Usage
Acyclovir is prescribed for the treatment of infections caused by herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), including:
- Genital herpes: Treatment and prevention of initial and recurrent episodes.
- Chickenpox (varicella): Treatment of chickenpox infections, particularly in individuals at risk of complications.
- Shingles (herpes zoster): Treatment of shingles infections to reduce pain and duration of symptoms.
- Herpes simplex encephalitis: Treatment of this severe and life-threatening infection of the brain.
- Mucocutaneous herpes simplex infections: Treatment of infections affecting the skin and mucous membranes, particularly in immunocompromised patients.
- Ocular HSV infections: Treatment of HSV keratitis.
Pharmacological Classification: Acyclovir belongs to the class of antiviral medications known as synthetic nucleoside analogues.
Mechanism of Action: Acyclovir inhibits viral DNA replication by acting as a competitive substrate for viral DNA polymerase, preventing further viral DNA synthesis and interrupting viral replication.
Alternate Names
- Aciclovir (International Nonproprietary Name)
Brand Names: Zovirax, Avirax, Acivir, etc. (Note: Brand names may vary regionally.)
How It Works
Pharmacodynamics: Acyclovir is selectively phosphorylated by viral thymidine kinase to acyclovir monophosphate, which is further converted to acyclovir triphosphate by cellular enzymes. Acyclovir triphosphate acts as a competitive inhibitor of viral DNA polymerase, leading to chain termination during viral DNA replication. This ultimately stops viral replication.
Pharmacokinetics:
- Absorption: Oral bioavailability is relatively low (15-30%).
- Distribution: Distributes widely, including to the cerebrospinal fluid (CSF).
- Metabolism: Minimally metabolized.
- Elimination: Primarily renally excreted as unchanged drug.
Mode of Action: Acyclovir requires activation by viral thymidine kinase, which makes it selective for infected cells. The active triphosphate form competes with deoxyguanosine triphosphate for incorporation into viral DNA, leading to chain termination and blocking viral replication.
Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: Acyclovir acts through enzyme inhibition of viral DNA polymerase.
Elimination Pathways: Primarily via renal excretion as the unchanged drug.
Dosage
Standard Dosage
Adults:
- Genital herpes (initial): 200 mg orally five times daily for 10 days or 400 mg orally three times daily for 7-10 days.
- Genital herpes (recurrent): 200 mg orally five times daily for 5 days, 400 mg orally three times daily for 5 days, 800 mg orally twice daily for 5 days, or 800 mg orally three times daily for 2 days.
- Chickenpox: 800 mg orally four times daily for 5 days.
- Shingles: 800 mg orally five times daily for 7-10 days.
Children:
- Chickenpox: 20 mg/kg orally (up to 800 mg per dose) four times daily for 5 days.
- Other pediatric doses should be determined by the physician based on weight and indication.
Special Cases:
- Elderly Patients: Dose adjustment may be needed for impaired renal function.
- Patients with Renal Impairment: Dose reduction is required based on creatinine clearance.
- Patients with Hepatic Dysfunction: No dosage adjustments are typically needed.
- Patients with Comorbid Conditions: Considerations should be made for interacting medications.
Clinical Use Cases
Dosing in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergencies should be guided by patient-specific factors and the clinical scenario, often involving IV administration and consultation with an infectious disease specialist. Specific guidelines are not universally established for these situations.
Dosage Adjustments
Dose adjustments are required for patients with renal impairment based on creatinine clearance. See detailed resources for specific adjustments.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Headache
- Dizziness
Rare but Serious Side Effects:
- Kidney problems
- Neurological symptoms (e.g., confusion, hallucinations, seizures)
- Thrombocytopenic purpura/hemolytic uremic syndrome
- Allergic reactions
Long-Term Effects:
Long-term side effects are uncommon, but chronic kidney disease can occur with prolonged use, particularly in patients with pre-existing renal impairment.
Adverse Drug Reactions (ADR):
Serious ADRs like acute renal failure, neurotoxicity, and severe allergic reactions necessitate immediate discontinuation of the drug and supportive care.
Contraindications
- Hypersensitivity to acyclovir or valacyclovir.
Drug Interactions
- Probenecid can decrease renal clearance of acyclovir.
- Nephrotoxic drugs can increase the risk of renal toxicity.
- Other drug interactions may exist and resources like Micromedex should be consulted for specific cases.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B
- Acyclovir crosses the placenta. Use during pregnancy should be weighed against the potential benefits and risks.
- Acyclovir is excreted in breast milk. Breastfeeding is generally considered safe while using acyclovir.
Drug Profile Summary
- Mechanism of Action: Inhibits viral DNA polymerase.
- Side Effects: Nausea, vomiting, headache, renal dysfunction (rare).
- Contraindications: Hypersensitivity.
- Drug Interactions: Probenecid, nephrotoxic drugs.
- Pregnancy & Breastfeeding: Generally safe, but consult guidelines.
- Dosage: See dosage section above.
- Monitoring Parameters: Renal function, especially in high-risk patients.
Popular Combinations
Acyclovir is typically used as a single agent. Combination therapy is not commonly used but may be considered in certain complex or resistant infections, under specialist guidance.
Precautions
- Renal function monitoring in patients with renal impairment.
- Maintain adequate hydration.
- Caution in patients with neurologic disorders.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Acyclovir?
A: Dosage varies by indication, age, and renal function. See the dosage section above for details.
Q2: Can Acyclovir be used during pregnancy?
A: Acyclovir is generally considered safe during pregnancy (Pregnancy Category B). The decision to use acyclovir should be made on a case-by-case basis by weighing the benefits and risks.
Q3: How is Acyclovir administered?
A: Acyclovir can be administered orally (tablets, capsules, suspension), intravenously, or topically (cream, ointment).
Q4: What are the common side effects of Acyclovir?
A: Common side effects include nausea, vomiting, diarrhea, and headache.
Q5: Are there any serious side effects of Acyclovir?
A: Rare but serious side effects include kidney problems, neurologic symptoms, blood disorders, and allergic reactions.
Q6: What are the contraindications to using Acyclovir?
A: The primary contraindication is a known hypersensitivity to acyclovir or valacyclovir.
Q7: Does Acyclovir interact with other medications?
A: Yes, Acyclovir can interact with certain medications like probenecid and nephrotoxic drugs. Consult resources for a comprehensive list of drug interactions.
Q8: Is Acyclovir effective in preventing herpes outbreaks?
A: Acyclovir can be used suppressively to reduce the frequency and severity of herpes outbreaks, but it does not cure the infection.
Q9: What monitoring is required for patients taking Acyclovir?
A: Monitoring of renal function is crucial, especially in patients with pre-existing renal impairment or those receiving high doses of acyclovir.
Q10: Can resistance to Acyclovir develop?
A: Yes, antiviral resistance can develop, particularly in immunocompromised individuals.
