Famvir 750 mg Film-Coated Tablets

The active ingredient is famciclovir.

Each tablet contains 750 mg of famciclovir.

For a full list of excipients see 6.1.

Film-coated tablet.

White, oval, film-coated tablet, biconvex, bevelled edges, debossed with “FAMVIR 750” on one side and plain on the reverse side.

Famvir is indicated for the treatment of herpes zoster (shingles) infection.

Dosage: Adults:

Oral administration, one 750 mg tablet once daily for seven days. The tablets should be taken at approximately the same time each day. Treatment should be initiated as early as possible in the course of the disease, promptly after diagnosis.

Elderly:

Dosage modification is not required unless renal function is impaired.

Renally Impaired:

As reduced clearance of penciclovir is related to reduced renal function, as measured by creatinine clearance, special attention should be given to dosage in patients with impaired renal function (see section 4.9). The following modifications in dosage are recommended.

For the treatment of herpes zoster infections:

When only serum creatinine is available, a nomogram of the following formula (Cockcroft and Gault) should be used to estimate creatinine clearance.

Formula to estimate creatinine clearance (ml/min/1.73 m²):

Renally impaired patients on haemodialysis:

For a patient on haemodialysis, a dosage interval of 48 hours is recommended for periods between dialysis. Since 4 hours haemodialysis results in approximately 75% reduction in plasma concentrations of penciclovir, the full dose of famciclovir should be administered immediately following dialysis.

Hepatically Impaired:

Dosage modification is not required.

Children:

There are currently insufficient data on the safety and efficacy of Famvir in children.

Administration:

Oral

Famvir is contra-indicated in patients with known hypersensitivity to famciclovir or other constituents of Famvir. It is also contra-indicated in those patients who have shown hypersensitivity to penciclovir.

Special attention should be paid to patients with impaired renal function as dosage adjustment is necessary (see sections 4.2 and 4.9). No special precautions are required for hepatically impaired or elderly patients with normal renal function.

No clinically significant interactions have been identified. Probenecid and other drugs that affect renal physiology could affect plasma levels of Penciclovir.

Pregnancy:

Although animal studies have not shown any embryotoxic or teratogenic effects with famciclovir or penciclovir, the safety of Famvir in human pregnancy has not been established. Famvir should, therefore , not be used during pregnancy or in nursing mothers unless the potential benefits of treatment outweigh any possible risk.

Lactation:

Studies in rats show that penciclovir is excreted in the breast milk of lactating females given oral famciclovir. There is no information on excretion in human milk.

There is no evidence that famciclovir (Famvir) will affect the ability of a patient to drive or to use machines. However, patients who experience dizziness, somnolence, confusion or other central nervous system disturbances while taking Famvir should refrain from driving or operating machinery.

Famciclovir has been well tolerated in human studies. Headache and nausea have been reported in clinical trials. These were generally mild or moderate in nature and occurred at a similar incidence in patients receiving placebo treatment.

The following table specifies the estimated frequency of adverse reaction based on all the spontaneous reports and literature cases that have been reported for Famvir since its introduction to the market.

Adverse reactions (Table 1) are ranked under headings of frequency, using the following convention: very common ( 1/10); Common ( 1/100, 1/10); uncommon ( 1/1,000, 1/100);, rare ( 1/10,000, 1/1,000);, very rare (<1/10,000) including isolated reports.

Table 1

Famciclovir has also been well tolerated in immunocompromised patients. Undesirable effects reported from clinical studies were similar to those reported in the immunocompetent population.

Overdosage experience with famciclovir is limited. A report of accidental acute overdosage (10.5 g) was asymptomatic. In a report of chronic use (10 g/day for two years), famciclovir was well tolerated. In the event of an overdose, symptomatic and supportive therapy should be given as appropriate. Acute renal failure has been reported rarely in patients with underlying renal disease where the famciclovir (Famvir) dosage has not been appropriately reduced for the level of renal function.

Penciclovir is dialysable and plasma concentrations are reduced by approximately 75% following 4 hour haemodialysis.

Pharmacotherapeutic group: Oral antiviral agent (ATC code: JO5A B09)

Famciclovir is the oral form of penciclovir, converted in the body to this active antiviral moiety. Famciclovir is rapidly converted in vivo into penciclovir, which has demonstrable in vivo activity against Herpes simplex virus (Type 1 and 2) and the Varicella zoster virus. The antiviral effect of orally administered famciclovir has been demonstrated in several animal models; this effect is due to in vivo conversion to penciclovir. Penciclovir targets virus-infected cells where it is rapidly and efficiently converted into the triphosphate (mediated via virus-induced thymidine kinase). Penciclovir triphosphate persists in infected cells for more than 12 hours where it inhibits replication of viral DNA. In uninfected cells treated with penciclovir, concentrations of penciclovir-triphosphate are only barely detectable. Accordingly, uninfected cells are unlikely to be affected by therapeutic concentrations of penciclovir.

General characteristics

Following oral administration, famciclovir is rapidly and extensively absorbed and rapidly converted to the active compound, penciclovir. Bioavailability of penciclovir after oral Famvir is 77%. Mean peak plasma concentrations of penciclovir, following 125 and 250 mg oral doses of famciclovir, were 0.8 and 1.6 micrograms/ml, respectively, and occurred at a median time of 45 minutes post-dose. Mean peak plasma concentration of penciclovir, following a 750 mg oral dose of famciclovir, was 4.9 micrograms/ml and occurred at a median time of 50 minutes post-dose. Plasma concentration-time curves of penciclovir are similar following single and repeat (t.i.d.) dosing.

The terminal plasma half-life of penciclovir after both single and repeat dosing with famciclovir is approximately 2.0 hours. There is no accumulation of penciclovir on repeated dosing with famciclovir. Penciclovir and its 6-deoxy precursor are poorly (<20%) bound to plasma proteins.

Famciclovir is eliminated principally as penciclovir and its 6-deoxy precursor which are excreted in urine unchanged. Famvir has not been detected in urine. Tubular secretion contributes to the renal elimination of the compound.

Characteristics in patients

Uncomplicated herpes zoster infection does not significantly alter the pharmacokinetics of penciclovir measured after oral administration of Famvir.

Carcinogenicity

In 2 year studies there were no changes seen at 200 mg/kg/d. At the maximally tolerated dose of 600 mg/kg/d in female rats there was an increased incidence of mammary adenocarcinoma, a common tumour in this strain of rats used in the studies. There was no effect on the incidence of neoplasia in male rats or in mice of either sex.

Genotoxicity

Famciclovir was not found to be genotoxic in a comprehensive battery of in vivo and in vitro tests designed to detect gene mutation, chromosomal damage and repairable damage to DNA. Penciclovir, in common with other drugs of this class, has been shown to cause chromosomal damage, but did not induce gene mutation in bacterial or mammalian cell systems, nor was there evidence of increased DNA repair in vitro.

Reproductive toxicity

Famciclovir is well tolerated in laboratory animals. In common with other drugs of this class, degenerative changes of the testicular epithelium were noted.

Famciclovir has been shown to have no significant effects on sperm count, morphology, or motility in man. Impaired fertility was observed in male rats given 500 mg/kg. There were no significant effects on fertility in female rats given famciclovir.

Tablet core:

Hydroxypropylcellulose

Magnesium Stearate (E572)

Sodium Starch Glycollate

Tablet coating:

Hypromellose

Macrogol 4000

Macrogol 6000

Titanium Dioxide (E171).

Not Applicable.

3 years.

Do not store above 30°C.

Store in the original package.

White, opaque, PVC/PVDC/ Aluminium foil blister packs containing 1 or 7 tablets.

Not all pack sizes may be marketed.

Novartis Pharmaceuticals UK Limited,

Frimley Business Park,

Frimley,

Camberley, Surrey, GU16 7SR

England

PA 13/106/4

Date of first authorisation: 20 October 1996

Date of last renewal: 30^th June 2009

July 2009