Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Novartis Pharmaceuticals UK Ltd, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, United Kingdom
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity to penciclovir.
In patients with impaired renal function dose adjustment is necessary (see sections 4.2 and 4.9).
Famciclovir has not been studied in patients with severe hepatic impairment. Conversion of famciclovir to its active metabolite penciclovir may be impaired in these patients resulting in lower penciclovir plasma concentrations, and thus a decrease of efficacy of famciclovir may occur.
Clinical response should be closely monitored, particularly in immunocompromised patients. Consideration should be given to intravenous antiviral therapy when response to oral therapy is considered insufficient.
Patients with complicated herpes zoster, i.e. those with visceral involvement, disseminated zoster, motor neuropathies, encephalitis and cerebrovascular complications should be treated with intravenous antiviral therapy.
Moreover, immunocompromised patients with ophthalmic zoster or those with a high risk for disease dissemination and visceral organ involvement should be treated with intravenous antiviral therapy.
Patients should be advised to avoid intercourse when symptoms are present even if treatment with an antiviral has been initiated. During suppressive treatment with antiviral agents, the frequency of viral shedding is significantly reduced. However, transmission is still possible. Therefore, in addition to therapy with famciclovir, it is recommended that patients use safer sex practices.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
No clinically significant interactions have been identified.
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.
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 (see section 4.4).
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.
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 (see section 5.3).
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 Famvir 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 Famvir arm) were retrospectively reviewed to obtain a frequency category for all adverse reactions mentioned below. The following table specifies the estimated frequency of adverse reactions based on all the spontaneous reports and literature cases that have been reported for Famvir since its introduction to the market.
Adverse reactions (Table 2) 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).
Table 2. Adverse reactions from clinical trials and post-marketing spontaneous reports:
Rare: Thrombocytopenia.
Uncommon: Confusional state (predominantly in the elderly).
Rare: Hallucinations.
Very common: Headache.
Common: Dizziness.
Uncommon: Somnolence (predominantly in the elderly).
Not known: Seizure*.
Rare: Palpitations.
Common: Nausea, vomiting, abdominal pain, diarrhoea.
Common: Abnormal liver function tests.
Rare: Cholestatic jaundice.
Not known: Anaphylactic shock*, anaphylactic reaction*.
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 Famvir 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.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Not applicable.
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