Famciclovir

Because reduced clearance of penciclovir is related to reduced renal function, as measured by creatinine clearance, special attention should be given to doses in patients with impaired renal function. Dose recommendations for adult patients with renal impairment are provided in Table 1.

Table 1. Dose recommendations for adult patients with renal impairment:

Concurrent use of probenecid may result in increased plasma concentrations of penciclovir, the active metabolite of famciclovir, by competing for elimination.

Therefore, patients receiving famciclovir at a dose of 500 mg three times daily co-administered with probenecid, should be monitored for toxicity. If patients experience severe dizziness, somnolence, confusion or other central nervous system disturbances, a dose reduction of famciclovir to 250 mg three times daily may be considered.

Famciclovir needs aldehyde oxidase to be converted into penciclovir, its active metabolite. Raloxifen has been shown to be a potent inhibitor of this enzyme in vitro. Co-administration of raloxifene could affect the formation of penciclovir and thus the efficacy of famciclovir. When raloxifen is co-administered with famciclovir the clinical efficacy of the antiviral therapy should be monitored.

Since 4 h haemodialysis resulted in up to 75% reduction in plasma penciclovir concentrations, famciclovir should be administered immediately following dialysis. The recommended dose regimens for haemodialysis patients are included in Table 1.

There is a limited amount of data (less than 300 pregnancy outcomes) from the use of famciclovir in pregnant women. Based on these limited amounts of information, the cumulative analysis of both prospective and retrospective pregnancy cases did not provide evidence indicating that the product causes any specific foetal defect or congenital anomaly. Animal studies have not shown any embryotoxic or teratogenic effects with famciclovir or penciclovir (the active metabolite of famciclovir). Famciclovir should only be used during pregnancy when the potential benefits of treatment outweigh the potential risks.

It is unknown whether famciclovir is excreted in human breast milk. Animal studies have shown excretion of penciclovir in breast milk. If the woman’s condition mandates treatment with famciclovir, discontinuation of breast-feeding may be considered.

Women of child-bearing potential

There are no data supporting any special recommendations in women of child-bearing potential.

Patients with genital herpes should be advised to avoid intercourse when symptoms are present even if treatment has been initiated. It is recommended that patients use safer sex practice.

Fertility

Clinical data do not indicate an impact of famciclovir on male fertility following long-term treatment at an oral dose of 250 mg twice daily.

No studies on the effects on the ability to drive and use machines have been performed. However, patients who experience dizziness, somnolence, confusion or other central nervous system disturbances while taking famciclovir should refrain from driving or operating machinery.

Headache and nausea have been reported in clinical studies. These were generally mild or moderate in nature and occurred at a similar incidence in patients receiving placebo treatment. All other adverse reactions were added during postmarketing.

The pooled global placebo or active controlled clinical trials (n=2326 for famciclovir arm) were retrospectively reviewed to obtain a frequency category for all adverse reactions mentioned below. The following list specifies the estimated frequency of adverse reactions based on all the spontaneous reports and literature cases that have been reported for famciclovir since its introduction to the market.

Adverse reactions are ranked under headings of frequency, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from available data).

Adverse reactions from clinical trials and post-marketing spontaneous reports:

Blood and lymphatic system disorders

Rare: Thrombocytopenia.

Psychiatric disorders

Uncommon: Confusional state (predominantly in the elderly).

Rare: Hallucinations.

Nervous system disorders

Very common: Headache.

Common: Dizziness.

Uncommon: Somnolence (predominantly in the elderly).

Not known: Seizure*.

Cardiac disorders

Rare: Palpitations.

Gastrointestinal disorders

Common: Nausea, vomiting, abdominal pain, diarrhoea.

Hepatobiliary disorders

Common: Abnormal liver function tests.

Rare: Cholestatic jaundice.

Immune system disorders

Not known: Anaphylactic shock*, anaphylactic reaction*.

Skin and subcutaneous tissue disorders

Common: Rash, pruritus.

Uncommon: Angioedema (e.g. face oedema, eyelid oedema, periorbital oedema, pharyngeal oedema), urticaria.

Not known: Serious skin reactions* (e.g. erythema multiforme, Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis), Hypersensitivity vasculitis*.

* Adverse drug reactions reported from post-marketing experience with famciclovir via spontaneous case reports and literature cases which have not been reported in clinical trials. Because these adverse drug reactions have been reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency. Frequency is therefore listed as “not known”.

Overall, adverse reactions reported from clinical studies with immunocompromised patients were similar to those reported in the immunocompetent population. Nausea, vomiting and abnormal liver function tests were reported more frequently, especially at higher doses.