Terbifin^® (Tablets, Cream, Spray) Instructions for Use

ATC Code

D01BA02 (Terbinafine)

Active Substance

Terbinafine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antifungal drug

Pharmacotherapeutic Group

Antifungal agent

Pharmacological Action

Terbinafine belongs to the group of allylamines and has a broad spectrum of activity against fungi that cause diseases of the skin, hair, and nails, including dermatophytes such as Trichophyton (e.g., T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum), Microsporum (e.g., M. canis), Epidermophyton floccosum, as well as yeasts of the genus Candida (e.g., C. Albicans) and Pityrosporum.

At low concentrations, Terbinafine has a fungicidal effect against dermatophytes, molds, and some dimorphic fungi. Activity against yeasts, depending on the species, can be fungicidal or fungistatic.

Terbinafine specifically inhibits an 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. The action of terbinafine is carried out by inhibiting the enzyme squalene epoxidase in the fungal cell membrane. This enzyme is not related to the cytochrome P450 system.

When Terbifin^® is administered orally, concentrations of the drug are created in the skin, hair, and nails that provide a fungicidal effect.

Pharmacokinetics

After oral administration, Terbinafine is well absorbed (>70%); the absolute bioavailability of terbinafine due to the first-pass effect is approximately 50%. After a single oral dose of 250 mg of terbinafine, its C_max is reached after 1.5 hours and is 1.3 µg/ml. With continuous administration of terbinafine, its C_max increased on average by 25% more compared to a single dose; AUC increased by 2.3 times. Based on the increase in AUC, the effective T_1/2 (30 hours) can be calculated. Food intake has a minor effect on the bioavailability of the drug (AUC increases by less than 20%), so no dose adjustment of Terbifin^® is required when taken with food.

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

Terbinafine is metabolized rapidly and substantially with the participation of at least seven cytochrome P450 isoenzymes, with the main role 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 mainly in the urine.

No changes in the equilibrium concentration of terbinafine in plasma depending on age were identified.

In pharmacokinetic studies of a single dose of Terbifin^® in patients with concomitant renal impairment (creatinine clearance <50 ml/min) and liver diseases, a possible decrease in drug clearance by 50% was shown.

Indications

• Mycoses of the scalp;
• Onychomycosis caused by dermatophyte fungi;
• Fungal skin infections – treatment of dermatomycosis of the trunk, legs, feet, as well as yeast skin infections caused by fungi of the genus Candida (for example, Candida albicans) – in cases where the localization, severity or prevalence of the infection justifies the advisability of oral therapy.

ICD codes

Dosage Regimen

Spray

Externally.

Adults. Terbifin^® spray can be applied 1 or 2 times a day, depending on the indications. Before using the drug, it is necessary to thoroughly clean and dry the affected areas. The drug is sprayed onto the affected areas in an amount sufficient for their thorough moistening, and, in addition, applied to the adjacent areas of both affected and intact skin.

Duration of treatment and frequency of drug application

dermatomycosis of the trunk, legs 1 week; 1 time per day

dermatomycosis of the feet 1 week; 1 time per day

pityriasis versicolor 1 week; 2 times per day

The dosage regimen of Terbifin^® spray in elderly persons does not differ from that described above.

Use of Terbifin^® spray in children.

Experience with the use of Terbifin^® spray in children is limited, therefore the use of the drug in children is not recommended.

Cream

Adults and children 12 years and older

The drug is applied to the skin once or twice a day. Before applying the cream, it is necessary to clean and dry the affected areas. The cream is applied in a thin layer to the affected skin and adjacent areas and rubbed in lightly.

For infections accompanied by intertrigo (under the breasts, in the interdigital spaces, between the buttocks, in the groin area), the areas where the cream is applied can be covered with gauze, especially at night.

Average duration of treatment

Dermatomycosis of the trunk, legs: 1 week 1 time per day

Dermatomycosis of the feet: 1 week 1 time per day

Skin candidiasis: 1-2 weeks 1 or 2 times per day

Pityriasis versicolor: 2 weeks 1 or 2 times per day

A decrease in the severity of clinical manifestations is usually noted in the first days of treatment. In case of irregular treatment or premature discontinuation, there is a risk of recurrence of the infection. If no signs of improvement are observed after two weeks of treatment, the diagnosis should be verified.

Use of the drug in elderly persons

There is no reason to believe that the dosage of the drug needs to be changed for elderly persons or that they experience side effects different from those in younger patients.

Use of the drug in children

The use of this drug in children under 12 years of age is not recommended.

Tablets

The duration of the course of treatment and the dosage regimen are set individually and depend on the localization of the process and the severity of the disease. Adults and children weighing more than 40 kg are usually prescribed orally after meals, 1 tablet (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 trunk, legs: 2-4 weeks.

Skin candidiasis: 2-4 weeks.

Complete disappearance of the manifestations of the infection and complaints associated with it may occur no earlier than a few weeks after mycological cure.

Hair and scalp infections

Recommended duration of treatment:

Mycosis of the scalp: 4 weeks.

Mycoses of the scalp are observed mainly in children.

Onychomycosis

The duration of treatment for most patients is from 6 to 12 weeks. For onychomycosis of the hands, 6 weeks of treatment is sufficient in most cases. For onychomycosis of the feet, 12 weeks of treatment is sufficient in most cases. Some patients who have a reduced rate of nail growth may require longer treatment. The optimal clinical effect is observed several months after mycological cure and cessation of therapy. This is determined by the time required for a healthy nail to grow back.

Use in elderly persons

There is no reason to believe that the dosage regimen of the drug needs to be changed for elderly persons or that they experience side effects different from those in younger patients. When using the drug in tablets in this age group, the possibility of concomitant impairment of liver or kidney function should be taken into account.

Adverse Reactions

Terbifin^® is generally well tolerated. Side effects are usually mild or moderate and transient. Below are the adverse events that were observed during clinical studies or after the drug was marketed.

The following gradations were used to assess the frequency of side effects: “very common” (≥1/10), “common” (≥1/100 to <1/10), “uncommon” (≥1/1000 to <1/100), “rare” (≥1/10000 to <1/1000), “very rare” (<1/10000), including isolated reports.

From the hematopoietic system very rare – neutropenia, agranulocytosis, thrombocytopenia, increased activity of “liver” transaminases, lymphopenia.

From the immune system very rare – anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus.

From the nervous system common – headache; uncommon – taste disturbances, including loss of taste (usually recovery occurs within a few weeks after discontinuation of treatment). There are isolated reports of cases of prolonged taste disturbances. In some cases, against the background of taking the drug, a decrease in food intake was noted, which led to significant weight loss.

From the liver rare – hepatobiliary dysfunction (predominantly of cholestatic nature), including very rare cases of severe liver failure (some with fatal outcome or requiring liver transplantation).

From the gastrointestinal tract very common – feeling of fullness in the stomach, loss of appetite, dyspepsia, nausea. Mild abdominal pain, diarrhea.

From the skin and subcutaneous tissue very common – non-severe skin reactions (rash, urticaria), very rare – serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis); psoriasis-like skin rashes or exacerbations of psoriasis. Very rare cases of hair loss have been reported, although a causal relationship of this phenomenon with taking the drug has not been established.

If a progressive skin rash develops, treatment with Terbifin^® should be discontinued.

From the musculoskeletal system very common – arthralgia, myalgia.

Other very rare – feeling of tiredness.

Contraindications

• Children weighing less than 40 kg;
• Chronic or active liver diseases;
• Severe renal failure (creatinine clearance less than 50 ml/min);
• Severe hepatic insufficiency;
• Hypersensitivity to terbinafine or any other component that is part of the drug.

With caution: in renal failure, alcoholism, bone marrow depression, tumors, metabolic diseases, occlusive vascular diseases of the extremities.

It is not recommended to prescribe Terbifin^® to patients with chronic or active liver diseases. Before prescribing Terbifin^® tablets, it is necessary to determine whether the patient has pre-existing liver diseases. Hepatotoxicity can occur both in patients with pre-existing liver diseases and without them. Patients prescribed Terbifin^® should be warned that it is necessary to immediately inform the attending physician about the occurrence of such symptoms during drug administration as persistent nausea, lack of appetite, feeling of tiredness, vomiting, pain in the right hypochondrium, jaundice, dark urine or light feces. If such symptoms appear, it is necessary to immediately stop taking the drug and conduct a study of liver function.

Use in Pregnancy and Lactation

Data from experimental studies do not suggest the presence of adverse events regarding fertility and toxic effects on the fetus. Since clinical experience with the use of Terbifin^® in pregnant women is very limited, the drug should not be used during pregnancy, except in cases where the expected benefit of therapy outweighs the potential risk.

Terbinafine is excreted in breast milk, therefore women receiving Terbifin^® orally should not breastfeed.

Use in Hepatic Impairment

Contraindicated in chronic or active liver diseases, in severe hepatic insufficiency.

Before prescribing Terbifin^® tablets, it is necessary to determine whether the patient has pre-existing liver diseases. Hepatotoxicity can occur both in patients with pre-existing liver diseases and without them. Patients prescribed Terbifin^® should be warned that it is necessary to immediately inform the attending physician about the occurrence of such symptoms during drug administration as persistent nausea, lack of appetite, feeling of tiredness, vomiting, pain in the right hypochondrium, jaundice, dark urine or light feces. If such symptoms appear, it is necessary to immediately stop taking the drug and conduct a study of liver function.

Use in Renal Impairment

With caution in renal failure.

Pediatric Use

Contraindicated in children weighing less than 40 kg.

Geriatric Use

There is no reason to believe that the dosage regimen of the drug needs to be changed for elderly persons or that they experience side effects different from those in younger patients. When using the drug in tablets in this age group, the possibility of concomitant impairment of liver or kidney function should be taken into account.

Special Precautions

It has been shown that Terbinafine inhibits metabolism mediated by the enzyme 2D6 (CYP2D6). Therefore, constant monitoring of patients receiving treatment with drugs that are predominantly metabolized with the participation of this enzyme (such as tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitors, class 1C antiarrhythmic drugs and type B monoamine oxidase inhibitors) simultaneously with Terbifin^® is necessary, in case the concomitantly used drug has a narrow therapeutic range.

Irregular use or premature termination of treatment increases the risk of relapse. If no improvement is observed after 2 weeks of treatment, it is necessary to re-determine the causative agent of the disease and its sensitivity to the drug.

Before starting and during treatment, monitoring of liver function indicators is necessary.

During treatment, it is necessary to observe general hygiene rules to prevent reinfection (through underwear, shoes).

Influence on the ability to drive vehicles and mechanisms

There are no data on the effect of Terbifin^® on the ability to drive a car and operate machinery.

Overdose

There are reports of several cases of overdose (the taken dose of the drug was up to 5 g), in which headache, nausea, pain in the epigastric region and dizziness were noted.

Recommended treatment in case of overdose includes measures to remove the drug, primarily by prescribing activated charcoal and gastric lavage; if necessary, symptomatic and supportive therapy is carried out.

Drug Interactions

Influence of other medicinal products on Terbinafine

Plasma clearance of terbinafine can be accelerated under the influence of drugs – metabolism inducers, and suppressed under the influence of cytochrome P450 inhibitors. If simultaneous use of the above drugs and Terbifin^® is necessary, appropriate adjustment of the dosage 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%. 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 medicinal products

Results of studies conducted in vitro and in healthy volunteers show that Terbinafine has little potential to suppress or enhance the clearance of most drugs that are metabolized with the participation of the cytochrome P450 system (for example, terfenadine, triazolam, tolbutamide or oral contraceptives), except for those that are metabolized with the participation of CYP2D6. Terbinafine does not affect the clearance of antipyrine or digoxin. There are reports of several cases of menstrual cycle disorders in patients taking Terbifin^® together with oral contraceptives, although the frequency of these disorders does not exceed the average frequency of such disorders in patients taking only oral contraceptives.

Terbinafine may enhance the effect of caffeine or increase its plasma concentration. Terbinafine reduces the clearance of caffeine by 20%. In in vivo and in vitro studies, it has been shown that Terbinafine inhibits metabolism mediated by the enzyme 2D6 (CYP2D6). These data may be clinically significant for those drugs that are metabolized predominantly by this enzyme: tricyclic antidepressants, beta-blockers. Selective serotonin reuptake inhibitors, class 1C antiarrhythmic drugs and type B monoamine oxidase inhibitors, – in the case where the concomitantly used drug has a narrow therapeutic range. Terbinafine reduces the clearance of desipramine by 82%.

Ethanol and other hepatotoxic drugs increase the risk of hepatotoxicity.

Terbinafine may weaken the effect of cyclosporine and reduce its plasma concentration. Terbinafine increases the clearance of cyclosporine by 15%.

Storage Conditions

Store in a light-protected place at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.