1 Name of Medicine
Famciclovir.
2 Qualitative and Quantitative Composition
Famciclovir-WGR tablets come in three strengths and contain either 125 mg, 250 mg or 500 mg of famciclovir.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Famciclovir-WGR 125. White to off-white, round tablet with 'FC' over 125 on one side and blank on the other side.
Famciclovir-WGR 250. White to off-white, round tablet with 'FC' over 250 on one side and blank on the other side.
Famciclovir-WGR 500. White to off-white, capsule-shaped tablet with 'FC 500' on one side and blank on the other side.
4 Clinical Particulars
4.9 Overdose
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Overdose 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.
Symptomatic and supportive therapy should be given as appropriate. Acute renal failure has been reported rarely in patients with underlying renal disease. The famciclovir dosage in these patients had not been appropriately reduced for the level of renal function.
Penciclovir is dialysable; plasma concentrations are reduced by approximately 75% following 4 hour haemodialysis.
5 Pharmacological Properties
5.3 Preclinical Safety Data
Data presented below include reference to area under the plasma concentration curve (24 hour AUC) for penciclovir in humans following the lowest and highest recommended doses for famciclovir (i.e. penciclovir AUC of 4.5 microgram.h/mL at 125 mg b.i.d. for acute recurrent genital herpes, and a penciclovir AUC of 27 microgram.h/mL at 500 mg t.i.d. for herpes infections in immunocompromised patients). This is based on the assumption that the pharmacokinetics in immunocompetent subjects are similar to the pharmacokinetics in immunocompromised subjects, as shown in the study on HIV patients (see Section 5.2 Pharmacokinetic Properties). If the higher values of AUC obtained in the renal transplant patients were used as a basis for comparison, the multiples specified here would be decreased. Exposures in animal studies are expressed as multiples of human exposures at the highest and lowest dosing schedules based on penciclovir AUC or body surface area.
Genotoxicity. Famciclovir and penciclovir (the active metabolite of famciclovir) were tested for genotoxic potential in a series of in vitro and in vivo assays. Famciclovir showed no genotoxic potential in a series of assays for gene mutations, chromosomal damage and DNA damage. Penciclovir was positive in the L5178Y mouse lymphoma assay for gene mutations/chromosomal damage, caused chromosomal aberrations in human lymphocytes in vitro and was positive in a mouse micronucleus assay in vivo when administered IV at doses toxic to bone marrow.
Carcinogenicity. The carcinogenic potential of famciclovir was evaluated in 2 year dietary studies in rats and mice. A significant increase in the incidence of mammary adenocarcinoma was seen in female rats receiving 600 mg/kg/day. No increases in tumour incidences were reported for male rats treated at doses of up to 240 mg/kg/day or in mice of either sex at doses of up to 600 mg/kg/day. At the no effect levels of 240 and 200 mg/kg/day in male and female rats, the daily exposures to penciclovir based on AUC were about 40 and 29 microgram.h/mL respectively, or approximately 1 to 8 times the human systemic exposures at 500 mg t.i.d or 125 mg b.i.d. Systemic exposures at the no effect dose in male and female mice were 65 and 46 microgram.h/mL respectively, or approximately 2 to 12 times the human systemic exposure (AUC).
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Famciclovir is a white or off-white crystalline powder. It is very soluble in water, methanol, ethanol and chloroform, slightly soluble in ethyl acetate, practically insoluble in ether.
Chemical structure. The chemical name for famciclovir is 2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol diacetate. Its structural formula is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSFAMCIC.gif C14H19N5O4. Molecular weight: 321.34.
CAS number. 104227-87-4.
7 Medicine Schedule (Poisons Standard)
Schedule 4 - Prescription Only Medicine.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/FAMWGRST.gif