococci. Pneumocandins are analogues of echinocandins (one of the classes of echinocandin lipoproteins). The name "pneumocandins" is due to the fact that they have activity against Pneumocystis carinii, and also against Candida And Aspergillus spp.. Like other echinocandin analogues, pneumocandins have little activity against cryptococci.

The first drug of this class approved for use is caspofungin (Cancidas, CancidasF, MK-0991) from Merck, produced in dosage form for intravenous administration (the bottle contains 50 mg of the drug, which is diluted in 0.9% sodium chloride solution). The drug is primarily intended for antifungal therapy of patients with invasive forms of aspergillosis, resistant to standard therapy or intolerant of other antifungal drugs. Recommended doses: on the first day, 70 mg once, then 50 mg intravenously once daily. Research in vitro showed that caspofungin is not an inhibitor or substrate of any enzymes of the cytochrome P450 system. Studies on healthy volunteers have shown that caspofungin does not interact with other antifungal drugs (itraconazole or Amph-B). When caspofungin is prescribed together with drug clearance inducers such as rifampicin, dexamethasone, carbamazepine, the caspofungin dose may be increased to 70 mg if there is no adequate clinical response. There are no data on the possibility of using caspofungin in parallel with cyclosporine, so this combination is not yet recommended. Side effects included fever, phlebitis, thrombophlebitis at the infusion site, headache, nausea, rash, skin erythema, mild elevation of liver enzymes, and cases of anaphylaxis (manufacturer information - www.merck.com).

Other drugs in this class, anidulafungin (V-echinocandin, manufactured by Versicor) and micafungin (FK-463, manufactured by Fujisawa) are in the last stage of clinical trials.

Pradimycins and benanomycins.

Pradimycins and benanomycins are fungicidal components that bind in a calcium-dependent mechanism to cell wall mannoproteins, which causes osmotic lysis and leakage of intracellular components, leading to the death of the fungal cell. A calcium-dependent effect on mammalian cells was not detected in these classes of antifungal agents. Pradimycins-benanomycins are fungicidal for many fungi, including those resistant to other antifungal agents. BMS-181184 has been shown to be effective, although less effective than traditional Amph-B, in experimental models for aspergillosis, candidiasis and cryptococcosis, although clinical studies in volunteers were interrupted due to its hepatotoxicity. Other water-soluble compounds from this group are currently being studied.

Nikkomycins.

Nikkomycins are inhibitors of the synthesis of chitin, an essential component of fungal cell walls.

Nikkomycin Z(Nikkomycin Z, SP-920704, manufacturer Shaman) effective in vivo And in vitro against dimorphic fungi C. immitis And B. dermatitidis, but only moderately active in vitro against C. albicans, Cryptococcus neoformans And Histoplasma capsulatum. Synergistic activity in vitro observed with the combination of nikkomycin Z with fluconazole or itraconazole against Candida spp.., Cr. neoformans And A. fumigatus And in vivo- against H. capsulatum. Accept per os; synergist with fluconazole and itraconazole. Nikkomycin was licensed to Bayer AG in 1995, primarily for use in the endemic mycoses in the United States, North American blastomycosis and coccidioidosis. Currently completing preclinical trials.

In this group of drugs, new antifungal compounds (Lys-Nva-FMDP) have recently been synthesized, which act as an inhibitor of glucose-6-phosphate synthetase (an enzyme that catalyzes the first step of chitin biosynthesis). Growth inhibition established H. capsulatum in vitro And in vivo, and no toxicity when tested on mice.

A recombinant human chitinase was also created, which was effective against experimental candidiasis and aspergillosis in animals, but showed significantly greater activity in combination with traditional Amph-B.

Allylamines and thiocarbamates.

Allylamines and thiocarbamates are synthetic fungicidal agents that are inhibitors of the enzyme squalene epoxidase, which, together with squalene cyclase, converts squalene to lanosterol. In the fungal wall, if squalene is not converted to lanosterol, the conversion of lanosterol to ergosterol is blocked. As a result of ergosterol depletion, the cell membrane of the fungus is damaged. There are two allylamine antifungal drugs, naftifine and terbinafine, and one thiocarbamate, tolnaftate. Naftifine and tolnaftate are drugs for topical use, while terbinafine is used for systemic treatment of dermatomycosis.

Terbinafine.

Terbinafine showed good activity in vitro against Aspergillus spp., Fusarium spp., dermatomycetes and other filamentous fungi, but variable activity against yeast-like fungi. However, in experimental models it was ineffective against invasive aspergillosis, systemic sporotrichosis, systemic candidiasis, or pulmonary cryptococcosis. However, activity was detected in vitro against Aspergillus spp., Candida spp., including triazole-resistant strains, and Pseudallescheria boydii in combination with azoles or Amph-B, as well as in experimental models of aspergillosis in combination with Amph-B and in cutaneous sporotrichosis. Currently, terbinafine is used mainly for the treatment of mycoses of the skin and onychomycosis, since when taken orally it creates antifungal concentrations in the nail bed. Terbinafine is ineffective in the treatment of pityriasis versicolor because the concentrations it creates in the stratum corneum are not high for a sufficient therapeutic effect. Although, unlike most azoles, terbinafine does not inhibit the cytochrome P450 system and, in particular, the isoenzyme CYP3A4, CYP3A4 may nevertheless play a role in the metabolism of terbenafine and its drug interactions. Considering that it is still metabolized through other liver mechanisms (only< 5% через систему цитохрома Р450), поэтому некоторые ингибиторы цитохрома Р450 (например, циметидин), могут снижать клиренс тербинафина. Рифампицин увеличивает клиренс фербинафина на 100%. Существует много метаболитов тербинафина, но среди них нет метаболитов с антифунгальной активностью. После приема per os 70-80% of terbinafine is adsorbed from the gastrointestinal tract. Eating does not significantly affect its bioavailability, so terbenafine can be taken with food or on an empty stomach. Terbinafine quickly diffuses from the blood vessels (through the dermis and epidermis) and concentrates in the fatty layer. It is also distributed into hair follicles, hair, skin, rich in sebaceous glands, remaining in high concentrations in hair follicles and nail beds. Its concentrations in the stratum corneum after 12 days of treatment exceed plasma levels by 75 times, and in the epidermis and dermis by 25 times. Blood cells contain approximately 8% of the administered terbinafine; it is missing in sweat. Terbenafine undergoes first-step metabolism, which involves no more than 5% of the total cytochrome P450 capacity. However, terbinafine competitively inhibits CYP2D6, which should be taken into account when used concomitantly with drugs metabolized by these isoenzymes (eg, amitriptyline).

Soldarins.

Soldarins represent a new class of potential antifungal agents that inhibit protein synthesis in pathogenic fungi. The main target of their action is elongation factor 2.

Quite a lot of new soldarins are being studied, including GM-193663, GM-237354, etc. Some of these components have activity in vitro against Candida spp. , Aspergillus spp ., Cryptococcus neoformans, Pneumocysti. carinii and some other mushrooms. A synergistic effect was obtained when combining soldarins with Amph-B, itraconazole and voriconazole against Aspergillus spp. and Scedossporium apiospermum. High efficiency proven in vivo with candidiasis and premonia caused by Pneumocystis carinii. It is likely that further research in this area will be continued.

Cationic peptides.

Cationic peptides of natural and artificial origin are incorporated into the ergosterol and cholesterol membranes of the fungal wall, which leads to cell lysis. These peptides have antifungal activity against Aspergillus spp. , Candida spp. , Cryptococcus neoformans and Fusarium spp.

Natural cationic peptides include cecropins, dermaseptins, indolicin, histatins, BPI (Bactericidal Permeability-Increasing) factor, lactoferrin and defensins. The synthetic cationic peptide Dolastin-10 targets intracellular tubulin and has potential fungicidal activity against Cr. neoformans.

From this group, Mycoprex (MycoprexD produced by Xoma), obtained from the human BPI factor produced by neutrophils, is undergoing preclinical trials.

The choice of drugs for various mycoses is presented in Table 7.

Table 7.

Drugs of choice for various fungal infections.

(Using data Andriole V.N., 1999)

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Change in nail color, thickening and deformation of the nail plate are the dominant symptoms of fungal infection. Activation of pathogenic microorganisms occurs under the influence of negative factors. Treatment of fingernail fungus is carried out using topical agents - Loceryl, Demicten, Mikozan. It is necessary to prescribe tablets for oral administration - Fluconazole, Terbinafine, etc. Treatment of fungus is not an easy task, since the disease often becomes chronic.

Etiology of fungal infection of the hands

Fungus on the fingernails appears due to infection by pathogenic microorganisms, or due to increased pathogenic activity of one’s own microflora.

Definitely, the pathogenesis of the disease is the growth and reproduction of fungal microflora. The following factors lead to the pathological process:

1. A disorder of cellular immunity, which is caused by various chronic pathologies - diabetes, HIV, AIDS, etc.
2. Long-term use of antibacterial drugs. Glucocorticosteroids, hormonal medications and some other medications provoke fungal activity.
3. The use of false nails, under which a favorable environment has been formed for the proliferation of pathogens.
4. Frequent contact with water. The risk group includes workers in canteens, public catering establishments, rest homes, sanatoriums, etc. The longer the upper limbs are in a humid environment, the higher the likelihood of getting sick.
5. The negative impact of chemicals and alkaline substances weakens the natural protection of the nail plate, which increases the risk of pathology.
6. Age-related changes are a factor in fungal infection. Experts note that every 10 years the likelihood of the disease increases several times.
7. Mechanical injuries, improper manicure, psychological problems, etc.

In most cases, fungi enter the nail through the nail bed, where they penetrate through small wounds and cracks. If a person has good immunity and no chronic diseases, then the fungus will not develop.

Clinical manifestations of fungal infection of the hands

Signs of fungus on the hands depend on the specific type of pathogen. Let's consider the clinical manifestations of dermatophyte infection:

• Severe itching of the palms;
• The appearance of peeling and cracks in the interdigital space;
• White stripes, spots, and yellow stains appear on the nail plate;
• Hyperemia of the skin around the nails, the appearance of tiny cracks;
• The appearance of the nail changes - it thickens, holes, bulges, grooves and other types of deformation appear;
• After a short time, the nail begins to collapse, the plate separates from the nail bed;
• The appearance of blisters, weeping, and erosions indicates that the fungal infection is complicated by a bacterial disease;
• Changes in skin color, appearance of scales, nodules, etc.

Important: excessive hygiene can play a bad joke on clean people. The first signs of infection appear in the interdigital space, and frequent washing washes away scales and mealy formations without leaving noticeable marks. This leads to the fact that a person finds out about his disease too late, and the severe stage is difficult to cure.

Clinical manifestations of infection with a yeast-like fungus of the Candida family:

1. Inflammatory processes in the nail fold, erosion and cracks.
2. Changes in the appearance of the nail plate - waves and grooves appear on the nail.
3. Fingers, nails, skin - everything becomes pathologically thicker.
4. Peeling, burning, severe itching.
5. When the form is advanced, there are painful sensations.

As medical practice shows, Candida is in most cases a “female” fungus. In addition to nails, there is often an infection in the oral cavity, the folds of the body and genitals are affected.

Types of fungi and variants of the course of the disease

Before you learn how to quickly cure fingernail fungus, let's look at the types of fungal diseases. In medicine, there are three types of onychomycosis of the hands:

• The normotrophic type is characterized by the appearance of spots and stripes on the nail; they are white or yellow. The shape and structure of the nail plate do not change;
• The onycholytic type is accompanied by a rapid lag of the nail plate from the bed; The nail color is gray, there is no natural shine. Over time, the nail falls off, the skin underneath becomes loose;
• The hypertrophic appearance is characterized by pitted edges of the nail, lack of shine, and thickening. Many patients complain of pain.

Each pathogen has special characteristics; accordingly, the clinical picture of the disease differs in many cases. Therefore, before prescribing drugs for the treatment of fingernail fungus, the doctor determines the course of the pathological process:

Often, fungal nail infections are complicated by bacterial inflammation of the nail fold. The picture is accompanied by an increase in body temperature, severe pain, swelling, and hyperemia. Sometimes purulent discharge is present.

Treatment options

To find out how to treat fingernail fungus, you need to visit a doctor and take the necessary tests. After identifying the exact pathogen, the doctor will write a treatment regimen. In addition to medicinal methods, you can use folk remedies for fingernail fungus.

Conservative therapy: topical agents and tablets

When the disease is diagnosed at the initial stage, but local anti-fungal agents are prescribed - ointment, cream, varnish, gel, etc.

Antifungal varnishes:

It is worth knowing: monotherapy with varnishes is carried out in cases where less than 50% of the nail plate is affected, while the shape and structure of the nail is not changed.

Treatment of fungus under fingernails is supplemented with tablets if the area of ​​fungal infection is more than 50%, there are changes in the color and structure of the nail plate, and there is a history of chronic pathologies.

Effective treatment of nail fungus is carried out with the following drugs:

1. Ketoconazole is a drug against fingernail fungus in tablet form. Prescribed to take 200 mg once a day. The duration of therapy is determined individually, but not more than 2 months. The drug has toxic components.
2. Fluconazole is taken for six months, the dosage is 150 mg (one tablet) once a week.
3. Terbinafine is an effective remedy for nail fungus, characterized by a cumulative effect, which allows you to quickly destroy pathogenic microorganisms.

Symptoms and treatment are always interconnected, so the doctor always prescribes the regimen. Even if everything seems clear, it is strictly not recommended to take medications for nail fungus on your own. Medicines have contraindications and can lead to local and systemic side effects.

Traditional treatment

How to treat nail fungus? Mycosis is one of those pathologies for which all remedies are good. Treatment with folk remedies must be approved by a doctor. This is an auxiliary method and is not used as monotherapy.

Recipes for fungal infections:

• Dissolve one tablespoon of sea salt in a liter of warm water. Make a hand bath. The duration of the manipulation is 20 minutes;
• Brew natural coffee, filter. Make baths from the cooled drink every other day.

A recipe will help destroy the fungus: pour a tablespoon of celandine with a glass of boiling water, keep it on low heat for five minutes. Leave for several hours. This remedy for fingernail fungus is used in the form of baths or lotions until improvement occurs.

When diagnosed with mycosis of the hands, you must follow all the doctor’s recommendations; it is strictly forbidden to interrupt the course of therapy on your own. The fight against fungal infection is a complex, lengthy, but necessary process, so you need to be patient.

Preparations for the treatment of nail fungus: effective and inexpensive

Fungal nail infection - onychomycosis - is not a rare disease. The shame is that it is extremely easy to get infected, but it is very difficult to get rid of. And you can’t do it without special medical supplies. Antifungal preparations for nails number more than one tenth of the items, differing in cost, release form and content of active ingredients. Choosing the right medicine among this variety is not easy.

Danger of disease

Signs of fungal infection can be easily determined with the naked eye: nails lose their natural shine and smoothness, acquire a yellowish or brown tint, thicken, and in advanced cases begin to flake, crumble and tear away from the nail bed.

This pathology is overwhelmingly characteristic of toenails. Fans of swimming pools, public baths and beaches are at greatest risk of contracting the fungus. At home, the infection is easily transmitted from the carrier to household members through shared shoes and hygiene items.

The list of antifungal agents includes local and systemic drugs. The former are intended for application to affected areas of the body, the latter are taken orally to achieve a complex therapeutic effect.

When choosing how to treat toenail fungus, you need to be guided by the recommendation of your doctor. Arbitrary use of drugs can provoke the development of resistance - persistence of the infection and subsequent relapse.

System Tools

Systemic medications are prescribed for long-term, rapidly progressing infections, hypertrophic lesions of the nail plates, and the spread of fungus to nearby tissues.

Capsules and tablets against nail fungus, produced by the Russian and foreign pharmaceutical industries, contain active fungicidal substances that are destructive to most types of known pathogens.

The names of the main ones:

• fluconazole;
• terbinafine;
• intraconazole;
• griseofulvin;
• ketoconazole

When taken orally, medications are absorbed into the cavities of the stomach or duodenum, penetrate the blood and tissues of the internal organs, providing a therapeutic effect.

Antimycotic drugs are developed on their basis and differ in the dosage of fungicides, the content of excipients, the release form, and the manufacturer. Despite the wide price range: from 20-30 to 2000 rubles, no significant differences between expensive drugs and cheap ones have been identified. Budget funds can cure fungus no worse than their high-cost counterparts. And given the need for long-term therapy - a successful course should last at least several months, the use of inexpensive but effective drugs is more justified and reasonable.

Antimycotic systemic agents are toxic and can cause side effects. It is unacceptable to take them simultaneously with hormonal contraception during pregnancy and lactation. In people with digestive disorders, such drugs provoke an exacerbation of diseases of the stomach, intestines, liver, and kidneys.

In some cases, absent-mindedness and deterioration of attention are likely to occur. Due to high toxicity, dosages for children and adults are strictly different.

Fluconazole

This active substance belongs to triazoles, effective against many types of dermatophytes, yeast fungi, and microsporia. Fluconazole inhibits cellular synthesis and prevents further spread of the fungus. Within 6-10 months after the nail plate is completely renewed, the disease can be considered cured.

• Fluconazole - capsules of domestic production with the same name, prolonged action. An inexpensive remedy for fungus that tops the popularity ratings. One capsule of 150 mg. It is enough to take once a week. The cost of packaging the drug is 30-50 rubles. A full course of treatment requires from 3 to 7 packages, depending on the severity of the infection.
• Mikosist is a drug from the Hungarian company Gedeon Richter, available in capsules of various dosages. The lower price limit is 200-250 rubles.
• Diflucan is a medicine for nail fungus based on fluconazole produced in Belgium. A package of 4 capsules costs about 500 rubles, which is significantly more expensive than Russian analogues.
• Forkan - antifungal capsules made in India. A package containing 1 capsule with a standard dosage costs about 200 rubles. The most expensive drug of all analogues.

Terbinafine

The allylamine group of broad-spectrum fungicides, which includes the active substance terbinafine hydrochloride, blocks metabolic processes in fungal cells and destroys mature spores.

Well-known domestic antimycotic drugs of this series:

Itraconazole

A synthetic substance made from triazole derivatives that helps cope with fungal infections of mold and yeast origin, dermatophytes. Treatment with drugs of this series has some peculiarities. The intake is carried out pulsed: you need to drink 400 mg daily for a week. means, then take a 3-week break and repeat the course.

• Itraconazole capsules from the domestic pharmaceutical company Biocom are a relatively inexpensive medicine for toenail fungus. Standard packaging of 14 pieces with a dosage of the active substance of 100 mg. costs no more than 300 rubles.
• The drug Irunin is similar to the previous one, containing 10 capsules of 100 mg each. costing 350-450 rubles.
• Rumicosis is another remedy with itraconazole capsules. One package contains 15 pieces, their price is about 500 rubles.

Considering that a course of treatment requires, on average, 2800 mg. medications (28 capsules), Intraconazole can be considered the most beneficial.

Griseofulvin

This chemically active substance effectively helps in suppressing the proliferation of fungi by destroying the membranes of their cells. Domestic pharmaceuticals produce the tablet drug Griseofulvin. The medicine contains 20 tablets of 125 mg. In severe forms of onychomycosis, a full course of treatment for nail fungus may require from 10 to 15 packages, each of which costs between 200-300 rubles.

Ketoconazole

Products containing ketoconazole are prescribed for candidiasis or mixed fungal infections. Due to the large number of adverse reactions, they are prescribed infrequently and only in the absence of serious chronic pathologies.

The following drugs are used in the treatment of mycoses:

External products

Topical medications for treating toenail fungus work directly on the affected area. They can be used as an addition to systemic therapy or independently.

In case of shallow localization of the infection and its initial stages, success can be achieved by choosing a special solution or varnish to treat the nail fungus, and to eliminate concomitant damage to the skin of the foot and the spaces between the toes - an ointment or cream.

Before using local medications, you must take hot foot baths with soap and soda. Steamed nails and the skin around them become softer and looser, absorbing medications more easily. The product should be applied not only to the nail itself, but also to areas of the skin within a radius of 1.5 cm. The fungus can nest near the nail plates and recur after visible recovery.

Solutions are considered the most effective topical antifungal agents for nails. The liquid penetrates the fabric faster and deeper, without leaving greasy marks or staining the shoes.

• Lamisil is a solution based on terbinafine, available in 15 ml bottles. This drug is considered by many to be the best remedy for toenail fungus. A lasting therapeutic effect is achieved after 14 days of daily use. But for a complete cure, it must be used until the nail is completely renewed. The cost of the medicine is quite affordable and amounts to 300-350 rubles.
• Lamitel is a solution in the form of a spray, very convenient for application to affected areas. Application is effective only in the early stages of mycoses. The course lasts 2-3 weeks. The cost of the drug is quite affordable: 150-200 rubles. per bottle.
• Nitrofungin is a liquid product with undecylenic acid in 25 ml glass bottles. A fairly inexpensive good remedy for treating fungus. It needs to be applied 2 times a day. The inconvenience is that the drug stains the nails - they turn yellow. Packaging price: from 200 to 300 rubles.
• Exoderil is a solution whose active ingredient is naftifine. Highly praised for its effectiveness. Used regularly, this drug relieves all symptoms of fungus in a short period. Accumulating in tissues, Exoderil prevents the re-development of infection. The price of a 10 ml bottle of this product is noticeably higher and amounts to about 600 rubles.

Lucky

One of the most convenient forms, does not require special skill in use. The therapeutic effect is achieved in mild, uncomplicated stages of mycoses. For deep lesions it is better to choose other means. If desired, varnishes can be applied under a decorative coating.

The most popular drugs of this type include:

• Loceril. The main active ingredient is amorolfine. You need to apply varnish once every 2 weeks. It can be used for the treatment and prevention of mycoses. It cannot be called cheap - the drug costs from 1200 rubles, but it is quite economical.
• Batrafen. The product contains the substance ciclopirox, which is effective against most types of fungus that affect nails. The average cost of one bottle is 1,500 rubles.

Ointments, creams and other dosage forms

Depending on your preferences, you can choose inexpensive but effective remedies in the most convenient forms for the treatment of nail onychomycosis.

Preparations with a viscous dense texture - creams and ointments, compared to liquids, fit worse into the nails, but are more suitable for eliminating concomitant mycoses of the skin of the feet. If desired, you can choose products based on synthetic or herbal ingredients that do not cause adverse reactions.

List of popular drugs:

• Fundizol. Cream based on natural ingredients. It includes: salicylic acid, celandine extract, oak bark and other natural fungicides. Apply the cream to prepared nails, which are then bandaged for several hours. The treatment period lasts up to 2 months. A tube of cream costs 90-100 rubles.
• Salicylic ointment. One of the most affordable means to eliminate fungus. It is used both for treatment and as prophylaxis and does not cause side effects. Cost of one package: about 30 rubles.
• Nogtimycin. Natural cream for painless removal of the affected nail plate. It is applied for several days, bandaging the diseased nail, then the exfoliated tissue is removed. Cost of the drug: about 100 rubles.
• Mikoket. Ointment with ketoconazole is effective against fungi of yeast origin. The treatment period is quite long - at least 3 months. Price of the drug: 120 rub.
• Nailitis. A composition based on tea tree oil and uric acid that destroys the diseased nail, in the place of which a healthy one subsequently grows. The price of a tube is no more than 200 rubles.
• Atifin. A cream produced in Slovenia, based on terbinafine, is used for 20-30 days. It must be applied several times a day. If mycosis is advanced, local treatment must be combined with antimycotics. The price of 15 grams of cream is 200-250 rubles.
• Bifosin. Produced in Russia. Fungicidal cream with bifonazole inhibits the activity of most fungi, while simultaneously loosening the affected nail surface. Can be used once a day, applied under a bandage. After 2 weeks, the diseased nail comes off completely. The product is an inexpensive drug: a 30 gram tube costs 70-80 rubles.
• Mikozan. The drug is in the form of serum. Easy to apply, absorbs quickly without leaving noticeable marks. Can be an alternative to using varnish. Treatment of advanced mycoses should be combined with the use of systemic antimycotics. A package of the product costs about 500 rubles.

When making a choice in favor of one remedy or another, one must not forget about the necessary precautions. The main cause of re-infection is infected shoes. And the most effective medications will not get rid of the fungus for a long time if you replace the shoes and boots that were worn during the period of illness with new ones.

Video on topic

Terbinafine tablets are a fungicidal antifungal drug. It is used to combat most fungal agents that can infect the human body. Available in several forms.

Composition and release form

The drug for nails, hair and skin is available in the form of white (white with a yellowish tint) tablets, separated by a score. Moreover, one tablet contains 250 mg of hydrochloride. The drug includes:

• microcrystalline cellulose 0.08 g;
• hydroxypropylcellulose 0.025 g;
• croscarmellose sodium 0.08 g;
• colloidal silicon dioxide 0.01 g;
• calcium stearate 0.005 g;
• lactose monohydrate to obtain a tablet weighing 0.5 g.

The product is also available in the form of a spray, ointment and varnish. The effect of the drug does not change depending on the form in which it is produced. However, if the product is used for topical application, it does not act comprehensively.

The tablets for hair, nails and skin contain the active ingredient terbinafine, which helps get rid of infection. Also, the entire composition is based on the effects of components for the complete restoration of nails.

Many companies are trying to introduce Terbinafine into medicines. In this way, with a full complex effect, the patient can easily cope with a fungal infection.

pharmachologic effect

The drug is an allylamine, which has a significant spectrum of action. It is perfectly activated in the fight against nail fungus on the hands and feet. The active substance actively affects the healing of skin and hair from this type of infection such as dermatophytes and yeast fungus.

An amazing advantage of taking the drug in tablet form is its concentration in the body. Thus, a fungicidal effect on the fungus occurs. But in order for the effect of treating various types of lichen to be noticeable, it is advisable to use Terbinafine spray, ointment or varnish.

Pharmacokinetics

A drug produced for topical application (varnish, spray or ointment) penetrates the sebaceous glands through the skin very quickly. If you take Terbinafine tablets as a complex treatment, then after some time the components that make up the medication begin to affect the entire body, including the nail plates on the hands and feet, as well as hair and skin.

In most cases, the drug for the treatment of nail fungus is excreted through the kidneys, skin and breast milk. The amount of active substance accumulated in the blood depends on the functioning of the liver, kidneys and the age of the patient. If there are any abnormalities, there may be a high concentration of the drug in the body.

Dosage

Taking the medication directly depends on the form of release. Ointment, varnish or other topical product is applied to damaged areas once or twice a day, depending on the type of fungus. If a patient is diagnosed with nail fungus on the toes or hands, it is recommended to use Terbinafine cream (ointment) or varnish. When a fungus is found on the skin or hair, a spray is prescribed.

Complex treatment with Terbinafine tablets instructions for use, includes specific dosage recommendations.

The product is approved for use to treat fungus, only for children over three years of age. The dosage for an adult is 250 mg. Take once a day after meals. For children whose weight is more than twenty and less than forty kilograms, this dose is 125 mg, also once a day. For children who weigh more than forty kilograms, the dosage is equal to an adult.

Treatment of a fungus or other infection of this type should be carried out only with the recommendations of a doctor. The dosage is also set. Indications for use are also determined by the doctor. Antifungal drugs (ointment, varnish, spray) are contraindicated for children.

Overdose

Patients using antifungal drugs must follow the dosage. Uncontrolled use of tablets can provoke overdose symptoms.

The main signs indicating that an overdose has occurred are:

• dizziness;
• headache;
• vomit;
• nausea;
• pain in the abdominal area;
• allergic reaction;
• frequent urination.

If symptoms of overdose are detected, the patient should immediately consult a doctor. These signs may occur even if the treatment was carried out using products such as a spray, varnish or ointment.

Treatment for symptoms of drug overuse should begin immediately. In this case, treatment should be carried out under the supervision of a doctor. The main task is to eliminate the components of the drug from the body.

Use during pregnancy

Terbinafine is strictly contraindicated during pregnancy, since its effect on a woman’s body during pregnancy and breastfeeding has not been studied. The lactation period is included in the contraindications, since the drug is excreted in breast milk.

Side effects

It is not recommended to start treating a fungus or skin infection with Terbinafine (varnish, ointment or spray) without a doctor's prescription. Because the patient may experience side effects. Side effects can occur from the following systems:

• digestive;
• blood;
• nervous.

Side effects appear on the skin in the form of an allergic reaction. Also, side effects of the drugs are reflected in the condition of the musculoskeletal drug in the form of arthralgia or myalgia.

Indications

Antifungal drugs (ointment, tablets, varnish or spray) have specific indications for use:

• damage to nails or skin;
• mycoses on the scalp;
• dermatomycosis of the skin;
• candidiasis of the mucous membrane or skin.

Indications are based on the results of a doctor’s examination and diagnostics performed. Indications should be established based on all factors related to the disease.

Contraindications

The drug includes in its conditions of use not only indications, but also contraindications. It is not recommended to take the drug if you have the following diagnoses:

• liver and kidney diseases;
• child's age up to three years;
• lactation;
• lactose deficiency or intolerance;
• body weight less than 20 kg;
• intolerance to the components of the drug.

Contraindications include a number of other health problems of the patient. These include alcoholism, mental illness, individual characteristics of the body, as well as cancer. Therefore, the method and dosage must be determined by a specialist. You should be most careful when treating childhood infections.

Application

The method of use of the drug depends on what it is prescribed for. Also, the diagnosis of the disease for which Terbinafine is used also affects the form of the drug. For example, for a scalp or skin infection, a spray or cream may be used. And if the nails are damaged, use a special varnish. You can apply the varnish to the area of ​​the fingernails and toenails.

The method of using Terbinafine tablets is considered a complex treatment. You must take the pills strictly as prescribed by your doctor. Self-medication with the drug is not allowed due to the presence of contraindications and the likelihood of side effects.

Reception features

The active component found in Terbinafine can be taken with contraceptives (oral). Menstrual irregularities may be associated with taking pills.

Exacerbations may occur with self-treatment. This happens due to incorrect dosage or premature termination of treatment procedures.

If the patient follows the doctor’s instructions, but also stops taking the medication when the first results appear, then the disease may return.

The average treatment course is one month. However, the time during which you will need to use the drug depends on the form and stage of the disease. If there are no results or any side effects occur, you should contact the doctor providing treatment.

Analogs

Terbinafine, like many medications, has analogues. All drugs are similar in their effect on the body. All analogues can be found in pharmacies.

In order to correctly purchase Terbinafine analogues, it is necessary to study the active ingredients that are components of the medications. However, only the doctor involved in the treatment can prescribe an analogue.

The most popular drug substitutes that have a similar effect on fungal infection as Terbinafine are: Binafin, medications from the Lamisil series, Mycoterbin, Tebicur, Terbifin, Cicodan.

Terbinafine is a remedy for eliminating infectious diseases of the scalp, skin or nail plate of the hands and feet. In order to get rid of pathological processes in the body, treatment is undoubtedly necessary. But which form of the drug is suitable for the patient is determined exclusively by a medical specialist. Therefore, despite the fact that medications are sold in pharmacies without a prescription, self-medication for diseases of this type is not recommended. It is better to consult a doctor to determine all the features associated with treatment.

When a disease of fungal etiology develops, the problem of choice is acute - there are a lot of drugs in the pharmacy, but you need to choose the one that will help in the shortest possible time and also leave as few side effects as possible.

Antifungal drugs include several groups - azole, polyene and allylamine drugs. In addition, there are drugs outside this classification.

For this reason, the question of rational choice of drug for treatment with such a variety of medications is not surprising. The most popular and advertised medications are the azoles, which include drugs such as Fluconazole and Itraconazole (Irunin). Patients are often faced with a choice of which is better: Fluconazole or Itraconazole.

What is this article about?

What to choose Fluconazole or Intraconazole?

Since both medications belong to the same pharmaceutical group of antifungal drugs, the question arises about which drug is better and whether these medications can be combined when carrying out complex antifungal therapy. Most doctors agree that these medications should not be taken together, as such therapy can increase the risk of side effects and negatively affect the overall health of the patient suffering from a mycotic infection.

When comparing these two medications, you may initially notice a significant difference in cost. Itraconazole has a price in Russia ranging from 390-460 rubles, and Fluconazole is only 35-60 rubles.

Both products have a wide spectrum of action and have pronounced fungicidal properties. Both drugs are not recommended for use during pregnancy and lactation.

Each of these drugs causes a small number of side effects, but they should not be combined.

Brief characteristics of Itroconazole - its properties and composition

Itraconazole contains the active substance of the same name, which fights many types of fungal pathogens. Its action is based on the fact that itraconazole, a triazole derivative, inhibits the cell wall of the fungus, thereby the pathogen loses its protective layer and dies. Effective against fungi such as Candida, Aspergillus, Histoplasma, Trichophytum and Epidermophytum. The spectrum of its action is extremely wide, which allows it to be prescribed in the most severe and combined cases.

The drug is taken orally, and its maximum amount in biological fluids is achieved after 4-5 hours. The half-life is 15-17 hours. In order for the concentration to remain stable for a long time and pathogenic flora to be exposed, it is necessary to drink the drug regularly, without skipping and increasing the dose. In the blood, the concentration increases gradually, reaching a maximum after 6 hours. The drug is transformed in the liver and is transported by special proteins. A special feature of the medicine is its deposition in cells that are rich in keratin, such as skin, hair and nails. Gradually the drug leaves the tissues, it depends on the rate of skin regeneration in a person.

In the cells of the mucous membranes the period is no more than three days.

Features of the use of Itraconazole

The main indication for which Itraconazole (Irunin) is prescribed is fungal infection of the skin, hair, nails and mucous membranes. It is also used for thrush, in particular for diseases of the vagina and intestines. The drug is used in dermatology, ophthalmology and otorhinolaryngology.

Itraconazole is used for systemic fungal pathologies, for example, mycoses of internal organs. For mycotic meningitis, the medicine is prescribed as a reserve drug.

The method of administration of the drug is oral. It is necessary to drink it after eating, preferably rich in vitamins and microelements. This is necessary so that the medicine penetrates the skin better and has a therapeutic effect. The most optimal are foods containing fats - meat, fish, nuts. You need to take the medication 2 capsules twice a day for a month. After this, it is necessary to take a break from taking it so that the liver restores its functionality and an overdose does not occur. If the patient has severe underlying immune system diseases, the dose must be increased to prevent relapse.

Despite its good effect on the body, Irunin can affect different body systems, such as:

1. Central nervous system. In many patients, taking the drug may be accompanied by unpleasant sensations in the forehead or back of the head, migraine-like conditions.
2. Allergy to any component of the drug, which increases depending on the dose. So, with an overdose of the drug, a reaction similar to Quincke's edema may develop. Hives and unbearable skin itching are also common.
3. Damage to the digestive system may manifest itself as symptoms such as pain in the epigastric region, nausea, retching or belching. Manifestations such as stool disorders such as diarrhea or constipation are common, and some patients also experience flatulence.
4. Changes in the blood, anemia or leukocytopenia may occur.

Patients with liver damage should not take this drug, as this can lead to the development of toxic hepatitis and, subsequently, cirrhosis and liver failure.

In addition, temporary damage to the organs of hearing and vision is possible - after stopping the use of the medicine, these symptoms disappear.

Brief description of Fluconazole - pharmacological properties and composition

Fluconazole is an antifungal drug that, like Itraconazole, has a broad spectrum of activity against fungal pathogens.

The mechanism of action of the active substance is inhibition of the cell wall and enzymes of the microorganism, which leads to the death of the pathogen. In addition, the high concentration of the drug in the skin and its appendages makes it possible to inhibit the proliferation of pathogenic flora.

It acts more selectively on fungal cells, in contrast to Itraconazole, which has more negative effects on the body, in particular on the cytochromes of human cells.

Used as a reserve antifungal agent. This means that Fluconazole is used for the most serious and life-threatening conditions, such as massive transplantation and subsequent fungal infection of internal organs. The drug is also extremely effective during chemotherapy and radiation therapy in patients with malignant processes. Combines well with antibiotics and cytostatics. The best effect is obtained in combination with, the active ingredient is terbinafin.

When taking Fluconazole, the quality and calorie content of the food consumed does not matter. You can drink it both after meals and on an empty stomach. Unlike Itraconazole, it is not so actively bound by plasma proteins, but despite this, it is also transformed in the liver. The highest concentration of the drug is achieved on the third day of administration due to the fact that the patient is given a double dose at the first dose. This allows you to eliminate a large amount of the pathogen at one time.

In blood and other fluids, the concentration of the drug is the same. This must be taken into account in cases where treatment occurs during pregnancy and lactation. It is necessary to take into account the risks for the mother and fetus, and only then prescribe therapy.

The highest concentration of the drug is in the skin and its appendages - hair and nails. The drug accumulates in them gradually, as well as being excreted. The medicine comes out of the skin a week after stopping taking it, and from the nails within six months.

Excretion of the drug through the kidneys provides a half-life of 25 hours.

In people with impaired kidney and urinary function, this process is disrupted and prolonged.

Features of the use of the drug Fluconazole

The main indication for prescribing this drug is massive or deep fungal infection of the skin, its appendages or internal organs. The drug works even in such difficult cases as fungal meningitis. For mycosis sepsis, this drug is widely used as the main method of treatment. In patients with acquired immunodeficiency syndrome, this medication is used as a permanent prophylactic agent that prevents the massive proliferation of fungal microorganisms.

Fluconazole is used when wearing dentures, in particular dentures, when there is a risk of developing a persistent fungal infection.

This drug is contraindicated in people who are allergic to one or more components of the drug. In this case, it is better to replace the drug with another one, with a composition similar in action, but different in structure.

You should not take Fluconazole together with drugs such as Erythromycin and Amiodarone - this can potentiate their effect on the body and lead to the development of many side effects.

Those people who have renal or liver failure must take the drug extremely carefully so as not to provoke the development of the terminal stage of the disease. During pregnancy, it is better to abstain from the drug or replace it with a safer analogue.

Side effects that the medication may cause:

1. From the digestive system - sharp pain in the abdomen, not associated with food intake, vomiting without nausea, retention of stool and gases are also possible.
2. Frequent symptoms from the central nervous system are headache and dizziness.
3. An allergy to the drug is considered a very dangerous side effect - this can be either swelling of the larynx or a massive skin reaction with rejection of the epidermis.
4. In the presence of heart disease, such as coronary artery disease or hypertension, the drug may cause rhythm disturbances and changes in voltage. This is felt by chest pain, a feeling of lack of air, tachycardia, palpitations.
5. Hair loss may develop after prolonged use of the drug.

Additionally, inappropriate behavior, development of psychosis, depression and hallucinations are possible from the mental side.

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Updated: 10/23/2018 11:47:03

Expert: Boris Kaganovich

Among all fungal infections, the most dangerous are systemic mycoses, which affect the internal organs of a person and can lead to death. Such severe diseases often occur in HIV-infected patients in the AIDS stage, with profoundly impaired immunity. But even an ordinary, healthy person with a normal immune status can experience fungal infections of the skin, and especially the nails. These diseases are called onychomycosis, and they can be cured with the correct use of antifungal drugs (they are called fungicides, or antimycotics), and with careful adherence to the principles of secondary prevention.

The fact is that, located deep in the nail plate, the fungus is protected from all harmful factors. It has the most favorable conditions for growth and reproduction, especially when it comes to toenails. A person almost always wears closed shoes during the day, especially in winter. This gives the fungi the necessary darkness and absence of harmful ultraviolet radiation, moisture and excess nutrients. The nail plate also mechanically protects the fungus. All this makes the treatment of onychomycosis difficult, especially if the damage to the nail plate is significant, but there are no indications for nail removal yet.

There are various remedies, both for local and internal use, for the treatment of onychomycosis. Medicines taken orally must be prescribed by a dermatologist, taking into account indications and contraindications. But even local treatment should begin after an initial consultation with a specialist and taking nail discharge for analysis to confirm the diagnosis. This rating includes the most modern and popular means for treating nail fungus. But, before we begin the review of fungicidal agents, it is necessary to talk a little about antifungal ointments and creams.

Ointments and creams do not cure nail fungus

There is a common misconception that using various ointments and creams can cure nail fungus. Unfortunately, this is far from the case. Ointments and creams are intended for application to the skin and mucous membranes. Only with proper use of the product does the active substance quickly absorb and create the necessary fungicidal concentration. Therefore, the entire rich range of creams and ointments for fungus is mainly intended for the treatment of dermatomycosis, or fungal skin lesions, for the treatment of vaginal candidiasis and other similar localizations.

Such well-known drugs as Nizoral-cream, Lamisil containing terbinafine, Zalain, Mifungar, Candide, and other soft dosage forms are too weak for the treatment of onychomycosis and are not intended for the treatment of nail fungus. They will not be able to penetrate the thickness of the nail, which consists of keratin. The keratin protein is quite strong, and the disappointment from such improper treatment of onychomycosis will be significant, especially if a lot of money is spent on a cream or ointment.

There is another danger here. Those minimal concentrations that will still pass through the nail and reach the fungus, but not kill it, will help it adapt to this active substance and develop resistance to fungicides in the fungus.

However, antifungal ointments and creams are quite used for onychomycosis of nails for application to the skin surrounding the nail, to the interdigital spaces, and can be used in complex therapy of onychomycosis to prevent the spread of fungus from the nail to nearby soft tissues. This is precisely what explains the inclusion of such an indication as “onychomycosis” in official instructions.

Important! The only exception when antifungal creams and ointments are indicated is when the patient's nail has already been completely removed and the product can be rubbed directly into the exposed nail bed. This is done several times a day until healthy nail tissue grows.

If we are talking about the popular salicylic ointment, then it is used as a keratolytic agent for foot fungi, and for nail fungi its task is to soften and remove excess keratinized masses, which accumulate in abundance mainly on the heels, in middle-aged and elderly people, and are a food source for the fungus. It is known that the crumbling masses released from under the nail affected by the fungus contain a large amount of mycelium - the “embryos” of the fungus.

Distributing over the inner surface of shoes, insoles and house slippers, socks, the mycelium of the fungus gets onto the keratinized masses, gradually moves from the subungual space to the skin, first to the area between the toes, and then to the feet. Therefore, the use of salicylic ointment for onychomycosis of toenails is indicated as a prophylactic agent that deprives fungi of nutrients. But this ointment is not a fungicidal, or a real antifungal drug with proven activity. Now you can move on to the rating of really popular and effective medications for the treatment of nail fungus.

Rating of the best remedies for nail fungus

The best fungicidal liquids and varnishes for nail fungus

It should be immediately explained that treating nail fungus with liquids and varnishes is a regular and daily process. There is a rule: until the nail plate is completely renewed, there is no guarantee that the fungus has been eliminated. It is known that nails on the toes renew themselves much more slowly than on the hands, and a complete replacement of the big toe nail can take from 9 months to one year.

Therefore, in the case of damage to the thumb (and this is what occurs most often), exactly this duration of treatment is necessary, and then about 2 more weeks of applying the product to a completely renewed and healthy nail plate are needed to avoid relapse. This applies to liquids; the same can be applied to antifungal varnishes, and even to folk remedies. If a patient treats nail fungus for one day or one month, then it will still be of no use. There will be a relapse of onychomycosis.

Important! Local remedies alone, that is, liquids and varnishes, can treat nail fungi only if a person has no more than 3 nails affected, and each of them is no more than 50% in area, counting from the free edge. In the event that a larger number of nails are affected, there is a fungal infection of the skin, or the fungal proliferation zone is localized on the growth side of the nail plate, then it is necessary to combine the application of local agents with taking antifungal drugs internally.

Exoderil (Mikoderil, Exostat) – naftifine

Exoderil for the treatment of onychomycosis is produced by the well-known pharmaceutical concern Sandoz, and is represented by a 1% naftifine solution. This compound belongs to the class of allylamines, and inhibits the synthesis of new elements of the fungal cell wall. To treat nail fungus, Exoderil is applied twice a day to the affected nail, being careful not to touch the periungual skin.

Before using the product for the first time, you need to trim the free edge of the nail plate as much as possible and grind the affected part of the nail parallel to its surface with a special file to make the nail plate in the affected area as thin as possible. This is necessary so that the concentration of naftifine under the nail plate is greatest.

The set also includes special disposable files, which are used to grind the surface of the nail for better contact of the liquid with the nail plate. This light sanding should be done before each application. Such treatment must be carried out for at least 4 months, without skipping, but the best period is 6 months. Exoderil can be purchased in bottles of 10, 20, and 30 ml. Their average cost is 520, 880, and 1350 rubles, respectively. in autumn 2018 prices for major cities of the Russian Federation.

Advantages and disadvantages

The advantage of Exoderil is its proven ability to cure onychomycosis caused by dermatophytes. If the nail is infected with yeast fungi, the drug may not kill the fungus, but only prevents its reproduction, that is, it acts fungistatically. This is why a primary fungal test carried out at a skin and venereal disease clinic is necessary.

The concentration of exoderil in the thickness of the nail for uncomplicated onychomycosis is considered sufficient to apply the product no more than 2 times a day. Naftifine is contraindicated in case of individual hypersensitivity, during pregnancy and breastfeeding. Sometimes side effects occur, especially if the liquid is accidentally applied to adjacent skin. Dryness, burning and redness of the skin may then occur. But if the medicine is applied according to the instructions without omissions, and all rules of prevention are followed, then the cure rate for onychomycosis will be very high.

Important! Each time when applying antifungal liquid or any varnish, it is necessary to use disposable files, spatulas, disposable napkins, and other disposable tools. It is strictly forbidden to grind and file the affected nail with one nail file, and it is even more prohibited to use this manicure file to treat other nails.

Varnish Batrafen - ciclopirox

Batrafen is a transparent varnish that contains the active ingredient ciclopirox-olamine. The varnish exhibits high fungicidal activity against more than 40 varieties of fungi. Ciclopirox inhibits the metabolism of fungal cells and prevents the exchange of their substances with the external environment.

The basic principles of preparing a nail for applying varnish are similar to the preparation of the Exoderil described above, since they are the same. First, the nail affected by the fungus is cut as short as possible, then the remaining nail plate should be sanded with a nail file to create an uneven surface. This will increase the area and strength of the varnish application. It is necessary to apply the varnish in a thin layer using specially attached disposable spatulas; the increase in effect will not depend on the thickness of the layer. The application procedure is as follows:

1. during the first month, varnish is applied every other day;
2. in the second month - twice a week;
3. in the third month - weekly.

During the course of treatment, it is necessary to remove all applied nail polish every week using a regular cosmetic nail polish remover, then cut the nail short again and prepare it for applying nail polish the next week.

As prescribed by the attending physician, depending on the type of fungus, other options are possible: for example, for a month and a half, the varnish is applied every other day, for the next month and a half - twice a week, for the next month and a half - weekly.

The maximum period of treatment with Batrafen should not exceed six months. Batrafen is produced by the well-known pharmaceutical company Sanofi-Aventis, and a small 3 ml bottle of varnish has an average cost of 2,200 rubles.

Advantages and disadvantages

Lac Batrafen is one of the most effective means for the treatment of onychomycosis, both as monotherapy for uncomplicated forms, and as complex therapy in combination with internal use of drugs. Batrafen is well tolerated and practically does not cause intolerance or allergic reactions. Once opened, a bottle of varnish can be stored for 6 months, provided it is tightly sealed. If the purchased bottle was kept closed, then its shelf life is no more than 3 years.

Of course, a relative disadvantage will be the high price, but you need to remember that this product really has proven effectiveness, and is still not available in analogues or generics. It is known that for people with very limited financial resources, doctors can prescribe cheap medications, such as Nystatin and Levorin tablets, and recommend smearing the affected fingers with iodine tincture. This type of treatment will be extremely cheap, but its effectiveness is practically close to zero.

Lac Lotseryl (Oflomil, Exolorfinlac) - amorolfine

Another representative of highly active varnishes against fungus is Loceryl. And, if Batrafen had no analogues or generics, then Lotseril had two of them: Oflomil and Exolorfinlac lacquer. The first drug is produced by Glenmark, and the second by Sandoz. The original Loceryl is produced by the French company Galderma.

The active ingredient of Loceril is amorolfine. Loceryl is sold as a set. The varnish is packaged in bottles of 2.5 or 5 ml. The varnish comes with special wipes with isopropyl alcohol, which are used to clean the nails before application, disposable nail files, as well as special spatulas for applying and evenly distributing the varnish. The active substance amorolfine disrupts the synthesis of the structural components of the fungal cell, which are represented by sterols. After abnormal and incorrectly synthesized sterols accumulate inside the fungal cell, the fungal cell gradually collapses.

The rules for applying Loceryl are simpler than those of Batrafen. It is necessary to apply varnish either once or twice a week. The sequence of operations is as follows: first, use a file to remove all areas of the nail plate affected by the fungus over the maximum area, cut off the free edge as much as possible, then treat the surface of the nail with wipes with isopropyl alcohol, then apply varnish. Unlike Batrafen, Lotseril has no limitation on the duration of the course of treatment. Treat as much as needed, up to a treatment duration of 1 year.

The cost of one small bottle of Loceryl 2.5 ml is 800 rubles. A small bottle of Oflomil varnish costs 688 rubles, and the cost of Exorolfinlac is 798 rubles for the same dosage. As you can see, the price range is small. The cost of a large bottle is, on average, 1,300 rubles.

Advantages and disadvantages

The only drawback of Loceryl and its analogues is such a side effect as a temporary slight burning sensation at the site of application of the varnish. This product is also contraindicated for use in children, meaning newborns and children under three years of age. The manufacturer recommends not using cosmetic varnish or artificial nails during treatment, as this may lead to insufficient treatment effectiveness and a relapse of onychomycosis. Loceryl is also a highly effective product with proven effectiveness, but, unlike Batrafen, it is much more affordable, and the consumer can purchase a bottle of 2.5 ml or 5 ml, depending on the duration of the upcoming course of treatment.

Important! The main advantage of all local drugs used to eliminate nail fungus is the absence of various side effects and symptoms of intoxication that can occur when prescribing drugs for internal use, and especially when overdosing them.

The disadvantage common to this group of drugs is that the drug cannot always reach the pathogen, especially if the fungus is located in the nail bed area or in the structures of the nail matrix. If the nail is significantly thickened, that is, there are symptoms of hyperkeratosis, then you need to resort to such means as removing the nail plate and cleaning the nail bed. If the fungus affects the nail matrix, then treatment with local remedies will not achieve its goal. Then it is recommended to prescribe systemic drugs prescribed in tablet form.

The best tablet drugs for oral administration

If a patient with onychomycosis has a fungal infection of the nails beyond the maximum permissible limits described above, then the doctor prescribes tablets along with local remedies for the treatment of onychomycosis. There are a very large number of antifungal agents, but since each original drug has 5-6 commercial copies, or generics, from other companies and even more, the number of the most effective tablets for treating nail fungus is significantly reduced.

Listed below are the medications that are used to treat onychomycosis. It is very important to understand that although local remedies for the treatment of nail fungus can independently cope with minor manifestations of infection, then tablet preparations used alone cannot cure nail fungus. Their task is to create a high concentration of an antifungal substance from the inside, in the blood. Thus, the fungus will have no chance to get rid of unfavorable living conditions. A local drug will act externally, and the tissues of the subungual space will be saturated with fungicides coming from the blood.

Lamisil (Terbizil, Binafin, Termicon, Exiter, Exifin) – terbinafine

In modern dermatological practice for the treatment of onychomycosis, terbinafine is the first-line drug, or the drug of choice. Terbinafine is a synthetic allylamine with a high level of antifungal activity. The mechanism of action of this substance is to disrupt the synthesis of structural elements of fungal cells. With long-term use of Lamisil tablets, a fungicidal concentration is created not only in the subungual space, but also in the skin and hair.

Taking Lamisil for onychomycosis, of any localization, requires 250 mg per day (once a day) on average for one and a half months. We are talking about adults and children weighing more than 10 kg. In some cases, treatment can last up to 3 months. The duration of treatment depends on the rate of nail growth, which varies individually.

Lamisil is an original drug, and therefore its cost is the highest. It is produced by the Swiss company Novartis Pharma, and the minimum cost of a two-week course of treatment, that is, a package of 14 tablets, is 1,820 rubles. The average cost of this package ranges from 2370 rubles. Of course, this is expensive for the average Russian consumer. After all, the cost of the course will already be more than 14 thousand rubles, if we take the average market price of the package.

More affordable options can also be offered. Thus, the drug terbinafine Teva, produced by the Israeli company of the same name, will cost 600 rubles, and for 28 tablets. Perhaps the most affordable is terbinafine, produced by the domestic company Vertex. So, 30 tablets of this drug, designed for a monthly course, can be found at a price of 400 rubles and more. But the question about the quality of the original substance and the results of treatment in this case remains open.

Advantages and disadvantages

Lamisil is the international standard for the treatment of not only onychomycosis, but also fungal diseases of other localizations. But, since this drug is quite serious, it has a range of side effects. It is usually well tolerated, but the most common side symptoms are headache, impaired taste, and rarely bile stagnation may occur. The most common symptoms include loss of appetite, a feeling of fullness in the stomach, and various allergic skin reactions, such as hives and rashes. Some patients complain of joint and muscle pain. Terbinafine may affect the way the body metabolizes other drugs.

That is why it is necessary to carry out treatment only under the supervision of a doctor. This drug is contraindicated during breastfeeding and pregnancy. Terbinafine is not used in children under two years of age, but in children over two years of age, extensive clinical experience has been accumulated in the use of this drug, and it is well tolerated.

Diflucan (Diflazon, Mikomax, Mikosist, Fangiflu, Flucostat) – fluconazole

Diflucan, also known as the original fluconazole, is also a powerful antifungal drug, and is used not only for onychomycosis, but also for skin lesions, severe fungal infections with damage to internal organs, including HIV infection, as well as for the development of fungi against the background decreased immunity in the treatment of malignant neoplasms.

Fluconazole is available in both tablets and capsules, and even in solutions for intravenous infusion. For the treatment of fungal nail infections, the most acceptable dosage of Diflucan is 150 mg per capsule. For onychomycosis, it is recommended to take fluconazole one such capsule weekly for 3 to 6 months. According to indications, the duration of the course can be changed by the attending physician. The same dosage of Diflucan is also used for mycoses of the feet, skin, and groin lesions. For comparison, we can point out that for deep and systemic fungal infections of internal organs, the use of fluconazole at a dosage of 2 capsules per day for up to a year or longer may be required, so the prescription of 150 mg per week can be considered very gentle.

Diflucan is produced by the well-known pharmaceutical company Pfizer, and a package of 12 capsules, designed for 3 months of treatment, which is a course of minimum duration, costs on average 2,200 rubles. Of course, this can also be considered a large amount, but still this is already the cost of an entire course, and it is 6 times lower than when using Lamisil.

There are more affordable options for fluconazole. So, one of the cheapest, if not the cheapest, is fluconazole - Verte, a domestic manufacturer of JSC Kanonpharma Production. Two capsules will cost only 20 rubles, respectively, the exchange rate cost of such domestic fluconazole, designed for 3 months of use, will be only 120 rubles. This is 18 times cheaper than the cost of the original drug. The largest part of the cost of any drug is the active ingredient, or substance. Therefore, the question of the ratio of price and quality in the case of choosing such a cheap drug will also be open.

Advantages and disadvantages

The main advantage of fluconazole in the treatment of fungal nail diseases is the excellent price/quality ratio when it comes to the original drug, Diflucan, and relatively expensive generics (Mikosist). Since you need to take the drug only once a week, the exchange rate compared to the original production of terbinafine is significantly lower. Therefore, a large number of doctors prefer Diflucan as a first-line treatment when necessary to prescribe treatment with oral medications.

However, such excessive use of fluconazole entails the risk of the emergence of insensitive varieties of fungi, similar to bacterial resistance that develops to commonly used antibiotics.

Just like any serious drug, it can cause side effects, although the drug is usually well tolerated. The most common symptoms are headache, abdominal discomfort, skin rash; with long-term use in high doses, toxic effects on the red bone marrow and liver toxicity are possible. Fluconazole interacts with a number of other drugs, so only a doctor should prescribe and monitor treatment. But good quality fluconazole will always be necessary in the treatment of fungal nail infections if there are indications for its use.

Orungal (Irunin, Kanditral, Orungamin, Orunit, Rumikoz) – itraconazole

Itraconazole is a reserve agent and is used in cases where there are contraindications to the use of terbinafine and fluconazole, or if the fungus develops resistance to the first two drugs for any reason, although such cases almost never occur in clinical practice.

The original itraconazole, or Orungal, is available in 100 mg capsules, and is used for fungal infections of the nails immediately after meals, and two schemes for its use are known:

1. according to the first treatment regimen for fungal nail infections, it is recommended to take 2 capsules per day (200 mg daily) for 3 months;
2. the second scheme involves taking 4 capsules per day (2 in the morning and in the evening), and it is used at 1 and 5 weeks from the start of treatment.

The first regimen is characterized by a low constant dosage, and the second regimen is characterized by a double, “shock” dosage, but not in the form of a constant, but an intermittent course. Itraconazole is not used to treat fungal nail infections in children. The manufacturer also recommends longer treatment for toenail lesions than for fingernail lesions. This is completely justified, since more comfortable conditions have been created for the pathogens of onychomycosis on the legs, and they are more protected, this was discussed in the introduction to the rating.

Orungal is produced by the famous pharmaceutical concern Janssen Silag, Italy. The cost of this drug is also very high. So, a package of 14 capsules costs an average of 3,150 rubles. Even if you try and find the minimum price, it is unlikely that you will find Orungal cheaper than 2200 rubles. This means that the cost of a three-month course under the first scheme will be over 28 thousand rubles, and under the second scheme – about 9 thousand, which is much more profitable.

As in all previous cases, there are more accessible and cheaper analogues. If you purchase the antifungal drug Orunit, produced by JSC Obolenskoye, at a pharmacy, then one package of 15 capsules will cost starting from 617 rubles, which means that the cost of a monthly course will be about three times cheaper.

Advantages and disadvantages

Itraconazole is relatively rarely used in the treatment of onychomycosis; it is not without reason that it is a reserve drug. Therefore, resistance to it develops less often, and the product justifies its high price. But, like any serious drug, Orungal has contraindications and side effects. Side effects often include an allergic rash, abdominal discomfort and a feeling of nausea; other side effects, such as increased urination, increased liver transaminases, and blurred vision, are rare. This means - no more often than with a frequency of 0.01%.

Orungal is contraindicated in case of severe liver damage, impaired renal function, in childhood (up to three years), during pregnancy, and during breastfeeding. Also a contraindication is chronic heart failure, as well as gastritis with reduced secretion, since the low acidity of gastric juice impairs the absorption of the active substance from the capsules. For the same reason, it is recommended to separate the use of itraconazole from antacid medications. This means that you need to take Orungal no later than 2 hours before taking Maalox, Almagel, Phosphalugel, omeprazole and other antacids, or 2 or more hours after their use.

With all the pros and cons, the treatment of nail fungi with tablets in all world medical practice is based on these whales - terbinafine, itraconazole, and fluconazole. Of course, there are other antifungal tablets that do not belong to these names, but their effectiveness is significantly lower, and sometimes completely absent, especially since it is not possible to quickly destroy fungi protected by the nail plate even with modern drugs.

Among such old drugs that appeared in pharmacology textbooks about 50 years ago, but are still produced and even prescribed, include Nystatin and Levorin tablets. So, Nystatin in the amount of 20 tablets is sold starting from 33 rubles, but if you are prescribed Nystatin for onychomycosis, look for another specialist. Even if you only have 33 rubles in your pocket, you will simply waste it.

The secret to properly treating nail fungus

If the dear reader has reached this section, then most likely he is looking for means for self-treatment. Otherwise, he would simply go to the pharmacy and buy what the doctor prescribed. Therefore, instead of listing folk remedies, it is necessary to know about those treatment conditions, without which the use of any, the most powerful antifungal drugs will either give a short-term effect or will be completely useless. Of course, we are talking about the rules of secondary prevention, which every person with onychomycosis must follow. We present them for the case of fungal infection of toenails:

1. the patient needs, after suspecting the presence of nail fungus, and even more so, after confirming the diagnosis, to purchase a separate basin for washing feet and for baths;
2. socks should be changed daily, it is highly advisable that after drying they are ironed with steam;
3. the skin on the feet must be treated with a special anti-fungal spray;
4. insoles should be changed as often as possible, or they should be ironed with steam just like socks;
5. to treat the inner surface of shoes, it is necessary to use special antifungal sprays for shoes, or regularly irradiate the inner surface of shoes with special dryers with ultraviolet radiation; in the summer, you can listen to shoes in the bright sun;
6. you should abandon closed slippers and switch to open flip-flops, which are also treated with antifungal compounds for shoes;
7. You should be conscious and not visit fitness centers, public baths, saunas and swimming pools during treatment, even if the fungal nail infection exists in a limited area, or you already have a certificate to visit the pool.

Finally, if the treatment of fungal infection of the legs was ineffective, you need to visit a doctor and make sure that there are no chronic diseases such as diabetes, vascular insufficiency of the lower extremities, immunodeficiency, and all those conditions that complicate the fight against the fungus .

Treatment of nail fungus is not easy, troublesome and time-consuming. When treating onychomycosis, it is no longer so much the use of the most expensive medications that is required, but rather careful adherence to the rules of secondary prevention and discipline, because regular treatment of nails and taking medications can last for many months. Only in this case will the fungal infection be defeated.