New dosage form for migraine treatment

In January, 2016, FDA approved Onzetra Xsail (Avanir Pharmaceuticals Inc.)- a fast-acting, low-dose sumatriptan dry powder formulation for the acute treatment of migraine with or without aura in adults.

Kathryn Wheeler

Aki YamamotoAlthough various sumatriptan formulations exist, each has limitations. Oral delivery is common, but has inconsistent effectiveness due to delayed absorption and requires a higher dose to overcome poor bioavailability. Nasal-spray delivery is associated with variable drug loss from drip-outs and accumulation at the nasal cavity floor, which is ultimately swallowed and subjected to challenges similar to those of oral delivery. Subcutaneous delivery is most effective. However, it is inconvenient, painful, and associated with high frequency of local and systemic side effects. Onzetra Xsail utilizes a novel closed-palate, breath-powered intranasal drug delivery system to overcome these limitations.

Efficacy

Sumatriptan is a 5HT_1B/1D receptor agonist. For migraine relief, it acts to constrict the intracranial blood vessels and inhibit pro-inflammatory neuropeptide release.

FDA approval was based on a double-blinded, multi-centered, placebo-controlled, parallel-group study. Males and females, 18-65 years of age, diagnosed with migraine who reported 1 to 8 migraine headaches per month in the past 12 months prior to screening were included in the study. Participants received Onzetra Xsail, 22mg or placebo, to treat moderate/severe migraine episodes. The primary endpoint was reduction in headache intensity 2 hours after treatment. Secondary endpoints included headache relief at other time points, pain freedom, relief of migraine-associated symptoms (nausea/vomiting, phonophobia, photophobia), reduction in clinical disability scale score, rescue medication use, and maintenance of headache response.

Statistically significant reduction in headache intensity 2 hours post-treatment was observed in the Onzetra group (67.6% v. 45.2%, p=0.002). Average time to meaningful pain relief was 47 minutes for participants receiving Onzentra Xsail; 19.4% of study participants experienced relief in as few as 15 minutes.

Significant differences favoring Onzentra Xsail regarding maintenance of relief at 24 and 48 hours post-administration were demonstrated. Use of rescue medication was significantly lower in Onzetra group (37.0% v. 51.9%, p=0.02 ).

Safety

Onzetra Xsail is used only if a diagnosis of migraine has been established, and is not indicated for migraine prevention or for hemiplegic or basilar migraine. The most common adverse effects reported were local (abnormal product taste, nasal discomfort, and rhinitis) and generally resolved within 2 hours of administration. Most adverse effects were mild/moderate in intensity.

Safety and efficacy has not been studied for treatment of cluster headaches or for use in patients under 18 years of age. Onzetra Xsail is pregnancy category C. Nursing mothers should avoid breastfeeding 12 hours post-treatment.

Triptans are contraindicated in ischemic/vasospastic CAD, arrhythmias, Wolff-Parkinson-White syndrome, stroke/TIA, peripheral vascular disease, ischemic bowel disease, uncontrolled hypertension, severe hepatic impairment, and hypersensitivity reaction. Precaution is warranted in patients with elevated seizure risk. The drug carries a warning for overuse headache and serotonin syndrome, especially with concomitant use of other medications that affect serotonin.

Dosage

The recommended dose of Onzetra Xsail is 22mg (one 11mg nosepiece in each nostril). A second dose of 22mg may be administered at least 2 hours after the first. The patient should consult a healthcare provider before administering a second dose. Maximum daily dose of this product is 44mg-or one Onzetra Xsail and another sumatriptan product separated by 2 hours.

To administer the medication, place the nosepiece into the delivery device and press the piercing button to pierce the capsule inside the nosepiece. Then, insert the nosepiece into a nostril and make a tight seal. Rotate the device to place the mouthpiece into the mouth and blow forcefully to deliver the drug powder into the nasal cavity. After administration, remove the first nosepiece and repeat the steps to administer the second 11mg nosepiece into the other nostril.

Aki Yamamoto is a PharmD Candidate, class of 2017 at the University of Connecticut in Storrs, CT. Kathryn Wheeler, PharmD, BCPS is Associate Clinical Professor of Pharmacy Practice at UCONN in Storrs.
 

References:

Onzentra Xsail [package insert] Aliso Viejo, CA: Avanir Pharmaceuticals, Inc.; January 2016.

Cady RK, McAllister PJ, Spierings EL, et al. A randomized, double-blind, placebo-controlled study of breath powered nasal delivery of sumatriptan powder (AVP-825) in the treatment of acute migraine (The TARGET Study). Headache. 2015;55:88-100.