Side Effects of Famvir (famciclovir)

Famvir (famciclovir) is a nucleoside analog antiviral drug active against the Herpes viruses, including herpes simplex 1 and 2 (cold sores and genital herpes) and varicella-zoster (shingles and chickenpox). 

Famvir relieves pain, burning, itching, and tingling, and also heals and prevents sores associated with herpes infections. It stops the spread of herpes virus in the body by preventing the replication of viral DNA that is necessary for viruses to multiply. 

Famvir is actually a "prodrug," that is, not active directly against viruses. Instead, Famvir is converted to penciclovir in the body, and it is the penciclovir that is active against the viruses. 

Famvir is active against the same viruses as acyclovir but has a longer duration of action. Therefore, it can be taken fewer times each day. Famvir does not cure or stop the spread of herpes infections. 

Common side effects of Famvir include

• headache,
• fatigue,
• nausea,
• vomiting,
• rash,
• diarrhea, and
• gas (flatulence).

Serious but rare side effects of Famvir include

• serious allergic reactions,
• serious skin reactions,
• yellowing skin and eyes (jaundice),
• abnormal liver function tests,
• reduced white blood cells (neutropenia) or platelets (thrombocytopenia), and
• kidney failure when higher than recommended doses are administered to patients with underlying kidney problems.

Drug interactions of Famvir include probenecid, which may reduce the kidney's removal of Famvir leading to higher concentrations of Famvir in the blood. This may lead to side effects from Famvir. 

Famvir has not been adequately studied in pregnant women. It is unknown if Famvir is excreted into breast milk. Consult your doctor before breastfeeding. 

The most common side effects associated with the use of famciclovir are:

• headache,
• fatigue,
• nausea,
• vomiting,
• rash,
• diarrhea, and
• flatulence.

Other important side effects which are serious, but rare, include

• serious allergic reactions,
• serious skin reactions,
• jaundice,
• abnormal tests of liver function, and
• reduced white blood cells (neutropenia) or platelets (thrombocytopenia).

Cases of kidney failure have been reported when higher than recommended doses of famciclovir were administered to patients with underlying kidney problems.

Acute renal failure is discussed in greater detail in other sections of the label.

The most common adverse events reported in at least 1 indication by >10% of adult patients treated with Famvir are headache and nausea.

Clinical Trials Experience In Adult Patients

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Immunocompetent Patients

The safety of Famvir has been evaluated in active-and placebo-controlled clinical studies involving

• 816 Famvir-treated patients with herpes zoster (Famvir, 250 mg three times daily to 750 mg three times daily);
• 163 Famvir-treated patients with recurrent genital herpes (Famvir, 1000 mg twice daily);
• 1,197 patients with recurrent genital herpes treated with Famvir as suppressive therapy (125 mg once daily to 250 mg three times daily) of which 570 patients received Famvir (open-labeled and/or double-blind) for at least 10 months; and
• 447 Famvir-treated patients with herpes labialis (Famvir, 1500 mg once daily or 750 mg twice daily). Table 2 lists selected adverse events.

Table 2 Selected Adverse Events (all grades and without regard to causality) Reported by ≥2% of Patients in Placebo-Controlled Famvir Trials*

Table 3 lists selected laboratory abnormalities in genital herpes suppression trials.

Table 3 Selected Laboratory Abnormalities in Genital Herpes Suppression Studies*

HIV-Infected Patients

In HIV-infected patients, the most frequently reported adverse events for Famvir (500 mg twice daily; n=150) and acyclovir (400 mg, 5x/day; n=143), respectively, were

• headache (17% vs. 15%),
• nausea (11% vs. 13%),
• diarrhea (7% vs. 11%),
• vomiting (5% vs. 4%),
• fatigue (4% vs. 2%), and
• abdominal pain (3% vs. 6%).

Postmarketing Experience

The adverse events listed below have been reported during postapproval use of Famvir. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• Blood and lymphatic system disorders: Thrombocytopenia
• Hepatobiliary disorders: Abnormal liver function tests, cholestatic jaundice
• Immune system disorders: Anaphylactic shock, anaphylactic reaction
• Nervous system disorders: Dizziness, somnolence, seizure
• Psychiatric disorders: Confusion (including delirium, disorientation, and confusional state occurring predominantly in the elderly), hallucinations
• Skin and subcutaneous tissue disorders: Urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema (e.g., face, eyelid, periorbital, and pharyngeal edema), hypersensitivity vasculitis
• Cardiac disorders: Palpitations

Potential For Famvir To Affect Other Drugs

• The steady-state pharmacokinetics of digoxin were not altered by concomitant administration of multiple doses of famciclovir (500 mg three times daily).
• No clinically significant effect on the pharmacokinetics of zidovudine, its metabolite zidovudine glucuronide, or emtricitabine was observed following a single oral dose of 500 mg famciclovir coadministered with zidovudine or emtricitabine.
• An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes.

Potential For Other Drugs To Affect Penciclovir

• No clinically significant alterations in penciclovir pharmacokinetics were observed following single-dose administration of 500 mg famciclovir after pretreatment with multiple doses of allopurinol, cimetidine, theophylline, zidovudine, promethazine, when given shortly after an antacid (magnesium and aluminum hydroxide), or concomitantly with emtricitabine.
• No clinically significant effect on penciclovir pharmacokinetics was observed following multiple-dose (three times daily) administration of famciclovir (500 mg) with multiple doses of digoxin.
• Concurrent use with probenecid or other drugs significantly eliminated by active renal tubular secretion may result in increased plasma concentrations of penciclovir.
• The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase.
• Interactions with other drugs metabolized by this enzyme and/or inhibiting this enzyme could potentially occur.
• Clinical interaction studies of famciclovir with cimetidine and promethazine, in vitro inhibitors of aldehyde oxidase, did not show relevant effects on the formation of penciclovir.
• Raloxifene, a potent aldehyde oxidase inhibitor in vitro, could decrease the formation of penciclovir.
• However, a clinical drug-drug interaction study to determine the magnitude of interaction between penciclovir and raloxifene has not been conducted.