Favirox, 125 mg 10 pcs

Interaction

Simultaneous use with probenecid may increase the concentration of penciclovir in blood plasma. To prevent the development of toxic reactions, patients receiving Favirox at a dose of 500 mg concomitantly with probenecid should be monitored, taking into account the possibility of reducing the dose of famiclovir.

There were no clinically significant changes in pharmacokinetic parameters of penciclovir when administered single time (500 mg dose) immediately after taking antacids (magnesium and aluminum hydroxide) or in patients who received prior treatment with allopurinol, cimetidine, theophylline, zidovudine, promethazine (multiple administration). No changes in the pharmacokinetic parameters of penciclovir, zidovudine, the zidovudine metabolite (zidovudine glucuronide) and emtricitabine were detected when famiclovir (500 mg dose) was taken alone together with emtricitabine or zidovudine.

There were no changes in the pharmacokinetic parameters of penciclovir and digoxin when using famiclovir (at a dose of 500 mg 3 times daily) together with digoxin alone and repeatedly.

Perhaps due to the fact that the conversion of the inactive metabolite 6-deoxypencyclovir (which is formed during deacetylation of famiclovir) into penciclovir is catalyzed by the enzyme aldehydoxidase, it is possible that drug interaction may occur when using Favirox together with the drugs metabolized with participation of this enzyme or which inhibit its activity.

When using famcyclovir together with cimetidine and promethazine, which are aldehydoxidase inhibitors in vitro, no disturbance of penciclovir formation from famcyclovir was found. However, when taking famcyclovir together with a potent in vitro aldehydoxidase inhibitor, raloxifene, it is possible that the formation of penciclovir from famcyclovir is impaired, and as a consequence, the effectiveness of famcyclovir is reduced. It is necessary to evaluate the clinical efficacy of antiviral therapy when used concomitantly with raloxifene.

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

In experimental studies, famcyclovir had no inducing effect on the cytochrome P450 system and did not inhibit the CYP3A4 enzyme.

Directions for use

The drug should be taken orally, regardless of meals, without chewing, 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).

Infections caused by VZV (herpes zoster), including ophthalmoherpes in immunocompetent patients:

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

Infection caused by VZV (herpes zoster) in immunocompromised patients:

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

Infection caused by HSV (labial or genital herpes) in immunocompromised patients:

-In the first episode of genital herpes, the recommended dose is 250 mg 3 times daily for 5 days;

-In recurrent genital herpes, 1000 mg 2 times daily for 1 day or 125 mg 2 times daily 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 daily for 1 day or 750 mg twice daily for 1 day.

Infection caused by HSV (orolabial or genital herpes) in immunocompromised patients:

The recommended dose is 500 mg twice daily for 7 days.

To prevent exacerbations of genital herpes (suppressive therapy), 250 mg 2 times daily is used. The duration of therapy depends on the severity of the disease. Periodic evaluation of possible disease course changes after 12 months is recommended. In HIV-infected patients the effective dose is 500 mg 2 times a day.

Patients aged ≥65 years.

In elderly patients with normal renal function, correction of the dosing regimen of famcyclovir is not necessary.

Patients with impaired renal function.

In patients with impaired renal function there is a decrease in clearance of penciclovir. Recommendations for dosing regimen adjustment in immunocompetent patients with impaired renal function based on creatinine clearance are presented in Table 1.

Recommendations for dosing regimen adjustment in immunocompromised patients with impaired renal function as a function of creatinine clearance are presented in Table 2.

Table 1. Dosing regimen correction in immunocompromised patients with impaired renal function

Table 2. Dosing regimen correction in immunocompromised patients with impaired renal function

table cellspacing=”0″ cellpadding=”0″ border=”1″>

Infection caused by VZV (herpes zoster)

Dosing regimen

Creatinine clearance

Adjusted dosing regimen <

500 mg 3 times daily for 10 days

≥60

500 mg 3 times daily for 10 days

40-59

500 mg 2 times daily for 10 days

20-39

500 mg once daily for 10 days

<20

250 mg once daily for 10 days <

Patients on hemodialysis or receiving a hemodialysis procedure

250 mg after each dialysis session for 10 days

Infection caused by HSV (orolabial or genital herpes)

500 mg 2 times daily for 7 days

≥40

500 mg 2 times daily for 7 days

/p>

20-39

500 mg once daily for 7 days

/p>

<20

250 mg once daily for 7 days

Patients on hemodialysis or receiving a hemodialysis procedure

250 mg after each dialysis session for 7 days

p> Patients with renal impairment who are on hemodialysis or receiving hemodialysis treatment.

Because penciclovir plasma concentrations decrease by 75% after a 4-hour hemodialysis procedure, famiclovir should be taken immediately after the hemodialysis procedure. See Tables 1 and 2 for a recommended dose adjustment regimen.

Patients with impaired liver function.

In patients with mild to moderate hepatic impairment, no dose adjustment is required. There is no experience of using the drug in patients with severe hepatic impairment.

Patients of the Negro race.

The efficacy of a 1-day, twice-daily dose of famcyclovir for the treatment of genital herpes recurrence in immunocompetent black patients was not greater than that of placebo. The clinical significance of drug dosing regimens for the treatment of both genital herpes relapses (within 2 or 5 days) and other infectious lesions caused by VZV and HSV is unknown.

Special Instructions

Treatment should begin as soon as the diagnosis is made.

Genital herpes is a sexually transmitted disease. During relapses, the risk of infection increases. If there are clinical signs of the disease, even if antiviral treatment is begun, patients should avoid sexual contact.

Impact on the ability to drive and/or operate motor vehicles

Introduction of Faviro is not expected. No effect of Favirox on driving and/or operating machinery is expected, but patients with dizziness, somnolence, mental confusion or other central nervous system disturbances during Favirox administration should refrain from driving and/or operating machinery during this period.

Synopsis

Circular, biconvex, film-coated white tablets.

Features

Absorption

Famcyclovir is a prodrug. After oral administration, famcyclovir is quickly and almost completely absorbed and quickly transformed into the pharmacologically active metabolite – penciclovir. Bioavailability of pencyclovir after oral intake is 77%. Increase of pencyclovir concentration in plasma is proportional to the increase in a single dose of famcyclovir in the range of 125-1000 mg.

According to a study, the maximum plasma concentration (C_max) of pencyclovir after oral doses of 125 mg, 250 mg or 500 mg of famcyclovir is reached after an average of 45 minutes and averages 0.8 µg/ml, 1.6 µg/ml and 3.3 µg/ml, respectively. Another study demonstrates the maximum concentration (C_max) of penciclovir after oral administration of 250 mg, 500 mg, or 1000 mg of famcyclovir at values of 1.5 µg/mL, 3.2 µg/mL, and 5.8 µg/mL, respectively.

The systemic bioavailability (area under the concentration-time curve (AUC)) of penciclovir is independent of the time of ingestion.

The AUC of penciclovir when taking penciclovir once and when dividing the daily dose of the drug into two or three doses coincide, which indicates that there is no cumulation of penciclovir in repeated administration of penciclovir.

Metabolism

Famcyclovir is quickly and completely converted to its pharmacologically active metabolite – penciclovir after oral administration.

Distribution

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

Famcyclovir is excreted mainly in the form of penciclovir and its 6-deoxy precursor, which are excreted unchanged through the kidneys; famcyclovir is not detected in the urine. The half-life (T_1/2) of penciclovir from plasma in the terminal phase after single and repeated doses is about 2 hours.

Pharmacokinetics in special cases

Patients with infection caused by VZV

Patients with uncomplicated infection caused by VZV show no significant changes in the pharmacokinetic parameters of penciclovir (T_1/2 penciclovir from plasma in the end phase after single and repeated doses of penciclovir is 2.8 and 2.7 hours, respectively).

Patients with impaired renal function

After receiving single and repeated doses of famcyclovir a linear relationship between the decrease in plasma clearance, renal clearance, the rate of excretion of penciclovir from blood plasma and the degree of renal impairment is observed. Pharmacokinetic peculiarities of using the drug in patients with severe (decompensated) renal dysfunction have not been studied.

Patients with hepatic impairment

In patients with mild to moderate hepatic impairment no increase in AUC of penciclovir has been observed. Pharmacokinetics of penciclovir in patients with severe hepatic impairment has not been studied. The conversion of famcyclovir into the active metabolite penciclovir in this group of patients may be impaired, which leads to lower concentrations of penciclovir in plasma and, as a consequence, a decrease in the effectiveness of famcyclovir.

Patients aged >65 years

In patients aged 65 to 79 years there is an increase of the average AUC of penciclovir by about 40% and a decrease of its renal clearance by about 20% compared to those younger than 65 years. These pharmacokinetic features of pencyclovir may be partially due to age-related changes in renal function in patients over 65 years of age. No dose adjustment is required in patients in this age group in the absence of impaired renal function.

Patient sex has no significant effect on the pharmacokinetic parameters of the drug (slight differences in the clearance of penciclovir in men and women). There is no need to adjust the dose of the drug depending on gender

Raciality

When using famcyclovir (single or multiple doses of 500 mg 1, 2, or 3 times daily), pharmacokinetic parameters of the drug did not differ from those of Caucasian race healthy volunteers and non-Hispanic patients with impaired renal or hepatic function.

Contraindications

Hypersensitivity to famcyclovir or any of the ingredients of the drug. Hypersensitivity to penciclovir.

Children under 18 years of age due to lack of efficacy and safety data in patients in this age group.

Severe hepatic impairment due to lack of efficacy and safety data in patients in this category.

Caution

Caution should be exercised when treating patients with impaired renal function who may require dosing adjustments.

Particular precautions are not required in elderly patients and patients with mild to moderate hepatic impairment.

Side effects

Clinical studies have shown good tolerability of famcyclovir, including in immunocompromised patients. Headache and nausea have been reported, but these were mild to moderate in frequency in patients receiving placebo. The remaining adverse events (AEs) have been identified in clinical practice during the post-registration period.

The NIs reported in clinical studies in immunocompromised patients were consistent with those reported in patients with normal immunity.

The World Health Organization (WHO) criteria were used to assess the incidence of adverse reactions: Very common (> 1/10); common (> 1/100, < 1/10); infrequent (> 1/1000, <1/100); rare (> 1/10000, < 1/1000); very rare (< 1/10000), frequency unknown.

Blood and lymphatic system disorders: rare – thrombocytopenia;

Mental disorders: infrequent – confusion (mostly in elderly patients); rare – hallucinations;

Nervous system disorders: very common – headache, frequent – dizziness, infrequent – somnolence (mostly in elderly patients), frequency unknown – seizures*;

Heart disorders: rare – feeling of “heart palpitations”;

Gastrointestinal disorders: frequent – nausea, vomiting, abdominal pain, diarrhea;

Liver and biliary tract disorders: rare – cholestatic jaundice;

Immune system disorders: frequency unknown – anaphylactic shock*, anaphylactic reaction*;

Skin and subcutaneous tissue disorders: frequent – rash, itching; infrequent – angioedema (swelling of the face, eyelids, periorbital area, throat), urticaria; frequency unknown – severe skin reactions* (including.erythema multiforme, Stephen-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis), allergic vasculitis).

Laboratory and instrumental data: often liver function abnormalities

* – NSCs not observed in clinical trials, identified in post-marketing observations, as well as those described in the literature. Because this information was obtained through spontaneous reporting, and because the exact number of patients who received the drug has not been determined, the frequency of these reactions cannot be estimated; therefore, the frequency of these reactions is stated as “unknown.

Overdose

There are limited data on famcyclovir overdose.

There have been described cases of famcyclovir overdose (10.5 g) without clinical manifestations.

Treatment: symptomatic and supportive. If the recommendations on dose reduction of famcyclovir were not followed with regard to renal function, acute renal failure has rarely been observed in patients with renal disease. Penciclovir, which is the active metabolite of famcyclovir, is excreted by hemodialysis. Plasma concentrations of penciclovir decrease by 75% after hemodialysis for 4 hours.

Pregnancy use

No embryotoxic and teratogenic effects of famcyclovir and penciclovir were observed in animal studies. In studies of oral administration of famcyclovir, pencyclovir was excreted with the milk of lactating rats. It is not known whether pencyclovir is excreted with breast milk in humans.