Famacivir - instructions for use, dose, side effects, contraindications

Excipients: giprolase (hydroxypropyl cellulose) 4.8 mg / 9.6 mg / 19.2 mg, lactose anhydrous 20.0 mg / 40.0 mg / 80.0 mg, silicon dioxide colloid (aerosil) 2.7 mg / 5.4 mg / 10.8 mg, microcrystalline cellulose 16.7 mg / 33.4 mg / 66.8 mg, carboxymethyl starch sodium (sodium starch glycolate) 9.0 mg / 18.0 mg / 36.0 mg, magnesium stearate 1.8 mg / 3 , 6 mg / 7.2 mg:

excipients for the shell: hypromellose (hydroxypropylmethylcellulose) 3.5 mg / 7.0 mg / 14.0 mg, macrogol 6000 (polyethylene glycol 6000) 1.0 mg / 2.0 mg / 4.0 mg, titanium dioxide 0.5 mg / 1.0 mg / 2.0 mg.

Description:

Tablets covered with a film coat of white or almost white color, round, biconvex (at a dosage of 125 mg and 250 mg) or biconvex, oblong with rounded mounds, with a risk (at a dosage of 500 mg). On the cross section, 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 human herpes viruses, including virus Varicella zoster and Herpes simplex 1 and 2 types, 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, becomes a triphosphate. Penciclovir triphosphate inhibits the replication of viral DNA (deoxyribonucleic acid). The intracellular half-life of penciclovir triphosphate for the culture of cells infected with Herpes simplex 1 is 10 hours; Herpes simplex 2 - 20 hours; Varicella zoster - 7 hours.

The concentration of penciclovir triphosphate in uninfected cells does not exceed the minimum detectable, therefore in therapeutic concentrations penciclovir does not affect uninfected cells.

As with acyclovir, resistance to penciclovir is most often associated with mutations in the gene for viral thymidine kinase, leading to a deficiency or disruption of the substrate specificity of the enzyme. Changes in the DNA polymerase gene are much less common.

The use of famciclovir for the treatment of herpes zoster (caused by the virus Varicella zoster) in immunocompetent patients and patients with reduced immunity, acceleration of healing of the skin and mucous membranes is noted. Famciclovir Effective in the treatment of various manifestations of ophthalmoherpes caused by the virus Varicella zoster. Famciclovir significantly reduces the severity and duration of postherpetic neuralgia in patients with herpes zoster.

One-day treatment with famciclovir of immunocompetent patients in the vine 1500 mg once a day or 750 mg twice a day promotes the rapid resolution of manifestations of recurrent labial herpes (caused by a virus Herpes simplex).

The use of famciclovir in immunocompetent patients at a dose of 1000 mg twice a day for 1 day, 125 mg twice a day for 5 days, or 500 mg twice a day for 3 days accelerates the healing of the skin and mucous membranes with relapse of genital herpes (caused by virus Herpes simplex).

Famciclovir 500 mg twice a day for 7 days is effective in treating various manifestations of herpes zoster in patients with reduced immunity due to infection with the human immunodeficiency virus (HIV). In HIV-infected patients famciclovir in a dose of 500 mg 2 times a day for 7 days accelerates the healing of the skin and mucous in the recurrence of genital herpes, and also reduces the number of days of virus isolation Herpes simplex (both with clinical manifestations, and without them). The use of famciclovir in patients with reduced immunity due to other causes has not been studied,

The efficacy of one-day administration of famciclovir 1000 mg twice daily for the treatment of recurrent genital herpes in immunocompetent patients of the Negroid race did not exceed that for placebo. The safety profile of a one-day administration of famciclovir 1000 mg twice daily for this category of patients was similar to that established earlier.

Pharmacokinetics:

Absorption

Famciclovir is a prodrug. After oral administration famciclovir quickly and almost completely absorbed and quickly converted into a pharmacologically active metabolite - penciclovir. Bioavailability of penciclovir after administration of famciclovir is 77%. An increase in the concentration of penciclovir in the blood plasma occurs in proportion to the increase in a single dose of famciclovir in the range of 125-1000 mg.

According to the study, the maximum concentration (C_max) penciclovir in blood plasma after ingestion of 125 mg, 250 mg or 500 mg of famciclovir is achieved on average after 45 minutes and averages 0.8 μg / ml, 1.0 μg / ml and 3.3 μg / ml, respectively.

Another study demonstrates C_max penciclovir after ingestion of 250 mg, 500 mg or 1000 mg of 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 into two or three doses coincide, indicating that there is no cumulation of penciclovir in repeated applications of famciclovir.

Metabolism

After oral administration famciclovir quickly and completely turns into a pharmacologically active metabolite - penciclovir.

Distribution

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

Excretion

Famciclovir is excreted mainly in the form of penciclovir and its 6-deoxy prodrug, which are excreted through the kidneys unchanged. Famciclovir in the urine is not found. Half-life (T_1/2) penciclovir from the blood plasma in the final phase after taking a single and repeated doses is about 2 hours.

Pharmacokinetics in special cases

Patients with an infection caused by a virus Varicella zoster

In patients with uncomplicated infection caused by the virus Varicella zoster, no significant changes in the pharmacokinetic parameters of penciclovirT_1/2) penciclovir from the blood plasma in the final phase after receiving a single and repeated doses of famciclovir is 2.8 and 2.7 hours, respectively).

Patients with impaired renal function

After taking single and repeated doses of famciclovir, a linear relationship is observed between a decrease in plasma clearance, renal clearance, the rate of excretion of penciclovir from the blood plasma, and the degree of impaired renal function. Pharmacokinetic features of famciclovir in patients with severe (decompensated) impaired renal function have not been studied.

Patients with hepatic impairment

In patients with impaired hepatic and mild liver function there is no increase in the value AUC penciclovir. The pharmacokinetics of penciclovir in patients with severe impairment of liver function has not been studied.The conversion of famciclovir into an active metabolite penciclovir in this group of patients may be impaired, which leads to a decrease in the concentration of penciclovir in the plasma and, as a consequence, a decrease in the efficacy of famciclovir.

Patients over the age of 65 years

In patients aged 65 to 70 years, an increase in the mean AUC Penciclovir by approximately 40% and a decrease in its renal clearance approximately 20% compared to persons under the age of 65. These pharmacokinetic features of penciclovir may be partly due to age-related changes in renal function in patients older than 65 years.

Floor

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

Race

When applied to famciclovir (single or multiple administration and a dose of 500 mg 1, 2 or 3 times a day) the pharmacokinetic parameters of famciclovir in healthy volunteers of the Negroid race and patients of the Negroid race with disturbances in the function of the nights or the liver did not differ from those of Caucasians of the Caucasoid race.

Indications:

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

Infections caused by Herpes simplex 1 and 2 types: treatment of primary infection, treatment and prevention of exacerbations of chronic infection.

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

Contraindications:

Hypersensitivity to famciclovir or other components of the drug.

Hypersensitivity to penciclovir.

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:

Caution should be exercised in the treatment of patients with impaired renal function, which may require adjustment of the dosing regimen.

Special precautions in elderly patients and in patients with impaired liver function of mild and moderate severity are not required. Experience with famciclovir in patients with severe (uncompensated) violations of liver function is absent.

The efficacy and safety of famciclovir in children has not been studied, so its use in this category of patients is not recommended,if only the potential benefit of therapy does not exceed the possible risk of complications.

Pregnancy and lactation:

Experimental studies have not revealed embryotoxic and teratogenic effects of famciclovir and penciclovir. However, since data on the safety of famciclovir in pregnant and lactating women women Not enough, the use of the drug Famacivir during pregnancy and during breastfeeding is possible only if the benefit from therapy for the mother exceeds the potential risk to the fetus and the baby.

In experimental studies with famciclovir (oral), penciclovir was isolated with breast milk. It is not known whether penciclovir with human breast milk.

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 (tingling, itching and burning).

Infection caused by a virus Varicella zoster (herpes zoster), the patients with normal immunity

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, virus-induced Varicella zoster, y patients with normal immunity

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

Infection caused by a virus Varicella zoster (herpes zoster in patients with reduced immunity

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

Infection caused by a virus Herpes simplex (labial or genital herpes), the patients with normal immunity:

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

with recurrences of genital herpes appoint 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; with relapses of labial herpes the recommended dose is 1500 mg once for 1 day or 750 mg 2 times a day for 1 day.

Infection caused by a virus Herpes simplex (labial or genital herpes), the patients with reduced immunity

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

To prevent exacerbations of recurrent infection caused by a virus Herpes simplex (suppressive therapy) prescribe 250 mg 2 times a day. The duration of therapy depends on the severity of the disease. It is recommended to periodically assess possible changes in the course of the disease after 12 months. In HIV-infected patients, the effective dose is 500 mg twice a day.

Patients over the age of 65 years. In elderly patients with normal renal function, 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. The following correction of the dosing regimen is recommended, depending on the creatinine clearance:

Infection caused by a virus Varicella zoster (herpes zoster), the patients with normal immunity:

Dosing regimen	Creatinine clearance, ml / min	Correctionspobathsth dosing regimen
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), the patients with reduced immunity;

Dosing regimen	Creatinine clearance, ml / min	Adjusted dosing regimen
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. Those on hemodialysis	250 mg after each dialysis session for 10 days

Infection caused by the Herpes simplex virus, in patients with normal immunity:

Dosing regimen		Creatinine clearance, ml / min	Adjusted dosing regimen
The first 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 2 times 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 3 doses of 250 mg every 12 hours	≥40		500 mg once, followed by 3 doses but 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

For prevention of exacerbation of recurrent infection caused by the virus Herpes simplex (suppressive therapy):

Dosing regimen	Creatinine clearance, ml / min	Adjusted dosing regimen
250 mg twice daily	≥40	250 mg twice daily
	20-39	125 mg twice daily
	<20	125 mg once daily
	Patients, on hemodialysis	125 mg after every dialysis session

Infection caused by a virus Herpes simplex (labial or genital herpes the patients with reduced immunity:

Dosing regimen	Creatinine clearance, ml / min	Adjusted dosing regimen
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 insufficiency, on hemodialysis. Since after a 4-hour hemodialysis, the concentration of penciclovir in plasma is reduced by 75%, famciclovir should be taken immediately after the procedure of hemodialysis. The recommended dose is 250 mg (for patients with herpes zoster) and 125 mg (for patients with genital herpes).

Patients with impaired hepatic function. For patients with impaired liver function of mild to moderate severity, dosage adjustment is not required.

Patients of the Negroid race. The efficacy of a one-day administration of famciclovir 1000 mg twice daily for the treatment of recurrence of genital herpes in immunocompetent patients of the Negroid race did not exceed that for placebo. The clinical significance of famciclovir dosing regimens for the treatment of both recurrences of genital herpes (within 2 or 5 days) and other infectious lesions caused by viruses Varicella zoster and Herpes simplex, is unknown.

Side effects:

The incidence of unwanted reactions is presented according to the WHO classification: very often (≥1 / 10 cases), often (≥1 / 100 and <1/10 cases) infrequently (≥1 / 1000 and <1/100 cases), rarely (≥ 1/10000 and <1/1000 cases) and very rarely (<1/10000 cases).The undesirable reactions that were noted in the postmarketing period of famciclovir and the incidence of which can not be calculated from available data are labeled "frequency unknown."

From the side of the blood and lymphatic system: rarely - thrombocytopenia.

Disorders of the psyche: infrequently - confusion (mainly in elderly patients); rarely - hallucinations.

From the nervous system: very often - headache; often - dizziness: infrequently - drowsiness (mainly in elderly patients).

Co sides of the heart: rarely - heart palpitations.

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

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

From the skin and subcutaneous tissues: often - a rash, itching; infrequently - angioedema (edema of the face, eyelids, periorbital area, pharynx), urticaria; frequency not known - severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis), lekotsitoklastichesky vasculitis (allergic).

Other: often - excessive sweating, very rarely - fever.

Overdose:

There are limited data on famciclovir overdose.

Treatment: symptomatic and supportive. If the recommendations for reducing the dose of famciclovir with non-compliance with renal function were not observed, patients with kidney disease rarely had cases of acute renal failure.

Penciclovir, which is an active metabolite of famciclovir, is excreted by hemodialysis. Concentrations of penciclovir in plasma are reduced by 75% after hemodialysis within 4 hours.

Interaction:

Simultaneous application with probenecid may lead to an increase in the concentration of penciclovir in the blood plasma. To prevent the development of toxic reactions and possible lowering of the dose, it is necessary to monitor patients receiving penciclovir in a dose of 500 mg concurrently with probenecid.

There were no clinically significant changes in the pharmacokinetic parameters of penciclovir when administered once (500 mg) immediately after taking antacid preparations (magnesium or aluminum hydroxide) or in patients who had been treated (repeatedly) with allopurinol, cimetidine, theophylline, zidovudine, promethazine .With a single administration of famciclovir (500 mg) along with emtricitabine or zidovudine, no changes in the pharmacokinetic parameters of penciclovir, zidovudine, the metabolite of zidovudine (zidovudine glucuronide), and emtricitabine were found.

With a single or multiple administration of famciclovir (500 mg 3 times daily), along with digoxin, there were no changes in the pharmacokinetic parameters of penciclovir and digoxin.

Considering that the conversion of an inactive metabolite of 6-deoxypenzyclovir (formed by the deacetylation of famciclovir) into penciclovir is catalyzed by the enzyme aldehyde oxidase, it is possible to develop drug interactions with famciclovir together with drugs metabolized with the participation of this enzyme or inhibiting its activity. When famciclovir is used together with cimetidine and promethazine, which are inhibitors of aldehyde oxidase in vitro, there was no decrease in the formation of penciclovir from famciclovir. However, with concomitant administration of famciclovir and a potent aldehyde oxidase inhibitor in vitro, raloxifene, a decrease in the formation of penciclovir from famciclovir, and as a consequence, the efficacy of famciclovir.It is necessary to evaluate the clinical efficacy of antiviral therapy with simultaneous application with raloxifene.

Given that famciclovir is a weak inhibitor of aldehyde oxidase in vitro, it is possible its effect on the pharmacokinetic parameters of drugs metabolized with the participation of this enzyme.

In experimental studies famciclovir did not exert an inducing influence on 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:

Treatment should be started immediately after diagnosis.

Caution should be exercised in the treatment of patients with impaired renal function, which may require adjustment of the dosing regimen.

Special precautions in elderly patients and in patients with impaired liver function of mild and moderate severity are not required.

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. During suppressive therapy with antiviral agents, the frequency of the spread of the viral infection is significantly reduced, however, the risk of transmission of infection theoretically exists. Therefore, patients should take appropriate protective measures during sexual intercourse.

The tablet formulation of the drug Famatsivir includes lactose, so it should not be used in patients with lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

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 of body weight: in female rats, a marked decrease in fertility was not observed.

Carried doses of famciclovir and duration of treatment

Famciclovir was well tolerated in the treatment of herpes zoster when administered at a dose of up to 750 mg 3 times inday and 7 days; in patients with genital herpes when administered at a dose of 750 mg 3 times daily for 5 days and at a dose of up to 500 mg 3 times daily for 10 days. It was also shown that famciclovir well tolerated with suppressive therapy at a dose of 250 mg 3 times a day for 12 months for the treatment of genital herpes.

Famciclovir was well tolerated in patients with reduced immunity in the treatment Varicella zoster when administered 500 mg 3 times a day for 10 days, and Herpes Simplex, when taken up to 500 mg twice a day for 7 days or 500 mg 2 times a day for 8 weeks.

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

The effect of the drug Famacivir on the ability to drive vehicles and work with mechanisms is not expected. However, patients who are dizzy, drowsy, confused, or otherwise disturbed by the central nervous system should refrain from driving and potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets, 125 mg, 250 mg and 500 mg.

Packaging:

By 3, 7, 10 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

By 1, 2, 3, 4 contour mesh packaging together with the instruction but application in a pack of cardboard.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002928

Date of registration:24.03.2015

The owner of the registration certificate:EvoFarm Ltd.EvoFarm Ltd. Russia

Manufacturer: & nbsp

EvoFarm Ltd. Russia

Information update date: & nbsp17.09.2015

Illustrated instructions

Instructions

Famacivir (Famacivir)