Nurses Compass
Drug Guide
Letermovir
Classification
Therapeutic: Antiviral, Antiviral for CMV infection
Pharmacological: DNA terminase complex inhibitor
FDA Approved Indications
- Prevention of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant (HSCT) recipients
Mechanism of Action
Inhibits the terminase complex of CMV, preventing viral DNA processing and packaging, thus inhibiting viral replication.
Dosage and Administration
Adult: 480 mg orally once daily, starting within 28 days after transplant, continued up to 100 days or until immunosuppressive therapy is discontinued.
Pediatric: Not indicated for pediatric use.
Geriatric: No specific dosage adjustment; consult clinical judgment.
Renal Impairment: No adjustment recommended for mild or moderate impairment; with severe impairment, use caution and monitor.
Hepatic Impairment: No specific dosage adjustment needed; use with caution and monitor closely.
Pharmacokinetics
Absorption: Rapid after oral administration with approximately 80% bioavailability.
Distribution: Extensively bound to plasma proteins.
Metabolism: Primarily metabolized via CYP3A4 and UGT1A1 pathways.
Excretion: Excreted mainly via feces, with minimal renal clearance.
Half Life: 12 hours.
Contraindications
- Hypersensitivity to letermovir or any component of the formulation.
Precautions
- Use with caution in patients with concomitant medications that prolong QT interval or are metabolized by CYP3A4. Regular monitoring of ECG is advised in at-risk populations.
Adverse Reactions - Common
- Gastrointestinal symptoms (nausea, diarrhea, constipation) (Uncommon to common)
- Headache (Uncommon)
Adverse Reactions - Serious
- Arrhythmias, including QT prolongation (Rare)
- Hepatotoxicity (Rare)
Drug-Drug Interactions
- CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) increase letermovir levels; CYP3A4 inducers (e.g., rifampin) decrease levels.
Drug-Food Interactions
- None significant.
Drug-Herb Interactions
- St. John’s Wort may induce CYP3A4 and reduce efficacy.
Nursing Implications
Assessment: Monitor for signs of CMV replication, assess liver function tests, monitor ECG in patients on QT-prolonging drugs.
Diagnoses:
- Risk for infection due to immunosuppression.
Implementation: Administer as prescribed, ensure adherence, monitor for side effects.
Evaluation: Efficacy assessed by monitoring CMV viral load; side effects observed and reported.
Patient/Family Teaching
- Inform about the importance of adherence to medication schedule.
- Report any signs of infection, liver problems, or arrhythmias immediately.
- Avoid grapefruit and grapefruit juice, which may affect drug levels.
Special Considerations
Black Box Warnings:
- None currently.
Genetic Factors: Genetic variations in CYP3A4 and UGT1A1 may affect drug metabolism.
Lab Test Interference: None significant.
Overdose Management
Signs/Symptoms: Unknown, but watch for signs of toxicity such as arrhythmias or liver dysfunction.
Treatment: Supportive care; no specific antidote. Contact poison control for guidance.
Storage and Handling
Storage: Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).
Stability: Stable under proper storage conditions for the duration of the labeled expiry date.