PITOLISANT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PITOLISANT (PITOLISANT).
Selective histamine H3 receptor antagonist/inverse agonist; increases histamine release in the brain, promoting wakefulness.
| Metabolism | Primarily metabolized by CYP3A4, with minor contribution from CYP2C19 and CYP3A5. |
| Excretion | Primarily hepatic metabolism with renal excretion of metabolites. Approximately 91% of the dose is recovered in urine (as metabolites) and 6% in feces (<1% unchanged). |
| Half-life | Terminal elimination half-life is approximately 10-12 hours in healthy adults, supporting once-daily dosing. |
| Protein binding | Approximately 87% bound to serum proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2.3 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 75-90%. |
| Onset of Action | Oral: Clinical effect (reduction in excessive daytime sleepiness) observed within 1-2 weeks of starting therapy. |
| Duration of Action | Effects persist for approximately 24 hours with once-daily administration, maintaining wakefulness throughout the day. |
17.8 mg orally once daily, titrated to a maximum of 35.6 mg once daily based on response and tolerability.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-89 mL/min: no adjustment; for GFR 15-29 mL/min: reduce dose to 8.9 mg once daily, max 17.8 mg once daily; for GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 8.9 mg once daily, max 17.8 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended, but monitor renal function due to age-related decline; start at lowest dose and titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PITOLISANT (PITOLISANT).
| Breastfeeding | Unknown if excreted in human milk. No M/P ratio available. Risk of adverse effects in breastfeeding infant cannot be excluded. Pitolisant is contraindicated during breastfeeding. |
| Teratogenic Risk | Pitolisant is contraindicated in pregnancy. Animal studies show embryofetal toxicity including reduced fetal weight and skeletal variations at maternal exposures below the human therapeutic dose. No adequate human data exist. First trimester exposure risk unknown; second and third trimester may cause fetal harm due to placental transfer. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to pitolisant or any of its excipients.","Severe hepatic impairment (Child-Pugh C)."]
| Precautions | ["May cause insomnia, nausea, and anxiety.","Monitor for psychiatric adverse reactions including depression and hallucinations.","Avoid driving or engaging in hazardous activities until patients know how the drug affects them.","Use caution in patients with renal or hepatic impairment.","Drug interactions with strong CYP3A4 inhibitors or inducers."] |
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| Fetal Monitoring |
| Not applicable as use is contraindicated. If accidental exposure occurs, monitor fetal growth via ultrasound; assess for neonatal adverse effects post-delivery. |
| Fertility Effects | In animal studies, pitolisant reduced fertility in male and female rats at doses below the human therapeutic dose. Effect on human fertility unknown; may impair spermatogenesis or ovulation. |