Afamcivir

Uses

Herpes zoster (shingles), Recurrent herpes labialis, Genital herpes, Acute treatment of recurrent mucocutaneous herpes in HIV-infected patients, Acute treatment of recurrent episodes of genital herpes, Suppression of recurrent episodes of genital herpes

Afamcivir is also used to associated treatment for these conditions: Acute Herpes Zoster, Herpes simplex of the genitals, Herpes simplex of the oral-labial, Recurrent Herpes simplex of the genital, Recurrent Herpes simplex of the oral-labial

How Afamcivir works

Afamcivir undergoes rapid biotransformation to the active antiviral compound penciclovir, which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). In cells infected with HSV-1, HSV-2 or VZV, viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted to penciclovir triphosphate by cellular kinases. In vitro studies demonstrate that penciclovir triphosphate inhibits HSV-2 DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited.

Dosage

Afamcivir dosage

Oral (Adult)-Herpes zoster (shingles): 500 mg tid for 7 days. Immunocompromised patients: 500 mg tid for 10 days.Haemodialysis patients: 250 mg after each dialysis run during 7 days. Immunocompromised patients: Same dose but treatment is given for 10 days.

• CrCl (mL/min) <20: 250 mg once daily for 7 days.
• CrCl (mL/min) 20-39: 500 mg once daily for 7 days.
• CrCl (mL/min) 40-59: 500 mg bid for 7 days.

Recurrent herpes labialis:

1.5 g as a single dose.Haemodialysis patients: 250 mg after dialysis run.

• CrCl (mL/min) <20: 250 mg as a single dose.
• CrCl (mL/min) 20-39: 500 mg as a single dose.
• CrCl (mL/min) 40-59: 750 mg as a single dose.

Genital herpes:

1st episode: 250 mg tid for 5 days. Immunocompromised patients: 500 mg bid for 7 days.Haemodialysis patients: 250 mg after each dialysis run during 5 days.

• CrCl (mL/min) <20: 250 mg once daily for 5 days.
• CrCl (mL/min) 20-39: 250 mg bid for 5 days.

Acute treatment of recurrent mucocutaneous herpes in HIV-infected patients:

500 mg bid for 7 days.Haemodialysis patients: 250 mg after each dialysis run during 7 days.

• CrCl (mL/min) <20: 250 mg once daily for 7 days.
• CrCl (mL/min) 20-39: 500 mg once daily for 7 days.

Acute treatment of recurrent episodes of genital herpes:

125 mg bid for 5 days or 1 g bid for 1 day. Immunocompromised patients: 500 mg bid for 7 days.Haemodialysis patients: 125 mg after each dialysis run during 5 days. Haemodialysis patients (immunocompromised): 250 mg after each dialysis run during 7 days.

• CrCl (mL/min) <20: 125 mg once daily for 5 days.
• CrCl (mL/min) ≥20: 125 mg bid for 5 days.
• CrCl (mL/min) <20: Immunocompromised: 250 mg once daily for 7 days.
• CrCl (mL/min) 20-39: Immunocompromised: 500 mg once daily for 7 days.

Suppression of recurrent episodes of genital herpes:

250 mg bid. Immunocompromised patients: 500 mg bid. Suppressive treatment is interrupted every 6-12 mth for observation.Haemodialysis patients: 125 mg after each dialysis run. Haemodialysis patients (immunocompromised): 250 mg after each dialysis run.

• CrCl (mL/min) 20: 125 mg once daily. Immunocompromised: 250 mg once daily.
• CrCl (mL/min) 20-39: 125 mg bid. Immunocompromised: 500 mg once daily.

Side Effects

Headache, nausea, diarrhoea, fatigue, dizziness, fever, paraesthesia, somnolence, vomiting, constipation, anorexia, abdominal pain, flatulence, dyspepsia; increased serum levels of ALT, alkaline phosphatase, total bilirubin and albumin; pruritus, pharyngitis, sinusitis, injury, generalised pain, rigors, back pain, arthralgia; increased serum phosphate, Na and K levels; abnormal leukocyte counts, purpura, angioedema.

Toxicity

Symptoms of overdose include constipation, diarrhea, dizziness, fatigue, fever, headache, nausea, and vomiting.

Precaution

Renal impairment. Pregnancy and lactation.

Interaction

Reduced renal excretion resulting to increased plasma concentration w/ probenecid. Raloxifen may reduce the formation of penciclovir, the active metabolite of famciclovir.

Food Interaction

• Take with or without food. The absorption is unaffected by food.

Afamcivir Disease Interaction

Major: renal dysfunctionModerate: liver disease

Volume of Distribution

• 1.08±0.17 L/kg [healthy male subjects following a single intravenous dose of penciclovir at 400 mg administered as a 1-hour intravenous infusion]

Elimination Route

77 %

Half Life

10 hours

Clearance

• 36.6 +/- 6.3 L/hr [healthy male]
• 0.48 +/- 0.09 L/hr/kg [healthy male]

Elimination Route

Active tubular secretion contributes to the renal elimination of penciclovir.

Pregnancy & Breastfeeding use

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

Hypersensitivity to famciclovir and penciclovir.

Acute Overdose

Acute renal failure in patients with renal disease. Management: Supportive and symptomatic treatment. May be removed by haemodialysis.

Storage Condition

Store at 20-25°C.

Innovators Monograph

You find simplified version here Afamcivir