Schedule H

Oral

• Tablets: 450 mg (film-coated)

• Oral solution (powder for reconstitution): 50 mg/mL (availability limited to select brands)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. CMV Retinitis in Immunocompromised Patients (HIV/AIDS) — Adults

Induction Phase:

Parameter Recommendation

Starting dose 900 mg orally twice daily with food

Titration Not applicable

Usual maintenance dose Not applicable (induction phase)

Maximum dose 900 mg twice daily

Duration: 21 days

Maintenance Phase:

Parameter Recommendation

Starting dose 900 mg orally once daily with food

Titration Not applicable

Usual maintenance dose 900 mg once daily

Maximum dose 900 mg once daily

Duration: Continue until immune reconstitution (CD4 count >100 cells/µL sustained for ≥3–6 months on ART)

Clinical Notes:

• Dose adjustment mandatory for renal impairment (see Renal Adjustment)

• Must be taken with food to enhance absorption

• Re-induction may be required for relapse

1. CMV Prophylaxis in Solid Organ Transplant Recipients — Adults

Parameter Recommendation

Starting dose 900 mg orally once daily with food

Titration Not applicable

Usual maintenance dose 900 mg once daily

Maximum dose 900 mg once daily

Duration by Transplant Type:

Kidney (D+/R−) 200 days (approximately 6 months)

Kidney (other risk) 100 days (approximately 3 months)

Heart/Lung 100–200 days

Liver 100–200 days

Pancreas 100–200 days

Clinical Notes:

• Initiate within 10 days of transplantation

• Dose adjustment essential for renal impairment

• D+/R− (donor seropositive/recipient seronegative) highest risk category

• Specialist transplant medicine input advised

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

CMV Disease in HSCT Recipients (treatment/preemptive) 900 mg BD (induction) then 900 mg OD (maintenance) Induction 14–21 days; maintenance guided by PCR OFF-LABEL • Specialist only • Indian tertiary HSCT centre practice

CMV Gastrointestinal Disease (esophagitis/colitis) 900 mg BD (induction) 21 days; maintenance if persistent immunosuppression OFF-LABEL • Step-down from IV ganciclovir • Specialist only

CMV Pneumonitis in transplant recipients 900 mg BD (induction) 21 days minimum OFF-LABEL • Specialist only • Often combined with CMV immunoglobulin

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

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

Parameter Recommendation

Starting dose 16 mg/kg orally twice daily with feeds

Titration Not applicable

Usual maintenance dose 16 mg/kg orally twice daily

Maximum dose 900 mg per dose

Duration: 6 months (may initiate with 6-week course and extend based on CNS involvement and response)

Clinical Notes:

• Oral solution (50 mg/mL) preferred for accurate dosing

• Improves hearing and neurodevelopmental outcomes when initiated within first month of life

• IV ganciclovir may be used initially if oral route not feasible

Safety Monitoring:

• Absolute neutrophil count (ANC): weekly for first 6 weeks, then every 2 weeks

• Serum creatinine and LFTs: monthly

• Audiological assessment: at baseline, 6 months, and 12 months

• Neurodevelopmental follow-up

1. CMV Prophylaxis in Paediatric Solid Organ Transplant Recipients

Age/Weight Dose Calculation Maximum Dose

Paediatric SOT Dose (mg) = 7 × BSA × CrCl (modified Schwartz) 900 mg once daily

Duration: 100–200 days depending on organ type and risk stratification

Clinical Notes:

• Specialist paediatric transplant setting only

• Use oral solution for children unable to swallow tablets

• Adjust dose based on renal function

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

CMV Prophylaxis in Paediatric HSCT 7–16 mg/kg once daily (calculated as above) 100 days OFF-LABEL • Specialist only • Indian paediatric HSCT protocols

Acquired CMV disease in immunocompromised children 16 mg/kg BD (induction), then OD (maintenance) Induction 21 days; maintenance until immune reconstitution OFF-LABEL • Specialist only

Age Restrictions:

• Safety established from birth for congenital CMV treatment

• Not recommended in preterm infants <32 weeks gestational age without specialist paediatric infectious diseases input

• Extreme vigilance for myelosuppression in neonates

CrCl (mL/min) Induction Dose Maintenance/Prophylaxis Dose

≥60 900 mg twice daily 900 mg once daily

40–59 450 mg twice daily 450 mg once daily

25–39 450 mg once daily 450 mg every 2 days

10–24 450 mg every 2 days 450 mg twice weekly

<10 Not recommended orally Not recommended orally

Haemodialysis:

• Oral valganciclovir not recommended — use IV ganciclovir under specialist supervision

• If oral unavoidable: 450 mg after each dialysis session (specialist decision only)

Peritoneal Dialysis:

• Not recommended orally — insufficient data

Notes:

• Calculate CrCl (Cockcroft-Gault) before each dose adjustment

• In paediatrics, use modified Schwartz formula for eGFR estimation

• Known hypersensitivity to valganciclovir or ganciclovir

• Severe neutropenia (ANC <500 cells/mm³) unless life-threatening CMV disease

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

• CrCl <10 mL/min (oral formulation not reliable — IV ganciclovir preferred)

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

• Pre-existing bone marrow suppression or cytopenias — increased myelotoxicity risk

• Concurrent myelosuppressive medications (zidovudine, cotrimoxazole, chemotherapy)

• Renal impairment — strict dose adjustment required

• Teratogenic and gonadotoxic — effective contraception mandatory during and after therapy

• Elderly patients — age-related renal decline; calculate CrCl before dosing

• Seizure history or CNS pathology — may lower seizure threshold

• Adequate hydration recommended to reduce crystalluria risk

Parameter Information

Risk Category Contraindicated — teratogenic and embryotoxic in animal studies

Overall Safety Avoid during pregnancy; human data inadequate

Preferred Alternatives No clearly safer alternative for CMV disease; IV ganciclovir under strict specialist supervision if life-threatening

When May Be Used Only for life-threatening or sight-threatening CMV disease where no alternative exists — specialist decision with documented informed consent

Contraception Mandatory — females during therapy and for 30 days after; males during therapy and for 90 days after

Monitoring If inadvertent exposure: detailed fetal anomaly scan; maternal CBC and renal function

Parameter Information

Compatibility Not recommended — potential for serious adverse effects in infant

Expected Milk Levels Unknown in humans; excreted in animal milk

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

Decision Avoid breastfeeding during therapy; if accidental exposure occurs, monitor infant

Infant Monitoring CBC, GI symptoms, feeding difficulties, weight gain

Parameter Recommendation

Starting dose Same as adult dosing, but calculate CrCl before dosing

Titration Slower dose escalation if concurrent illness or frailty

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

Extra monitoring CBC more frequently (weekly during induction); renal function every 1–2 weeks

Risk factors Higher susceptibility to neutropenia; increased risk of confusion with CNS CMV disease; polypharmacy

Interacting Drug Effect & Mechanism Management

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

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

Didanosine Increased didanosine AUC by 50–100%; risk of pancreatitis, peripheral neuropathy, lactic acidosis Monitor for didanosine toxicity; consider dose reduction or alternative

Mycophenolate mofetil Increased levels of both drugs (competition for renal tubular secretion); additive neutropenia Monitor CBC closely; dose adjustment may be needed

Probenecid Decreased renal clearance of ganciclovir; increased ganciclovir levels by ~40% Avoid combination if possible; if used, monitor for toxicity

Interacting Drug Effect Management

Cotrimoxazole Additive bone marrow suppression Monitor CBC closely

Dapsone Additive myelosuppression Monitor CBC

Amphotericin B Additive nephrotoxicity Monitor renal function frequently; consider liposomal formulation

Cyclosporine Additive nephrotoxicity Monitor renal function; adjust valganciclovir dose accordingly

Tacrolimus Additive nephrotoxicity Monitor renal function; adjust valganciclovir dose accordingly

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

Fluoroquinolones Possible CNS stimulation; theoretical seizure risk Monitor especially in elderly

• Neutropenia, leukopenia (most common dose-limiting toxicity)

• Anaemia

• Thrombocytopenia

• Diarrhoea

• Nausea, vomiting

• Headache

• Tremor

• Elevated serum creatinine (mild, transient)

• Pyrexia

Adverse Effect Clinical Action

Severe neutropenia (ANC <500/mm³) / Agranulocytosis Hold therapy; consider G-CSF; resume at reduced dose when ANC >1000/mm³

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

Pancytopenia / Bone marrow aplasia Discontinue permanently; haematology consultation

Seizures Discontinue; neurology consultation; rule out other causes

Acute renal failure Hold therapy; supportive care; consider dialysis

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

Severe hypersensitivity / Anaphylaxis Immediate discontinuation; supportive care

During induction CBC with differential: twice weekly (minimum weekly); renal function: weekly

During maintenance/prophylaxis CBC with differential: every 2 weeks initially, then monthly; renal function: every 2–4 weeks

In transplant recipients CMV viral load (PCR): per institutional protocol (typically weekly during high-risk period)

Long-term use Monthly CBC; periodic renal and hepatic function; ophthalmological examination if CMV retinitis

• Valcyte (Roche)

• Valgan (Cipla)

• Valganciclovir (Generic — multiple manufacturers)

• Virovanc (Intas)

• Valtro (Sun Pharma)

• Cymeval (Hetero)

• Valzyr (Zydus)

Note: Oral solution (50 mg/mL) availability limited — confirm with pharmacy or hospital supply

Note: Not included in NLEM 2022; high-cost drug. Partially covered under organ transplant insurance schemes and government transplant programmes. Significant price variation between brands.

• Valganciclovir provides bioavailability equivalent to IV ganciclovir (~60% converted to ganciclovir) — allows outpatient management and early hospital discharge

• Always calculate CrCl before initiating and adjust dose every 1–2 weeks during treatment — renal function directly determines dosing

• Do not confuse with valacyclovir — completely different spectrum (valganciclovir for CMV; valacyclovir for HSV/VZV)

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

• Strict contraception counselling is mandatory for both males (90 days post-therapy) and females (30 days post-therapy) — teratogenicity risk is significant

• Take with food — improves absorption and reduces GI adverse effects

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

Valganciclovir; antiviral; CMV retinitis; CMV prophylaxis; transplant; congenital CMV; ganciclovir prodrug; myelosuppression; neutropenia; renal-adjusted; HIV opportunistic infection; HSCT

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 Transplant and Paediatric Infectious Diseases Guidelines

• ICMR Transplant Infection Guidelines

• API Textbook of Medicine, 11th Edition

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

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• IAP Guidelines (Paediatric CMV)

• WHO Model Formulary for Children (supportive)

• Indian tertiary hospital protocols (AIIMS, PGI Chandigarh, NIMS)

• Manufacturer Product Inserts (India-licensed)