Schedule H

Oral, Intravenous (IV), Topical

• Tablets: 200 mg, 400 mg, 800 mg

• Oral suspension: 200 mg/5 mL

• Injection (lyophilized powder for reconstitution): 250 mg, 500 mg, 1 g vials

• Topical cream/ointment: 5% w/w

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Herpes Simplex Virus (HSV) Infections — Genital and Orolabial

Primary Genital/Orolabial HSV (First Episode):

Parameter Dose Clinical Notes

Starting dose 400 mg orally three times daily OR 200 mg orally five times daily Initiate within 72 hours of symptom onset

Titration Not applicable Fixed dosing

Usual maintenance dose 400 mg three times daily

Maximum dose 200 mg five times daily (1000 mg/day)

Duration 7–10 days Extend to 14 days if healing incomplete

Recurrent Genital HSV (Episodic Treatment):

Parameter Dose Clinical Notes

Starting dose 800 mg orally twice daily OR 400 mg three times daily Start at prodrome or within 24 hours of lesion onset

Titration Not applicable

Usual maintenance dose 800 mg twice daily

Maximum dose 800 mg twice daily

Duration 5 days Patient-initiated therapy effective

Suppressive Therapy (≥6 recurrences per year):

Parameter Dose Clinical Notes

Starting dose 400 mg orally twice daily

Titration Not applicable

Usual maintenance dose 400 mg twice daily

Maximum dose 400 mg twice daily

Duration Long-term; reassess need every 6–12 months May reduce to 200 mg twice daily if stable

Severe/Disseminated HSV or Immunocompromised:

Parameter Dose Clinical Notes

Starting dose 5–10 mg/kg IV every 8 hours Based on ideal body weight (IBW)

Titration Not applicable

Usual maintenance dose 5–10 mg/kg IV every 8 hours

Maximum dose 10 mg/kg IV every 8 hours

Duration 7–14 days Switch to oral when lesions begin crusting

1. Herpes Zoster (Shingles)

Immunocompetent Adults:

Parameter Dose Clinical Notes

Starting dose 800 mg orally five times daily Start within 72 hours of rash onset for maximum benefit

Titration Not applicable

Usual maintenance dose 800 mg five times daily

Maximum dose 4000 mg/day (800 mg × 5)

Duration 7–10 days

Immunocompromised / Disseminated / Ophthalmic Zoster:

Parameter Dose Clinical Notes

Starting dose 10 mg/kg IV every 8 hours Based on IBW; infuse over 1 hour minimum

Titration Not applicable

Usual maintenance dose 10 mg/kg IV every 8 hours

Maximum dose 10 mg/kg every 8 hours

Duration 7–10 days Ophthalmology consultation mandatory for HZO

1. Varicella (Chickenpox)

Adults and Adolescents (≥13 years):

Parameter Dose Clinical Notes

Starting dose 800 mg orally five times daily Start within 24 hours of rash onset

Titration Not applicable

Usual maintenance dose 800 mg five times daily

Maximum dose 4000 mg/day

Duration 5–7 days

Immunocompromised or Severe Varicella:

Parameter Dose Clinical Notes

Starting dose 10 mg/kg IV every 8 hours

Titration Not applicable

Usual maintenance dose 10 mg/kg IV every 8 hours

Maximum dose 10 mg/kg every 8 hours

Duration 7–10 days Until no new lesions for 48 hours

1. HSV Encephalitis

Parameter Dose Clinical Notes

Starting dose 10 mg/kg IV every 8 hours Do NOT delay empiric therapy pending CSF PCR results

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

1. Neonatal HSV Infection (CNS/Disseminated/SEM Disease)

Parameter Dose Comments

Starting dose 20 mg/kg IV every 8 hours Based on actual body weight

Titration Not applicable

Usual maintenance dose 20 mg/kg IV every 8 hours

Maximum dose 20 mg/kg every 8 hours

Duration (SEM) 14 days Skin, Eye, Mouth disease

Duration (CNS/Disseminated) 21 days Repeat CSF PCR before stopping

Suppressive Therapy Post-Treatment:

• Oral: 300 mg/m²/dose three times daily for 6 months

• Requires absolute neutrophil count monitoring

• Specialist supervision mandatory

1. HSV Gingivostomatitis / Mucocutaneous HSV (>3 months of age)

Weight/Age Dose Frequency Duration

<40 kg 20 mg/kg/dose (max 400 mg) Three times daily 5–7 days

≥40 kg 400 mg Three times daily 5–7 days

Dosing Summary:

• Starting dose: 20 mg/kg/dose orally three times daily

• Titration: Not applicable

• Usual maintenance dose: 20 mg/kg/dose three times daily

• Maximum dose: 400 mg per dose; 1200 mg/day

1. Varicella (Chickenpox) — High-Risk Children Only

Age Dose Frequency Duration Comments

2–12 years 20 mg/kg/dose (max 800 mg) Four times daily 5 days Start within 24 hours of rash

12 years 800 mg Five times daily 5 days Adult dosing

Indications for treatment (not routine in uncomplicated varicella):

• Immunocompromised children

• Chronic skin or pulmonary disease

• On chronic salicylate therapy

• Receiving intermittent corticosteroids

• Secondary household cases (more severe)

1. Herpes Zoster in Children

Parameter Dose Comments

Immunocompetent 20 mg/kg/dose orally four times daily (max 800 mg/dose) 7 days

Immunocompromised 10 mg/kg IV every 8 hours 7–10 days

1. HSV Encephalitis in Children

Parameter Dose Comments

Starting dose 10–20 mg/kg IV every 8 hours Higher dose (20 mg/kg) for neonates and young infants

Titration Not applicable

Usual maintenance dose 10–20 mg/kg IV every 8 hours

Maximum dose 20 mg/kg every 8 hours

Duration 14–21 days Repeat CSF HSV PCR recommended before discontinuation

Secondary Indications — Paediatrics (Off-label, if any)

Varicella Prophylaxis Post-Exposure (High-Risk) — OFF-LABEL

Parameter Details

Indication Post-exposure prophylaxis in immunocompromised children when VZIG unavailable

Dose 20 mg/kg/dose orally four times daily (max 800 mg/dose)

Duration 7 days; start 7–10 days post-exposure

Specialist only Yes — Paediatric infectious diseases

Evidence basis Limited data; used in Indian tertiary care when VZIG unavailable

Not recommended below 3 months of age for oral therapy except for HSV under specialist supervision. Neonatal HSV requires IV therapy.

Oral Therapy:

25 800 mg five times daily No adjustment

10–25 800 mg every 8 hours Reduce frequency

<10 800 mg every 12 hours

10 400 mg three times daily No adjustment

<10 200 mg every 12 hours

Intravenous Therapy:

50 No adjustment; standard dose every 8 hours

25–50 Standard dose every 12 hours

10–25 Standard dose every 24 hours

<10 50% of standard dose every 24 hours

Haemodialysis Standard dose after each dialysis session (acyclovir is dialyzable)

CAPD 50% of standard dose every 24 hours

CRRT Standard dose every 12–24 hours; adjust per effluent rate

Key Point: Ensure adequate hydration (≥1 L oral fluids or IV hydration) with all IV acyclovir to prevent crystalline nephropathy. Infuse IV acyclovir over minimum 1 hour.

Acyclovir is primarily renally excreted; hepatic impairment alone does not significantly affect pharmacokinetics.

• Known hypersensitivity to acyclovir or valacyclovir

• Known hypersensitivity to any component of the formulation

• Renal impairment — increased risk of neurotoxicity and crystalline nephropathy; dose adjustment required

• Dehydration or hypovolaemia — ensure adequate hydration, especially with IV use

• Elderly patients — reduced renal function; increased CNS toxicity risk

• Pre-existing neurological conditions — may be exacerbated

• Concurrent nephrotoxic drugs — increased renal toxicity risk

• Thrombotic thrombocytopenic purpura/Haemolytic uraemic syndrome (TTP/HUS) history — rare reports with high-dose therapy

• Immunocompromised patients on prolonged therapy — risk of acyclovir-resistant HSV/VZV strains

Aspect Recommendation

Risk category Generally considered safe; extensive human pregnancy data without increased teratogenicity

First trimester Use if clearly indicated; no confirmed teratogenic risk but specialist consultation recommended

Second/Third trimester Safe; commonly used for genital herpes suppression from 36 weeks to prevent neonatal transmission

Use in pregnancy Preferred antiviral for HSV/VZV in pregnancy; IV acyclovir preferred over valacyclovir for severe disease

Preferred alternatives None required; acyclovir is first-line

Monitoring Maternal renal function and hydration; routine fetal monitoring

Aspect Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low; infant receives <1% of maternal dose

Preferred alternatives None required; acyclovir is preferred

Recommendations Continue breastfeeding during maternal acyclovir therapy

Infant monitoring Observe for GI upset, rash (rare); no specific monitoring required

Aspect Recommendation

Starting dose Start at lower end of dose range; calculate renal function before dosing

Titration Not applicable for acute therapy; adjust based on renal function

Special considerations Age-related decline in renal function often underestimated by serum creatinine; use Cockcroft-Gault or eGFR

Extra risks Increased CNS toxicity (confusion, agitation, hallucinations, tremor, myoclonus); crystalline nephropathy; dehydration

Monitoring Baseline and periodic renal function; neurological status; hydration status

Drug Interaction Management

Probenecid Inhibits renal tubular secretion of acyclovir → increased acyclovir levels (up to 40%) Monitor for toxicity; consider dose reduction if prolonged concurrent use

Nephrotoxic drugs (amphotericin B, aminoglycosides, cyclosporine, tacrolimus, IV contrast) Additive nephrotoxicity Avoid concurrent IV use if possible; ensure adequate hydration; monitor renal function daily

Mycophenolate mofetil Altered clearance of both drugs; increased levels of both Use with caution in transplant patients; monitor for toxicity

Theophylline Possible increased theophylline levels Monitor theophylline levels if concurrent use

Drug Interaction Management

Zidovudine Additive CNS toxicity (drowsiness, lethargy) Monitor neurological status in HIV patients

Lithium Possible increased lithium levels Monitor lithium levels

Methotrexate Theoretical interaction via renal excretion Monitor renal function

Valproic acid May reduce valproic acid levels (limited data) Monitor valproic acid levels if clinically indicated

Cimetidine Reduced renal clearance of acyclovir Generally not clinically significant; monitor

Oral:

• Nausea, vomiting

• Diarrhoea

• Headache

• Malaise, fatigue

• Abdominal pain

Intravenous:

• Injection site reactions (phlebitis, pain)

• Nausea, vomiting

• Elevated serum creatinine (usually reversible)

• Headache

Topical:

• Mild burning, stinging at application site

• Dry skin, flaking

• Pruritus

Adverse Effect Clinical Notes

Crystalline nephropathy / Acute kidney injury Risk with rapid IV infusion, dehydration, high doses; ensure hydration and slow infusion (≥1 hour); usually reversible

Neurotoxicity (Acyclovir encephalopathy) Confusion, agitation, hallucinations, tremor, myoclonus, seizures; higher risk in renal impairment, elderly, IV use; discontinue and evaluate

Thrombotic thrombocytopenic purpura / Haemolytic uraemic syndrome (TTP/HUS) Rare; reported with high-dose IV therapy in immunocompromised; discontinue immediately

Stevens-Johnson Syndrome / TEN Very rare; discontinue immediately if mucocutaneous lesions develop

Severe hypersensitivity / Anaphylaxis Rare; discontinue immediately

Bone marrow suppression Rare; leukopenia, thrombocytopenia with prolonged therapy

Action: Discontinue acyclovir and evaluate if neurological symptoms, significant renal function decline, or severe hypersensitivity occurs.

During IV therapy Serum creatinine every 48–72 hours; urine output; neurological assessment daily; injection site inspection

Prolonged oral therapy (suppressive) Renal function every 3–6 months; reassess need for suppression every 6–12 months

Neonatal therapy CBC with differential (for neutropenia) weekly; renal function twice weekly

High-dose/Immunocompromised More frequent renal function monitoring; CBC weekly

• Zovirax (GSK) — originator brand

• Acivir (Cipla)

• Herpex (Torrent)

• Cyclovir (Ranbaxy/Sun Pharma)

• Acyclostad (Stada/Lupin)

• Lovir (Glenmark)

• Ocuvir (FDC)

• Acylex (Alkem)

• Multiple generic manufacturers

Note: No significant FDCs available; all formulations are single-agent.

• Listed in NLEM 2022 (tablets 200 mg, 400 mg; injection)

• Under DPCO/NPPA price control for scheduled formulations

• Available through government supply at public health facilities

1. Timing is critical — acyclovir efficacy is maximized when started within 72 hours of rash onset for zoster, 24 hours for varicella, and as early as possible for HSV encephalitis. Do not delay IV acyclovir pending CSF PCR in suspected HSV encephalitis.

1. Use ideal body weight for IV dosing — in obese patients, calculate IV acyclovir dose using ideal body weight (IBW) to avoid overdose and toxicity; acyclovir distributes into lean body mass.

1. Hydration prevents nephrotoxicity — crystalluria and nephropathy are preventable; ensure ≥1–2 L oral fluids daily or adequate IV hydration; infuse IV acyclovir over minimum 1 hour (preferably 1–2 hours).

1. Valacyclovir offers better bioavailability — for oral therapy requiring high doses (e.g., zoster), consider valacyclovir as prodrug with 3–5× better bioavailability; acyclovir oral bioavailability is only 15–20%.

1. Not effective against CMV or EBV — acyclovir has poor activity against cytomegalovirus; do not use for CMV disease (use ganciclovir/valganciclovir instead).

1. Reassess suppressive therapy annually — for patients on long-term genital herpes suppression, reassess need every 6–12 months; many patients can discontinue after 1 year with reduced recurrence frequency.

1. Topical acyclovir has limited efficacy — oral therapy is significantly more effective for genital and severe orolabial herpes; topical use is minimally beneficial and should not replace systemic therapy for significant disease.

acyclovir; antiviral; HSV; herpes simplex; herpes zoster; varicella; chickenpox; shingles; HSV encephalitis; neonatal HSV; pregnancy-safe; NLEM India; renal-adjust; Schedule H

RxIndia v1.0 — 29 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• NLEM 2022

• API Textbook of Medicine

• AIIMS Adult Treatment Protocols

• IAP Guidelines for Paediatric Antiviral Use

• WHO Model List of Essential Medicines (supportive)

• Harrison's Principles of Internal Medicine (supportive)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)