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

Excipients: sodium starch glycolate 8.26 mg, 16.52 mg, 27.35 mg, hydroxypropylcellulose 3.86 mg, 7.73 mg, 15.48 mg, magnesium stearate 1.24 mg, 2.48 mg, 4.1 mg; sheath (Opadry OY-S-28924): hypromellose 2.42 mg, 4.84 mg, 8.01 mg, titanium dioxide 0.99 mg, 1.98 mg, 3.28 mg, polyethylene glycol 4000 0.36 mg, 0.72 mg, 1.20 mg, polyethylene glycol 6000- 0.36 mg, 0.72 mg, 1.20 mg.

Tablets coated with a coat, 125 mg and 250 mg, contain lactose anhydrous (excipient) 26.85 mg and 53.69 mg.

Description:

Tablets 125 and 250 mg: white round biconvex tablets with beveled edges, covered with a shell, with engraving "FV"on the one hand, and" 125 "or" 250 "on the other.

Tablets 500 mg: white oval biconvex tablets with beveled edges, covered with a shell, with engraving "FV500 "on one side.

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, turns into 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 o'clock.

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 of 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.

Use of the drug for the treatment of herpes zoster (caused by a 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. The drug significantly reduces the severity and duration of postherpetic neuralgia in patients with herpes zoster. One-day treatment with famciclovir of immunocompetent patients at a dose of 1500 mg once a day or 750 mg 2 times a day promotes the rapid resolution of manifestations of recurrent labial herpes (caused by the virus Herpes simplex).

The use of the drug 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 2 times a day for 3 days accelerates the healing of the skin and mucous membranes with recurrence 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, the drug at a dose of 500 mg twice a day for 7 days accelerates the healing of the skin and mucous membranes with relapse 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 drug administration at a dose of 1000 mg twice a day in 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 taking Famvir® 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. According to the study, 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 on average0.8 μg / ml, 1.6 μg / ml and 3.3 μg / ml, respectively. Another study demonstrates the maximum concentration (C_mOh) 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 food intake.

AUC penciclovir with a single admission of famciclovir and when dividing the daily dose of the drug 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. The half-life (T_1/2) of penciclovir from the 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 penciclovir (T_1/2) of penciclovir from the plasma in the final phase after taking 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 the drug in patients with severe (decompensated) renal dysfunction were not studied.

Patients with hepatic impairment

In patients with impaired liver function of mild and moderate severity, 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 aged> 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 by approximately 20% compared to individuals younger than 65 years. 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 does not have a significant effect on the pharmacokinetic parameters of the drug (slight differences in the clearance of penciclovir in men and women).

Race

In applying famciclovir (single or multiple dose in a dose of 500 mg of 1, 2 or 3 times a day) pharmacokinetic parameters of the drug in healthy volunteers and patients blacks blacks with impaired renal or hepatic function were not different from those of Caucasian individuals.

Indications:

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

- Infections caused by a virus Herpes simplex I and II types: treatment of primary infection; treatment and prevention of exacerbations of chronic infection;

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

Contraindications:

Hypersensitivity to famciclovir or any of the components of the drug. Hypersensitivity to penciclovir.

Carefully:

Care should be taken when treatment of patients with impaired renal function, which may require correction of the dosing regimen.

Special precautions are elderly patients and patients with impaired liver function it takes. Experiments with the use of the drug in patients with severe (decompensated) violations of liver function are absent.

Use in children

The efficacy and safety of Famvir® in children have not been studied, and therefore its use in this category of patients is not recommended, unless the potential benefit of therapy exceeds the possible risk of complications.

Pregnancy and lactation:

Experimental studies have not revealed embryotoxic and teratogenic effects of famciclovir and penciclovir. However, since safety data applications preparation Famvir® in pregnant and lactating women not enough, its use during pregnancy and during lactation is possible only if the benefits of therapy for the mother exceed the potential risk to the fetus and the baby.

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

Dosing and Administration:

The drug should be taken orally, regardless of food intake, without chewing, washing with water. Treatment with the drug 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), in 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 is recommended; the dose is 250 mg 3 times a day or 500 mg 2 times 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.

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), in 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 recurrence of labial herpes -1500 mg once for 1 day or 750 mg twice a day for 1 day.

Infection, virus-induced Herpes simplex (labial or genital herpes), in patients with reduced immunity

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 evaluate 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 aged> 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 due to viruses Varicella zoster (herpes zoster), in patients with normal immunities:

Dosing regimen	Creatinine clearance	Adjusted 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 1 time per 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 with the virus Varicella zoster (shingles) in patients with reduced immunity:

Dosing regimen	Creatinine clearance	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 daily for Julia
	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 Herpes simplex viruses in patients with normal immunity:

The first episode:

Dosing regimen	Creatinine clearance	Adjusted dosing regimen
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:

Dosing regimen	Creatinine clearance	Adjusted dosing regimen
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 DAYS
	20-39	500 mg once
	from 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-h doses of 250	>40	500 mg once, followed by 3 doses of 250 mg every 12 hours
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, followed by 250 in a day
	Patients, on hemodialysis	250 mg once after a dialysis session

With recurrence of labial herpes:

Dosing regimen	Creatinine clearance	Adjusted dosing regimen
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 2 times 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 viruses Herpes simplex (suppressive therapy):

Dosing regimen	Creatinine clearance	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 each dialysis session
	<20	250 mg once a day for 7 days
	Patients on hemodialysis	250 mg after each dialysis session for 7 days

Patients with renal disease deficiency, located 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 hepatic impairment

For patients with impaired liver function of mild and moderate severity, dose adjustment is not required.

Patients of the Negroid race

The efficacy of one-day administration of Famwir® at a dose of 1000 mg twice a day for the treatment of recurrence of genital herpes in immunocompetent patients of the Negroid race did not exceed that for placebo. Clinical significance of 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:

Clinical studies have shown a good tolerability of Famvir®, including in patients with reduced immunity. Headache and nausea have been reported, but these events were mild or moderate and were noted with the same frequency as patients receiving placebo. The remaining undesirable phenomena (AEs) were identified as a result of postmarketing observations.

The adverse events reported in clinical trials in patients with reduced immunity coincided with those observed in patients with normal immunity.

To assess the incidence of adverse reactions, the following criteria were used: very often (> 1/10); often (from> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), the frequency is unknown.

Violations from the blood and lymphatic system: rarely - thrombocytopenia.

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

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

Heart Disease: rarely - heart palpitations.

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

Disturbances from the liver and bile ducts: rarely - cholestatic jaundice.

Disturbances from the skin and subcutaneous tissues: often - a rash, itching; infrequently - angioedema (swelling of the face, eyelids, periorbital area, pharynx), urticaria; frequency unknown - severe skin reactions * (including erythema multiforme exudative, Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis), leukocytoclastic vasculitis (allergic).

Laboratory and instrumental data: often - violations of liver function.

* - AEs, not noted during clinical trials, revealed in post-marketing observations,as well as those described in the literature.

Overdose:

There are limited data on famciclovir overdose.

Treatment: symptomatic and supportive. If the recommendations for reducing the dose of famciclovir are not respected, taking into account kidney function in patients with kidney disease has rarely been reported 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 h.

Interaction:

Co-administration with probenecid can lead to an increase in the concentration of penciclovir in blood plasma. To prevent the development of toxic reactions and possible dose reduction, it is necessary to monitor patients, who received the drug Famvir® at a dose of 500 mg concurrently with probenecid.

There were no clinically significant changes in pharmacokinetic parameters of penciclovir when administered once (at a dose of 500 mg) at once to the field of antacid preparations (magnesium or aluminum hydroxide) or in patients who received prior treatment (multiple administration) 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 application of famciclovir (500 mg 3 times daily), there was no change in digoxin pharmacokinetic parameters penciclovir and digoxin. Considering that the conversion of the inactive metabolite of 6-deoxypenzyclovir (which is formed during the deacetylation of famciclovir) in penciclovir catalyzed by the enzyme aldehyde oxidase, drug interaction with the use of the drug Famvir® 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 aldehyde oxidase in vitro, There was no reduction in the formation of penciclovir from famciclovir. However, when taking famciclovir along with 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 effectiveness of antiviral therapy with simultaneous use 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.

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.

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 tablets of the drug 125 mg, 250 mg and 500 mg include lactose (26.9 mg, 53.7 mg and 107.4 mg, respectively).Famvir® should not be used in patients with rare hereditary disorders, associated with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.

Famciclovir does not have expressed influence on spermogram, morphology or motility of human spermatozoa. 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, there was no marked decrease in fertility.

Carried doses of Famvira® and duration of treatment

Famvir® well tolerated in treatment Herpes Zoster when applied in a dose of up to 750 mg 3 times a day for 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 the drug was well tolerated with suppressive therapy in a dose 250 mg 3 times a day for 12 months for the treatment of genital herpes. Famvir® 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 twice a day for 8 weeks.

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

It is not expected that Famwira® will influence the ability to drive vehicles and / or work with machinery However, patients who, with the use of Famwir®, dizziness, drowsiness, confusion, or other disorders from the central nervous system, you should refrain from driving and / or working with machinery during the period of application of the drug.

Form release / dosage:

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

Packaging:

Tablets coated with a coating, 125 mg, 250 mg for 7 or 10 pcs. in the blister pack. 1, 2, 3 or 4 blisters together with instructions for use in a cardboard bundle.

Tablets coated with a coating, 500 mg for 3, 7 or 10 pcs. in the blister pack. 1,2, 3 or 4 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep in original packaging.

The drug should be stored out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N016000 / 01

Date of registration:05.10.2009

The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland

Manufacturer: & nbsp

NOVARTIS FARMACEUTICA, S.A. Spain

Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC

Information update date: & nbsp18.09.2015

Illustrated instructions

Instructions

Famvir® (Famvir®)