Usage
- Ganciclovir is primarily used to treat and prevent cytomegalovirus (CMV) infections in immunocompromised individuals, such as those with AIDS, organ transplant recipients, or those undergoing chemotherapy. It is particularly crucial in preventing CMV retinitis, a sight-threatening inflammation of the retina.
- Pharmacological Classification: Antiviral (specifically, a synthetic guanosine analog)
- Mechanism of Action: Ganciclovir inhibits viral DNA replication by interfering with viral DNA polymerase. It acts as a “false” building block incorporated into viral DNA, thus halting further viral replication.
Alternate Names
- Ganciclovir sodium
- Brand Names: Cytovene®, Cymevene, Ganciclovir SXP
How It Works
- Pharmacodynamics: Ganciclovir is a synthetic nucleoside analog that, once phosphorylated to its active triphosphate form within infected cells, competes with deoxyguanosine triphosphate for incorporation into viral DNA. This incorporation results in chain termination, thereby inhibiting viral DNA polymerase and halting CMV replication.
- Pharmacokinetics:
- Absorption: Bioavailability of oral ganciclovir is low (around 5%), while IV administration provides 100% bioavailability. The prodrug Valganciclovir has a significantly higher oral bioavailability.
- Metabolism: Ganciclovir is minimally metabolized.
- Elimination: Primarily via renal excretion (over 90%), with a half-life of 2-4 hours in individuals with normal renal function. Hemodialysis reduces ganciclovir plasma concentrations.
- Mode of Action: Ganciclovir competitively inhibits the binding of deoxyguanosine triphosphate to CMV DNA polymerase, terminating viral DNA elongation.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: The primary mechanism is enzyme inhibition (viral DNA polymerase).
- Elimination pathways: Predominantly renal excretion.
Dosage
Standard Dosage
Adults:
- Induction: 5 mg/kg IV infusion over 1 hour every 12 hours for 14-21 days for CMV retinitis, and for 7-14 days for CMV prophylaxis in transplant recipients.
- Maintenance: 5 mg/kg IV infusion over 1 hour once daily or 6 mg/kg once daily for 5 days a week. Maintenance therapy duration depends on individual clinical situation and risk of relapse.
Children:
- Pediatric dosing should be determined by the physician and adjusted based on weight, renal function, and the severity of infection. Congenital CMV often requires prolonged treatment, sometimes up to 6 months.
- Pediatric safety considerations include close monitoring of hematological parameters due to potential bone marrow suppression.
Special Cases:
- Elderly Patients: Dose adjustments are based on renal function, as creatinine clearance typically declines with age.
- Patients with Renal Impairment: Dose reductions are necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: No dose adjustment is typically needed.
- Patients with Comorbid Conditions: For patients with comorbidities, particularly those receiving myelosuppressive or nephrotoxic drugs, careful monitoring of blood counts and renal function is essential.
Clinical Use Cases
- The primary clinical uses of IV ganciclovir include treatment of CMV retinitis, CMV disease in other organ systems, and prevention of CMV disease in transplant recipients. Dosing generally follows the standard recommendations outlined above.
- Intubation, surgical procedures, mechanical ventilation, and ICU use: Ganciclovir might be administered in these settings if CMV infection is suspected or documented.
- Emergency Situations: In emergency situations associated with CMV infections (though these are uncommon), ganciclovir might be administered following standard guidelines.
Dosage Adjustments
- Dose modifications are crucial in patients with renal impairment and those with hematological toxicity.
- Consider drug interactions (e.g., with imipenem-cilastatin, didanosine, zidovudine, probenecid, mycophenolate mofetil) which necessitate close monitoring or dosage adjustments.
Side Effects
Common Side Effects
- Fever, diarrhea, nausea, vomiting, headache, anemia, neutropenia, thrombocytopenia, leukopenia, abdominal pain, anorexia, asthenia, cough, dyspnea, elevated creatinine.
Rare but Serious Side Effects
- Seizures, severe bone marrow suppression (pancytopenia), severe allergic reactions (anaphylaxis), confusion, hallucinations, psychosis, retinal detachment.
Long-Term Effects
- Infertility (due to gonadal toxicity), potential carcinogenicity.
Adverse Drug Reactions (ADR)
- Myelosuppression, nephrotoxicity.
Contraindications
- Hypersensitivity to ganciclovir, valganciclovir, or acyclovir.
- Severe neutropenia or thrombocytopenia.
Drug Interactions
- Imipenem-cilastatin (increased risk of seizures)
- Didanosine (increased didanosine toxicity)
- Probenecid (decreased ganciclovir clearance)
- Mycophenolate mofetil (increased myelosuppression and nephrotoxicity)
- Zidovudine (increased myelosuppression)
- Other nephrotoxic or myelosuppressive agents
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Ganciclovir is contraindicated in pregnancy unless the benefits outweigh the substantial risks to the fetus (teratogenic). It causes birth defects in animal models. Effective contraception is essential.
- Breastfeeding: Ganciclovir should be avoided during breastfeeding due to the potential for serious adverse effects in the infant. Breastfeeding can be resumed approximately 3 days after the last dose.
Drug Profile Summary
- Mechanism of Action: Inhibits viral DNA polymerase.
- Side Effects: Bone marrow suppression, fever, nausea, diarrhea, headache.
- Contraindications: Hypersensitivity, severe neutropenia or thrombocytopenia, pregnancy.
- Drug Interactions: Imipenem-cilastatin, didanosine, probenecid, mycophenolate mofetil, zidovudine.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, avoid during breastfeeding.
- Dosage: 5 mg/kg IV q12h for induction, then 5 mg/kg IV daily for maintenance. Dose adjustments based on renal function.
- Monitoring Parameters: Blood counts (CBC with differential), renal function (creatinine clearance), liver function tests.
Popular Combinations
- Combinations with other antivirals are not typically used for CMV treatment.
Precautions
- General Precautions: Monitor blood counts, renal function, and liver function regularly. Patients with renal impairment require dose adjustments.
- Specific Populations: Pregnant women (contraindicated), breastfeeding mothers (avoid), children (dose adjustments).
- Lifestyle Considerations: Ganciclovir can cause drowsiness, dizziness, and seizures. Advise patients to avoid driving or operating machinery until these side effects resolve.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ganciclovir?
A: Standard adult induction dose is 5 mg/kg IV every 12 hours for 14-21 days (for retinitis) or 7-14 days (prophylaxis). Maintenance dose is 5 mg/kg IV daily or 6 mg/kg IV for 5 days a week. Pediatric and renal impairment doses require adjustments.
Q2: What are the common side effects of Ganciclovir?
A: Common side effects include fever, nausea, diarrhea, headache, and bone marrow suppression (neutropenia, anemia, thrombocytopenia).
Q3: What are the serious side effects of Ganciclovir?
A: Serious side effects may include seizures, severe bone marrow suppression (pancytopenia), and severe allergic reactions.
Q4: Can Ganciclovir be used during pregnancy?
A: Ganciclovir is contraindicated during pregnancy due to its teratogenic effects.
Q5: Can Ganciclovir be used during breastfeeding?
A: Ganciclovir is generally avoided during breastfeeding because it may cause adverse effects in the nursing infant.
Q6: How is Ganciclovir administered?
A: Ganciclovir is administered via intravenous infusion over 1 hour.
Q7: What are the main drug interactions with Ganciclovir?
A: Important interactions include imipenem-cilastatin, didanosine, probenecid, mycophenolate mofetil, and zidovudine.
Q8: How should Ganciclovir be dosed in patients with renal impairment?
A: Dose adjustments are essential in renal impairment based on creatinine clearance.
Q9: What is the mechanism of action of Ganciclovir?
A: Ganciclovir inhibits viral DNA replication by competitively inhibiting viral DNA polymerase.
Q10: What monitoring is required during Ganciclovir therapy?
A: Monitor complete blood counts (CBC), renal function, and liver function tests regularly.
