Ganciclovir
Ganciclovir
Generic Name
Ganciclovir
Mechanism
* Phosphorylation by the CMV-encoded UL97 kinase to ganciclovir monophosphate, then by cellular kinases to the active triphosphate.
* The triphosphate competitively inhibits viral DNA polymerase, blocking DNA chain elongation.
* When incorporated into the nascent viral DNA, it terminates synthesis and induces lethal mutations.
Pharmacokinetics
* Absorption: Oral bioavailability ranges from 15 % to 40 % (dose‑dependent).
* Distribution: Widely distributed; CNS penetration is limited.
* Metabolism: No major hepatic metabolism; primarily renal excretion.
* Half‑life: ~2.4 h (IV); ~12 h (oral).
* Special populations: Renal dose adjustment required; dose reduction or discontinuation if CrCl < 30 mL/min.
Indications
* CMV retinitis in patients with AIDS.
* CMV disease (retinitis, pneumonia, esophagitis, visceral disease) in solid‑organ or hematopoietic stem‑cell transplant recipients.
* Prophylaxis of CMV disease in high‑risk transplant patients (e.g., CMV‑seropositive recipients of CMV‑seronegative grafts).
Contraindications
* Contraindicated in patients with severe neutropenia, thrombocytopenia, or bone‑marrow suppression (ANC < 1000/µL, platelets < 50 000/µL).
* Warning: Nephrotoxicity is uncommon but can occur; monitor renal function.
* Caution: Ocular toxicity (retinal pigment changes) with prolonged therapy.
* Avoid if hypersensitive to any component.
Dosing
| Form | Dose | Frequency | Route | Notes |
| IV | 2 mg/kg per 12 h infusion | q12 h | 30‑60 min infusion | Initiate 1 h before first IV dose. |
| Oral | 5 mg/kg per 12 h (≈15 mg/kg total daily) | q12 h | B.i.d. | Dose split; adjust for renal function. |
| Oral | 10 mg/kg per 12 h (≈30 mg/kg total daily) | q12 h | B.i.d. | Used for severe disease; higher Cmax but may increase myelosuppression. |
*Subcutaneous route*: 22 mg/mL in 5 mL syringe, q12 h (alternative when IV not feasible).
Adverse Effects
* Common:
* Myelosuppression – neutropenia, anemia, thrombocytopenia (≤ 15 %).
* Nausea, vomiting, diarrhea.
* Headache, dizziness.
* Serious:
* Severe bone‑marrow suppression (pancytopenia).
* Renal dysfunction (rare).
* Retinal pigmentary changes (rare, with long‑term use).
* Hypersensitivity reactions (rare).
Monitoring
* Baseline: CBC with differential, serum creatinine, BUN.
* During therapy:
* CBC twice weekly for 4 weeks, then weekly.
* Renal function twice weekly.
* Ophthalmologic exam every 2–3 months during prolonged therapy.
* Therapeutic drug monitoring: Not routinely required but may be considered in special cases (e.g., undetectable viral load despite therapy).
Clinical Pearls
* Pulsed infusion strategy lowers peak plasma concentration, sparing the bone marrow without compromising efficacy.
* UL97 kinase activity is essential for activation; strains lacking this enzyme (e.g., UL97 mutations) confer resistance—but this is rare.
* Add-on therapy: Whenever feasible, combine with foscarnet for multidrug‑resistant CMV to prevent selection of resistant mutants.
* Renal adjustment: Every 10 mL/min of CrCl ↑, extend the dosing interval by 6 h (e.g., 2 mg/kg q18 h).
* Rebound CMV activity can occur after discontinuation—consider extending prophylaxis until at least 6 months post‑transplant or until immune reconstitution (CD4⁺ > 200 cells/µL) in AIDS patients.
* Subcutaneous route is a viable alternative when IV access is difficult; ensure drug is mixed with normal saline at 0.5 mg/mL dilution to avoid extravasation injury.
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• *This drug card is intended as a quick reference; always consult current guidelines, package insert, and institutional protocols before prescribing.*