Acyvir

FDA/EMA-Approved Indications

• Genital Herpes Simplex Virus (HSV-2)
• Treatment of initial and recurrent episodes
• Chronic suppressive therapy in patients with frequent recurrences
• Herpes Labialis (HSV-1)
• Treatment of cold sores (perioral herpes)
• Herpes Zoster (Shingles – VZV)
• Treatment of acute episodes, especially within 72 hours of rash onset
• Varicella (Chickenpox – VZV)
• Treatment in adolescents (≥13 years), adults, and immunocompromised children
• Herpes Simplex Encephalitis
• First-line treatment via IV administration
• Neonatal HSV Infection
• Initial treatment and suppressive therapy after IV phase
• HSV Mucocutaneous Infections in Immunocompromised Patients
• Including patients undergoing chemotherapy or organ transplantation

Clinically Accepted Off-Label Uses

• HSV Prophylaxis in bone marrow/solid organ transplant recipients or HIV-positive patients
• Bell’s Palsy, in combination with corticosteroids (when HSV suspected)
• Eczema Herpeticum
• HSV Keratitis, with ophthalmic acyclovir (3% ointment)

A. Oral Tablets / Capsules (200 mg, 400 mg)

• Initial Genital Herpes:
• 200 mg 5 times daily for 10 days, or
• 400 mg 3 times daily for 7–10 days
• Recurrent Genital Herpes:
• 200 mg 5 times daily for 5 days, or
• 800 mg twice daily for 5 days
• Chronic Suppressive Therapy:
• 400 mg twice daily, or
• 200 mg 3–5 times daily
• Herpes Zoster (Shingles):
• 800 mg 5 times daily for 7–10 days
• Varicella (Chickenpox, age ≥13 years):
• 800 mg 4 times daily for 5 days

B. Oral Suspension (200 mg/5 mL)

• Pediatric Varicella (2–12 years):
• 20 mg/kg per dose (max 800 mg) orally 4 times daily for 5 days
• HSV in Immunocompromised Children:
• 20 mg/kg orally 4 times daily (max 800 mg per dose)
• Neonatal HSV Suppressive Therapy (after IV):
• 300 mg/m² orally every 8 hours for up to 6 months

C. Intravenous (IV Injection – 250 mg/vial)

• HSV Encephalitis (Adults):
• 10 mg/kg IV every 8 hours for 14–21 days
• Neonatal HSV:
• 20 mg/kg IV every 8 hours for 14–21 days
• HSV/VZV in Immunocompromised Patients:
• 5–10 mg/kg IV every 8 hours for 7–10 days

Renal Impairment:
Adjust dosing based on creatinine clearance (CrCl). Ensure adequate hydration to prevent nephrotoxicity.

D. Topical Cream (5%)

• Herpes Labialis (Cold Sores):
• Apply thin layer to affected area 5 times daily (every 3–4 hours while awake) for 4 days
• Begin at earliest symptoms (tingling, burning, itching)

E. Ophthalmic Ointment (3%)

• HSV Keratitis:
• Apply a 1 cm ribbon to the lower conjunctival sac 5 times daily until healing, then 3 times daily for 3 additional days

Acyclovir is a guanine nucleoside analog that requires activation by viral thymidine kinase, converting it to acyclovir monophosphate. Host cell kinases further phosphorylate it to acyclovir triphosphate, the active form. This inhibits viral DNA polymerase, incorporating into viral DNA and causing premature chain termination. It selectively targets infected cells, sparing normal host cells and effectively suppressing HSV-1, HSV-2, and VZV replication.

• Absorption:
• Oral bioavailability: 10–20%
• Food has minimal effect
• Distribution:
• Wide tissue distribution, including CNS (CSF ~50% of plasma)
• Crosses placenta and appears in breast milk
• Metabolism:
• Minimal hepatic metabolism
• Excretion:
• Primarily renal (>90% unchanged) via glomerular filtration and tubular secretion
• Half-Life:
• ~2.5–3.3 hours (normal renal function)
• Up to 20 hours in renal failure
• Onset of Action:
• Clinical effects within 24–72 hours

• Pregnancy:
• FDA Category B
• No evidence of fetal harm in animal studies or pregnancy registries
• Commonly used in late pregnancy to reduce HSV transmission risk
• Lactation:
• Excreted in breast milk in low amounts
• Considered safe; no adverse effects reported in breastfed infants

• Class: Antiviral
• Subclass: Nucleoside analog – DNA polymerase inhibitor

• Known hypersensitivity to acyclovir, valacyclovir, or formulation components
• Severe renal impairment without dose adjustment
• History of acyclovir-associated neurotoxicity

• Renal Toxicity:
• Crystalluria and nephropathy may occur, especially with IV use
• Maintain adequate hydration
• Neurotoxicity:
• Especially in elderly or renally impaired: confusion, hallucinations, tremors
• Monitor:
• Renal function (especially in IV use)
• CNS status in high-risk populations
• IV site for local reactions (e.g., phlebitis)

Common

• Gastrointestinal: Nausea, vomiting, diarrhea
• Neurological: Headache, dizziness, fatigue
• Skin: Rash, irritation (topical), injection site reactions (IV)

Serious (Rare)

• Acute kidney injury
• Encephalopathy, seizures
• Stevens-Johnson syndrome
• Thrombotic thrombocytopenic purpura (immunocompromised patients)

Side effects often occur within the first few days and are dose-dependent in IV formulations.

• Probenecid, Cimetidine: Reduce renal clearance → ↑ acyclovir levels
• Nephrotoxic drugs (e.g., cyclosporine, amphotericin B): ↑ risk of renal toxicity
• Zidovudine: May increase neurotoxic effects
• Enzyme involvement: Minimal CYP450 interaction; not significantly metabolized hepatically

• CDC 2021–2024: Reaffirms acyclovir as first-line for HSV-1, HSV-2, and VZV; recommends in pregnancy and immunocompromised patients
• WHO/NICE: Continues to recommend acyclovir for HSV encephalitis, neonatal HSV, and shingles
• No significant FDA or EMA label changes in past 3 years

• Store at 15°C–25°C (59°F–77°F)
• Protect from moisture and light
• Do not freeze
• Shake suspension well before use
• Use reconstituted IV solutions promptly; discard within recommended window