Terbinafin-Teva, tablets 250 mg 14 pcs

Pharmacotherapeutic group: antifungal agent.

Code ATX: [D01BA02]

Pharmacological properties

Pharmacodynamics

Terbinafine belongs to the group of allilamines and has a wide spectrum of antifungal action. In low concentrations it has fungicidal activity against dermatophytes (Тгусһутон rubrum, Тгусһутон mentagrophytes, Тгусһутон tonsurans, Тгусһутон verrucosum, Тгусһутон violaceum, Microsporum canis, Epidermophyton floccosum), yeast fungi, mainly Candida albicans. Activity against yeast fungi, depending on their species, may be fungicidal or fungistatic.

Terbinafine disrupts the early stage of biosynthesis of the main component of the cell membrane of fungi (ergosterol) by inhibiting the enzyme squalene epoxidase.

In oral administration it is ineffective in the treatment of variegated herpes caused by Pityrosporum ovale, Pityrosporum orbiculare (Malassezia furfur).

Pharmacokinetics

Ingestion absorbs more than 70%. Absolute bioavailability is reduced by 40% due to the “first pass” effect. After a single oral dose of 250 mg the time to reach maximum concentration (TC_max) is about 2 hours; maximum concentration (C_max) is 1 µg/ml. The area under the curve “concentration – time” (AUC) is 4.56 µg×h/ml; AUC increases by 20% when concomitantly taken with food. With prolonged use C_max increases by 25%, AUC – 2.5 times. Effective elimination half-life (T_1/2) is about 36 h, terminal T_1/2 200-400 h (indicates prolonged excretion from skin and adipose tissue). Equilibrium concentration (C_ss) is independent of age. Plasma concentration of terbinafine is independent of sex.

Binding to plasma proteins is more than 99%. It is rapidly distributed in the tissues, penetrates into the dermal layer of the skin and nail plates. It penetrates into the secretion of sebaceous glands and accumulates in high concentrations in hair follicles, hair, skin and subcutaneous tissue. It is subjected to significant biotransformation, the resulting metabolites have no antifungal activity. It is excreted by the kidneys at 70%.

It does not accumulate in the body. The age of patients does not affect the pharmacokinetics of terbinafine, but elimination may be reduced with renal or hepatic damage, leading to high concentrations of terbinafine in the blood.

It is excreted with breast milk.

Indications

– Scalp mycoses (Trichophytosis, Microsporia).

– Fungal skin and nail diseases (onychomycosis) caused by Trychophyton spp. rubrum, T. mentagrophytes, T. verrucosum, T. violacaeum), Microsporum spp. (M. canis, M. gypseum) and Epidermophyton floccosum.

– Severe, widespread dermatomycoses of smooth skin of the trunk and extremities, requiring systemic treatment.

– Candidiasis of the skin.

Active ingredient

Composition

How to take, the dosage

Ingestion, after meals.

Adults

250 mg once daily.

Children over 3 years

In body weight between 20 and 40 kg, 125 mg once daily.

In body weight over 40 kg, 250 mg once daily.

Elderly patients do not require dose adjustment.

Patients with chronic renal insufficiency (CKR over 50 ml/min) – 125 mg once daily.

The duration of treatment depends on the indication and the severity of the disease.

Fungal skin infections:the duration of treatment for interfinger, plantar or “toe” type localization of infection is 2-6 weeks; for mycoses of other body areas: shins – 2-4 weeks, torso – 2-4 weeks; for mycoses caused by fungi of the genus Candida – 2-4 weeks; for mycoses of the scalp – about 4 weeks, for infection with Microsporum canis – more than 4 weeks.

Onychomycosis:the duration of therapy averages 6-12 weeks. For nail infections of the fingers and toes (with the exception of the big toe), or when the patient is young, the duration of treatment may be less than 12 weeks. For big toe infections, a 3-month course of treatment is usually sufficient. Some patients with reduced nail growth may need longer treatment.

Interaction

Dose adjustment of terbinafine is required when concomitant use with cytochrome P450 isoenzyme inhibitors and inducers that may slow down and speed up excretion of terbinafine from the body. Cimitidine decreases the excretion rate of terbinafine by 30%, and rifampicin increases the excretion rate of terbinafine by 100%.

The in vitro and in vivo studies have shown that terbinafine, by inhibiting the CYP2P6 isoenzyme, disrupts the metabolism of tricyclic antidepressants, selective serotonin reuptake inhibitors (desipramine, fluvoxamine), beta-adrenoblockers (metoprolol, propranolol), antiarrhythmic agents (flecainide, propafenone), monoamine oxidase B inhibitors (selegiline) and antipsychotic agents (chlorpromazine, haloperidol).

Terbinafine does not significantly affect the excretion rate of tolbutamine, terfinadine, triazolam, oral contraceptives, which are metabolized by other cytochrome P450 isoenzymes (except for CYP2P6 isoenzyme).

Terbinafine does not affect the excretion rate of antipyrine and digoxin.

The simultaneous use of terbinafine and oral contraceptives may lead to menstrual cycle disorders.

Terbinafine may increase the effectiveness of caffeine, by increasing its plasma concentrations and decreasing the elimination rate by 21%.

Terbinafine may decrease the elimination rate of desipramine by 82%.

Terbinafine may decrease the effectiveness of cyclosporine, by reducing its plasma concentrations by 15%.

When used simultaneously with warfarin, it may affect the prothrombin test values: blood clotting time and the international normalized ratio.

Concomitant use with ethanol or drugs with hepatoxic effect causes risk of drug-induced liver injury.

Special Instructions

If terbinafine is used irregularly or if treatment is stopped prematurely, it may lead to a recurrence of the disease.

If no improvement is seen after 2 weeks of treatment of the skin infection, the causative agent and its sensitivity to the drug should be determined again.

The systemic use in onychomycosis is justified only if most of the nails are affected, if pronounced subnail hyperkeratosis is present, and if previous topical therapy has been ineffective.

In the treatment of onychomycosis, the clinical response confirmed by the laboratory is usually observed in a few months after mycological cure and discontinuation of the treatment, due to the rate of growth of healthy nails. Nail plate removal is not required when treating onychomycosis of the hands for 3 weeks and onychomycosis of the feet for 6 weeks.

The clearance of terbinafine may be reduced in the presence of liver disease.

Synopsis

Contraindications

Hypersensitivity to the drug components; chronic or active liver disease, chronic renal failure (creatinine clearance (CK) less than 50 ml/min), children under 3 years of age and with body weight less than 20 kg (for this dosage form), lactation, pregnancy.

With caution

Chronic renal failure (CK more than 50 ml/min), alcoholism, suppression of medullary hematopoiesis, tumors, metabolic diseases, vascular occlusive disease of the extremities.

Side effects

Frequency of side effects is classified according to the recommendations of the World Health Organization: very frequently, at least 10%; frequently, at least 1% but less than 10%; infrequently, at least 0.1% but less than 1%; rarely, at least 0.01% but less than 0.1%; very rarely, less than 0.01%, including isolated cases.

From the digestive system: very common – feeling of gastric fullness, decreased appetite, dyspepsia, nausea, abdominal pain, diarrhea; infrequent – disorders or loss of taste sensation (recovery occurs within a few weeks after stopping treatment), increased activity of “liver” transaminases; rare – cholestasis, jaundice, hepatitis; in individual cases – long-term taste disorders, leading to refusal to eat and significant weight loss, hepatic failure.

With the blood and lymphatic system:very rarely – neutropenia, thrombocytopenia, agranulocytosis, lymphopenia, single cases of pancytopenia.

Skin disorders:very rarely – psoriasis-like rash, exacerbation of psoriasis, acute generalized pustular exanthema.

Allergic reactions:very common – rash, urticaria; very rare – angioedema, malignant epidermal erythema (Stevens-Johnson syndrome), anaphylactoid reactions, toxic epidermal necrolysis (Lyell’s syndrome).

Musculoskeletal system disorders:very often – arthralgia, myalgia.

From the central and peripheral nervous system:often – headache; rarely – paresthesia, hypoesthesia, dizziness; very rarely – depression, anxiety.

Hearing organ and labyrinth disorders: very rarely, vertigo.

Others: rarely, malaise, weakness; very rarely, systemic lupus erythematosus, including cutaneous form.

Overdose

Pregnancy use

Similarities