Favirox pills 250mg, 21pcs

Composition

Each film-coated tablet contains 250 mg:

Active ingredient:

famciclovir – 250.00 mg;

excipients:

pregelatinized starch-37.40 mg,

microcrystalline cellulose-22.00 mg,

croscarmellose sodium-20.40 mg,

sodium lauryl sulfate-3.40 mg,

colloidal anhydrous silicon dioxide-3.40 mg,

stearic acid-3.40 mg;

film coating:

Opadray white OY-S-28924 (hypromellose-5 cP-3.74 mg, titanium dioxide-2.04 mg, hypromellose-15 cP-1.24 mg, macrogol-4000-0.74 mg, macrogol-6000-0.74 mg) – 8.50 mg.

Clinical pharmacology

After oral use, famciclovir is rapidly converted to penciclovir, which has activity against human herpes viruses, including Varicella Zoster (VZV) and Herpex Simplex (HSV) types 1 and 2, as well as Epstein-Barr and cytomegalovirus viruses.

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

The intracellular half-life of penciclovir triphosphate for the 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 detectable, so in 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 significantly less common.

The use of famciclovir for the treatment of herpes zoster (caused by VZV) in immunocompetent patients and patients with reduced immunity, accelerated healing of the skin and mucous membranes is noted. Famciclovir is effective in the treatment of various manifestations of VZV-induced ophthalmic herpes. Famciclovir significantly reduces the severity and duration of postherpetic neuralgia in patients with herpes zoster.

One-day treatment with famciclovir in immunocompetent patients at a dose of 1500 mg once a day or 750 mg twice a day contributes to the rapid resolution 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 in case of relapse of genital herpes (caused by HSV).

Famciclovir 500 mg twice daily for 7 days is effective in the treatment of 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 in a dose of 500 mg 2 times a day for 7 days accelerates the healing of the skin and mucous membranes with a relapse of genital herpes, and also reduces the number of days of HSV discharge (both with and without clinical manifestations). The use of famciclovir in patients with reduced immunity due to other causes has not been studied.

The efficacy of one-day use of famciclovir at a dose of 1000 mg 2 times a day for the treatment of recurrent genital herpes in immunocompetent black patients did not exceed that of placebo. The safety profile of one-day use of the drug at a dose of 1000 mg 2 times a day in this category of patients was similar to that established earlier.

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 relapses of genital herpes in immunocompetent patients;

– treatment of relapses of genital herpes in immunocompromised patients;

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

* Labial herpes (HSV infection):

– treatment of relapses of labial herpes in immunocompetent patients;

– treatment of relapses of orolabial herpes in immunocompromised patients.

Recommendations for use

The drug should be taken orally, regardless of food intake, without chewing, with water. Treatment with the drug should be started as early as possible, immediately after the appearance of the first symptoms of diseases (tingling, itching and burning).

Infection caused by VZV (herpes zoster), 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.

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

-With the first episode of genital herpes, the recommended dose is 250 mg 3 times a day for 5 days;

-With recurrent genital herpes 1000 mg is prescribed 2 times a day for 1 day or 125 mg 2 times a day for 5 days or 500 mg once followed by the application of 3 doses of 250 mg every 12 h

-labeling With recurrent 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.

For the prevention of exacerbations of genital herpes (suppressive therapy),250 mg is used 2 times a day. The duration of therapy depends on the severity of the disease. 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.

In elderly patients with normal renal function, no dosage adjustment of famciclovir is required.

Patients with impaired renal function.

In patients with impaired renal function, there is a decrease in the 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 adjusting the dosage regimen in immunocompromised patients with impaired renal function, depending on creatinine clearance, are presented in table 2.

Table 1. Dosage adjustment in immunocompetent patients with impaired renal function

Table 2. Dosage adjustment in immunocompromised patients with impaired renal function

Patients with renal insufficiency who are undergoing hemodialysis or receiving a hemodialysis procedure.

Since the plasma concentration of penciclovir decreases by 75% after 4-hour hemodialysis, famciclovir should be taken immediately after the hemodialysis procedure. The recommended dose adjustment regimen is described in tables 1 and 2.

Patients with impaired liver function.

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

Patients of the black race.

The efficacy of one-day use of famciclovir at a dose of 1000 mg 2 times a day for the treatment of recurrent genital herpes in immunocompetent black patients did not exceed that of placebo. The clinical significance of the drug dosage regimens for the treatment of both recurrent genital herpes (within 2 or 5 days) and other infectious lesions caused by VZV and HSV is unknown.

Contraindications

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

* Children under 18 years of age due to the lack of data on efficacy and safety in patients of this age category.

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

With caution

Caution should be exercised when treating patients with impaired renal function who may need to adjust the dosage regimen.

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

Side effects

Clinical studies have shown good tolerability of famciclovir, including in patients with reduced immunity. Cases of headache and nausea have been reported, but these events were mild to moderate and occurred with the same frequency in patients receiving placebo. Other adverse events (AES) were detected in clinical practice when using the drug in the post-marketing period.

AES reported in clinical trials in immunocompromised patients were similar to those reported in patients with normal immunity.

To assess the frequency of adverse reactions, the World Health Organization (WHO) criteria were used: very common (> 1/10); often (from >> 1/100, >>< 1/10); infrequently (> 1/1000, < 1/10); infrequently (><1/100); rarely (> 1/10000, <1/100); rarely (>< 1/1000); very rarely (

Disorders of the blood and lymphatic system: rarely-thrombocytopenia;

Mental disorders: infrequently-confusion (mainly in elderly patients); rarely-hallucinations;

Nervous system disorders: very often – headache, often-dizziness, infrequently-drowsiness (mainly in elderly patients), frequency unknown-convulsions*;

Disorders of the heart: rarely-a feeling of “palpitation”;

Disorders of the gastrointestinal tract: often – nausea, vomiting, abdominal pain, diarrhea;

Liver and biliary tract disorders: rarely-cholestatic jaundice;

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

Skin and subcutaneous tissue disorders: often-rash, pruritus; infrequently-angioedema (swelling of the face, eyelids, periorbital region, pharynx), urticaria; frequency unknown-severe skin reactions* (including erythema multiforme, Stephen – Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), allergic vasculitis).

Laboratory and instrumental data: often-impaired liver function indicators

* – AE, not observed in clinical studies, identified in post-marketing observations, as well as described in the literature. Since information about these AES is obtained by spontaneous reporting and the exact number of patients taking the drug is not determined, it is not possible to estimate the frequency of these reactions, and therefore “frequency unknown”is indicated for these AES

If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

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 receiving Favirox 500 mg concomitantly with probenecid should be monitored, taking into account the possibility of reducing the dose of famciclovir.

There were no clinically significant changes in the pharmacokinetic parameters of penciclovir when it was administered once (at a dose of 500 mg) immediately after taking antacids (magnesium and aluminum hydroxide) or in patients who had previously received treatment with allopurinol, cimetidine, theophylline, zidovudine, promethazine (multiple use). No changes in the pharmacokinetic parameters of penciclovir, zidovudine, the zidovudine metabolite (zidovudine glucuronide), or emtricitabine were detected with a single 500 mg dose of famciclovir together with emtricitabine or zidovudine.

No changes in the pharmacokinetic parameters of penciclovir and digoxin were observed with single and repeated use of famciclovir (at a dose of 500 mg 3 times a day) together with digoxin.

Given that the conversion of the inactive metabolite 6-deoxypencyclovir (formed during deacetylation of famciclovir) to penciclovir is catalyzed by the enzyme aldehyde oxidase, it is possible to develop drug interactions when using Favirox together with drugs that are metabolized with the participation of this enzyme or inhibit its activity.

When using famciclovir together with cimetidine and promethazine, which are aldehyde oxidase inhibitors in vitro, there was no violation of the formation of penciclovir from famciclovir. However, when taking famciclovir together with a powerful in vitro aldehyde oxidase inhibitor, raloxifene, the formation of penciclovir from famciclovir may be disrupted, and as a result, the effectiveness of famciclovir may decrease. It is necessary to evaluate the clinical efficacy of antiviral therapy when administered concomitantly with raloxifene.

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

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

Overdose

There are limited data on famciclovir overdose.

Cases of overdose of famciclovir (10.5 g) were described without clinical manifestations.

Treatment: symptomatic and supportive. Acute renal failure has rarely been reported in patients with kidney disease who do not follow the recommendations for reducing the dose of famciclovir based on renal function. Penciclovir, an active metabolite of famciclovir, is eliminated by hemodialysis. Plasma concentrations of penciclovir are reduced by 75% after hemodialysis for 4 hours.

Description

Film-coated tablets,250 mg:

Round, biconvex tablets, film-coated, white in color with a chamfer and a risk on one side of the tablet.

Functional features

Absorption

Famciclovir is a prodrug. After oral use, famciclovir is rapidly and almost completely absorbed and rapidly converted to the pharmacologically active metabolite penciclovir. The bioavailability of penciclovir after oral use of famciclovir is 77%. The increase in the concentration of penciclovir in plasma is proportional to the 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 use of 125 mg,250 mg or 500 mg of famciclovir is reached on average after 45 minutes and averages 0.8 mcg / ml,1.6 mcg / ml and 3.3 mcg / ml, respectively. Another study shows the maximum concentration (cmax) of penciclovir after oral use of 250 mg,500 mg, or 1000 mg of famciclovir at 1.5 mcg / ml,3.2 mcg / ml, and 5.8 mcg/ml, respectively.

The systemic bioavailability (area under the concentration – time curve (AUC)) of penciclovir does not depend on the time of food intake.

AUC of penciclovir with a single dose of famciclovir and when dividing the daily dose of the drug into two or three doses coincide, which indicates that there is no accumulation of penciclovir with repeated applications of famciclovir.

Metabolism

After oral use, famciclovir is rapidly and completely converted to the pharmacologically active metabolite penciclovir.

Distribution

Plasma protein binding of penciclovir and its 6-deoxy precursor is less than 20%.

Elimination

Famciclovir is mainly excreted in the form of penciclovir and its 6-deoxy precursor, which are excreted unchanged through the kidneys; famciclovir is not detected in the urine. _{The end-phase half-life (T 1/2) of penciclovir after single and repeated doses is approximately 2 hours.}

Pharmacokinetics in special cases

Patients with VZV infection

In patients with uncomplicated VZV infection, no significant changes in the pharmacokinetic parameters of penciclovir are detected (T_1/2 of penciclovir from 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 the decrease in plasma clearance, renal clearance, the rate of release of penciclovir from blood plasma, and the degree of impaired renal function. Pharmacokinetic characteristics of the drug in patients with severe (decompensated) renal impairment have not been studied.

Patients with impaired liver function

In patients with mild to moderate hepatic impairment, there is no increase in the AUC of penciclovir. The pharmacokinetics of penciclovir in patients with severe hepatic impairment have not been studied. Conversion of famciclovir to the active metabolite penciclovir in this group of patients may be impaired, which leads to a decrease in the concentration of penciclovir in plasma and, as a result, a decrease in the effectiveness of famciclovir.

Patients aged >65 years>

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

Gender

The patient’s gender does not significantly affect the pharmacokinetic parameters of the drug (slight differences in the clearance of penciclovir in men and women). No gender-specific dose adjustment is required

Racial background

When using famciclovir (a single or multiple dose of 500 mg 1,2 or 3 times a day), the pharmacokinetic parameters of the drug in healthy black volunteers and black patients with impaired renal or liver function did not differ from those in Caucasian people.

Special instructions

Treatment should begin 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 initiated, patients should avoid sexual contact.

During suppressive therapy with antiviral agents, the frequency of virus isolation decreases markedly, but, nevertheless, the risk of transmission remains. In connection with the above, during treatment with the drug during this period, the rules of safe sexual behavior should be observed.

Influence on the ability to drive a car and/or other mechanisms

No effect of Favirox on the ability to drive vehicles and/or work with mechanisms is expected, however, patients who experience dizziness, drowsiness, confusion or other central nervous system disorders while using Favirox should refrain from driving vehicles and/or working with mechanisms during the period of use of the drug.

Form of production

Film-coated tablets,250 mg:

7 tablets each in a PVC/PE/PVDC / Al blister.

3 blisters with instructions for use in a cardboard box.

Storage conditions

Store at a temperature not exceeding 25 °C in the original packaging.

Shelf life

2 years

Active ingredient

Famciclovir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets