Terbinafine-MFF 250 mg 10 tablets

• onychomycosis caused by dermatophyte fungi;
• mycoses of the scalp;
• fungal skin infections - treatment of dermatomycoses of the trunk, lower legs, feet, as well as yeast infections of the skin caused by fungi of the genus Candida (e.g., Candida albicans) - in cases where the localization, severity, or extent of the infection justify the use of oral therapy.

For oral use, regardless of food intake, taken with water.
The duration of treatment depends on the indication and severity of the disease. It is advisable to take the medication at the same time each day.
Adults
250 mg once daily.
Skin infections
Recommended duration of treatment:
• dermatophyte infection of the feet (interdigital, plantar, or sock-like) - 2 - 6 weeks;
• dermatophyte infection of the body, shins - 2 - 4 weeks;
• candidiasis of the skin - 2 - 4 weeks.
Complete disappearance of infection manifestations and related complaints may occur no earlier than several weeks after mycological cure.
Hair and scalp infections
Recommended duration of treatment: tinea capitis - 4 weeks.
Tinea capitis is predominantly observed in children.
Onychomycosis
The duration of treatment for most patients is from 6 to 12 weeks.
For onychomycosis of the hands, in most cases, 6 weeks of treatment is sufficient.
For onychomycosis of the feet, in most cases, 12 weeks of treatment is sufficient.
Some patients with reduced nail growth may require longer treatment.
Optimal clinical effect is observed several months after mycological cure and cessation of therapy. This is determined by the time required for healthy nail regrowth.
Use in children
In children over 3 years old and weighing more than 20 kg, the medication is administered once daily. The single dose depends on body weight and is:
• for children weighing 20 to 40 kg - 125 mg (1/2 of a 250 mg tablet);
• for children weighing more than 40 kg - 250 mg.
Use in elderly patients
There is no reason to believe that elderly patients require a change in the dosing regimen of the medication or that they experience side effects different from those in younger patients. When administering the medication in this age group, the possibility of concomitant liver or kidney dysfunction should be considered.

Composition per tablet
Active ingredient:
Terbinafine (Terbinafine hydrochloride) - 0.281 g*
*Corresponds to 250 mg of terbinafine base
Excipients:
Colloidal silicon dioxide (aerosil) - 0.002 g
Calcium stearate - 0.002 g
Potato starch - 0.029 g
Microcrystalline cellulose (MCC-200) - 0.047 g
Lactose monohydrate - 0.008 g
Croscarmellose sodium (Polyplasdone XL-10) - 0.008 g
Croscarmellose sodium (Polyplasdone XL) - 0.008 g
Povidone K 90 (Plasdone K-90) - 0.005 g
Tablet weight - 0.390 g

Tablets of white or almost white color, with a faint specific odor, flat-cylindrical shape with a bevel and score line.

• hypersensitivity to terbinafine or any other component of the product;
• breastfeeding period;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• children under 3 years of age, weighing up to 20 kg for this dosage;
• chronic or active liver disease;
• impaired kidney function (creatinine clearance less than 580 ml/min or plasma creatinine concentration greater than 300 µmol/l), as the use of the product in this category of patients is insufficiently studied.

With caution
• bone marrow suppression;
• cutaneous lupus erythematosus or systemic lupus erythematosus;
• psoriasis.

Use during pregnancy and breastfeeding
Data from experimental studies do not provide grounds to suggest the presence of adverse effects on fertility and toxic effects on the fetus. Since clinical experience with terbinafine in pregnant women is very limited, the product should not be used during pregnancy, except in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.
Terbinafine is excreted in breast milk, therefore women taking terbinafine orally should not continue breastfeeding.

Irregular use or premature discontinuation of treatment increases the risk of relapse.
If no improvement is observed after 2 weeks of treatment, it is necessary to re-evaluate the pathogen and its sensitivity to terbinafine.
Before starting terbinafine tablets, liver function tests should be conducted. Hepatotoxicity may occur in patients with pre-existing liver disease as well as in those without. During therapy, periodic liver function tests are recommended (4 - 6 weeks after the start of treatment). Treatment with terbinafine should be immediately discontinued if liver enzyme levels increase. Patients prescribed terbinafine should be warned to immediately inform their healthcare provider of any symptoms such as persistent nausea, loss of appetite, fatigue, vomiting, pain in the right upper quadrant, jaundice, dark urine, or pale stools. If such symptoms occur, the medication should be stopped immediately, and liver function tests should be performed.
Caution is advised when administering the drug to patients with bone marrow suppression, cutaneous lupus erythematosus, or systemic lupus erythematosus.
Severe skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms) have been reported very rarely during terbinafine use.
Very rare cases of changes in blood cell composition (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia) have been noted with terbinafine. If qualitative or quantitative changes in blood elements occur, the cause of the disturbances should be established, and consideration should be given to reducing the drug dosage or, if necessary, discontinuing terbinafine therapy.
Since the use of the drug in patients with renal impairment (creatinine clearance less than 50 ml/min or plasma creatinine concentration greater than 300 µmol/l) is insufficiently studied, terbinafine is not recommended for this category of patients.
In patients with a history of psoriasis, terbinafine should be used with caution, as there are reports of exacerbation of the condition.
Systemic use for onychomycosis is justified only in cases of total involvement of most nails, presence of significant subungual hyperkeratosis, or ineffectiveness of prior local therapy.
When treating onychomycosis, clinical response is usually observed several months after mycological cure and cessation of treatment, which is due to the rate of healthy nail growth. Removal of nail plates during treatment of hand onychomycosis within 3 weeks and foot onychomycosis within 6 weeks is not required.
It has been shown that terbinafine inhibits metabolism mediated by isoenzyme 2D6 (CYP2D6). Therefore, continuous monitoring of patients receiving concomitant treatment with drugs primarily metabolized by this isoenzyme (tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitors, antiarrhythmic drugs (class IA, IB, IC), antipsychotic drugs, and monoamine oxidase B inhibitors) is necessary if the concomitant drug has a narrow therapeutic concentration range.
When treating with terbinafine, general hygiene rules should be followed to prevent the possibility of reinfection through clothing and footwear. During treatment (after 2 weeks) and at the end, antifungal treatment of shoes, socks, and stockings should be performed.
Effect on the ability to drive vehicles and operate machinery
The effect of terbinafine on the ability to drive vehicles and operate machinery has not been studied. If dizziness occurs during terbinafine therapy, patients should not drive vehicles and/or engage in potentially hazardous activities that require increased attention and quick psychomotor reactions.

The drug is generally well tolerated; side effects are usually mild or moderate and transient in nature.
When assessing the frequency of side effects, the classification of the World Health Organization (WHO) is used: very common (≥1/10); common (≥1/100 - < 1/10); uncommon (≥1/1000 - < 1/100); rare (≥1/10000 - < 1/1000); very rare (< 1/10000), including individual reports; frequency unknown - it is not possible to establish the frequency of occurrence based on available data. Disorders of the blood system: uncommon - anemia; very rare - neutropenia, agranulocytosis, thrombocytopenia, pancytopenia. Disorders of the immune system: very rare - anaphylactoid reactions (including angioedema), skin and systemic lupus erythematosus (or exacerbation). Disorders of the psyche: common - depression; uncommon - anxiety. Disorders of the nervous system: very common - headache; common - dizziness, taste disturbances, up to loss of taste (usually recovery occurs within a few weeks after discontinuation of treatment); uncommon - paresthesia, hypesthesia. There are individual reports of prolonged taste disturbances. In some cases, exhaustion was noted against the background of drug intake. Disorders of the eye: uncommon - vision impairment. Disorders of the ear and labyrinth: uncommon - tinnitus. Disorders of the liver and biliary tract: Rare - hepatobiliary dysfunction (predominantly of cholestatic nature), including liver failure, including very rare cases of severe liver failure (some with fatal outcomes or requiring liver transplantation; in most cases where liver failure developed, patients had serious concomitant systemic diseases and the causal relationship between liver failure and terbinafine intake was questionable), hepatitis, jaundice, cholestasis, increased activity of "liver" enzymes. Disorders of the digestive system: very common - abdominal distension, decreased appetite, dyspepsia, nausea, mild abdominal pain, diarrhea. Disorders of the skin and subcutaneous tissue: very common - rash, urticaria; uncommon - photosensitivity reactions; very rare - Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, erythema multiforme, toxic skin rash, exfoliative dermatitis, bullous dermatitis, psoriasis-like skin rashes or exacerbation of psoriasis, alopecia. Disorders of the musculoskeletal and connective tissue: very common - arthralgia, myalgia. General disorders: common - fatigue; uncommon - increased body temperature. Laboratory and instrumental data: uncommon - weight loss (secondary to taste disturbances). Based on spontaneous reports received during the post-registration period and literature data, the following adverse events have been identified, the frequency of which cannot be established due to the imprecise number of patients: Disorders of the immune system: anaphylactic reactions; serum sickness-like syndrome. Disorders of the eye: blurred vision, decreased visual acuity. Disorders of the skin and subcutaneous tissue: drug rash with eosinophilia and systemic symptoms (rash, edema, fever, and lymphadenopathy). Disorders of the ear and labyrinth: hearing loss, hearing impairment. Disorders of the vessels: vasculitis. Disorders of the nervous system: loss of smell, including for an extended period; decreased sense of smell. Disorders of the digestive system: pancreatitis. Disorders of the musculoskeletal and connective tissue: rhabdomyolysis. General disorders: flu-like syndrome. Disorders of the blood and lymphatic system: anemia. Laboratory and instrumental data: increased activity of creatine phosphokinase in the blood plasma. If any of the side effects listed in the instructions worsen or you notice any other side effects not listed in the instructions, inform your doctor!There have been reports of several overdose cases (the ingested dose of terbinafine was up to 5 g), in which the following were noted: headache, dizziness, nausea, pain in the epigastric region, increased urination, rash. The recommended treatment in case of overdose includes, first and foremost, the administration of activated charcoal and gastric lavage; if necessary, symptomatic and supportive therapy is conducted.Influence of Other Medications on Terbinafine The plasma clearance of terbinafine may be accelerated by drugs that induce metabolism and suppressed by inhibitors of cytochrome P450. If simultaneous use of the aforementioned drugs and terbinafine is necessary, appropriate dosage adjustments of the latter may be required. Cimetidine may enhance the effect of terbinafine or increase its concentration in plasma. Cimetidine reduces the clearance of terbinafine by 33%. Fluconazole increases the Cmax and AUC of terbinafine by 52% and 69%, respectively, due to the inhibition of isoenzymes CYP2C9 and CYP3A4. Similar increases in terbinafine exposure may occur with other drugs that inhibit isoenzymes CYP2C9 and CYP3A4, such as ketoconazole and amiodarone. Rifampicin may weaken the effect of terbinafine or reduce its concentration in plasma. Rifampicin increases the clearance of terbinafine by 100%.Influence of Terbinafine on Other Medications In vivo and in vitro studies have shown that terbinafine inhibits metabolism mediated by isoenzyme 2D6 (CYP2D6). This data may be clinically significant for those drugs that are predominantly metabolized by this enzyme: tricyclic antidepressants, beta-blockers (metoprolol, propranolol), selective serotonin reuptake inhibitors, antiarrhythmic drugs (class IA, IB, IC), antipsychotic drugs (chlorpromazine, haloperidol), and type B monoamine oxidase inhibitors (selegiline) - in cases where the concurrently used drug has a narrow therapeutic concentration range. Terbinafine reduces the clearance of desipramine by 82%. In studies on healthy volunteers with active metabolism of dextromethorphan (a cough suppressant and substrate of CYP2D6), terbinafine increased the metabolic ratio of dextromethorphan/dextrorphan in urine by 16 - 97 times. Thus, terbinafine in individuals with high CYP2D6 activity may reduce the activity of the latter. Terbinafine reduces the clearance of caffeine by 19% when administered intravenously. Rare cases of changes in INR and/or prothrombin time have been noted when used concurrently with warfarin.Drug Interactions with No or Minimal Impact Results from in vitro studies and healthy volunteers show that terbinafine has a minimal potential to inhibit or enhance the clearance of most drugs that are metabolized by the cytochrome P450 system (e.g., terfenadine, triazolam, tolbutamide, or oral contraceptives), except for those metabolized by isoenzyme CYP2D6. Terbinafine does not affect the clearance of phenazone or digoxin. Terbinafine does not have a significant effect on the pharmacokinetics of fluconazole. No clinically significant interactions have been identified between terbinafine and the components of co-trimoxazole (trimethoprim and sulfamethoxazole), zidovudine, or theophylline. There have been reports of several cases of menstrual cycle disturbances in female patients taking the drug alongside oral contraceptives, although the frequency of these disturbances does not exceed the average frequency of such disturbances in patients taking only oral contraceptives. Terbinafine increases the clearance of cyclosporine by 15%.Interaction with Food and Beverages Food has a minimal effect on the bioavailability of terbinafine (AUC increase

Terbinafine is an allylamine that has a broad spectrum of activity against fungi causing skin, hair, and nail diseases, including dermatophytes such as Trichophyton (e.g., Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton verrucosum, Trichophyton violaceum), Microsporum (e.g., Microsporum canis), Epidermophyton floccosum, as well as yeast fungi of the genus Candida (e.g., Candida albicans) and Malassezia. At low concentrations, terbinafine exhibits fungicidal activity against dermatophytes, molds, and some dimorphic fungi. The activity against yeast fungi may be fungicidal or fungistatic, depending on the species.

By inhibiting squalene epoxidase in the fungal cell membrane, which is not part of the cytochrome P450 system, terbinafine specifically suppresses the early stage of sterol biosynthesis in the fungal cell, leading to a deficiency of ergosterol, intracellular accumulation of squalene, and fungal cell death.

When taken orally, concentrations of the drug are created in the skin, hair, and nails that ensure fungicidal action.

After oral administration, terbinafine is well absorbed (>70%); the absolute bioavailability is approximately 50% (first-pass effect). After a single oral dose of 250 mg of terbinafine, the maximum plasma concentration (Cmax) is 1.3 µg/ml, and the time to reach maximum concentration (Tmax) is 1.5 hours.

With continuous administration of terbinafine, its Cmax increases on average by 25% compared to a single dose; the area under the concentration-time curve (AUC) increases by 2.3 times. Based on the increase in AUC, the effective half-life is 30 hours. Food moderately affects the bioavailability of the drug (AUC increases by less than 20%), but no dose adjustment of terbinafine is required when taken with food.

The binding to plasma proteins is 99%. Terbinafine quickly penetrates the dermal layer of the skin and concentrates in the lipophilic stratum corneum. Terbinafine also penetrates the secretions of sebaceous glands, leading to high concentrations in hair follicles, in hair, and in skin rich in sebaceous glands. It is also known that terbinafine penetrates the nail plates within the first few weeks of therapy.

Terbinafine is rapidly metabolized and significantly involves at least seven cytochrome P450 isoenzymes, with the main roles played by isoenzymes CYP2C9, CYP1A2, CYP3A4, CYP2C8, and CYP2C19. As a result of the biotransformation of terbinafine, metabolites are formed that lack antifungal activity and are primarily excreted by the kidneys. Repeated administration of terbinafine, leading to increased plasma concentration, is accompanied by a three-phase elimination with a terminal half-life of about 16.5 days. No changes in the steady-state concentration of terbinafine in plasma have been identified based on age.

Pharmacokinetic studies in patients with concomitant renal impairment (creatinine clearance less than 50 ml/min) and liver diseases have shown the possibility of a 50% reduction in the clearance of the drug.