Usage
Valganciclovir is prescribed for the treatment and prevention of cytomegalovirus (CMV) infections, particularly in immunocompromised individuals such as those with AIDS or transplant recipients. It is also used to treat CMV retinitis in AIDS patients. It is classified as an antiviral agent.
Valganciclovir’s mechanism of action involves its conversion to ganciclovir, which inhibits viral DNA polymerase, thus preventing viral replication.
Alternate Names
Valganciclovir is also known as the L-valyl ester of ganciclovir. A popular brand name under which it is marketed is Valcyte®.
How It Works
Pharmacodynamics: Valganciclovir is a prodrug of ganciclovir. After oral administration, it is rapidly absorbed and hydrolyzed to ganciclovir, primarily by intestinal and hepatic esterases. Ganciclovir is then actively transported into CMV-infected cells. Inside the cells, ganciclovir is phosphorylated to ganciclovir triphosphate, which is the active form of the drug. Ganciclovir triphosphate competes with deoxyguanosine triphosphate for incorporation into viral DNA by viral DNA polymerase. Incorporation of ganciclovir triphosphate into viral DNA results in chain termination and inhibition of viral DNA synthesis.
Pharmacokinetics: Valganciclovir has high oral bioavailability, achieving significantly higher plasma concentrations of ganciclovir compared to oral ganciclovir. It is metabolized to ganciclovir, which is primarily excreted unchanged by the kidneys. The half-life of ganciclovir is prolonged in patients with renal impairment.
Mode of Action: Ganciclovir triphosphate inhibits viral DNA polymerase, ultimately leading to chain termination and inhibition of viral DNA replication.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Valganciclovir/ganciclovir’s primary mode of action is the inhibition of viral DNA polymerase. It does not have significant receptor binding, enzyme inhibition (other than viral DNA polymerase), or neurotransmitter modulation effects related to its antiviral activity.
Elimination Pathways: Ganciclovir, the active form of valganciclovir, is primarily eliminated through renal excretion (approximately 90%). A small portion is eliminated through feces.
Dosage
Standard Dosage
Adults:
- CMV Retinitis Induction: 900 mg twice daily for 21 days with food.
- CMV Retinitis Maintenance: 900 mg once daily with food.
- CMV Prevention in Transplant Patients: 900 mg once daily with food, starting within 10 days of transplantation and continuing for up to 100-200 days depending on the type of transplant.
Children (Congenital CMV):
- 16 mg/kg every 12 hours, administered orally with feeds. Doses are calculated based on body surface area (BSA) and weight. IV ganciclovir is preferred as initial therapy in acute, severe CMV disease.
Special Cases:
- Elderly Patients: Close monitoring of renal function and dose adjustment as needed.
- Patients with Renal Impairment: Dose adjustment based on creatinine clearance is crucial.
- Patients with Hepatic Dysfunction: Insufficient data; use with caution.
- Patients with Comorbid Conditions: Close monitoring for potential drug interactions and adverse effects.
Clinical Use Cases
Valganciclovir dosages in clinical use cases such as intubation, surgical procedures, mechanical ventilation, and ICU use are typically consistent with the standard dosage recommendations or adjusted based on renal function. In emergency situations, intravenous ganciclovir is often preferred for faster action.
Dosage Adjustments
Dose adjustments are primarily based on creatinine clearance. Specific guidelines should be consulted.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, headache, fever, insomnia, abdominal pain, peripheral neuropathy, anemia, neutropenia, thrombocytopenia.
Rare but Serious Side Effects:
Seizures, bone marrow suppression (pancytopenia, aplastic anemia), severe neutropenia, Stevens-Johnson syndrome, toxic epidermal necrolysis, retinal detachment.
Long-Term Effects:
Infertility (male and female), increased risk of malignancy.
Adverse Drug Reactions (ADR):
Severe neutropenia, bone marrow suppression, anaphylaxis.
Contraindications
Hypersensitivity to valganciclovir, ganciclovir, or acyclovir. Severe neutropenia, thrombocytopenia, anemia.
Drug Interactions
Imipenem/cilastatin, zidovudine, probenecid, mycophenolate mofetil, didanosine, other myelosuppressive agents.
Pregnancy and Breastfeeding
Pregnancy Category C. Valganciclovir can cause fetal harm. Effective contraception is mandatory during treatment and for a period after treatment (30 days for women, 90 days for men). Breastfeeding is contraindicated due to the potential for serious adverse effects in nursing infants.
Drug Profile Summary
- Mechanism of Action: Inhibits viral DNA polymerase.
- Side Effects: Neutropenia, anemia, thrombocytopenia, nausea, vomiting, diarrhea, headache.
- Contraindications: Hypersensitivity, severe bone marrow suppression.
- Drug Interactions: Zidovudine, probenecid, mycophenolate mofetil.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Refer to detailed dosage section.
- Monitoring Parameters: Complete blood counts, renal function, liver function.
Popular Combinations
Often used in combination with other antiviral or immunosuppressive agents in transplant recipients.
Precautions
Close monitoring of blood counts, renal function, and liver function is necessary. Precautions are particularly important in patients with pre-existing renal dysfunction, bone marrow suppression, or those receiving myelosuppressive medications. Valganciclovir is mutagenic and teratogenic in animal studies. Appropriate handling precautions should be followed.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Valganciclovir?
A: Refer to the dosage section for specific recommendations for adults, children, and special populations.
Q2: How is Valganciclovir administered?
A: Orally, with food.
Q3: What are the most common side effects of Valganciclovir?
A: Neutropenia, anemia, thrombocytopenia, nausea, vomiting, diarrhea, headache.
Q4: What are the serious side effects of Valganciclovir that require urgent attention?
A: Severe neutropenia, seizures, bone marrow suppression, Stevens-Johnson syndrome, retinal detachment.
Q5: Can Valganciclovir be used during pregnancy or breastfeeding?
A: No, Valganciclovir is contraindicated in pregnancy and breastfeeding.
Q6: What are the key drug interactions with Valganciclovir?
A: Zidovudine, probenecid, mycophenolate mofetil, imipenem/cilastatin. Refer to the drug interactions section for a complete list.
Q7: How should Valganciclovir dosage be adjusted in patients with renal impairment?
A: Dose reduction is necessary based on creatinine clearance. Specific guidelines should be consulted.
Q8: What patient monitoring is required during Valganciclovir therapy?
A: Regular monitoring of complete blood counts (CBC) including platelets, renal function tests (serum creatinine, creatinine clearance), and liver function tests is essential. More frequent monitoring might be required in patients with pre-existing cytopenias, renal impairment, or those receiving concurrent myelosuppressive medications.
Q9: What is the mechanism of action of Valganciclovir?
A: Valganciclovir is a prodrug that is metabolized to ganciclovir. Ganciclovir inhibits viral DNA polymerase, thus blocking CMV replication.
Q10: What is the difference between Valganciclovir and Ganciclovir?
A: Valganciclovir is the L-valyl ester prodrug of ganciclovir, offering improved oral bioavailability compared to ganciclovir itself. Adults should use Valganciclovir tablets, not oral solution. However, the pediatric solution can be prescribed for younger patients.
