ONZETRA XSAIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ONZETRA XSAIL (ONZETRA XSAIL).
Sumatriptan is a 5-HT1B/1D receptor agonist that binds with high affinity to serotonin 5-HT1B and 5-HT1D receptors, leading to vasoconstriction of intracranial blood vessels and inhibition of trigeminal nerve transmission. Succinic acid is an excipient without therapeutic activity.
| Metabolism | Sumatriptan is metabolized primarily by monoamine oxidase A (MAO-A) to an indole acetic acid metabolite. Approximately 40% of the drug undergoes first-pass metabolism. |
| Excretion | Sumatriptan is eliminated primarily by renal excretion (about 60% as unchanged drug and metabolites) and fecal elimination (about 40%). The major metabolite is the indole acetic acid analog, which is inactive. |
| Half-life | Sumatriptan has a terminal elimination half-life of approximately 2.5 hours (range 1.5–4 hours). This short half-life is consistent with its use for acute migraine attacks, where rapid onset and limited duration are desired. |
| Protein binding | Sumatriptan is approximately 14–21% bound to plasma proteins, primarily albumin. The low protein binding contributes to its rapid distribution and clearance. |
| Volume of Distribution | The volume of distribution for sumatriptan is approximately 2.4 L/kg in healthy subjects. This relatively large Vd indicates extensive distribution into tissues, consistent with its lipophilic nature and ability to cross the blood-brain barrier. |
| Bioavailability | The absolute bioavailability of sumatriptan administered via the intranasal powder device (ONZETRA XSAIL) is approximately 17% relative to subcutaneous injection. This is higher than oral sumatriptan (about 14%) due to avoidance of first-pass metabolism. |
| Onset of Action | Sumatriptan nasal powder (22 mg) demonstrates onset of headache relief within 15–30 minutes after administration, with some patients experiencing relief as early as 10 minutes. |
| Duration of Action | The duration of action for sumatriptan nasal powder is typically 2–4 hours. If headache recurs, a second dose may be taken after at least 2 hours, with a maximum of 2 doses per 24 hours. |
1.5 mg sumatriptan (one dose) administered intranasally at onset of migraine; may repeat once after 1 hour if needed, not to exceed 3 mg in 24 hours.
| Dosage form | POWDER |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). Use caution in moderate hepatic impairment (Child-Pugh B); no specific dose adjustment defined. No adjustment in mild impairment. |
| Pediatric use | Not recommended for use in pediatric patients (<18 years) due to lack of safety and efficacy data. |
| Geriatric use | Not recommended for use in elderly patients ≥65 years due to increased risk of adverse events and lack of efficacy data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ONZETRA XSAIL (ONZETRA XSAIL).
| Breastfeeding | It is not known whether sumatriptan or diclofenac are excreted in human milk following intranasal administration; however, both are excreted in animal milk. The M/P ratio for sumatriptan is not available for intranasal route; for diclofenac, the M/P ratio is approximately 0.05 following oral administration. Caution is advised, and the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ONZETRA XSAIL and any potential adverse effects on the breastfed child from the drug or underlying maternal condition. |
| Teratogenic Risk | Pregnancy Category C. Animal studies have shown developmental toxicity including increased embryo-fetal mortality and reduced fetal weight at maternal exposures similar to the maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women. ONZETRA XSAIL should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. First trimester risks include potential for neural tube defects; second and third trimester risks include potential for uterine hyperstimulation and fetal distress due to ergot alkaloid properties. |
■ FDA Black Box Warning
NOT RECOMMENDED for patients with risk factors for CAD unless a cardiovascular evaluation has established no clinically significant CAD.
| Serious Effects |
["History of coronary artery disease (CAD) or coronary vasospasm","Wolff-Parkinson-White syndrome or other accessory cardiac conduction pathway disorders","History of stroke or transient ischemic attack","Peripheral vascular disease","Ischemic bowel disease","Uncontrolled hypertension","Recent use (within 24 hours) of another 5-HT1B/1D agonist or ergotamine-containing drug","Concomitant administration with MAO-A inhibitor or recent use (within 2 weeks) of an MAO-A inhibitor","Hemiplegic or basilar migraine","Severe hepatic impairment","Hypersensitivity to sumatriptan or any component of the formulation"]
| Precautions | ["Risk of myocardial ischemia and/or infarction and other coronary vasospasms","Life-threatening arrhythmias including ventricular tachycardia and ventricular fibrillation","Cerebral hemorrhage, subarachnoid hemorrhage, and stroke","Gastrointestinal ischemic reactions including bowel infarction","Increased blood pressure, including hypertensive crisis","Serotonin syndrome, particularly with concomitant serotonergic drugs","Severe anaphylactic/anaphylactoid reactions","Withdrawal of therapy needed if overuse headache develops"] |
Loading safety data…
| Fetal Monitoring | Monitor fetal heart rate and uterine activity during use due to potential for uterotonic effects. Assess for signs of fetal distress, premature labor, and reduced fetal movements. Monitor maternal blood pressure and heart rate. In case of overdose, monitor for serotonin syndrome symptoms. |
| Fertility Effects | No human data on fertility. In animal studies, sumatriptan did not impair fertility in rats at doses up to 160 mg/kg/day. Diclofenac may impair female fertility in animal studies and may delay or inhibit ovulation in humans. The effect is reversible upon discontinuation. |