Schedule H

Intravenous

• IV injection: 500 mg lyophilised powder for reconstitution (as ganciclovir sodium)

• Oral formulation: NOT AVAILABLE in India (Valganciclovir is the oral prodrug available)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Cytomegalovirus (CMV) Retinitis in Immunocompromised Patients — Adults

(HIV/AIDS, post-transplant immunosuppression)

Induction Phase:

Parameter Recommendation

Starting dose 5 mg/kg IV every 12 hours

Titration Not applicable

Usual maintenance dose Not applicable (induction phase)

Maximum dose 5 mg/kg per dose

Duration: 14–21 days

Maintenance Phase:

Parameter Recommendation

Starting dose 5 mg/kg IV once daily (7 days/week) OR 6 mg/kg IV once daily (5 days/week)

Titration Not applicable

Usual maintenance dose 5 mg/kg IV once daily

Maximum dose 6 mg/kg/day

Duration: Until immune reconstitution or lifelong in persistent immunosuppression

Clinical Notes:

• Adjust dose based on renal function (see Renal Adjustment)

• Consider transition to oral valganciclovir for long-term maintenance when clinically stable

• Infuse over minimum 1 hour — avoid rapid IV bolus

1. CMV Prophylaxis in Solid Organ Transplant Recipients — Adults

(When valganciclovir not available or oral route not feasible)

Parameter Recommendation

Starting dose 5 mg/kg IV once daily

Titration Not applicable

Usual maintenance dose 5 mg/kg IV once daily

Maximum dose 5 mg/kg/day

Duration: 7–14 days post-transplant initially; total prophylaxis duration up to 100–200 days depending on organ type and risk stratification

Clinical Notes:

• Specialist use only — transplant medicine/infectious diseases input essential

• Valganciclovir is preferred for prophylaxis in most transplant programmes when oral route available

• Dose adjustment essential for renal impairment

1. CMV Gastrointestinal Disease (Esophagitis/Colitis) in Immunocompromised Patients — Adults

Parameter Recommendation

Starting dose 5 mg/kg IV every 12 hours

Titration Not applicable

Usual maintenance dose 5 mg/kg IV every 12 hours (induction); maintenance may not be required

Maximum dose 5 mg/kg per dose

Duration: 14–21 days (induction); maintenance not always required if immune reconstitution achieved

Clinical Notes:

• Step-down to oral valganciclovir when patient is clinically stable and tolerating oral intake

• Secondary prophylaxis considered in patients with persistent immunosuppression

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

CMV Pneumonitis in transplant recipients 5 mg/kg IV every 12 hours 14–21 days; guided by response OFF-LABEL • Specialist only • Often combined with CMV immunoglobulin • Indian tertiary transplant centre practice

HHV-6 Encephalitis post-HSCT 5 mg/kg IV every 12 hours Minimum 3 weeks OFF-LABEL • Specialist only • Limited evidence; case series

EBV-associated PTLD (adjunctive) 5 mg/kg IV every 12 hours Variable OFF-LABEL • Specialist only • Not standard therapy; investigational

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Symptomatic Congenital CMV Disease with Neurological Involvement — Neonates/Infants

Parameter Recommendation

Starting dose 6 mg/kg IV every 12 hours

Titration Not applicable

Usual maintenance dose 6 mg/kg IV every 12 hours

Maximum dose 6 mg/kg per dose

Duration: 6 weeks

Clinical Notes:

• Oral valganciclovir (16 mg/kg/dose BD) is preferred when oral route feasible

• IV ganciclovir used in neonates unable to tolerate oral medications

• Improves hearing and neurodevelopmental outcomes when initiated early

1. CMV Prophylaxis in High-Risk Paediatric Transplant Recipients

Parameter Recommendation

Starting dose 5 mg/kg IV once daily

Titration Not applicable

Usual maintenance dose 5 mg/kg IV once daily

Maximum dose 5 mg/kg/day

Duration: Variable — determined by organ type, donor/recipient CMV serostatus, and institutional protocol

Clinical Notes:

• Specialist setting only — paediatric transplant/infectious diseases supervision mandatory

• Convert to oral valganciclovir when feasible

1. CMV Disease (Retinitis/GI/Pneumonitis) in Paediatric Immunocompromised Patients

Parameter Recommendation

Starting dose (Induction) 5 mg/kg IV every 12 hours

Titration Not applicable

Usual maintenance dose 5 mg/kg IV once daily

Maximum dose 5 mg/kg per dose

Duration: Induction 14–21 days; maintenance until immune reconstitution

Safety Monitoring:

• Complete blood count with differential: twice weekly during induction, weekly during maintenance

• Renal function: twice weekly initially, then weekly

• Neurodevelopmental follow-up in congenital CMV

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

CMV Pneumonitis 5 mg/kg IV every 12 hours 14–21 days OFF-LABEL • Specialist only

Severe disseminated CMV disease 5 mg/kg IV every 12 hours Guided by response OFF-LABEL • Specialist only

Age Restrictions:

• No absolute lower age limit for IV ganciclovir — used in neonates for congenital CMV

• Use in infants <3 months only under specialist paediatric infectious diseases or neonatology supervision

• Extreme vigilance for myelosuppression in neonates

CrCl (mL/min) Induction Dose Maintenance Dose

≥70 5 mg/kg IV every 12 hours 5 mg/kg IV once daily

50–69 2.5 mg/kg IV every 12 hours 2.5 mg/kg IV once daily

25–49 2.5 mg/kg IV once daily 1.25 mg/kg IV once daily

10–24 1.25 mg/kg IV once daily 0.625 mg/kg IV once daily

<10 (or Haemodialysis) 1.25 mg/kg IV three times weekly (post-dialysis) 0.625 mg/kg IV three times weekly (post-dialysis)

Notes:

• Calculate CrCl before each dose in unstable patients

• Administer post-haemodialysis on dialysis days

• Peritoneal dialysis: Limited data — use haemodialysis dosing with caution

• Known hypersensitivity to ganciclovir or valganciclovir

• Severe neutropenia (<500 cells/mm³) unless life-threatening CMV disease where benefit outweighs risk

• Severe thrombocytopenia (<25,000/mm³) unless life-threatening disease

• Concurrent use with imipenem-cilastatin (significantly increased seizure risk)

• Pre-existing bone marrow suppression or cytopenias — increased risk of severe myelosuppression

• Renal impairment — dose reduction essential; accumulation causes toxicity

• History of seizures or CNS pathology — increased seizure risk

• Concurrent myelosuppressive agents (zidovudine, cotrimoxazole) — additive toxicity

• Reproductive toxicity — teratogenic and spermatotoxic in animal studies; advise contraception

• Phlebitis risk — avoid rapid IV bolus; infuse over minimum 1 hour via large vein

• Carcinogenic potential demonstrated in animal studies

Parameter Information

Risk Category Teratogenic — embryotoxicity and fetotoxicity demonstrated in animals

Overall Safety Avoid unless life-threatening or sight-threatening CMV disease with no safer alternative

Preferred Alternatives No clearly safer alternative for active CMV disease; risk-benefit discussion mandatory

When May Be Used Life-threatening CMV disease (retinitis, pneumonitis, encephalitis) — specialist decision with documented informed consent

Monitoring Fetal anomaly scan; maternal CBC and renal function

Parameter Information

Compatibility Not recommended — potential for serious adverse effects in infant

Expected Milk Levels Unknown; presumed moderate-high based on pharmacokinetics

Preferred Alternatives No suitable alternative for CMV disease; consider temporary cessation of breastfeeding

Decision Avoid breastfeeding during therapy and for at least 1 week after last dose

Infant Monitoring If unavoidable exposure: monitor infant CBC, feeding, growth

Parameter Recommendation

Starting dose Lower end of dosing range; calculate CrCl before dosing

Titration Not applicable

Special considerations Age-related decline in renal function — CrCl calculation mandatory

Extra monitoring CBC more frequently; renal function twice weekly initially

Risk factors Higher susceptibility to myelosuppression and neurotoxicity (confusion, hallucinations); polypharmacy increases interaction risk

Interacting Drug Effect & Mechanism Management

Imipenem-Cilastatin Significantly increased seizure risk (mechanism unclear) CONTRAINDICATED — avoid combination

Zidovudine Additive severe myelosuppression (both cause neutropenia/anaemia) Avoid concurrent use if possible; if essential, monitor CBC very closely

Didanosine Increased didanosine levels (up to 100% increase); pancreatitis and neuropathy risk Monitor for didanosine toxicity; consider dose reduction

Mycophenolate mofetil Increased levels of both drugs (competition for renal tubular secretion) Monitor for neutropenia and GI toxicity; dose adjustment may be needed

Interacting Drug Effect Management

Probenecid Decreased renal clearance of ganciclovir; increased ganciclovir levels Monitor for toxicity; consider dose reduction

Cotrimoxazole Additive bone marrow suppression Monitor CBC closely

Cyclosporine Additive nephrotoxicity Monitor renal function frequently

Tacrolimus Additive nephrotoxicity Monitor renal function frequently

Amphotericin B Additive nephrotoxicity Monitor renal function; consider liposomal formulation

Tenofovir Competition for renal tubular secretion; increased levels of both Monitor renal function and for toxicity

Dapsone Additive myelosuppression Monitor CBC

• Neutropenia (most common dose-limiting toxicity)

• Thrombocytopenia

• Anaemia

• Fever

• Nausea, vomiting, diarrhoea

• Elevated serum creatinine

• Rash

• Headache

• Phlebitis at infusion site

Adverse Effect Clinical Action

Severe neutropenia (<500/mm³) Hold therapy; consider G-CSF; resume at reduced dose when recovered

Severe thrombocytopenia (<25,000/mm³) Hold therapy; platelet transfusion if bleeding; resume cautiously

Pancytopenia / Bone marrow failure Discontinue; haematology consultation

Seizures Discontinue; neurology consultation; rule out other causes

Anaphylaxis / Severe hypersensitivity Immediate discontinuation; supportive care

Retinal detachment (in CMV retinitis) Ophthalmology emergency; may be disease-related or drug-related

Renal failure (in overdose or accumulation) Hold therapy; supportive care; consider dialysis

During induction CBC with differential twice weekly; renal function twice weekly

During maintenance CBC with differential weekly; renal function weekly

Long-term/Chronic use Monthly CBC; periodic renal and hepatic function; ophthalmological examination (for CMV retinitis)

Additional CMV viral load (PCR) to monitor treatment response in transplant/HIV settings

• Cymevene (Roche)

• Cyvograf (Cipla)

• Ganciclovir (Generic — multiple manufacturers)

• Cytogan (Natco)

• Gfy (Micro Labs)

FDCs: Not applicable

Note: Not included in NLEM 2022; high-cost drug. Available in government tertiary care hospitals for transplant and HIV programmes. Significant price variation between brands.

• Always calculate real-time creatinine clearance before each ganciclovir dose — renal function directly determines dosing

• Neutropenia is the dose-limiting toxicity — twice-weekly CBCs during induction are non-negotiable

• Infuse slowly over minimum 1 hour through large-bore cannula to reduce phlebitis risk — never give as rapid IV bolus

• Valganciclovir (oral prodrug) is preferred for outpatient maintenance and prophylaxis — transition when patient is clinically stable

• In transplant patients, monitor CMV viral load (PCR) to guide treatment duration and assess for resistance

• Reproductive counselling essential — effective contraception required during and for 90 days after therapy (both males and females)

Ganciclovir; antiviral; CMV retinitis; cytomegalovirus; transplant prophylaxis; congenital CMV; myelosuppression; neutropenia; renal-adjusted; HIV opportunistic infection; valganciclovir alternative

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NACO ART Guidelines (for CMV in HIV)

• AIIMS Delhi Clinical Protocols

• API Textbook of Medicine, 11th Edition

• Harrison's Principles of Internal Medicine, 21st Edition

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian Transplant Guidelines (ISOT protocols)

• IAP Infectious Diseases Chapter recommendations (paediatric CMV)

• Manufacturer Product Inserts (India-licensed)