Terbinafine 250 mg 28 tablets

Indications

- 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 skin infections caused by fungi of the genus Candida (e.g., Candida albicans) - in cases where the localization, severity, or extent of the infection justify the appropriateness of oral therapy.

Method of application and doses

The drug is taken orally, regardless of food intake, with water. It is advisable to take the drug at the same time each day. The duration of treatment depends on the indication and severity of the disease.
Adults
250 mg once a day.
Skin infections
Recommended duration of treatment:
Dermatomycosis of the feet (interdigital, plantar, or sock type): 2-6 weeks
Dermatomycosis 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.
Infections of hair and scalp
Recommended duration of treatment:
Mycosis of the scalp: 4 weeks.
Mycoses of the scalp are predominantly observed in children.
Onychomycosis
The duration of treatment for most patients is from 6 to 12 weeks.
In cases of onychomycosis of the hands, 6 weeks of treatment is usually sufficient.
In cases of onychomycosis of the feet, 12 weeks of treatment is usually 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 growth.
Use in children
In children over 3 years old and weighing more than 20 kg, the drug is taken once a day.
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); over 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 drug or that they experience side effects different from those in younger patients. When using the drug in tablet form in this age group, the possibility of concomitant liver or kidney function impairment should be considered.

Section: Composition

For 1 tablet:
Active ingredient: terbinafine hydrochloride 281.0 mg, equivalent to terbinafine 250.0 mg.
Excipients: lactose monohydrate (milk sugar) - 102.8 mg, sodium carboxymethyl starch type A - 25.8 mg, hypromellose - 12.9 mg, colloidal silicon dioxide - 3.2 mg, magnesium stearate - 4.3 mg

Round, flat-cylindrical tablets of white or almost white color, with a score on one side and beveled edges on two sides.

Contraindications

Increased sensitivity to terbinafine or to any other component of the drug; 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 50 ml/min or plasma creatinine concentration greater than 300 μmol/l), as the use of the drug in this category of patients is insufficiently studied.

With caution:

Bone marrow suppression, skin 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 regarding fertility and toxic effects on the fetus. Since clinical experience with the use of terbinafine in pregnant women is very limited, the drug 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, so women taking terbinafine orally should not continue breastfeeding.

Special instructions

Irregular use or premature termination of treatment increases the risk of relapse. If no improvement in condition is observed after 2 weeks of treatment, it is necessary to re-identify the causative agent of the disease and its sensitivity to terbinafine. Before starting the use of terbinafine tablets, liver function tests should be conducted. Hepatotoxicity may occur in patients with pre-existing liver diseases 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 in case of increased liver enzyme activity. 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 that occur during treatment. If such symptoms appear, the use of the drug should be immediately stopped, and liver function tests should be conducted. Caution should be exercised when administering the drug to patients with bone marrow suppression, skin lupus erythematosus, or systemic lupus erythematosus. Serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms) have been reported very rarely during terbinafine use. Extremely rare cases of changes in blood cell composition (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia) have been noted with terbinafine use. If qualitative or quantitative changes in blood cell elements occur, the cause of the disturbances should be established, and consideration should be given to reducing the drug dose 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) has not been sufficiently 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 disease. Systemic use for onychomycosis is justified only in cases of total involvement of most nails, presence of pronounced subungual hyperkeratosis, or ineffectiveness of previous local therapy. When treating onychomycosis, a 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 is not required for the treatment of hand onychomycosis within 3 weeks and foot onychomycosis within 6 weeks. 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 of classes IA, IB, IC, antipsychotic drugs, and type B monoamine oxidase 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 linen 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 therapy with the drug, patients should not drive vehicles and/or operate machinery.

Section: Side Effects

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 following gradations were used: "very common" (greater than or equal to 1/10), "common" (greater than or equal to 1/100 and less than 1/10), "uncommon" (greater than or equal to 1/1000 and less than 1/100), "rare" (greater than or equal to 1/10000 and less than 1/1000), "very rare" (less than 1/10000), including individual reports.
Disorders of the hematopoietic 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 of these conditions).
Nervous system disorders: very common - headache; common - dizziness, taste disturbances, up to loss of taste (usually recovery occurs within a few weeks after discontinuation of treatment); uncommon - paresthesias, hypesthesias. There are individual reports of prolonged taste disturbances. In some cases, exhaustion was noted against the background of drug intake.
Psychiatric disorders: common - depression; uncommon - anxiety.
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 a 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 of liver failure with 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 exacerbations of psoriasis, alopecia.
Disorders of the musculoskeletal and connective tissue: very common - arthralgia, myalgia.
General disorders: common - fatigue; uncommon - fever.
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.
Vascular disorders: vasculitis.
Nervous system disorders: loss of smell, including for a prolonged 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 if you notice any other side effects not listed in the instructions, inform your doctor.

Section: Overdose

There have been reports of several cases of overdose (the dose of terbinafine taken was up to 5 g), in which headache, dizziness, nausea, pain in the epigastric region, frequent urination, and rash were noted. The recommended treatment in case of overdose includes measures to eliminate the drug, primarily by administering activated charcoal and gastric lavage; if necessary, symptomatic and supportive therapy is conducted.

Interaction

Influence of other drugs 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 adjustment of the dosing regimen of the latter may be required.
Cimetidine may enhance the effect of terbinafine or increase its plasma concentration. 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. Such an increase in terbinafine exposure may occur with the use of other drugs that inhibit isoenzymes CYP2C9 and CYP3A4, such as ketoconazole and amiodarone.
Rifampicin may weaken the effect of terbinafine or reduce its plasma concentration. Rifampicin increases the clearance of terbinafine by 100%.
Influence of terbinafine on other drugs
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 isoenzyme: tricyclic antidepressants, beta-blockers (metoprolol, propranolol), selective serotonin reuptake inhibitors, antiarrhythmic drugs of classes 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 that have no or minimal effect
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 that are metabolized by CYP2D6. Terbinafine does not affect the clearance of phenazone or digoxin.
Terbinafine has no 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 along with oral contraceptives, although the frequency of these disturbances does not exceed the average frequency of such disturbances in patients taking only oral contraceptives.
Terbinafine may reduce the plasma concentration or the clinical effects of the following drugs.
Terbinafine increases the clearance of cyclosporine by 15%.
Interaction with food and beverages
Food has a minimal effect on the bioavailability of terbinafine (increase in AUC

Section: Pharmacodynamics

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 verrucosum, Trichophyton violaceum, Trichophyton tonsurans), Microsporum (e.g., Microsporum canis), Epidermophyton floccosum, as well as yeast fungi of the genus Candida (e.g., C. albicans) and Malassezia. At low concentrations, terbinafine exerts fungicidal activity against dermatophytes, molds, and some dimorphic fungi. The activity against yeast fungi, depending on their species, can be fungicidal or fungistatic. Terbinafine, by inhibiting squalene epoxidase in the fungal cell membrane (not related to the cytochrome P450 system), 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 the drug is taken orally, concentrations are created in the skin, hair, and nails that provide fungicidal action.

Section: Pharmacokinetics

After oral administration, terbinafine is well absorbed (>70%), with an absolute bioavailability of about 50% (the "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 increased on average by 25% compared to a single dose; the area under the "concentration-time" curve (AUC) increased by 2.3 times. Based on the increase in AUC, the effective half-life can be calculated (30 hours). Food intake 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, hair, and sebaceous gland-rich skin. It has also been shown that terbinafine penetrates the nail plates in the first few weeks after the start of therapy.
Terbinafine is rapidly metabolized to a significant extent with the involvement of 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 do not possess 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 function impairment (creatinine clearance < 50 ml/min) and liver diseases have shown the possibility of a 50% reduction in the clearance of the drug.