Famciclovir-Teva - instructions for use, dose, side effects, contraindications

Excipients: Prosalt [microcrystalline cellulose 98%, silica colloidal dioxide 2%] SMCC 50 11.05 mg / 22.08 mg / 44.17 mg sodium carboxymethylstarch 8.00 mg / 16.01 mg / 32.01 mg low substituted giproloza 3.20 mg / 6.40 mg / 12.80 mg croscarmellose sodium 8.00 mg / 16.01 mg / 32.01 mg Prosolv [98% microcrystalline cellulose, colloidal silicon dioxide 2%] SMCC 90 8.25 mg / 16.50 mg / 33.00 mg, sodium stearyl fumarate 1.50 mg / 3.00 mg / 6.01 mg;

film sheath Foam II white Y-22-7719 6.6 mg / 9.9 mg / 13.2 mg (titanium dioxide (E 171) 1.98 mg / 2.97 mg / 3.96 mg, polydextrose FCC (E 1200) 1.584 mg / 2.376 mg / 3.168 mg Hypromellose 3 cp (E 464) 1.188 mg / 1.782 mg / 2.376 mg hypromellose 6 cP (E 464) 1.018 mg / 1,528 mg / 2,307 mg, triacetin (E 1518) 0.495 mg / 0.743 mg / 0.99 mg hypromellose 50 cP (E 464) 0.170 mg / 0.254 mg / 0.339 mg macrogol 8000 0.165 mg / 0.247 mg / 0.330 mg).

Description:

Dosage of 125 mg. Round tablets covered with a film shell of white or almost white color, engraved with "8117" on one side and "93" on the other side.

Dosage of 250 mg. Round tablets covered with a film shell of white or almost white color, with engraving "8118" on one side and "93" on the other side.

Dosage 500 mg. The capsule tablet, coated with a white or almost white film shell, engraved with "8119" on one side and "93" on the other side.

* In the cross section of the tablets, the nucleus is white or almost white in color.

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 viruses Herpes simplex 1 st, 2 nd type and Varicella zoster, as well as Epstein-Barr viruses and cytomegalovirus. Penciclovir enters the virus-infected cells, where, under the action of viral thymidine kinase, it rapidly converts to monophosphate, which in turn, with the participation of cellular enzymes, turns into triphosphate. Penciclovir triphosphate is found in virus-infected cells for more than 12 hours, suppressing the synthesis of viral DNA (deoxyribonucleic acid) and the replication of viruses. Half-life of penciclovir triphosphate in cells affected by viruses Varicella zoster, Herpes simplex 1 st, 2 nd type, 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 0.3% in patients with normal immunity, and in patients with impaired immunity - 0.19%. Resistance was manifested only at the beginning of treatment and did not develop during treatment or after the termination of therapy.

In patients with herpes zoster, the severity and duration of postherpetic neuralgia significantly decreases.

In patients with impaired immunity 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 It is quickly and almost completely absorbed and converted into an active penciclovir. Bioavailability of penciclovir is 77%. An increase in the concentration of penciclovir in plasma occurs in proportion to the increase in a single dose of famciclovir in the range of 125-1000 mg. The maximum concentration (C_mOh) penciclovir after ingestion of 125 mg, 250 mg or 500 mg of famciclovir is achieved on average 45 minutes and is 0.8 μg / ml, 1.6 μg / ml and 3.3 μg / ml, respectively. Other studies demonstrate C_mOh penciclovir after ingestion of 250 mg, 500 mg or 1000 mg, famciclovir in the values of 1.5 μg / ml, 3.2 μg / ml and 5.8 μg / ml, respectively.

Systemic bioavailability (area under the concentration-time curve (AUC)) penciclovir does not depend on the time of eating. AUC penciclovir with a single administration of famciclovir and when dividing the daily dose of famciclovir by two or three doses are similar, indicating that penciclovir is not accumulated in repeated applications of famciclovir.

The binding to blood plasma proteins of penciclovir and its 6-deoxy precursor is less than 20%.

Famciclovir is excreted mainly in the form of penciclovir and its 6-deoxy progenitor, which are excreted in the urine unchanged. Famciclovir in the urine is not found. The half-life (T_1/2) penciclovir from the blood plasma in the final phase after a single and repeated dose of famciclovir is about 2 hours.

Pharmacokinetics in special cases

In patients with an infection caused by a virus Varicella zoster, no significant changes in pharmacokinetic parameters of penciclovir are detected. T_1/2Penciclovir in the final phase after a single and multiple doses of famciclovir is 2.8 and 2.7 hours, respectively.

Patients with renal insufficiency

In patients with renal insufficiency, after a single and multiple dose of famciclovir, a linear relationship between a decrease in plasma clearance, renal clearance, the rate of excretion of penciclovir from the blood plasma, and the severity of renal failure are noted. Pharmacokinetic features of famciclovir in patients with severe (decompensated) impaired renal function have not been studied.

Patients with impaired hepatic function

In patients with impaired liver function of mild and moderate severity AUC does not change. The pharmacokinetics of penciclovir in patients with severe impairment of liver function has not been studied.It is impossible to exclude the possibility of disrupting the process of conversion of famciclovir into an active metabolite penciclovir in this group of patients, which may be accompanied by a decrease in the concentration of penciclovir in the blood plasma and, as a consequence, a decrease in the effectiveness of famciclovir.

Patients of advanced age (over 65 years)

In patients aged 65-70 years, there was an increase in the mean AUC Penciclovir by approximately 40% and decreased renal clearance of penciclovir by approximately 20% compared with patients under the age of 65, which may be partly due to age-related changes in kidney function in patients older than 65 years.

Pharmacokinetic features associated with sex

The sex of the patient has no significant effect on the pharmacokinetic parameters of famciclovir (minor differences in clearance of penciclovir in men and women).

Pharmacokinetic features associated with race

When famciclovir is used (single or multiple doses of 500 mg 1, 2 or 3 times a day) in healthy volunteers of the Negroid race and patients of the Negroid race with impaired renal or hepatic function,the differences in pharmacokinetic parameters were revealed in comparison with the use of famciclovir in similar groups of patients of the Caucasoid race.

Indications:

- Infections caused by the virus Varicella-zoster (herpes zoster), including ophthalmoherpes; to reduce the risk of occurrence and duration of postherpetic neuralgia.

- Infections caused by viruses Herpes simplex 1 st, 2 nd types, including primary and recurrent infection (treatment of primary infection, treatment and prevention of exacerbation of chronic infection).

- Infections caused by viruses Varicella-zoster and Herpes simplex 1 st, 2 nd types (labial and genital herpes), in patients with reduced immunity.

Contraindications:

Hypersensitivity to famciclovir, penciclovir or any component of the drug, children under 18 years of age (due to lack of data on efficacy and safety).

Carefully:

Renal failure, severe (decompensated) violations of liver function (no experience of use).

Pregnancy and lactation:

Experimental studies have not revealed embryotoxic and teratogenic effects of famciclovir and penciclovir.

In experimental studies with the use of famciclovir inside, penciclovir was isolated with breast milk. It is not known whether penciclovir with breast milk in women.

However, since the safety of famciclovir in pregnant and lactating women is not established, its use in pregnancy and during breastfeeding is possible only if the benefits of therapy for the mother exceed the potential risk to the fetus and the baby.

Dosing and Administration:

Inside, regardless of food intake, without chewing, washing with water. Treatment should be started as soon as possible, immediately after the appearance of the first symptoms of the disease.

Adults

Infections caused by the virus Varicella-zoster (herpes zoster), patents with normal immune status

The recommended dose is 500 mg 3 times a day for 7 days. This method of application allows to reduce the duration of postherpetic neuralgia.

In the acute phase of the disease for the resolution of skin manifestations, the recommended dose is 250 mg 3 times a day or 500 mg twice a day or 750 mg once a day for 7 days.

Ophthalmoherpes caused by a virus Varicella-zoster, in patients with normal immunity

The recommended dose is 500 mg 3 times a day for 7 days.

Infections caused by the virus Varicella-zoster (herpes zoster) the patients with reduced immunity

The recommended dose is 500 mg 3 times a day for 10 days.

Infections caused by the virus Herpes simplex (labial and genital herpes) y patients with normal immunity

- with primary infection of genital herpes: the recommended dose is 250 mg 3 times a day for 5 days;

- with relapses of genital herpes: 1000 mg twice a day for 1 day or 125 mg twice a day for 5 days or 500 mg once, followed by the use of 3 doses of 250 mg every 12 hours;

- at relapses of labial herpes: 1500 mg once daily for 1 day or 750 mg 2 times a day for 1 day.

Infections caused by the virus Herpes simplex (labial and genital herpes) the patients with reduced immunity

The recommended dose is 500 mg twice a day for 7 days.

For the prevention of exacerbations of recurrent infection, caused by a virus Herpes simplex (suppressive therapy) - 250 mg twice a day. The duration of therapy depends on the severity of the disease. Periodic evaluation of possible changes in the course of the disease after 12 months. In patients infected with HIV, the effective dose is 500 mg 2 times a day.

Patients of advanced age (over 65 years): dose adjustment is not required in elderly patients with normal renal function

Application the children. The efficacy and safety of famciclovir in children have not been studied, so the use of Famciclovir-Teva in children is not recommended.

Patients with renal insufficiency

In patients with renal insufficiency, there is a decrease in clearance of penciclovir. It is recommended to correct the dosage regimen depending on the creatinine clearance (CC) (see Table 1).

Table 1. Correction of the dosing regimen of the drug Famciclovir-Teva in patients with renal insufficiency.

Dosing regimen	CK (ml / min)	Correction of the dosing regimen
Infection caused by a virus Varicella-zoster (herpes zoster) in patients with normal immune status
500 mg 3 times a day for 7 days	>60	500 mg 3 times a day for 7 days
	40-59	500 mg twice a day for 7 days
	20-39	500 mg once a day for 7 days
	<20	250 mg once a day for 7 days
	Patients on hemodialysis	250 mg after each dialysis session for 7 days
250 mg 3 times a day for 7 days	>40	250 mg 3 times a day for 7 days
	20-39	500 mg once a day for 7 days
	<20	250 mg once a day for 7 days
	Patients on hemodialysis	250 mg after each dialysis session for 7 days
500 mg twice a day for 7 days	>40	500 mg twice a day for 7 days
	20-39	500 mg once a day for 7 days
	<20	250 mg once a day for 7 days
	Patients on hemodialysis	250 mg after each dialysis session for 7 days
750 mg once a day for 7 days	>40	750 mg twice a day for 7 days
	20-39	500 mg once a day for 7 days
	<20	250 mg once a day for 7 days
	Patients on hemodialysis	250 mg after each dialysis session for 7 days
Infection caused by a virus Varicella-zoster (herpes zoster) in patients with reduced immunity
500 mg 3 times a day for 10 days	>60	500 mg 3 times a day for 10 days
	40-59	500 mg twice a day for 10 days
	20-39	500 mg once a day for 10 days
	<20	250 mg once a day for 10 days
	Patients on hemodialysis	250 mg after each dialysis session for 10 days
Infection caused by viruses Herpes simplex 1 st, 2 nd type in patients with normal immune status
Primary episode
250 mg 3 times a day for 5 days	>40	250 mg 3 times a day for 5 days
	20-39	250 mg twice a day for 5 days
	<20	250 mg once a day for 5 days
	Patients on hemodialysis	250 mg after each dialysis session for 5 days
With recurrence of genital herpes
1000 mg 2 times a day for 1 day	>60	1000 mg twice a day for 1 day
	40-59	500 mg twice a day for 1 day
	20-39	500 mg once
	<20	250 mg once
	Patients on hemodialysis	250 mg once after a dialysis session
125 mg twice a day for 5 days	>20	125 mg twice a day for 5 days
	<20	125 mg once
	Patients on hemodialysis	125 mg after each dialysis session for 5 days
500 mg once, followed by the use of 3 doses of 250 mg every 12 hours	>40	500 mg once, followed by the use of 3 doses of 250 mg every 12 hours
	20-39	250 mg once, followed by the use of 3 doses of 250 mg every 12 hours
	<20	250 mg once with subsequent application of 250 mg every other day
	Patients on hemodialysis	250 mg once after a dialysis session
With recurrence of labial herpes
1500 mg once	>60	1500 mg once
	40-59	750 mg once
	20-39	500 mg once
	<20	250 mg once
	Patients on hemodialysis	250 mg once after a dialysis session
750 mg twice a day	>60	750 mg twice a day for 1 day
	40-59	750 mg once
	20-39	500 mg once
	<20	250 mg once
	Patients on hemodialysis	250 mg once after a dialysis session
To prevent exacerbations of recurrent infection caused by Herpes simplex 1 st, 2 nd types (suppressive therapy)
250 mg twice daily	>40	250 mg twice daily
	20-39	125 mg twice daily
	<20	125 mg once daily
	Patients on	125 mg after each session
	hemodialysis	dialysis
Infection, virus-induced Herpes simplex 1 st, 2 nd type (labial or genital herpes) in patients with reduced immunity
500 mg twice a day for 7 days	>40	500 mg twice a day for 7 days
	20-39	500 mg once a day for 7 days
	<20	250 mg once a day for 7 days
	Patients on hemodialysis	250 mg after each dialysis session for 7 days

Patients with renal failure receiving hemodialysis. Since after 4 h of hemodialysis, the concentration of penciclovir in the blood plasma is reduced by approximately 75%, the dose of Famciclovir-Teva 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 compensation stage, dose adjustment is not required.Data on the use of famciclovir in severe decompensated chronic liver diseases are not available, so there are no precise recommendations for dosing of the drug Famciclovir-Teva in this category of patients.

Patients of the Negroid race. The effectiveness of a one-day dose at a dose of 1000 mg twice a day for the treatment of recurrence of genital herpes in immunocompetent patients of the Negroid race does not exceed that for placebo. The clinical significance of dosing regimens for the treatment of both recurrent genital herpes (within 2 or 5 days) and other infectious diseases caused by the virus Varicella-zoster and Herpes simplex 1 st, 2 nd types, is unknown.

Side effects:

The incidence of side effects is classified according to the following criteria: very often - not less than 10%; often - not less than 1% and less than 10%; infrequently - not less than 0.1% and less than 1%; rarely - not less than 0.01% and less than 0.1%; very rarely - less than 0.01%, including single messages.

From the system of blood and blood-forming organs: rarely - thrombocytopenia.

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

From the gastrointestinal tract: often - nausea, vomiting, diarrhea, abdominal pain.

From the side of the liver and bile-excreting tracts: often - an increase in the concentration of bilirubin and the activity of "hepatic" transaminases; rarely - cholestatic jaundice.

Allergic reactions: often - skin rash, itching; infrequently - angioedema (edema of the face, eyelids, periorbital area, pharynx), urticaria; unknown frequency - severe skin reactions: erythema multiforme, Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis).

From the side of the musculoskeletal system: very rarely - myalgia, arthralgia.

From the urinary system: rarely - hypercalcemia, changes in QC; very rarely - hemolytic-uremic syndrome (with the use of high doses of famciclovir in patients with reduced immunity).

Other: often - increased sweating; very rarely - a fever.

Overdose:

There are limited data on famciclovir overdose.

Treatment: symptomatic and supportive. When non-compliance with recommendations to reduce the dose of famciclovir with regard to kidney function in patients with kidney disease, there were rarely casesacute renal failure. Penciclovir, which is an active metabolite of famciclovir, is excreted by hemodialysis. Concentrations of penciclovir in blood plasma are reduced by 75% after hemodialysis for 4 hours.

Interaction:

Probenecid and other drugs that affect the functional state of the kidneys can affect the concentration of penciclovir in the blood plasma. To prevent the development of toxic reactions and a possible reduction in famciclovir dose, it is necessary to monitor the condition of patients taking 500 mg of famciclovir with probenecid.

There were no clinically significant changes in the pharmacokinetic parameters of penciclovir in single-dose famciclovir 500 mg immediately after taking antacid preparations (magnesium and aluminum hydroxide), or in patients receiving treatment with famciclovir (multiple administration) with allopurinol, cimetidine, theophylline, zidovudine, promethazine .

With a single application of famciclovir 500 mg at the same time as emtricitabine or zidovudine, there was no change in the pharmacokinetics of penciclovir, zidovudine, metabolite (zidovudine glucuronide), and emtricitabine.With a single and repeated application of famciclovir (500 mg 3 times daily), the pharmacokinetic interaction was not observed simultaneously with digoxin.

Considering that the conversion of an inactive metabolite of 6-deoxypenzyclovir (formed by the deacetylation of famciclovir) into penciclovir catalyzed by the enzyme aldehyde oxidase, it is possible to drug interaction with the simultaneous use of famciclovir and drugs that metabolize with the participation of aldehyde oxidase, or drugs that inhibit the activity of aldehyde oxidase. With simultaneous application in vitro Famciclovir with aldehyde oxidase inhibitors (cimetidine and promethazine) to reduce the formation of famciclovir penciclovir was not observed. However, when famciclovir is used simultaneously with raloxifene, a decrease in the formation of penciclovir and, as a consequence, a decrease in the efficacy of famciclovir. It is necessary to monitor the clinical efficacy of famciclovir when used concomitantly with raloxifene.

In experimental studies famciclovir did not affect the cytochrome P450 system and did not inhibit the isoenzyme CYP3A4.

It is necessary to take into account the possibility of interaction with drugs that are excreted from the body by active tubular secretion (for example, acetylsalicylic acid and ibuprofen).

Special instructions:

Caution should be exercised when treating Famciclovir-Teva in patients with impaired renal function, which may require adjustment of the dosing regimen (see section "Method of administration and dose").

Special precautions in elderly patients are not required.

Genital herpes is transmitted sexually. During the recurrence of genital herpes, the risk of contracting a sexual partner increases. It is necessary to inform patients about the need to refrain from sexual intercourse when symptoms of the disease appear even in the case of the onset of antiviral treatment. Despite the fact that during the treatment with Famciclovir-Teva the frequency of virus isolation decreases, the risk of transmission of infection persists. It is recommended to use condoms during the treatment of genital herpes with the drug Famciclovir-Teva.

Famciclovir does not exert a marked effect on spermogram, morphology or motility of human sperm.The decrease in fertility was noted in the experimental model in male rats receiving famciclovir in a dose of 500 mg / kg; In female rats, there was no marked decrease in fertility.

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

The effect of the drug Famciclovir-Teva on the ability to drive vehicles and / or work with mechanisms is not expected. However, patients who experience dizziness, drowsiness, confusion, or other disturbances from the central nervous system when taking the Famciclovir-Teva drug should refrain from managing motor vehicles and / or working with machinery during the period of drug use.

Form release / dosage:Tablets coated with a film coating, 125 mg, 250 mg, 500 mg.

Packaging:

Dosage of 125 mg. For 10 tablets in a blister of PVC / aluminum or PVC / PE / Acrylic foil. For 1 or 3 blisters per pack of cardboard along with instructions for use.

Dosage of 250 mg. For 7 tablets in a blister of PVC / aluminum or PVC / PE / Acrylic foil. For 3 blisters per pack of cardboard along with instructions for use.

For 10 tablets in a blister of PVC / aluminum or PVC / PE /Aclar foil.For 3 or 9 blisters in a pack of cardboard along with instructions for use.

Dosage of 500 mg. For 3 tablets in a blister of PVC / aluminum or PVC / PE /Aclar foil. For 1 blister in a pack of cardboard along with instructions for use.

For 7 tablets in a blister of PVC / aluminum or PVC / PE /Aclar foil. For 3 blisters per pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001740

Date of registration:02.07.2012

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA CANADA, Ltd. Canada

Representation: & nbspTeva Teva Israel

Information update date: & nbsp18.09.2015

Illustrated instructions

Instructions

Famciclovir-Teva (Famciclovir-Teva)