Terbinafin, cream 1% 15 g

Terbinafine is an antifungal agent. It has a broad spectrum of action against fungi that cause skin, hair and nail diseases, including:

• dermatophytes such as Trichophyton (e.g., T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum), Microsporum (e.g., M. canis), Epidermophyton floccosum;
• degenerative fungi of the genus Candida (e.g., C. albicans) and Pityrosporum.

In low concentrations terbinafine has fungicidal effect against dermatophytes, molds and some dimorphic fungi. Activity against yeast fungi, depending on their species, may be fungicidal or fungistatic.

The mechanism of action is associated with specific suppression of the early stage of sterol biosynthesis in the fungal cell. This leads to a deficit of ergosterol and to intracellular accumulation of squalene, which causes cell death of the fungus. The action of terbinafine is performed by inhibiting the enzyme squaleneepoxidase in the cell membrane of the fungus. This enzyme does not belong to the cytochrome P450 system. Terbinafine has no significant effect on the metabolism of hormones or other drugs.

Pharmacokinetics

When terbinafine is administered orally, concentrations of the drug are created in the skin, hair and nails to provide fungicidal action.

After a single oral dose of 250 mg of terbinafine, its maximum plasma concentration is reached after 2 hours and is 0.97 µg/ml. The half-absorption period is 0.8 hours, and the half-distribution period is 4.6 hours. Although the bioavailability of terbinafine is moderately altered by food, but not to such an extent that correction of the drug dose is required.

Terbinafine is largely bound to plasma proteins (99%). It quickly penetrates through the dermal layer of the skin and concentrates in the lipophilic stratum corneum. Terbinafine also penetrates into the sebaceous gland secretion, resulting in high concentrations in hair follicles, hair and sebaceous gland-rich skin. Terbinafine has also been shown to penetrate the nail plates in the first few weeks of therapy.

Terbinafine is metabolized rapidly and to a significant extent with the participation of at least seven cytochrome P450 isoenzymes, with CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19 isoenzymes playing the major role. As a result of biotransformation of terbinafine metabolites are formed, which have no antifungal activity and are excreted mainly with the urine. The terminal elimination half-life is 17 hours. There is no evidence of cumulation of the drug in the body. No changes of terbinafine plasma equilibrium concentration depending on age have been found, but in patients with impaired renal or hepatic function the drug excretion rate may be delayed, resulting in higher terbinafine blood concentrations.

Less than 5% of the dose is absorbed when the spray or cream is applied topically, so the systemic effects of the drug are minimal.

Indications

Mycoses of the scalp (trichophytia, microsporia).
Fungal diseases of the skin and nails (onychomycosis) caused by Trychophyton (T. rubrum, T. mentagrophytes, T. verrucosum, T. violaccum), Microsporum (M. canis, M. gypseum) and Epidermophyton floccosum.
Severe, widespread dermatomycosis of smooth skin of the trunk and extremities, requiring systemic treatment.
Candidiasis of the skin and mucous membranes.

Pharmacological effect

Terbinafine is an antifungal agent. Has a wide spectrum of action against fungi that cause diseases of the skin, hair and nails, including:

dermatophytes such as Trichophyton (eg T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum), Microsporum (eg M. canis), Epidermophyton floccosum;
yeast fungi of the genus Candida (for example, C. albicans) and Pityrosporum.

In low concentrations, terbinafine has a fungicidal effect against dermatophytes, molds and some dimorphic fungi. Activity against yeast fungi, depending on their type, can be fungicidal or fungistatic.

The mechanism of action is associated with the specific suppression of the early stage of sterol biosynthesis in the fungal cell. This leads to ergosterol deficiency and intracellular accumulation of squalene, which causes the death of the fungal cell. Terbinafine works by inhibiting the enzyme squalene epoxidase in the cell membrane of the fungus. This enzyme does not belong to the cytochrome P450 system. Terbinafine does not have a significant effect on the metabolism of hormones or other drugs.

Pharmacokinetics

When terbinafine is administered orally, concentrations of the drug are created in the skin, hair and nails, providing a fungicidal effect.

After a single oral dose of terbinafine at a dose of 250 mg, its maximum plasma concentration is reached after 2 hours and is 0.97 mcg/ml. The half-life of absorption is 0.8 hours, and the half-life of distribution is 4.6 hours. Although the bioavailability of terbinafine varies moderately under the influence of food, it is not to such an extent that dose adjustment of the drug is required.

Terbinafine is highly bound to plasma proteins (99%). It quickly penetrates the dermal layer of the skin and concentrates in the lipophilic stratum corneum. Terbinafine also penetrates the secretions of the sebaceous glands, which leads to the creation of high concentrations in the hair follicles, hair and skin rich in sebaceous glands. Terbinafine has also been shown to penetrate the nail plates within the first few weeks after initiation of therapy.

Terbinafine is metabolized quickly and substantially with the participation of at least seven isoenzymes of cytochrome P450, with the main role being played by the isoenzymes CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19. As a result of the biotransformation of terbinafine, metabolites are formed that do not have antifungal activity and are excreted primarily in the urine. The terminal half-life is 17 hours. There is no evidence of drug accumulation in the body. There were no changes in the steady-state plasma concentration of terbinafine depending on age, but in patients with impaired renal or hepatic function, the rate of elimination of the drug may be slowed, resulting in higher concentrations of terbinafine in the blood.

When a spray or cream is applied topically, less than 5% of the dose is absorbed, thus the systemic exposure of the drug is minimal.

Active ingredient

Terbinafine

Composition

1 g of cream contains:

Active substance:

terbinafine hydrochloride 10 mg;

Excipients:

benzyl alcohol,

polysorbate 60 (tween 60),

sorbitan monostearate,

cetyl alcohol,

isopropyl myristate,

cetyl palmitate,

sodium hydroxide,

purified water.

Pregnancy

In experimental studies, the teratogenic properties of terbinafine were not identified.

The use of the drug during pregnancy is possible in cases where the expected benefit to the mother outweighs the possible risk to the fetus. Terbinafine is excreted in breast milk.

If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Contraindications

Hypersensitivity, severe hepatocellular and renal failure, blood diseases, tumors, metabolic diseases, vascular pathology of the extremities, pregnancy, breastfeeding, children (up to 12 years).

Side Effects

Feeling of heaviness and pain in the epigastric region, taste disturbance, loss of appetite, nausea, diarrhea, cholestasis, neutropenia, thrombocytopenia, allergic skin reactions; burning sensation, redness of the skin and itching in the area where the cream is applied.

Interaction

There are no known drug interactions for terbinafine ointment/cream.

Overdose

Symptoms:

headache, dizziness, nausea, vomiting, epigastric pain, frequent urination, rash.

Treatment:

measures to eliminate the drug (gastric lavage, taking activated charcoal); if necessary, symptomatic maintenance therapy.

Storage conditions

In a dry place, at a temperature not exceeding 25°C

Shelf life

3 years

Manufacturer

Vertex, Russia