Minaker - instructions for use, doses, side effects, contraindications

film sheath: hypromellose (2910) 1.2 mg, 2.4 mg or 4.8 mg, macrogol (8000) 0.3 mg, 0.6 mg or 1.2 mg, titanium dioxide E 171 0.9 mg, 1, 8 mg or 3.6 mg, respectively.

Description:

Tablet 125 mg: round biconvex tablets, covered with a film shell of white color, on one side an engraving of "ARC", on the other - "FAM"over" 125 ".

Tablet 250 mg: round biconvex tablets, covered with a film shell of white color, on one side an engraving of "ARC", on the other - "FAM"over" 250 ".

Tablet 500 mg: oval biconvex tablets, covered with a film shell of white color, on one side engraving "ARC", on the other - "FAM 500".

Pharmacotherapeutic group:Antiviral agent

ATX: & nbsp

J.05.A.09 Famciclovir

Pharmacodynamics:

After oral administration famciclovir quickly turns into a penciclovir, which has activity against human herpes viruses, including virus Varicella zoster and Herpes simplex I and II, a also Epstein-Barr viruses and cytomegalovirus.

Penciclovir gets in virus-infected cells, which under the action of the viral thymidine kinase is rapidly converted to monophosphate which, in turn, with the participation of cellular enzymes to the triphosphate passes. Penciclovir triphosphate is found in virus-infected cells for more than 12 hours, suppressing the synthesis of viral DNA and the replication of viruses. Half-life of penciclovir triphosphate in cells affected by viruses Varicella zoster, Herpes simplex I and II, is 9, 10 and 20 hours, respectively. The concentration of penciclovir triphosphate in uninfected cells does not exceed the minimum detectable, therefore in therapeutic concentrations penciclovir does not affect uninfected cells.

Penciclovir is active against recently detected aciclovir-resistant strains of the virus Herpes simplex with a modified DNA polymerase.

The incidence of resistance to famciclovir (penciclovir) does not exceed 0,19-0,3% in patients with impaired immune status. Purpose famciclovir significantly reduces the severity and duration of postherpetic neuralgia in patients with herpes zoster.

In patients with impaired immune status due to infection with the human immunodeficiency virus (HIV) famciclovir in a dose of 500 mg 2 times a day reduces the number of days of virus isolation Herpes simplex (both with clinical manifestations, and without them).

Pharmacokinetics:

After oral administration famciclovir quickly, intensely and evenly absorbed and converted into penciclovir, which has antiviral activity. Bioavailability of penciclovir after administration of famciclovir is 77% (69.5-84.5%) inward. When taking famciclovir concomitantly with the intake of food, the absorption of the drug slows down, and C_mOh (the maximum concentration in blood plasma) of penciclovir may decrease by 50%, but the overall bioavailability remains practically unchanged.

In a study involving healthy male volunteers, the pharmacokinetic parameters of penciclovir after a single oral administration of famciclovir were characterized by linearity in the dose range of famciclovir from 125 to 750 mg. FROM_mOh penciclovir (range), calculated on the basis of dose-normalized values recorded after a single dose of famciclovir in all healthy volunteers in clinical trials, after a single dose of 500 mg mg of famciclovir averaged 3.3 μg / ml (range 1.3- 6.3 μg / ml) and reached an average of 0.89 hours after taking the drug (range 0.5-5.0 hours). The terminal half-life of penciclovir averaged 2.3 hours (range 0.99-5.26 hours). The pharmacokinetic parameters of penciclovir after a single oral administration of famciclovir in patients with uncomplicated shingles were almost identical to the pharmacokinetic parameters recorded in healthy volunteers of the same age. Repeated oral administration of famciclovir every 8 hours for 7 days did not significantly affect the pharmacokinetic parameters of penciclovir in patients with shingles that were identical to those recorded after a single dose of famciclovir. The degree of binding of penciclovir and its precursor to 6-deoxypenzyclovir with plasma proteins is low (<20%). Penciclovir freely distributed between plasma and blood cells.

Metabolism

After oral administration famciclovir in plasma and urine is not determined or its amount is minimal, since famciclovir quickly turns into a penciclovir by deacetylation and oxidation. AT in vitro A study using human liver microsomes showed that cytochrome P450 does not play a significant role in the metabolism of famciclovir. The conversion of 6-deoxypenzyclovir is catalyzed by aldehyde oxidase.

Excretion

Famciclovir is not detected in plasma and urine or its amount is minimal because famciclovir is subjected to intensive metabolism at the "first passage" through the liver and turns into penciclovir. The main metabolites, determined in plasma and urine, are penciclovir (67 ± 4% radioactivity in the plasma 1.5 hours after oral administration of 500 mg [¹⁴C] famciclovir and 82 ± 2.2% radioactivity in daily urine) and, to a lesser extent, its precursor 6-deoxypenzyclovir, which does not have antiviral activity (11 ± 4% in plasma and 7 ± 0.5% in urine in the corresponding time points). Other metabolites that do not possess antiviral activity and are determined in urine in small amounts are monoacetylated penciclovir and 6-deoxy monoacetylated peniclovir (<0.5% dose each).

The magnitude of renal clearance of penciclovir exceeds the creatinine clearance, which indicates the role of active tubular secretion and glomerular filtration in the elimination of the drug through the lice. A small, clinically insignificant decrease in the mean renal clearance of penciclovir is observed in women compared to men, as well as in elderly people compared to those of younger age. It is believed that in both cases, the differences are related to the sex-related or age-related decline in renal function. In addition, the mean half-life of women (2.0 hours) and elderly persons (2.7 hours) does not require a dose adjustment according to age or sex in patients with normal renal function or mild kidney failure (see "Method application and dose ").

Indications:

Infections caused by Varicella-zoster (herpes zoster), including ophthalmoherpes.

Infection caused by Herpes simplex (type I and II): primary infection, exacerbation of chronic infection, suppression of recurrent infection (for prevention of exacerbation).

Infections caused by viruses Varicella-zoster and Herpes simplex (type I and II) in HIV-infected patients.

Contraindications:

Hypersensitivity to famciclovir or to any of the ingredients of the dosage form or packaging components; pregnancy; the period of breastfeeding; children's age till 18 years.

Carefully:

Renal failure.

Pregnancy and lactation:

Contraindicated in pregnancy.

Famciclovir penetrates into breast milk, so it is recommended either to give up breastfeeding, or to interrupt the use of famciclovir.

Dosing and Administration:

Inside, adults, regardless of food intake, without chewing, washing with water.

- Infections caused by Varicella zoster in patients with normal immune status.

The recommended dose is 250 mg Zraz per day or 500 mg twice daily or 750 mg once a day for 7 days (acute phase of the disease).

- With ophthalmoherpes the recommended dose is 500 mg three times a day for 7 days.

- Infections caused by Varicella zoster in patients with a decreased immune status. The recommended dose is 500 mg three times a day for 10 days.

- Herpetic infection caused by Herpes simplex types I and II the patients with normal immune status.

The recommended dose for a primary infection is 250 mg 3 times a day for 5 days. Treatment should begin already in the prodromal period or immediately after the appearance of the first symptoms of the disease; with recurrences of chronic infection, adults are prescribed 125 mg twice a day for 5 days.

- Herpetic infection caused by Herpes simplex types I and II the patients with a decreased immune status.

The recommended dose is 500 mg twice a day for 7 days. Treatment should be started as soon as possible, immediately after the appearance of the first symptoms of the disease.

- As a suppressive therapy for recurrent herpetic infection prescribe 250 mg 2 times a day. It is recommended that the drug be taken periodically every 12 months to assess possible changes in the course of the disease.

In HIV-infected patients, the effective dose is 500 mg twice daily.

- Elderly patients. Provided that the kidney function is preserved, correction of the dosing regimen of famciclovir is not required.

- Patients with impaired renal function. In patients with impaired renal function, there is a decrease in clearance of penciclovir. An adequate correction is recommended dosage regimen depending on the creatinine clearance:

Infection caused by herpes zoster (regardless of the patient's immune status)

Creatinine clearance (ml / min / 1.73 m²)	Dosing regimen
>40	250 mg / 500 mg 3 times daily or 500 mg twice a day
30-39	250 mg 2-3 times a day
10-29	125 mg 2-3 times a day

Infection caused by the herpes simplex virus in patients with normal immune status

The first episode:
Creatinine clearance (ml / min / 1.73 m²):	Dosing regimen:
> 30	250 mg 3 times a day
10-29	125 mg 3 times a day
Recurrent infection:
Creatinine clearance (ml / min / 1.73 m²) >10	Dosing regimen: 125 mg 3 times a day

Infection caused by the herpes simplex virus in patients with a decreased immune status

Creatinine clearance (ml / min / 1.73 m²)	Dosing regimen
>40	500 mg twice a day
30-39	250 mg twice daily
10-29	125 mg twice daily
Suppressive therapy for recurrent herpetic infection
Creatinine clearance (ml / min / 1.73 m²)	Dosing regimen
>30	250 mg twice daily
10-29	125 mg twice daily

Patients with renal insufficiency who are on hemodialysis

Since after 4 hours of hemodialysis, the concentration of penciclovir in the plasma is reduced by approximately 75%, the dose of famciclovir should be taken immediately after the hemodialysis procedure. The recommended dose is 250 mg (for patients with Herpes zoster) and 125 mg (for patients with genital herpes).

Patients with impaired hepatic function

In patients with liver disease in the stage of compensation, dose adjustment is not required.

Data on the use of famciclovir in severe decompensated chronic liver diseases are absent, so there are no precise recommendations for dosing famciclovir in this category of patients.

Side effects:

Famciclovir is well tolerated by patients, including patients with reduced immune status.

To assess the incidence of adverse reactions, the following criteria were used: very often (> 1/10); often (from> 1/100, <1/10); sometimes (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), including individual messages.

On the part of the hematopoiesis system: very rarely - thrombocytopenia.

From the side of the central nervous system: rarely - headache, confusion (mainly in elderly patients); very rarely - dizziness, drowsiness (mainly in elderly patients), hallucinations.

From the digestive system: rarely - nausea; very rarely vomiting, jaundice.

From the skin: very rarely - rash, itching, severe skin reactions.

Allergic reactions: very rarely - hives, severe skin reactions (including manyformular erythema).

Overdose:

The described cases of overdose (10.5 g) of famciclovir were not accompanied clinical manifestations.

Treatment: conducting symptomatic and maintenance therapy. If the recommendations for diminishing the dose of famciclovir are not taken into account, taking into account the kidney function in patients with kidney diseases, cases of acute renal failure are noted.

Penciclovir is excreted by hemodialysis. Concentrations of penciclovir in plasma are reduced by 75% after hemodialysis for 4 hours.

Interaction:

Clinically significant pharmacokinetic interactions of famciclovir with other drugs have not been reported.

No effect of famciclovir on the cytochrome P450 system was detected.

Drugs that block tubular secretion can increase the concentration of penciclovir in the plasma.

After the previous multiple intake cimetidine, allopurinol or theophylline clinically significant changes in the pharmacokinetic parameters of penciclovir after a single dose of famciclovir 500 mg were not detected.

In addition, there were no clinically significant changes in the pharmacokinetic parameters of penciclovir with multiple (three times daily) intake of famciclovir (500 mg) and digoxin. After a single dose of 0.375 mg of digoxin and 500 mg of famciclovir in 12 healthy male volunteers, an increase in C_mOh (maximum concentration in plasma) of digoxin by 19 ± 18% in comparison with isolated reception of digoxin. Changes AUC_o_-_t(the area under the curve of the "concentration-time" dependence from the zero time to the time point "t") digoxin, where t was between 10 and 72 hours, it was not found. In a study involving 22 healthy volunteers, the pharmacokinetic parameters of penciclovir and digoxin did not change with simultaneous repeated administration of famciclovir (500 mg 3 times daily) and digoxin for 14 days.

Probenecid and other drugs that affect kidney function can lead to a change in plasma concentrations of penciclovir. The conversion of 6-deoxypenzyclovir into penciclovir is catalyzed by aldehyde oxidase. Clinically significant drug interactions due to this enzyme are not described in the literature.Interactions with other drugs metabolized by aldehyde oxidase are possible.

Special instructions:

Treatment should be started immediately after diagnosis.

Genital herpes is a sexually transmitted disease. During relapse, the risk of infection increases. In the presence of clinical manifestations of the disease, even in the case of the initiation of antiviral treatment, patients should avoid sexual contact.

Use in children

Safety and effectiveness of the drug in children under the age of 18 years are not established.

Application in elderly patients

Of the 816 patients with shingles receiving famciclovir in clinical trials, 248 (30.4%) of patients were over 65 years of age and 103 (13%) were older than 75 years. In general, there was no difference between younger and elderly patients regarding safety.

Effect on the ability to drive transp. cf. and fur:

In very rare cases famciclovir may cause dizziness, drowsiness and confusion. Patients who have such symptoms on the background of famciclovir should take special care when driving or using other mechanisms.

Form release / dosage:

Tablets coated with a film coating, 125 mg, 250 mg, 500 mg.

Packaging:

By 3, 10, 20, 21 or 30 tablets in high-density polyethylene (LDPE) bottles, sealed with a lid of PVD. On 1 bottle together with the instruction on application place in a pack from a cardboard.

10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil. For 1, 2 or 3 contour squares, together with the instructions for use, are placed in a pack of cardboard.

For hospitals: For 100 tablets in a bottle of high-density polyethylene (LDPE), sealed with aluminum foil or paper with a laminated coating and sealed with a screw cap of PVD. For 90 bottles together with instructions for use are placed in cardboard boxes. The number of instructions should correspond to the number of bottles.

Storage conditions:

In a dry place, at a temperature of no higher than 25 ° C.

Shelf life:

3 years.

The drug should not be used after the period indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001185

Date of registration:11.11.2011 / 11.09.2012

Expiration Date:Unlimited

The owner of the registration certificate:Apothec Inc.Apothec Inc. Canada

Manufacturer: & nbsp

APOTEX, Inc. Canada

Representation: & nbspAPOTEX Inc. APOTEX Inc. Canada

Information update date: & nbsp09.06.2018

Illustrated instructions

Instructions

Minacer® (Menaker®)