Nurses Compass
Drug Guide
Pitolisant Hydrochloride
Classification
Therapeutic: Central Nervous System Stimulant / Wakefulness-Promoting Agent
Pharmacological: Histamine H3 Receptor Antagonist / Inverse Agonist
FDA Approved Indications
- Narcolepsy with or without cataplexy
Mechanism of Action
Pitolisant acts as an antagonist/inverse agonist at histamine H3 receptors, leading to increased release of histamine and other neurotransmitters, which promotes wakefulness.
Dosage and Administration
Adult: Initial dose of 8.9 mg once daily, can be increased to 17.8 mg once daily based on response and tolerability.
Pediatric: Not approved for pediatric use.
Geriatric: No specific adjustments, but caution and close monitoring recommended due to potential for increased adverse effects.
Renal Impairment: Use with caution; no specific adjustment provided.
Hepatic Impairment: Start at lower doses; monitoring advised.
Pharmacokinetics
Absorption: Well absorbed orally, with a Tmax of approximately 1 hour.
Distribution: Highly protein-bound (~90%).
Metabolism: Metabolized primarily via CYP2D6 and CYP3A4 pathways.
Excretion: Excreted mainly in urine as metabolites; half-life approximately 10 hours.
Half Life: Approximately 10 hours.
Contraindications
- Hypersensitivity to pitolisant or excipients.
Precautions
- Use cautiously in patients with history of QT prolongation or arrhythmias, hepatic impairment, or significant cardiovascular disease. Monitoring of cardiac status is recommended.
Adverse Reactions - Common
- Insomnia (Common)
- Nausea (Common)
- Headache (Common)
Adverse Reactions - Serious
- QT prolongation / arrhythmias (Rare)
- Seizures (Rare)
- Liver function abnormalities (Rare)
Drug-Drug Interactions
- CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) increase plasma concentrations of pitolisant.
- CYP3A4 inhibitors (e.g., ketoconazole) may increase risk of adverse effects.
Drug-Food Interactions
N/ADrug-Herb Interactions
N/ANursing Implications
Assessment: Monitor for signs of central nervous system stimulation, sleep disturbances, and cardiac issues, including ECG if indicated.
Diagnoses:
- Disturbed sleep pattern related to drug effects.
- Risk for cardiac arrhythmias related to QT prolongation.
Implementation: Administer as prescribed, usually once daily in the morning. Monitor EKGs if patient has risk factors.
Evaluation: Assess improvements in wakefulness and alertness, and monitor for adverse effects.
Patient/Family Teaching
- Take medication as directed, preferably in the morning.
- Report any signs of abnormal heartbeat, chest pain, or seizures.
- Avoid alcohol and CNS depressants.
- Inform healthcare provider about all medications, especially CYP2D6 or CYP3A4 inhibitors.
Special Considerations
Black Box Warnings:
- QT prolongation and risk of arrhythmias, including torsade de pointes.
Genetic Factors: CYP2D6 poor metabolizers may have increased exposure.
Lab Test Interference: No specific known interference.
Overdose Management
Signs/Symptoms: Severe dizziness, cardiac arrhythmias, seizures.
Treatment: Supportive care; consider activated charcoal if ingestion is recent; cardiac monitoring; ECG; manage seizures as per protocols.
Storage and Handling
Storage: Store at room temperature, 20°C to 25°C (68°F to 77°F).
Stability: Stable under recommended storage conditions.