Description
Description
Round, biconvex film-coated tablets, white.
Release form
Film-coated tablets, 125 mg:
10 tablets in PVC / PE / PVDC / Al blister.
1 blister with instructions for use in a cardboard boxAchke.
Pharmacological action of
After ingestion, famciclovir rapidly turns into penciclovir, which is active against human herpes viruses, including Varicella Zoster virus (VZV) and Herpex Simplex (HSV) types 1 and 2, as well as Epstein-Barr viruses and cytomegalovirus.
Penciclovir enters the virus-infected cells, where, under the influence of viral temidine kinase, it quickly turns into monophosphate, which in turn passes into triphosphate. Penciclovir triphosphate inhibits the replication of viral DNA (deoxyribonucleic acid).
Intracellular elimination half-life of penciclovir triphosphate for culture of cells infected with HSV 1 is 10 hours, HSV 2 – 20 hours VZV – 7 hours.
The concentration of penciclovir triphosphate in uninfected cells does not exceed the minimum determined, therefore, at therapeutic concentrations, penciclovir does not affect uninfected cells.
As with acyclovir, resistance to penciclovir is most often associated with mutations in the viral thymidine kinase gene, leading to a deficiency or violation 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 VZV) in immunocompetent and immunocompromised patients has accelerated healing of the skin and mucous membranes. Famciclovir is effective in treating various manifestations of ophthalmic herpes caused by VZV. Famciclovir 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 helps to quickly resolve the manifestations of recurrent labial herpes (caused by HSV).
The use of the drug in immunocompetent patients at a dose of 1000 mg 2 times a day for 1 day, 125 mg 2 times 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 relapse of genital herpes ( caused by HSV).
Famciclovir at a dose of 500 mg 2 times 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 2 times 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 HSV excretion (both with clinical manifestations and without them). The use of famciclovir in patients with reduced immunity due to other reasons has not been studied.
The efficacy of famciclovir 1000 mg 2 times 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 one-day administration of the drug at a dose of 1000 mg 2 times a day in this category of patients was similar to that established previously.
Indications
· Herpes zoster (VZV infection):
– for the treatment of herpes zoster, including ophthalmic herpes in immunocompetent patients
– for the treatment of herpes zoster in immunocompromised patients.
· Genital herpes (HSV infection):
– treatment of the first episode and relapse of genital herpes in immunocompetent patients
– treatment of relapses of genital herpes in immunocompromised patients
– for the prevention of exacerbations of genital herpes infections and
· Labial herpes (HSV infection):
– treatment of relapses of labial herpes in immunocompetent patients
– treatment of relapses of orolabial herpes of immunocompromised patients.
Contraindications
· Hypersensitivity to famciclovir or any of the components of the drug. Hypersensitivity to penciclovir.
· Children under 18 years of age due to a lack of data on efficacy and safety in patients of this age category.
· Severely impaired hepatic function due to lack of data on efficacy and safety in patients of this category.
Caution
Caution should be exercised in the treatment of patients with impaired renal function, which may require dosage adjustment.
Special precautions in elderly patients and patients with impaired liver function of mild to moderate severity are not required.
Recommendations for use
The drug should be taken orally, regardless of food intake, without chewing, with water. Treatment with the drug should begin as soon as possible, immediately after the onset of the first symptoms of the disease (tingling, itching and burning).
VZV (herpes zoster) infection, including ophthalmic herpes in immunocompetent patients:
The recommended dose is 500 mg 3 times a day for 7 days.
VZV (herpes zoster) infection in immunocompromised patients:
The recommended dose is 500 mg 3 times a day for 10 days.
HSV infection (labial or genital herpes) in immunocompetent patients:
– For the first episode of genital herpes, the recommended dose is 250 mg 3 times a day for 5 days
– 1000 mg 2 times a day for relapses of genital herpes for 1 day or 125 mg 2 times a day for 5 days or 500 mg once, followed by 3 doses of 250 mg every 12 hours.
– For relapses of labial herpes – 1500 mg once for 1 day or 750 mg 2 times in day for 1 day.
HSV infection (orolabial or genital herpes) in immunocompromised patients:
The recommended dose is 500 mg 2 times a day for 7 days.
250 mg 2 times a day are used to prevent exacerbations of genital herpes (suppressive therapy). The duration of therapy depends on the severity of the disease. A periodic assessment of possible changes in the course of the disease after 12 months is recommended. In HIV-infected patients, the effective dose is 500 mg 2 times a day.
Patients ¥65 years of age.
In elderly patients with normal renal function, famciclovir dosage regimen adjustment is not required.
Patients with impaired renal function.
In patients with impaired renal function, there is a decrease in clearance of penciclovir. Recommendations for correcting the dosage regimen in immunocompetent patients with impaired renal function depending on creatinine clearance are presented in table 1.
Recommendations for adjusting the dosing regimen in immunocompromised patients with impaired renal function depending on creatinine clearance are presented in table 2.
Table 1. Dosing regimen correction for immunocompetent patients with impaired renal function
VZV infection (herpes zoster) srdrdlk 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 2 times a day for 7 days
20 39
500 mg 1 time per day for 7 days
<20 250 mg 1 time per day for 7 days Patients on hemodialysis, or receiving hemodialysis procedure 250 mg after each dialysis session for 7 days HSV infection Genital herpes, the first episode of 250 mg 3 times a day for 5 days 40 250 mg 3 times a day for 5 days 20 39 250 mg 2 times a day for 5 days <20 250 mg 1 time per day for 5 days Patients on hemodialysis or receiving hemodialysis 250 mg after each dialysis session during 5 days For relapses 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 2 times a day for 1 day 20 39 500 mg once <20 250 mg once Patients on hemodialysis, or receiving hemodialysis procedure 250 mg once after a dialysis session 125 mg 2 times a day for 5 days 20 125 mg 2 times a day for 5 days <20 125 mg 1 time per day for 5 days Patients on hemodialysis or receiving 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 250 mg every 12 hours 20 39 250 mg once, followed by 3 doses about 250 mg every 12 hours <20 250 mg dose followed using 250 mg per day following Patients on dialysis, or receiving hemodialysis procedure 250 mg once after a dialysis session For the prevention of exacerbations of genital herpes (suppressive therapy) 250 mg 2 times a day 40 250 mg 2 times a day 20 39 125 mg 2 times a day srd <20 125 mg 1 time per day Hemodialysis patients or receiving hemodialysis 125 mg after each dialysis Lab herpes 1500 mg once 60 1500 mg once 40 50 40 59 40 59 20 39 500 mg single dose <20 250 mg single dose Patient Options on hemodialysis, caused by VZV (herpes zoster) Dosing schedule Creatinine clearance Adjusted dosing schedule 500 mg 3 times a day for 10 days 60 500 mg 3 times a day for 10 days 40 59 500 mg per day for 10 days 20 39 500 mg 1 time per day for 10 days <20 250 mg 1 time per day for 10 days Patients on hemodialysis or receiving hemodialysis 250 mg after each dialysis session for 10 days HSV infection (orolabial or genital herpes) 500 mg 2 times a day for 7 days 40 500 mg 2 times a day for 7 days 20 39 500 mg 1 time per day for 7 days < 20 250 mg once daily for 7 days Patients undergoing hemodialysis or receiving hemodialysis 250 mg after each dialysis session for 7 days Patients with renal failure undergoing hemodialysis or receiving hemodialysis. Since plasma concentration of penciclovir decreases by 75% after 4-hour hemodialysis, famciclovir should be taken immediately after the hemodialysis procedure. The recommended dose adjustment scheme is described in Tables 1 and 2. Patients with impaired liver function. For patients with impaired hepatic function of mild to moderate severity, dose adjustment is not required. There is no experience with the use of the drug in patients with severe liver dysfunction. Patients of the Negroid race. The efficacy of famciclovir 1000 mg 2 times 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 dosing regimens for the treatment of both relapses of genital herpes (within 2 or 5 days) and other infectious lesions caused by VZV and HSV is unknown. Use in pregnancy and lactation In animal studies, the embryotoxic and teratogenic effects of famciclovir and penciclovir were not detected. In studies using famciclovir inside, the release of penciclovir with milk from lactating rats was noted. It is not known whether penciclovir with breast milk is excreted in humans. However, since there is insufficient safety data on the use of famciclovir in pregnant and lactating women, its use during pregnancy and during breastfeeding is possible only if the benefits of therapy for the mother outweigh the potential risk to the fetus and the baby. There are no data requiring special recommendations for patients with preserved reproductive potential. Famciclovir does not have a pronounced effect on the spermogram, morphology or motility of human sperm. A decrease in fertility was noted in the experimental model in male rats treated with famciclovir at a dose of 500 mg / kg body weight, in female rats a marked decrease in fertility was not observed. Composition Each film-coated tablet 125 mg contains: active ingredient: famciclovir – 125.00 mg excipients: pregelatinized starch – 18.70 mg, microcrystalline cellulose – 11.00 mg, croscarmellose sodium 20 mg, sodium lauryl sulfate – 1, 70 mg, anhydrous colloidal silicon dioxide – 1.70 mg, stearic acid – 1.70 mg film coating: Opadry white OY-S-28924 (hypromellose-5cP – 1.87 mg, titanium dioxide – 1.02 mg, hypromellose -15cP – 0.62 mg, macrogol-4000 – 0.37 mg, macrogol-6000 – 0.37 mg) – 4.25 mg. Side effects of Clinical studies have shown good tolerability of famciclovir, including in patients with reduced immunity. Cases of headache and nausea were reported, however, these phenomena were mild or moderate and were observed with the same frequency in patients receiving placebo. Other adverse events (AEs) were identified in clinical practice when using the drug in the post-registration period. AEs reported in clinical trials in immunocompromised patients coincided with those observed in patients with normal immunity. The World Health Organization (WHO) criteria were used to assess the incidence of adverse reactions: very often (> 1/10) often (from> 1/100, <1/10) infrequently (> 1/1000, <1/100) rarely (> 1/10000, <1/1000) is very rare (<1/10000), the frequency is unknown. Disorders from the blood and lymphatic system: rarely – thrombocytopenia Mental disorders: infrequently – confusion (mainly in elderly patients) rarely – hallucinations Disorders from the nervous system: very often – headache, often – dizziness, infrequently – drowsiness (mainly in elderly patients), frequency unknown – cramps * Disorders from the heart: rarely – sensation of a heartbeat Disorders from the gastrointestinal tract: often – nausea, vomiting, abdominal pain, diarrhea Disorders from the liver and biliary tract: rarely – cholestatic jaundice Disorders from the immune system: frequency unknown – anaphylactic shock *, anaphylactic reaction * Disorders from the skin and skin tissue: often – a rash, itching infrequently – angioedema (swelling of the face, eyelids, periorbital region, pharynx), urticaria, frequency unknown – severe skin reactions * (including erythema multiforme, Steven-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), allergic vasculitis). Laboratory and instrumental data: often – impaired liver function indicators * – AEs not observed during clinical trials, identified in post-marketing observations, as well as described in the literature. Since information on AE data was obtained by the method of spontaneous reporting and the exact number of patients taking the drug was not determined, it is not possible to estimate the frequency of occurrence of these reactions, and therefore, frequency is unknown is indicated for AE data aggravated, or you notice any other side effects not listed in the instructions, notify your doctor. Drug interactions Concomitant use with probenecid may lead to an increase in the concentration of penciclovir in blood plasma. To prevent the development of toxic reactions, patients should be monitored, receiving the drug Favirox in a dose of 500 mg simultaneously with probenecid, given the possibility of reducing the dose of famciclovir. There were no clinically significant changes in the pharmacokinetic parameters of penciclovir when it was used once (at a dose of 500 mg) immediately after taking antacids (magnesium and aluminum hydroxide) or in patients who had previously been treated with allopurinol, cimetidine, theophylline, zidovudine, promethazine (multiple doses ) With a single dose of famciclovir (at a dose of 500 mg) together with emtricitabine or zidovudine, no pharmacokinetic parameters of penciclovir, zidovudine, a metabolite of zidovudine (zidovudine glucuronide), and emtricitabine were detected. With a single and multiple use of famciclovir (at a dose of 500 mg 3 times a day), no changes in the pharmacokinetic parameters of penciclovir and digoxin were observed with digoxin. Considering that the conversion of the inactive metabolite of 6-deoxypenciclovir (formed during the deacetylation of famciclovir) to penciclovir is catalyzed by the aldehyde oxidase enzyme, drug interaction may develop with the use of the drug Favirox along with drugs metabolized by this enzyme or inhibiting its activity. When using famciclovir together with cimetidine and promethazine, which are inhibitors of aldehyde oxidase in vitro, there was no violation of the formation of penciclovir from famciclovir. However, when taking famciclovir together with a potent aldehyde oxidase inhibitor in vitro, raloxifene, a possible violation of the formation of penciclovir from famciclovir, and as a result, a decrease in the effectiveness of famciclovir. It is necessary to evaluate the clinical efficacy of antiviral therapy while using raloxifene. Given that famciclovir is a weak inhibitor of aldehydroxidase in vitro, its effect on the pharmacokinetic parameters of drugs metabolized by this enzyme is possible. In experimental studies, famciclovir did not have an inducing effect on the cytochrome P450 system and did not inhibit the CYP3A4 enzyme. overdose There is limited data on famciclovir overdose. The cases of famciclovir overdose (10.5 g) have not been reported with clinical manifestations. Treatment: symptomatic and supportive. Failure to follow the recommendation to reduce the dose of famciclovir with renal function in patients with kidney disease has rarely noted cases of acute renal failure. Penciclovir, an active metabolite of famciclovir, is displayed during hemodialysis. Penziclovir plasma concentrations are reduced by 75% after hemodialysis for 4 hours Storage conditions Do not store above 25 ° C in original packaging. Shelf life 2 years. Deystvuyushtee substance Famciclovir Conditions of release from drugstores Prescription Dosage PMA
