Favirox, 125 mg 10 pcs

Famcyclovir rapidly converts after oral administration to penciclovir, which has activity against human herpes viruses, including Varicella Zoster virus (VZV) and Herpex Simplex (HSV) types 1 and 2, as well as Epstein-Barr and cytomegalovirus.

Penciclovir enters virus-infected cells where it is rapidly converted to monophosphate by viral temidinkinase, which in turn is converted to triphosphate. Penciclovir triphosphate inhibits the replication of viral DNA (deoxyribonucleic acid).

The period of intracellular half-life of penciclovir triphosphate for cell culture 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 detectable, so in therapeutic concentrations penciclovir has no effect on uninfected cells.

As with acyclovir, resistance to penciclovir is most often associated with mutations in the viral thymidine kinase gene, resulting in deficiency or impaired substrate specificity of the enzyme. Changes in the DNA polymerase gene are significantly less common.

The use of famcyclovir for treatment of herpes zoster (caused by VZV) in immunocompetent patients and patients with reduced immunity is noted to accelerate healing of skin and mucosa. Famiclovir is effective in treating various manifestations of ophthalmoherpes caused by VZV. Famiclovir significantly reduces the severity and duration of post-herpetic neuralgia in patients with herpes zoster.

Daily treatment with famcyclovir in immunocompetent patients at a dose of 1500 mg once daily or 750 mg twice daily promotes rapid resolution of manifestations of recurrent labial herpes (caused by HSV).

The use of the drug in immunocompetent patients in 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 healing of skin and mucosa in recurrent genital herpes (caused by HSV).

Famcyclovir at a dose of 500 mg twice daily for 7 days is effective in treating various manifestations of herpes zoster in patients with reduced immunity due to infection with human immunodeficiency virus (HIV). In HIV-infected patients, the drug in a dose of 500 mg twice daily for 7 days accelerates the healing of skin and mucosa in genital herpes recurrence, and also reduces the number of days of HSV excretion (both with clinical manifestations and without them). The use of famcyclovir in patients with reduced immunity due to other causes has not been studied.

The efficacy of a 1-day, twice-daily dose of famcyclovir for the treatment of recurrent genital herpes in immunocompetent black patients was not greater than that of placebo. The safety profile of once-daily doses of 1000 mg 2 times daily in this patient population was similar to that previously established.

Indications

– Herpes zoster (infection caused by VZV):

– For treatment of herpes zoster, including ophthalmoherpes in immunocompetent patients;

– For treatment of herpes zoster in immunocompromised patients.

– Genital herpes (infection caused by HSV):

– Treatment of first episode and recurrent genital herpes in immunocompromised patients;

– Treatment of recurrent genital herpes in immunocompromised patients;

– for the prevention of genital herpes exacerbations (suppressive therapy) in immunocompromised and immunocompromised patients.

– Labial herpes (infection caused by HSV):

– Treatment of relapses of labial herpes in immunocompromised patients;

– Treatment of relapses of orolabial herpes in immunocompromised patients.

Active ingredient

Composition

Each film-coated tablet, 125 mg contains:

the active ingredient:

famcyclovir – 125.00 mg;

excipients:

Pregelatinized starch – 18.70 mg,

microcrystalline cellulose – 11.00 mg,

croscarmellose sodium – 10.20 mg,

p> sodium lauryl sulfate – 1.70 mg,

colloidal anhydrous silica – 1.70 mg,

stearic acid – 1.70 mg;

film coating:

Opadray 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.

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

Infection caused by VZV (herpes zoster)

Dosing regimen

Creatinine clearance

Adjusted dosing regimen

500 mg 3 times daily for 7 days

≥60

500 mg 3 times daily for 7 days

40-59

500 mg 2 times daily for 7 days

20-39

500 mg once daily for 7 days

<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

Infection caused by HSV

Genital herpes, first episode

250 mg 3 times daily for 5 days

≥40

250 mg 3 times daily for 5 days

20-39

250 mg 2 times daily for 5 days

<20

250 mg once daily for 5 days

Patients on hemodialysis or receiving a hemodialysis procedure

250 mg after each dialysis session for 5 days

For relapses of genital herpes

1000 mg 2 times daily for 1 day

≥60

1000 mg 2 times daily for 1 day

40-59

500 mg 2 times daily for 1 day

20-39

500 mg once

<20

250 mg once

Patients on hemodialysis or receiving a hemodialysis procedure

250 mg once after a dialysis session

125 mg 2 times daily for 5 days

≥20

125 mg 2 times daily for 5 days

<20

125 mg once daily for 5 days

Patients on hemodialysis or receiving a hemodialysis procedure

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 h

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

Patients on hemodialysis or receiving a 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 daily

20-39

125 mg 2 times daily

<20

125 mg 1 time per day

Patients on hemodialysis or receiving a hemodialysis procedure

125 mg after each dialysis session

Labial herpes

1500 mg once

≥60

1500 mg once

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.

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 (Cmax) 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 (Cmax) 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%.

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

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