Description
Release form
Suspension for intramuscular administration of prolonged action p1rorewfp tablets film-coated, white with risks on both sides of the tablet.
Release form
Film-coated tablets, 500 mg:
7 tablets in PVC / PE / PVDC / Al blister.
3 blisters with instructions for use in a cardboard box.
Pharmacological action of
Pharmacotherapeutic group: Antiviral agent
ATX:
J.05.AB09 Famciclovir
Pharmacodynamics: After oral administration, famciclovir is rapidly converted to penciclovir, which has activity against Herpesvirus Z and Viruses, the viruses of Simplezoster and the herpes Viruses and the herpes zoster viruses (human herpes viruses) (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 goes 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 recurrence 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.
Pharmacokinetics: Absorption of
famciclovir is a prodrug. After oral administration, famciclovir is rapidly and almost completely absorbed and rapidly converted into a pharmacologically active metabolite, penciclovir.
The bioavailability of penciclovir following oral administration of famciclovir is 77%. An increase in the concentration of penciclovir in plasma occurs in proportion to an increase in a single dose of famciclovir in the range of 125-1000 mg.
According to the study, the maximum concentration (Cmax) of penciclovir in blood plasma after oral administration of 125 mg, 250 mg or 500 mg of famciclovir is reached on average after 45 minutes and averages 0.8 μg / ml, 1.6 μg / ml and 3 3 μg / ml, respectively. Another study demonstrates the maximum concentration (Cmax) of 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)) of penciclovir is independent of meal times.
AUC of penciclovir with a single dose of famciclovir and when the daily dose of the drug is divided into two or three doses is the same, which indicates the absence of cumulation of penciclovir with repeated uses of famciclovir.
Metabolism
After oral administration, famciclovir quickly and completely turns into a pharmacologically active metabolite – penciclovir.
Distribution of
The plasma protein binding of penciclovir and its 6-deoxy precursor is less than 20%.
Excretion of
Famciclovir is excreted mainly in the form of penciclovir and its 6-deoxy precursor, which are excreted through the kidneys unchanged. Famciclovir is not detected in the urine. The half-life (T1 / 2) of penciclovir from plasma in the final phase after taking single and repeated doses is about 2 hours.
Pharmacokinetics in special cases
Patients with VZV infection
In patients with uncomplicated VZV infection, significant changes in the pharmacokinetic parameters of penciclovir are not detected (T1 / 2 of penciclovir in 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, there is a linear relationship between a decrease in plasma clearance, renal clearance, the rate of release of penciclovir from blood plasma and the degree of impaired renal function.
The pharmacokinetic features of the drug in patients with severe (uncompensated) impaired renal function have not been studied.
Patients with impaired liver function
In patients with impaired hepatic function of mild to moderate severity, there is no increase in the AUC value of penciclovir. The pharmacokinetics of penciclovir in patients with severe hepatic impairment has not been studied.
The conversion of famciclovir to the active metabolite of penciclovir in this group of patients may be impaired, which leads to a decrease in the concentration of penciclovir in plasma and, as a consequence, a decrease in the effectiveness of famciclovir.
Patients> 65 years of age
Patients aged 65 to 79 years have an average AUC increase of penciclovir of approximately 40% and a decrease in renal clearance of approximately 20% compared with persons younger than 65 years of age. These pharmacokinetic features of penciclovir may be partially due to age-related changes in renal function in patients over 65 years of age.
Dose adjustment is not required in patients of this age group in the absence of impaired renal function.
Gender
Gender of the patient does not significantly affect the pharmacokinetic parameters of the drug (slight differences in the clearance of penciclovir in men and women). No dose adjustment is required depending on gender.
Racial affiliation
When using famciclovir (single or multiple doses of 500 mg 1, 2 or 3 times a day), the pharmacokinetic parameters of the drug in healthy volunteers of the Negroid race and patients of the Negroid race with impaired renal or hepatic function did not differ from those in Caucasian patients race.
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 recurrence of genital herpes in immunocompromised patients
for the prevention of exacerbations of genital herpes (suppressive and immune
Lab-cold herpes (HSV infection):
treatment of relapse of labial herpes in immunocompetent patients
treatment of relapse 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 liver 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.
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.
Special instructions
Treatment should be started immediately after diagnosis.
Genital herpes is a sexually transmitted disease. During relapses, the risk of infection increases. In the presence of clinical manifestations of the disease, even if antiviral treatment is started, patients should avoid sexual intercourse.
During suppressive antiviral therapy, the frequency of virus release is markedly reduced, but, nevertheless, the risk of transmission of infection remains. In connection with the foregoing, during treatment with the drug during this period, the rules of safe sexual behavior should be observed.
Impact on the ability to drive transp. Wed and fur.: Favirox is not expected to affect the ability to drive vehicles and / or work with mechanisms, but for patients who experience dizziness, drowsiness, confusion, or other disorders of the central nervous system when using Favirox, should refrain from driving and / or working with mechanisms during the period of use of the drug.
Composition
Each film-coated tablet 500 mg contains:
active ingredient: famciclovir – 500.00 mg
excipients: pregelatinized starch – 74.80 mg, microcrystalline cellulose – 44.00 mg, croscarmellose sodium 80 mg, sodium lauryl sulfate – 6.80 mg, anhydrous colloidal silicon dioxide – 6.80 mg, stearic acid – 6.80 mg
film coating: Opadry white OY-S-28924 (hypromellose-5cP – 7.48 mg, titanium dioxide – 4.08 mg, hypromellose-15cP – 2, 48 mg, macrogol-4000 – 1.48 mg, macrogol-6000 – 1.48 mg) – 17.00 mg.
Dosage and administration
The drug should be taken orally, regardless of food intake, without chewing, drinking 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
– For relapses of genital herpes, 1000 mg 2 times a day 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 a 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 aged? 65 years of
In elderly patients with normal renal function, dosage adjustment of famciclovir is not required.
Patients with impaired renal function
In patients with impaired renal function, there is a decrease in clearance of penciclovir.
Recommendations for adjusting the dosage regimen in immunocompetent patients with impaired renal function depending on creatinine clearance are presented in table 1.
Recommendations for correcting the dosage regimen in immunocompetent patients with impaired renal function depending on creatinine clearance are presented in table 2.
Table 1. Correction of the dosing regimen in immunocompetent patients with impaired renal function
VZV infection (herpes zoster)
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 Hemodialysis patients or receiving hemodialysis 250 mg after each dialysis session for 7 days HSV infection Genital herpes, first episode of 250 mg 3 times daily 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 procedure 250 mg after each dialysis session for 5 days In case of relapse 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 times a 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 of 250 mg every 12 hours 20-39 250 mg once, followed by 3 doses of 250 mg every 12 hours <20 250 mg once, followed by 250 mg the next day Hemodialysis patients or receiving the hemodialysis procedure 250 mg once after a dialysis session To prevent 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 <20 125 mg 1 time per day Hemodialysis patients or undergoing hemodialysis 125 mg after each dialysis session Labial herbal 1500 mg single-dose ? 60 1500 mg once 40-59 750 mg once 20-39 500 mg once <20 250 mg once Patients on hemodialysis, or receiving hemodialysis procedure 250 mg once after a dialysis session 750 mg 2 times a day ? 60 750 mg 2 times a day for 1 day 40-59 750 mg once 20-39 500 mg once <20 250 mg once Patients on hemodialysis or receiving hemodialysis procedure 250 mg after a dialysis session Table 2. Correction of the dosage regimen in immunocompromised patients with impaired renal function Infection, caused by VZV (herpes zoster) 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 2 times a 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 Hemodialysis patients 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 1 time per day for 7 days Patients on hemodialysis or receiving hemodialysis 250 mg after each dialysis session for 7 days Patients with kidney failure on hemodialysis or receiving hemodialysis Since after a 4-hour hemodialysis, the concentration of penciclovir in plasma is reduced by 75%, 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 liver function of mild to moderate severity, dose adjustment of the drug is not required. There is no experience with the drug in patients with severe liver dysfunction. Patients of the Negroid race The effectiveness of a daily dose of famciclovir 1000 mg 2 times a day 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. Side effects of Clinical trials have shown good tolerance to 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) very rarely (<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), the frequency is unknown – convulsions * Disorders of the heart: rarely – palpitations Disorders of the gastrointestinal tract: often – nausea, vomiting, abdominal pain, diarrhea Violation liver and biliary tract disorders: rarely – cholestatic jaundice Immune system disorders: frequency unknown – anaphylactic shock *, anaphylactic reaction * Disorders from the skin and subcutaneous tissues: often – rash, itching infrequently – angioedema (swelling of the face, eyelids, periorbital region, pharynx), urticaria frequency unknown – severe skin reactions * (including erythema multiforme , Stevens-Johnson syndrome, Lyell 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 spontaneous reporting and the exact number of patients taking the drug was not determined, it is not possible to assess the frequency of occurrence of these reactions, therefore, the frequency unknown is indicated for these AEs. If any of the side effects indicated in the instructions are aggravated, or you notice any other side effects not listed in the instructions, inform 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, there were no changes in the pharmacokinetic parameters of penciclovir, zidovudine, the metabolite of zidovudine (zidovudine glucuronide), and emtricitabine. 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 together with digoxia. 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 overdose with famciclovir. 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 excreted in hemodialysis. Penticlovir plasma concentrations decreased 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 Terms and conditions prescription dosage form tablets
