Famciclovir: Package Insert and Label Information

FAMCICLOVIR- famciclovir tablet, film coated
Teva Pharmaceuticals USA, Inc.

1 INDICATIONS AND USAGE

1.1 Immunocompetent Adult Patients

Herpes labialis (cold sores): Famciclovir tablets are indicated for the treatment of recurrent herpes labialis in adult patients.

Genital herpes:

Recurrent episodes: Famciclovir tablets are indicated for the treatment of recurrent episodes of genital herpes. The efficacy of famciclovir tablets when initiated more than 6 hours after onset of symptoms or lesions has not been established.

Suppressive therapy: Famciclovir tablets are indicated for chronic suppressive therapy of recurrent episodes of genital herpes in adult patients. The efficacy and safety of famciclovir tablets for the suppression of recurrent genital herpes beyond 1 year have not been established.

Herpes zoster (shingles): Famciclovir tablets are indicated for the treatment of herpes zoster in adult patients. The efficacy of famciclovir tablets when initiated more than 72 hours after onset of rash has not been established.

1.2 HIV-Infected Adult Patients

Recurrent orolabial or genital herpes: Famciclovir tablets are indicated for the treatment of recurrent episodes of orolabial or genital herpes in HIV-infected adults. The efficacy of famciclovir tablets when initiated more than 48 hours after onset of symptoms or lesions has not been established.

Limitation of Use

The efficacy and safety of famciclovir tablets have not been established for:

• Patients with first episode of genital herpes
• Patients with ophthalmic zoster
• Immunocompromised patients other than for the treatment of recurrent orolabial or genital herpes in HIV-infected patients
• Black and African American patients with recurrent genital herpes

2 DOSAGE AND ADMINISTRATION

Famciclovir tablets may be taken with or without food.

2.1 Dosing Recommendation in Immunocompetent Adult Patients

Herpes labialis (cold sores): The recommended dosage of famciclovir tablets for the treatment of recurrent herpes labialis is 1500 mg as a single dose. Therapy should be initiated at the first sign or symptom of herpes labialis (e.g., tingling, itching, burning, pain, or lesion).

Genital herpes:

Recurrent episodes: The recommended dosage of famciclovir tablets for the treatment of recurrent episodes of genital herpes is 1000 mg twice daily for 1 day. Therapy should be initiated at the first sign or symptom of a recurrent episode (e.g., tingling, itching, burning, pain, or lesion).

Suppressive therapy: The recommended dosage of famciclovir tablets for chronic suppressive therapy of recurrent episodes of genital herpes is 250 mg twice daily.

Herpes zoster (shingles): The recommended dosage of famciclovir tablets for the treatment of herpes zoster is 500 mg every 8 hours for 7 days. Therapy should be initiated as soon as herpes zoster is diagnosed.

2.2 Dosing Recommendation in HIV-Infected Adult Patients

Recurrent orolabial or genital herpes: The recommended dosage of famciclovir tablets for the treatment of recurrent orolabial or genital herpes in HIV-infected patients is 500 mg twice daily for 7 days. Therapy should be initiated at the first sign or symptom of a recurrent episode (e.g., tingling, itching, burning, pain, or lesion).

2.3 Dosing Recommendation in Patients with Renal Impairment

Dosage recommendations for adult patients with renal impairment are provided in Table 1 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

* Hemodialysis
Table 1: Dosage Recommendations for Adult Patients with Renal Impairment
Indication and Normal Dosage Regimen	Creatinine Clearance (mL/min)	Adjusted Dosage Regimen Dose (mg)	Dosing Interval
Single-Day Dosing Regimens
Recurrent Genital Herpes
1000 mg every 12 hours for 1 day	≥60	1000	every 12 hours for 1 day
	40 to 59	500	every 12 hours for 1 day
	20 to 39	500	single dose
	<20	250	single dose
	HD *	250	single dose following dialysis
Recurrent Herpes Labialis
1500 mg single dose	≥60	1500	single dose
	40 to 59	750	single dose
	20 to 39	500	single dose
	<20	250	single dose
	HD *	250	single dose following dialysis
Multiple-Day Dosing Regimens
Herpes Zoster
500 mg every 8 hours	≥60	500	every 8 hours
	40 to 59	500	every 12 hours
	20 to 39	500	every 24 hours
	<20	250	every 24 hours
	HD *	250	following each dialysis
Suppression of Recurrent Genital Herpes
250 mg every 12 hours	≥40	250	every 12 hours
	20 to 39	125	every 12 hours
	<20	125	every 24 hours
	HD *	125	following each dialysis
Recurrent Orolabial or Genital Herpes in HIV-Infected Patients
500 mg every 12 hours	≥40	500	every 12 hours
	20 to 39	500	every 24 hours
	<20	250	every 24 hours
	HD *	250	following each dialysis

3 DOSAGE FORMS AND STRENGTHS

Famciclovir Tablets are available in three strengths:

• 125 mg: White, round, film-coated, unscored tablets, debossed with “8117” on one side and “93” on the other side
• 250 mg: White, round, film-coated, unscored tablets, debossed with “8118” on one side and “93” on the other side
• 500 mg: White, capsule-shaped, film-coated, unscored tablets, debossed with “8119” on one side and “93” on the other side

4 CONTRAINDICATIONS

Famciclovir is contraindicated in patients with known hypersensitivity to the product, its components, or Denavir^® (penciclovir cream).

5 WARNINGS AND PRECAUTIONS

5.1 Acute Renal Failure

Cases of acute renal failure have been reported in patients with underlying renal disease who have received inappropriately high doses of famciclovir for their level of renal function. Dosage reduction is recommended when administering famciclovir to patients with renal impairment [see Dosage and Administration (2.3), Use in Specific Populations (8.6)].

6 ADVERSE REACTIONS

Acute renal failure is discussed in greater detail in other sections of the label [see Warnings and Precautions (5) ].

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

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

* Patients may have entered into more than one clinical trial. † 7 days of treatment ‡ 1 day of treatment § daily treatment
Table 2: Selected Adverse Events (all grades and without regard to causality) Reported by Greater than or Equal to 2% of Patients in Placebo-Controlled Famciclovir Trials *
Incidence
Events	Herpes Zoster †		Recurrent Genital Herpes ‡		Genital Herpes- Supression §		Herpes Labialis ‡
	Famciclovir (n=273) %	Placebo (n=146) %	Famciclovir (n=163) %	Placebo (n=166) %	Famciclovir (n=458) %	Placebo (n=63) %	Famciclovir (n=447) %	Placebo (n=254) %
Nervous System
Headache	22.7	17.8	13.5	5.4	39.3	42.9	8.5	6.7
Paresthesia	2.6	0.0	0.0	0.0	0.9	0.0	0.0	0.0
Migraine	0.7	0.7	0.6	0.6	3.1	0.0	0.2	0.0
Gastrointestinal
Nausea	12.5	11.6	2.5	3.6	7.2	9.5	2.2	3.9
Diarrhea	7.7	4.8	4.9	1.2	9.0	9.5	1.6	0.8
Vomiting	4.8	3.4	1.2	0.6	3.1	1.6	0.7	0.0
Flatulence	1.5	0.7	0.6	0.0	4.8	1.6	0.2	0.0
Abdominal Pain	1.1	3.4	0.0	1.2	7.9	7.9	0.2	0.4
Body as a Whole
Fatigue	4.4	3.4	0.6	0.0	4.8	3.2	1.6	0.4
Skin and Appendages
Pruritus	3.7	2.7	0.0	0.6	2.2	0.0	0.0	0.0
Rash	0.4	0.7	0.0	0.0	3.3	1.6	0.0	0.0
Reproductive (Female)
Dysmenorrhea	0.0	0.7	1.8	0.6	7.6	6.3	0.4	0.0

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

* Percentage of patients with laboratory abnormalities that were increased or decreased from baseline and were outside of specified ranges. † n values represent the minimum number of patients assessed for each laboratory parameter.
Table 3: Selected Laboratory Abnormalities in Genital Herpes Suppression Studies *
Parameter	Famciclovir (n=660) † %	Placebo (n=210) † %
Anemia (<0.8 x NRL)	0.1	0.0
Leukopenia (<0.75 x NRL)	1.3	0.9
Neutropenia (<0.8 x NRL)	3.2	1.5
AST (SGOT) (>2 x NRH)	2.3	1.2
ALT (SGPT) (>2 x NRH)	3.2	1.5
Total Bilirubin (>1.5 x NRH)	1.9	1.2
Serum Creatinine (>1.5 x NRH)	0.2	0.3
Amylase (>1.5 x NRH)	1.5	1.9
Lipase (>1.5 x NRH)	4.9	4.7

NRH = Normal Range High. NRL = Normal Range Low.

HIV-infected patients: In HIV-infected patients, the most frequently reported adverse events for famciclovir (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%).