Makindo Medical Notes

Related Subjects: |Herpes Varicella-Zoster (Shingles) Infection |Chickenpox Varicella Infection |Varicella Cerebral Vasculopathy |Herpes Viruses |Herpes Zoster Ophthalmicus (HZO) Shingles |MonkeyPox |Mumps |Measles |Rubella (German Measles) |Epstein-Barr Virus infection |Cytomegalovirus (CMV) infections |CMV retinitis infections |Toxoplasmosis

Cytomegalovirus (CMV) infection is particularly important in immunocompromised patients (especially when CD4 < 100 in HIV). ⚠️ Severe CMV disease requires IV Ganciclovir or Foscarnet — NOT aciclovir, as CMV lacks the viral thymidine kinase required for aciclovir activation.

📖 About

Always check the BNF link here for the most up-to-date guidance.

• Ganciclovir (IV) remains the gold standard for CMV treatment.
• Valganciclovir is the oral prodrug, rapidly converted to ganciclovir, widely used for treatment and prophylaxis in transplant and HIV medicine.

⚡ Mechanism of Action

• Structural analogue of guanosine (a nucleoside).
• Phosphorylated by CMV UL97 kinase → then converted to active ganciclovir triphosphate.
• This acts as a competitive inhibitor of viral DNA polymerase, terminating viral DNA synthesis.
• Less selective than aciclovir → more toxic to host cells.

💊 Indications & Dosing (Adults)

• CMV Disease (e.g., colitis, pneumonitis, retinitis): IV ganciclovir 5 mg/kg every 12 hours for 14–21 days (or until recovery).
• CMV Retinitis: Valganciclovir 900 mg PO twice daily for 21 days → then 900 mg once daily (maintenance).
• Post-Transplant Prophylaxis: Valganciclovir 900 mg once daily for 100–200 days depending on organ transplanted (e.g., 200 days for renal).
• 💡 Oral valganciclovir (900 mg BD) ≈ IV ganciclovir (5 mg/kg BD) in bioequivalence.

🔄 Interactions

• ⚠️ Myelosuppressive drugs (e.g., zidovudine, co-trimoxazole) → ↑ risk of bone marrow toxicity.
• ❗ Imipenem–cilastatin + ganciclovir → may precipitate seizures.
• Probenecid → ↑ ganciclovir concentration (renal clearance interaction).
• Always review full ARV and transplant drug list for overlapping toxicities.

⚠️ Cautions

• Do NOT give as IV bolus → risk of severe toxicity. Must be infused over ≥1 hour.
• Adjust dose in renal impairment (eGFR-based dosing essential).
• Women of childbearing potential must use contraception; ganciclovir is teratogenic and mutagenic in animal studies.
• Occupational handling requires care → considered cytotoxic.

🚫 Contraindications

• Refer to BNF for full list.
• Absolute: Hypersensitivity to ganciclovir/valganciclovir.
• Relative: Severe bone marrow suppression or renal failure without capacity for monitoring/dose adjustment.

💥 Side Effects

• 🩸 Myelosuppression: Neutropenia, anaemia, thrombocytopenia (most dose-limiting).
• 🌡️ Fever, chills, diarrhoea, malaise, weight loss.
• 🧠 CNS: Headache, dizziness, confusion, seizures (rare).
• 👁️ Ocular: Retinal detachment reported in CMV retinitis patients.
• GI upset: Nausea, vomiting, abdominal pain.

🧾 Key Clinical Pearls

• Always check baseline FBC, U&E before starting therapy and monitor regularly.
• Consider growth factor support (e.g., G-CSF) if neutropenia develops but treatment must continue.
• IV foscarnet is used if resistance (UL97 mutation) or intolerance to ganciclovir occurs.
• Aciclovir is not effective for CMV because CMV lacks thymidine kinase.