Nurses Compass
Drug Guide
Lonafarnib
Classification
Therapeutic: Antiviral, Antineoplastic, Farnesyltransferase inhibitor
Pharmacological: Farnesyltransferase inhibitor
FDA Approved Indications
- Treatment of Hutchinson-Gilford Progeria Syndrome (HGPS) and processing-deficient Progeria
Mechanism of Action
Lonafarnib inhibits farnesyltransferase, an enzyme involved in the post-translational modification of proteins like progerin, which is implicated in the pathogenesis of progeria. This inhibition prevents the farnesylation of progerin, reducing cellular abnormalities associated with the disease.
Dosage and Administration
Adult: Typically 200 mg twice daily with food; dosage may vary based on patient response and tolerability.
Pediatric: Dosing varies based on age and weight; specific dosing guidelines should be followed as per FDA approval and clinical guidelines.
Geriatric: No specific adjustments required but monitor for increased sensitivity to side effects.
Renal Impairment: Use with caution; dosage adjustments may be necessary based on renal function.
Hepatic Impairment: Use with caution; no specific guidelines established.
Pharmacokinetics
Absorption: Well absorbed orally, with food enhancing absorption.
Distribution: Widely distributed in body tissues.
Metabolism: Primarily metabolized in the liver by CYP3A4.
Excretion: Excreted mainly via feces; minimal renal excretion.
Half Life: Approximately 3-4 hours.
Contraindications
- Hypersensitivity to lonafarnib or any components of the formulation.
Precautions
- Use with caution in patients with hepatic impairment, as the drug is metabolized by the liver. Monitor for nausea, diarrhea, and other side effects. Consider drug interactions with CYP3A4 inhibitors or inducers.
Adverse Reactions - Common
- Nausea (Common)
- Diarrhea (Common)
- Fatigue (Common)
- Elevated liver enzymes (Uncommon)
Adverse Reactions - Serious
- Blood clots and thromboembolic events (Rare)
- Severe infections (Rare)
- Liver failure (Rare)
Drug-Drug Interactions
- CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) increase lonafarnib levels.
- CYP3A4 inducers (e.g., rifampin, carbamazepine) decrease efficacy.
Drug-Food Interactions
N/ADrug-Herb Interactions
N/ANursing Implications
Assessment: Monitor for adverse effects such as gastrointestinal symptoms, liver function abnormalities, and signs of bleeding or clotting issues.
Diagnoses:
- Risk for bleeding related to clotting abnormalities
- Impaired liver function
Implementation: Administer with food to improve absorption. Monitor laboratory values regularly, including liver function tests.
Evaluation: Assess for improvement in clinical symptoms of progeria and monitor for adverse effects.
Patient/Family Teaching
- Take medication exactly as prescribed, with food.
- Report any signs of bleeding, severe nausea, or unusual fatigue.
- Attend regular follow-up appointments for laboratory monitoring.
Special Considerations
Black Box Warnings:
- None currently specified by the FDA.
Genetic Factors: Genetic mutations in LMNA are involved in progeria; no impact on drug therapy but relevant for understanding disease.
Lab Test Interference: May affect lipid and liver function tests.
Overdose Management
Signs/Symptoms: Gastrointestinal symptoms, fatigue, or more severe adverse reactions.
Treatment: Supportive care; no specific antidote. Hospitalization and symptomatic treatment as needed.
Storage and Handling
Storage: Store at room temperature, 20°C to 25°C (68°F to 77°F). Keep container tightly closed.
Stability: Stable under recommended storage conditions; check expiration date.