No

Antiviral Agent

Management of acute herpes zoster (shingles) and recurrent episodes of genital herpes; treatment of recurrent herpes simplex in immunocompetent patients

B

Clinical effects on the fetus: Use only if the benefit to the patient clearly exceeds the potential risk to the fetus

Breast-feeding/lactation: Due to potential for excretion of famciclovir in breast milk and for its associated tumorigenicity, discontinue nursing or discontinue the drug during lactation

Hypersensitivity to famciclovir

Has not been studied in immunocompromised patients or patients with ophthalmic or disseminated zoster; dosage adjustment is required in patients with renal insufficiency (Cl_cr <60 mL/minute) and in patients with noncompensated hepatic disease; safety and efficacy have not been established in children <18 years of age; animal studies indicated increases in incidence of carcinomas, mutagenic changes, and decreases in fertility with extremely large doses

1% to 10%:

Central nervous system: Fatigue (4% to 6%), fever (1% to 3%), dizziness (3% to 5%), somnolence (1% to 2%), headache

Dermatologic: Pruritus (1% to 4%)

Gastrointestinal: Diarrhea (4% to 8%), vomiting (1% to 5%), constipation (1% to 5%), anorexia (1% to 3%), abdominal pain (1% to 4%), nausea

Neuromuscular & skeletal: Paresthesia (1% to 3%)

Respiratory: Sinusitis/pharyngitis (2%)

<1%: Rigors, arthralgia, upper respiratory infection

Supportive and symptomatic care is recommended; hemodialysis may enhance elimination

Increased effect/toxicity:

Digoxin: C_max of digoxin increases by ~19%

Probenecid: Penciclovir serum levels significantly increase

Theophylline: Penciclovir AUC/C_max may increase and renal clearance decrease, although not clinically significant

After undergoing rapid biotransformation to the active compound, penciclovir, famciclovir is phosphorylated by viral thymidine kinase in HSV-1, HSV-2, and VZV-infected cells to a monophosphate form; this is then converted to penciclovir triphosphate and competes with deoxyguanosine triphosphate to inhibit HSV-2 polymerase (ie, herpes viral DNA synthesis/replication is selectively inhibited)

Absorption: Food decreases the maximum peak concentration and delays the time to peak; AUC remains the same

Distribution: V_dss: 0.98-1.08 L/kg

Protein binding: 20%

Metabolism: Rapidly deacetylated and oxidized to penciclovir (not by cytochrome P-450)

Bioavailability: 77%; T_max: 0.9 hours

Half-life: Penciclovir: 2-3 hours (10, 20, and 7 hours in HSV-1, HSV-2, and VZV-infected cells); linearly decreased with reductions in renal failure

Elimination: >90% of penciclovir is eliminated unchanged in urine; C_max and T_max are decreased and prolonged, respectively in patients with noncompensated hepatic impairment

Adults: Oral:

Recurrent herpes simplex in immunocompetent patients: 125 mg twice daily for 5 days

Genital herpes:

Recurrent episodes: 125 mg twice daily for 5 days

Prophylaxis: 250 mg twice daily

Dosing interval in renal impairment:

Cl_cr 40-59 mL/minute: Administer 500 mg every 12 hours

Cl_cr 20-39 mL/minute: Administer 500 mg every 24 hours

Cl_cr <20 mL/minute: Unknown

May be taken with food or on an empty stomach

May cause sedation

None reported

No information available to require special precautions

No effects or complications reported

Take for prescribed length of time, even if condition improves. Do not discontinue without consulting prescriber. This is not a cure for genital herpes. You may experience mild GI disturbances (eg, nausea, vomiting, constipation, or diarrhea), fatigue, headaches, or muscle aches and pains. If these are severe, contact prescriber. Breast-feeding precautions: Do not breast-feed.

Tablet: 125 mg, 250 mg, 500 mg

Alrabiah FA and Sacks SL, "New Antiherpesvirus Agents. Their Targets and Therapeutic Potential," Drugs, 1996, 52(1):17-32.

Boike SC, Pue MA, and Freed MI, "Pharmacokinetics of Famciclovir in Subjects With Varying Degrees of Renal Impairment," Clin Pharmacol Ther, 1994, 55(4):418-26.

Boyd MR, Safrin S, and Kern ER, "Penciclovir: A Review of Its Spectrum of Activity, Selectivity, and Cross Resistance Pattern," Antiviral Chem Chemother, 1993, 4:3-11.

De Clercq E, "Antivirals for the Treatment of Herpesvirus Infections," J Antimicrob Chemother, 1993, 32(Suppl A):121-32.

Gill KS and Wood MJ, "The Clinical Pharmacokinetics of Famciclovir," Clin Pharmacokin, 1996, 31(1):1-8.

Goffin E, Horsmans Y, Pirson Y, et al, "Acute Necrotico-Hemorrhagic Pancreatitis After Famciclovir Prescription," Transplantation, 1995, 59(8):1218-9.

Luber AD and Flaherty JF Jr, "Famciclovir for Treatment of Herpesvirus Infections," Ann Pharmacother, 1996, 30(9):978-85.

Perry CM and Wagstaff AJ, "Famciclovir. A Review of Its Pharmacological Properties and Therapeutic Efficacy in Herpesvirus Infections," Drugs, 1995, 50(2):396-415.

Pue MA and Benet LZ, "Pharmacokinetics of Famciclovir in Man," Antiviral Chem Chemother, 1993, 4(Suppl 1):47-55.

Sacks SL, "Genital Herpes Simplex Virus and Its Treatment Focus on Famciclovir," Semin Dermatol, 1996, 15(2 Suppl 1):32-6.

Tyring SK, Barbarash RA, Nahlik JE, et al, "Famciclovir for the Treatment of Acute Herpes Zoster: Effects on Acute Disease and Postherpetic Neuralgia," Ann Intern Med, 1995, 123(2):89-96.

Tyring SK, "Efficacy of Famciclovir in the Treatment of Herpes Zoster," Semin Dermatol, 1996, 15(2 Suppl 1):27-31.