Usage
Famciclovir is prescribed for the treatment of various infections caused by herpes viruses, including:
- Herpes zoster (shingles): Treatment should ideally commence within 48 hours, but no later than 72 hours, of rash onset for optimal efficacy.
- Recurrent genital herpes: Treatment aims to reduce the frequency, duration, and severity of outbreaks.
- Herpes labialis (cold sores): Famciclovir can be used to treat and prevent outbreaks in immunocompetent adults.
- Herpes simplex infections in immunocompromised patients: This includes treatment and suppression of both genital and orolabial herpes.
Pharmacological Classification: Famciclovir is an antiviral medication.
Mechanism of Action: Famciclovir is a prodrug of penciclovir. After oral administration, famciclovir is rapidly converted to penciclovir. Penciclovir then inhibits viral DNA polymerase, thereby blocking viral replication.
Alternate Names
How It Works
Pharmacodynamics: Famciclovir’s antiviral activity stems from its active metabolite, penciclovir. Penciclovir is a guanosine analog that, once inside infected cells, is phosphorylated to penciclovir triphosphate. Penciclovir triphosphate competitively inhibits herpesvirus DNA polymerase, preventing viral DNA synthesis and replication.
Pharmacokinetics:
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Absorption: Famciclovir is well-absorbed orally and rapidly converted to penciclovir. The bioavailability of penciclovir from famciclovir is approximately 77%. Food does not significantly affect absorption.
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Metabolism: Famciclovir is rapidly metabolized in the gut and liver to penciclovir.
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Elimination: Penciclovir is primarily eliminated by the kidneys, with approximately 75% of the dose excreted unchanged in the urine.
Mode of Action: Penciclovir triphosphate specifically targets and inhibits herpesvirus DNA polymerase. This targeted action ensures selective toxicity towards virus-infected cells with minimal impact on host cells.
Elimination Pathways: Primarily renal excretion of unchanged penciclovir. Minor hepatic metabolism also contributes to elimination.
Dosage
Standard Dosage
Adults:
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Herpes Zoster: 500 mg every 8 hours for 7 days. Treatment should be initiated within 72 hours of rash onset.
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Recurrent Genital Herpes:
- 125 mg twice daily for 5 days
- 500 mg stat, followed by 250 mg every 12 hours for two more doses (total of three doses)
- 1000 mg twice daily for 1 day
- Suppression: 250 mg twice daily for up to 12 months
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Herpes Labialis (Cold Sores): 1500 mg as a single dose. Alternative dosing includes 750 mg twice on day 1 or 500 mg statim followed by 250 mg twice over the next day.
Children:
The safety and efficacy of famciclovir have not been established in children under 18 for most indications, except for a weight-based pediatric formulation tested in children 1-12 years old with HSV or VZV infection. General usage in children is not recommended.
Special Cases:
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Elderly Patients: Dosage adjustments are generally unnecessary unless renal function is impaired.
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Patients with Renal Impairment: Dosage adjustments are essential. See “Dosage Adjustments” section.
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Patients with Hepatic Dysfunction: No dosage adjustments are necessary for patients with well-compensated hepatic impairment.
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Patients with Comorbid Conditions: No specific dosage recommendations are available for patients with comorbid conditions like diabetes or cardiovascular disease, except regarding renal function.
Clinical Use Cases
Famciclovir is not indicated for use in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest. Its use is limited to the herpesvirus infections mentioned previously.
Dosage Adjustments
Renal Impairment: Dosage modifications are based on creatinine clearance:
- CrCl 30-50 mL/min: Reduce dose by 50%.
- CrCl 10-29 mL/min: Reduce dose by 75%.
- CrCl < 10 mL/min or Hemodialysis: Administer full dose post-hemodialysis or every 48 hours for non-herpes labialis indications.
Side Effects
Common Side Effects:
Rare but Serious Side Effects:
- Hallucinations
- Confusion
- Seizures
- Thrombocytopenia
- Anaphylactic shock
- Cholestatic jaundice
Long-Term Effects:
No specific long-term side effects have been consistently reported.
Adverse Drug Reactions (ADR):
Serious ADRs include anaphylaxis, thrombocytopenia, and severe hepatic dysfunction.
Contraindications
- Hypersensitivity to famciclovir or penciclovir.
- Hypersensitivity to any component of the formulation.
Drug Interactions
- Probenecid increases penciclovir plasma levels.
- Raloxifene may reduce famciclovir efficacy.
- Digoxin levels can increase with famciclovir.
- Live attenuated vaccines (e.g., varicella, zoster) should be avoided during famciclovir use.
- Talimogene laherparepvec’s efficacy is reduced by famciclovir.
Pregnancy and Breastfeeding
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Pregnancy: Famciclovir is a pregnancy category B drug. Use only if the potential benefits outweigh the risks.
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Breastfeeding: Famciclovir is excreted in breast milk. Use with caution, considering potential neonatal effects. Discontinuation of breastfeeding may be considered.
Drug Profile Summary
- Mechanism of Action: Inhibits herpesvirus DNA polymerase.
- Side Effects: Headache, nausea (common); hallucinations, confusion, seizures, thrombocytopenia, anaphylactic shock, cholestatic jaundice (rare but serious)
- Contraindications: Hypersensitivity to famciclovir, penciclovir, or formulation components.
- Drug Interactions: Probenecid, raloxifene, digoxin, live attenuated vaccines, talimogene laherparepvec.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: Refer to “Dosage” section.
- Monitoring Parameters: Renal function (especially in patients with renal impairment).
Popular Combinations:
Famciclovir is not typically used in combination with other antiviral agents for the treatment of herpesvirus infections.
Precautions
- Renal function should be monitored in patients with renal impairment.
- Consider alternative antiviral agents for pregnant and breastfeeding women.
- Close monitoring for hypersensitivity reactions is advised.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Famciclovir?
A: Dosage depends on the indication and patient-specific factors. Refer to the “Dosage” section for detailed information.
Q2: Can Famciclovir cure herpes infections?
A: No, famciclovir does not cure herpes infections. It reduces the frequency, duration, and severity of outbreaks, but the virus remains latent in the body.
Q3: What are the common side effects of Famciclovir?
A: The most commonly reported side effects are headache and nausea.
Q4: Is Famciclovir safe for use during pregnancy?
A: Famciclovir is a pregnancy category B drug. Its use during pregnancy should be carefully considered, weighing the potential benefits against potential risks to the fetus.
Q5: How should Famciclovir be administered in patients with renal impairment?
A: Dosage adjustments based on creatinine clearance are crucial in patients with renal impairment. See “Dosage Adjustments” section.
Q6: Can Famciclovir interact with other medications I am taking?
A: Yes, potential drug interactions exist. See “Drug Interactions” section. Inform your doctor about all medications you are currently taking.
Q7: Can Famciclovir be used to treat chickenpox?
A: No, famciclovir is not indicated for the treatment of chickenpox.
Q8: What should I do if I miss a dose of Famciclovir?
A: Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and return to your regular dosing schedule. Do not double the dose to catch up.
A: Seek immediate medical attention if you experience signs of a severe allergic reaction (difficulty breathing, swelling of face or throat) or any other severe side effects like hallucinations, confusion, or seizures.
