Famvir Information
Famvir () indications And Usage
Recurrent orolabial or genital herpes
:
The efficacy and safety of Famvir () have not been established for:
Famvir () dosage And Administration
Famvir () may be taken with or without food.
Recurrent orolabial or genital
herpes
:
Dosage recommendations for adult patients with renal impairment are provided in Table 1 [see ]
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Famvir () dosage Forms And Strengths
Famvir () tablets are available in three strengths:
Famvir () contraindications
Famvir () is contraindicated in patients with known hypersensitivity to the product, its components, or Denavir (penciclovir cream).
Famvir () warnings And Precautions
Famvir () Adverse Reactions
Acute renal failure is discussed in greater detail in other sections of the label [see
The most common adverse events reported in at least 1 indication by >10% of adult patients treated with Famvir () are headache and nausea.
Famvir () drug Interactions
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 co-administered with zidovudine or emtricitabine.
An study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes.
No clinically significant alterations in penciclovir pharmacokinetics were observed following single-dose administration of 500 mg famciclovir after pre-treatment 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, inhibitors of aldehyde oxidase, did not show relevant effects on the formation of penciclovir. Raloxifene, a potent aldehyde oxidase inhibitor , 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.
Famvir () use In Specific Populations
In animal reproduction studies, pregnant rats and rabbits received oral famciclovir at doses (up to 1000 mg/kg/day) that provided 2.7 to 10.8 times (rats) and 1.4 to 5.4 times (rabbits) the human systemic exposure based on AUC. No adverse effects were observed on embryo-fetal development. In other studies, pregnant rats and rabbits received intravenous famciclovir at doses (360 mg/kg/day) 1.5 to 6 times (rats) and (120 mg/kg/day) 1.1 to 4.5 times (rabbits) or penciclovir at doses (80 mg/kg/day) 0.3 to 1.3 times (rats) and (60 mg/kg/day) 0.5 to 2.1 times (rabbits) the MRHD based on body surface area comparisons. No adverse effects were observed on embryo-fetal development.
The efficacy and safety of Famvir () tablets have not been established in pediatric patients. The pharmacokinetic profile and safety of famciclovir experimental granules mixed with OraSweet were studied in two open-label studies.
Study 1 was a single-dose pharmacokinetic and safety study in infants 1 month to
Study 2 was an open-label, single-dose pharmacokinetic, multiple-dose safety study of famciclovir experimental granules mixed with OraSweet in children 1 to
A total of 100 patients were enrolled in the multiple-dose safety part of the study; 47 subjects with active or latent HSV infection and 53 subjects with chickenpox. Patients with active or latent HSV infection received famciclovir twice a day for seven days. The daily dose of famciclovir ranged from 150 mg to 500 mg twice daily depending on the patient’s body weight. Patients with chickenpox received famciclovir three times daily for seven days. The daily dose of famciclovir ranged from 150 mg to 500 mg three times daily depending on the patient’s body weight. The clinical adverse events and laboratory test abnormalities observed in this study were similar to these seen in adults. The available data are insufficient to support the use of famciclovir for the treatment of children with chickenpox or infections due to HSV for the following reasons:
Chickenpox:
Genital herpes:
Herpes labialis:
Of 816 patients with herpes zoster in clinical studies who were treated with Famvir () , 248 (30.4%) were ≥65 years of age and 103 (13%) were ≥75 years of age. No overall differences were observed in the incidence or types of adverse events between younger and older patients. Of 610 patients with recurrent herpes simplex (type 1 or type 2) in clinical studies who were treated with Famvir () , 26 (4.3%) were >65 years of age and 7 (1.1%) were >75 years of age. Clinical studies of Famvir () in patients with recurrent genital herpes did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects.
No famciclovir dosage adjustment based on age is recommended unless renal function is impaired [see ]. In general, appropriate caution should be exercised in the administration and monitoring of Famvir () in elderly patients reflecting the greater frequency of decreased renal function and concomitant use of other drugs.
Apparent plasma clearance, renal clearance, and the plasma-elimination rate constant of penciclovir decreased linearly with reductions in renal function. After the administration of a single 500 mg famciclovir oral dose (n=27) to healthy volunteers and to volunteers with varying degrees of renal impairment (CL ranged from 6.4 to 138.8 mL/min), the following results were obtained (Table 4):
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CR
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§
In a multiple-dose study of famciclovir conducted in subjects with varying degrees of renal impairment (n=18), the pharmacokinetics of penciclovir were comparable to those after single doses.
A dosage adjustment is recommended for patients with renal impairment [see ]
Famvir () overdosage
Appropriate symptomatic and supportive therapy should be given. Penciclovir is removed by hemodialysis.
Famvir () description
The active ingredient in Famvir () tablets is famciclovir, an orally administered prodrug of the antiviral agent penciclovir. Chemically, famciclovir is known as 2-[2-(2-amino-9-purin-9-yl)ethyl]-1,3-propanediol diacetate. Its molecular formula is CHNO; its molecular weight is 321.3. It is a synthetic acyclic guanine derivative and has the following structure
Famciclovir is a white to pale yellow solid. It is freely soluble in acetone and methanol, and sparingly soluble in ethanol and isopropanol. At 25°C famciclovir is freely soluble (>25% w/v) in water initially, but rapidly precipitates as the sparingly soluble (2%-3% w/v) monohydrate. Famciclovir is not hygroscopic below 85% relative humidity. Partition coefficients are: octanol/water (pH 4.8) =1.09 and octanol/phosphate buffer (pH 7.4) =2.08.
Famvir () tablets contain 125 mg, 250 mg or 500 mg of famciclovir, together with the following inactive ingredients: hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, polyethylene glycols, sodium starch glycolate and titanium dioxide.
Famvir () clinical Pharmacology
Famciclovir is the diacetyl 6-deoxy analog of the active antiviral compound penciclovir. Following oral administration famciclovir undergoes rapid and extensive metabolism to penciclovir and little or no famciclovir is detected in plasma or urine. Penciclovir is predominantly eliminated unchanged by the kidney. Therefore, the dose of Famvir () needs to be adjusted in patients with different degrees of renal impairment [see ].
Penciclovir concentrations increased in proportion to dose over a famciclovir dose range of 125 mg to 1000 mg administered as a single dose. Table 5 shows the mean pharmacokinetic parameters of penciclovir after single administration of Famvir () to healthy male volunteers.
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max
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Following oral single-dose administration of 500 mg famciclovir to seven patients with herpes zoster, the AUC (mean ± SD), C, and t were 12.1±1.7 mcg hr/mL, 4.0±0.7 mcg/mL, and 0.7±0.2 hours, respectively. The AUC of penciclovir was approximately 35% greater in patients with herpes zoster as compared to healthy volunteers. Some of this difference may be due to differences in renal function between the two groups.
There is no accumulation of penciclovir after the administration of 500 mg famciclovir three times daily for 7 days.
Penciclovir C decreased approximately 50% and t was delayed by 1.5 hours when a capsule formulation of famciclovir was administered with food (nutritional content was approximately 910 Kcal and 26% fat). There was no effect on the extent of availability (AUC) of penciclovir. There was an 18% decrease in C and a delay in t of about 1 hour when famciclovir was given 2 hours after a meal as compared to its administration 2 hours before a meal. Because there was no effect on the extent of systemic availability of penciclovir, Famvir () can be taken without regard to meals.
Distribution
Following the oral administration of a single 500 mg dose of radiolabeled famciclovir to three healthy male volunteers, 73% and 27% of administered radioactivity were recovered in urine and feces over 72 hours, respectively. Penciclovir accounted for 82% and 6-deoxy penciclovir accounted for 7% of the radioactivity excreted in the urine. Approximately 60% of the administered radiolabeled dose was collected in urine in the first 6 hours.
After intravenous administration of penciclovir in 48 healthy male volunteers, mean ± SD total plasma clearance of penciclovir was 36.6±6.3 L/hr (0.48±0.09 L/hr/kg). Penciclovir renal clearance accounted for 74.5±8.8% of total plasma clearance.
Renal clearance of penciclovir following the oral administration of a single 500 mg dose of famciclovir to 109 healthy male volunteers was 27.7±7.6 L/hr. Active tubular secretion contributes to the renal elimination of penciclovir.
The plasma elimination half-life of penciclovir was 2.0±0.3 hours after intravenous administration of penciclovir to 48 healthy male volunteers and 2.3±0.4 hours after oral administration of 500 mg famciclovir to 124 healthy male volunteers. The half-life in 17 patients with herpes zoster was 2.8±1.0 hours and 2.7±1.0 hours after single and repeated doses, respectively.
Race: A retrospective evaluation was performed to compare the pharmacokinetic parameters obtained in Black and Caucasian subjects after single and repeat once-daily, twice-daily, or three times-daily administration of famciclovir 500 mg. Data from a study in healthy volunteers (single dose), a study in subjects with varying degrees of renal impairment (single and repeat dose) and a study in subjects with hepatic impairment (single dose) did not indicate any significant differences in the pharmacokinetics of penciclovir between Black and Caucasian subjects.
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50
Cross-resistance
Famvir () nonclinical Toxicology
Famciclovir had no effect on general reproductive performance or fertility in female rats at doses up to 1000 mg/kg/day (2.7 to 10.8x the human AUC).
Two placebo-controlled studies in a total of 130 otherwise healthy men with a normal sperm profile over an 8-week baseline period and recurrent genital herpes receiving oral Famvir () (250 mg twice daily) (n=66) or placebo (n=64) therapy for 18 weeks showed no evidence of significant effects on sperm count, motility or morphology during treatment or during an 8-week follow-up.
Juvenile toxicity study in
rats
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Famvir () clinical Studies
A randomized (2:1), double-blind, placebo-controlled trial was conducted in 304 immunocompetent Black and African American adults with recurrent genital herpes. Patients self-initiated therapy within 6 hours of the first sign or symptom of a recurrent genital herpes episode with either Famvir () 1000 mg twice daily (n=206) or placebo (n=98) for 1 day. The median time to healing among patients with non-aborted lesions was 5.4 days in Famvir () -treated patients (n=152) as compared to 4.8 days in placebo-treated patients (n=78). The median difference in time to healing between the placebo and Famvir () -treated groups was -0.26 days (95% CI: -0.98 to 0.40).
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Famvir () -treated patients had approximately 1/5 the median number of recurrences as compared to placebo-treated patients. Higher doses of Famvir () were not associated with an increase in efficacy.
Two randomized, double-blind trials, 1 placebo-controlled and 1 active-controlled, were conducted in 964 immunocompetent adults with uncomplicated herpes zoster. Treatment was initiated within 72 hours of first lesion appearance and was continued for 7 days.
In the placebo-controlled trial, 419 patients were treated with either Famvir () 500 mg three times daily (n=138), Famvir () 750 mg three times daily (n=135) or placebo (n=146). The median time to full crusting was 5 days among Famvir () 500 mg-treated patients as compared to 7 days in placebo-treated patients. The times to full crusting, loss of vesicles, loss of ulcers, and loss of crusts were shorter for Famvir () 500 mg-treated patients than for placebo-treated patients in the overall study population. The effects of Famvir () were greater when therapy was initiated within 48 hours of rash onset; it was also more profound in patients 50 years of age or older. Among the 65.2% of patients with at least 1 positive viral culture, Famvir () treated patients had a shorter median duration of viral shedding than placebo-treated patients (1 day and 2 days, respectively).
There were no overall differences in the duration of pain before rash healing between Famvir () - and placebo-treated groups. In addition, there was no difference in the incidence of pain after rash healing (postherpetic neuralgia) between the treatment groups. In the 186 patients (44.4% of total study population) who developed postherpetic neuralgia, the median duration of postherpetic neuralgia was shorter in patients treated with Famvir () 500 mg than in those treated with placebo (63 days and 119 days, respectively). No additional efficacy was demonstrated with higher dose of Famvir () .
In the active-controlled trial, 545 patients were treated with one of three doses of Famvir () three times daily or with acyclovir 800 mg five times daily. Times to full lesion crusting and times to loss of acute pain were comparable for all groups and there were no statistically significant differences in the time to loss of postherpetic neuralgia between Famvir () and acyclovir-treated groups.
Famvir () how Supplied/storage And Handling
Famvir () tablets are supplied as film-coated tablets as follows: 125 mg in bottles of 30; 250 mg in bottles of 30; 500 mg in bottles of 30 and Single Unit Packages of 50 (intended for institutional use only).
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
Famvir () Patient Counseling Information
See FDA-Approved Patient Labeling (Patient Information)
There is no evidence that Famvir () will affect the ability of a patient to drive or to use machines. However, patients who experience dizziness, somnolence, confusion or other central nervous system disturbances while taking Famvir () should refrain from driving or operating machinery.
Because Famvir () contains lactose (Famvir () 125 mg, 250 mg and 500 mg tablets contain lactose 26.9 mg, 53.7 mg and 107.4 mg, respectively), patients with rare hereditary problems of galactose intolerance, a severe lactase deficiency or glucose-galactose malabsorption should be advised to discuss with their healthcare provider before taking Famvir () .
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