Terbinafine-KV 250mg 2p x 14 tablets — Made in Ukraine — Free Delivery

Pharmacological properties

Pharmacodynamics. Terbinafine is an allylamine that has a broad spectrum of antifungal activity against skin, hair and nail infections caused by dermatophytes such as trichophyton (e.g. t. rubrum, t. mentagrophytes, t. verrucosum, t. tonsurans, t. violaceum), microsporum (e.g. microsporum canis), epidermophyton floccosum and yeasts of the genus candida (e.g. candida albicans) and pityrosporum. in low concentrations, it has a fungicidal effect against dermatophytes, molds and some dimorphic fungi. activity against yeast fungi, depending on their type, can be fungicidal or fungistatic.

Terbinafine specifically promotes the early stage of sterol biosynthesis in the fungal cell. This leads to a deficiency of ergosterol 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.

When taken orally, the preparation accumulates in the skin in concentrations that provide the fungicidal effect of the preparation.

Pharmacokinetics. After oral administration, terbinafine is well absorbed (70%); the bioavailability of terbinafine, which is part of Terbinafine-KB tablets, as a result of first-pass metabolism is about 50%. A single oral dose of 250 mg of terbinafine provided an average plasma Cmax of 1.30 μg / ml 1.5 hours after taking the preparation. In the equilibrium state, compared with a single dose, the Cmax of terbinafine was on average 25% higher, and the plasma AUC increased 2.3 times. Based on the increase in plasma AUC, the effective T1 / 2 (~ 30 h) can be calculated. Food intake has a moderate effect on the bioavailability of terbinafine (increase in AUC by less than 20%), but not so much that dose adjustment is required. Terbinafine strongly binds to blood plasma proteins. It diffuses rapidly across the dermis and concentrates in the lipophilic stratum corneum.

Terbinafine is also excreted in sebum and thus reaches high concentrations in hair follicles, hair and sebum-rich skin. It has also been proven that terbinafine is distributed into the nail plate in the first weeks after the start of therapy. Terbinafine is metabolized rapidly and extensively by at least seven CYP isoenzymes, with significant contributions from CYP 2C9, CYP 1A2, CYP 3A4, CYP 2C8 and CYP 2C19. Due to the biotransformation of terbinafine, metabolites are formed that do not show antifungal activity and are excreted mainly in the urine. T½ is 17 hours. There is no evidence of preparation accumulation in the body.

There were no changes in the pharmacokinetics of the preparation depending on the patient's age, but the rate of elimination of the preparation from the body may be reduced in patients with impaired renal or hepatic function, which leads to an increase in the level of terbinafine in the blood.

Bioavailability of Terbinafine-KB does not depend on food intake. Studies of the pharmacokinetics of single doses of the preparation with the participation of patients with impaired renal function (creatinine clearance 50 ml / min) or with pre-existing liver diseases have shown that the clearance of Terbinafine-KB can be reduced by about 50%.

Indications

Fungal infections of the skin and nails caused by trichophyton (eg t. Rubrum, t. Mentagrophytes, t. Verrucosum, t. Violaceum), microsporum canis and epidermophyton floccosum.

1. Ringworm (trichophytosis of smooth skin, trichophytosis of the perineum and dermatophytosis of the feet), when the localization of the lesion, the severity or prevalence of infection determine the appropriateness of oral therapy.

2. Onychomycosis.

Application

The preparation is intended for oral administration.

Adults are prescribed 1 tablet of 250 mg 1 time per day.

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

Skin infections. Recommended duration of treatment:

dermatophytosis of the feet (interdigital, plantar / moccasin-like) - 2–6 weeks;

trichophytosis of smooth skin - 4 weeks;

trichophytosis of the perineum - 2-4 weeks.

The complete disappearance of the symptoms of infection can occur only a few weeks after the absence of pathogens has been identified using laboratory control.

Scalp infections. The recommended duration of treatment for fungal infections of the scalp is 4 weeks.

Fungal lesions of the scalp are noted mainly in children.

Onychomycosis. The duration of treatment for most patients is from 6 weeks to 3 months. Treatment periods may be less than 3 months in patients with fingernails, toenails other than the thumb, or in young patients. For toenail lesions, 3 months is usually sufficient, although some patients may require treatment for 6 months or longer. Patients requiring longer treatment are identified by the reduced rate of nail growth during the first weeks of treatment.

The complete disappearance of the symptoms of infection can occur only a few weeks after the absence of pathogens has been identified using laboratory control.

Special patient groups

Patients with impaired liver function. Terbinafine-KB tablets are not recommended for use in patients with chronic or active liver disease.

Patients with impaired renal function. The use of the preparation Terbinafine-KB in tablets in patients with impaired renal function has not been properly studied and therefore is not recommended for this group of patients.

Children. It was found that the profile of adverse events in the use of terbinafine in children is similar to that in adults. There is no evidence of any new, unusual, or more serious reactions than those noted in adult patients. At this time, information on the use of terbinafine in children is limited, therefore, the use of the preparation is not recommended in this age group of patients.

Elderly patients. There is no evidence that it is necessary to change the dose of the preparation for elderly patients or that they have adverse reactions that differ from those in younger patients. In this age group, when using the preparation, the possibility of impaired liver or kidney function should be taken into account.

Contraindications

Hypersensitivity to terbinafine or any excipient of the preparation.

Side effects

Adverse reactions are usually mild to moderate and transient.

Blood and lymphatic system disorders: neutropenia, agranulocytosis, thrombocytopenia, anemia, pancytopenia.

From the immune system: anaphylactoid reactions (including angioedema), systemic lupus erythematosus, reactions similar to those of serum sickness.

From the side of metabolism and nutrition: decreased appetite.

From the side of the psyche: anxiety and depressive symptoms secondary to taste disorders.

From the nervous system: headache, paresthesia, hypesthesia, dizziness, anosmia, including persistent anosmia, hyposmia; taste disturbances, including loss of taste (usually recovers a few weeks after stopping the preparation). Very rarely, long-term disturbances in taste have been reported, sometimes resulting in decreased food intake and significant weight loss.

From the side of the organ of vision: blurred vision, decreased visual acuity.

On the part of the organs of hearing and balance: vertigo; hearing loss, hearing impairment, tinnitus.

On the part of the cardiovascular system: vasculitis.

From the digestive system: gastrointestinal symptoms (feeling of fullness in the stomach, dyspepsia, nausea, abdominal pain, diarrhea); pancreatitis.

From the liver and biliary tract: cases of serious liver dysfunction, including liver failure, increased liver enzymes, jaundice, cholestasis and hepatitis. If liver dysfunction develops, treatment with Terbinafine-KB should be discontinued. Very rarely, there have been reports of severe liver failure (some fatal or requiring liver transplantation). In most cases of liver failure, patients had serious underlying systemic diseases, and a causal relationship with terbinafine was questionable.

On the part of the skin and subcutaneous tissue: mild forms of skin reaction (rash, urticaria); psoriasis-like rashes or worsening of psoriasis; eosinophilia, exfoliative and bullous dermatitis, severe skin reactions (eg acute generalized exanthematous pustulosis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), photosensitivity (eg photodermatosis, photosensitivity reaction and polymorphic photodermatosis.), alopecia Treatment with Terbinafine-KB should be discontinued if progressive rashes develop on the skin.

From the musculoskeletal system and connective tissue: reactions from the musculoskeletal system (arthralgia, myalgia), rhabdomyolysis.

General disorders: malaise; fatigue; flu-like diseases, pyrexia.

The results of laboratory studies: an increase in the level of CPK in the blood, changes in prothrombin time (lengthening, shortening) in patients who were simultaneously taking warfarin.

Special instructions

Liver function. terbinafine-kV tablets are not recommended for use in patients with chronic or active liver disease. Before prescribing terbinafine-kV in tablets, it is necessary to assess all existing liver diseases.

Hepatotoxicity can be noted in patients with and without previous liver disease, therefore periodic monitoring of liver function is recommended (after 4-6 weeks of treatment). The use of the preparation Terbinafine-KB in tablets should be discontinued immediately in case of an increase in the activity of indicators of functional liver function tests. In patients taking Terbinafine-KB tablets, cases of serious liver failure have very rarely been reported (some of them were fatal or required a liver transplant). In most cases of liver failure, patients had serious underlying systemic diseases, and the causal relationship with taking Terbinafine-KB in tablets was questionable.

Patients taking Terbinafine-KB should be warned to immediately inform their doctor about any signs or symptoms suggestive of liver dysfunction, such as pruritus, unexplained persistent nausea, decreased appetite, anorexia, jaundice, vomiting, fatigue, right-sided pain in the upper abdomen or dark colored urine or discolored stools. Patients with these symptoms should discontinue oral terbinafine and the patient's liver function should be evaluated immediately.

Disturbance of taste. With the use of the preparation, taste disturbances and loss of taste have been reported. This can lead to poor appetite, weight loss, anxiety, and symptoms of depression. If symptoms of taste disturbance occur, the preparation should be discontinued.

Smell disorder. Impairment and loss of smell have also been reported. These disorders can disappear after stopping therapy, but can also be prolonged (more than 1 year) or permanent. If a violation of the sense of smell is detected, the use of the preparation should be discontinued.

Depression symptoms. During treatment with the preparation, depressive symptoms may occur, which may require treatment.

Dermatological effects. Very rarely, serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported in patients who received Terbinafine-KB in tablets. In the event of progressive skin rashes, treatment with Terbinafine-KB in tablets should be discontinued.

Terbinafine-KB should be used with caution in patients with psoriasis, as there have been reports of very rare exacerbations of psoriasis.

Hematological effects. Very rarely, pathological changes in the blood (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia) have been reported in patients receiving terbinafine tablets. It is necessary to assess the cause of any pathological change in the blood in patients and consider a possible change in the treatment regimen, including discontinuation of treatment with Terbinafine-KB in tablets.

Studies of the pharmacokinetics of a single dose of the preparation in patients with liver disease have shown that the clearance of Terbinafine-KB can be reduced by about 50%.

Kidney function. The use of Terbinafine-KB in tablets in patients with impaired renal function (creatinine clearance 50 ml / min or plasma creatinine level 300 μmol / L) has not been properly studied and therefore is not recommended.

Other. Terbinafine-KB should be used with caution in patients with lupus erythematosus, as there have been reports of very rare exacerbations of this pathology.

Use during pregnancy and lactation. Clinical experience with the use of terbinafine in pregnant women is very limited, therefore, Terbinafine-KB should not be used during pregnancy, unless the woman's clinical condition requires treatment with oral terbinafine and the expected benefit to the mother outweighs any potential risk to the fetus.

Terbinafine passes into breast milk, so women who are breastfeeding should not be treated with Terbinafine-KB.

Children. Data on the use of the preparation in children are limited, so its use is not recommended in patients of this age group.

The ability to influence the reaction rate when driving or operating other mechanisms. There are no data on the effect of Terbinafine-KB on the ability to drive vehicles and work with mechanisms. Patients who develop dizziness as an undesirable effect of the preparation should avoid driving and operating machinery.

Interactions

The effect of other preparations on terbinafine. plasma clearance of terbinafine can be increased by preparations that induce metabolism, and can be reduced by preparations that inhibit cytochrome p450. if concomitant treatment with such preparations is necessary, the dose of terbinafine-kv should be adjusted accordingly.

Medicines that can increase the effect or plasma concentrations of terbinafine. Cimetidine reduced terbinafine clearance by 30%.

Fluconazole increased the Cmax and AUC of terbinafine by 52 and 69%, respectively, due to inhibition of the CYP 2C9 and CYP 3A4 enzymes. The same increase in indicators is possible with the simultaneous use of preparations that suppress CYP 2C9 and CYP 3A4 with terbinafine, such as ketoconazole and amiodarone.

Medicines that can reduce the action or plasma concentrations of terbinafine. Rifampicin increased terbinafine clearance by 100%.

Effect of terbinafine on other medicinal products. Terbinafine has little potential to suppress or enhance the clearance of preparations metabolized by the cytochrome P450 system (eg terfenadine, triazolam, tolbutamine, or oral contraceptives), except for those preparations that are metabolized by CYP 2D6.

Terbinafine does not affect the clearance of phenazone or digoxin.

No effect of terbinafine on the pharmacokinetics of fluconazole was observed. In addition, there was no clinically significant interaction between terbinafine and concomitantly used preparations with a possible interaction potential, such as trimethoprim / sulfamethoxazole, zidovudine or theophylline.

Some cases of menstrual irregularities (intermenstrual bleeding and irregular menstrual cycle) have been reported in patients taking Terbinafine-KB concurrently with oral contraceptives, although the frequency of these violations remains within the frequency of adverse reactions in patients taking only oral contraceptives.

Medicines, the action or plasma concentrations of which can be increased by terbinafine. Terbinafine reduced the clearance of intravenous caffeine by 21%.

Terbinafine is known to inhibit CYP 2D6-mediated metabolism. These findings may be clinically relevant for patients taking preparations that are metabolized by CYP 2D6, such as tricyclic antidepressants, β-adrenergic receptor blockers, selective serotonin reuptake inhibitors, antiarrhythmics (including class 1A, 1B, and 1C), and MAO inhibitors type B, in the case when the preparation has a small range of therapeutic concentration.

Terbinafine reduced the clearance of desipramine by 82%.

In patients in whom the metabolic processes of dextromethorphan (antitussive preparations and a marker substrate CYP 2D6) passed quickly, terbinafine increased the metabolic interaction coefficient of dextromethorphan / dextrorphan in urine by an average of 16–97 times. Thus, the use of terbinafine can lead to a change in the status of fast metabolizers of CYP 2D6 to the status of slow metabolizers.

Medicines, the effect or plasma concentrations of which can be reduced by terbinafine. Terbinafine increased cyclosporine clearance by 15%.

In patients taking terbinafine concomitantly with warfarin, changes in the international normalized ratio (INR) and / or prothrombin time were rarely detected.

Overdose

There are several cases of overdose (oral administration of up to 5 g of terbinafine).

Symptoms: headache, nausea, epigastric pain, dizziness.

Treatment: elimination of the preparation primarily with the help of activated carbon and, if necessary, the use of symptomatic supportive therapy.

Storage conditions

At a temperature not higher than 25 ° C.