In clinical trials, the highest single doses of sumatriptan nasal spray administered without significant reactions were 40 mg to 12 volunteers and 40 mg to 85 subjects with migraine, which is twice the highest single recommended dose. In addition, 12 volunteers were administered a total daily dose of 60 mg (20 mg 3 times daily) for 3.5 days without significant adverse reactions.
Overdose in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation.
The elimination half-life of ONZETRA Xsail is about 3 hours , and therefore monitoring of patients after overdose with ONZETRA Xsail should continue for at least 15 hours or while symptoms persist.
It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.
ONZETRA Xsail is contraindicated in patients with:
The following serious adverse reactions are discussed in more detail in other sections of the prescribing information:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug, and may not reflect the rates observed in practice.
Table 1 lists adverse reactions that occurred in 2 placebo-controlled clinical trials in 301 patients with migraine who took at least 1 dose of ONZETRA Xsail or placebo. Only adverse reactions that occurred at a frequency of 2% or more with ONZETRA Xsail and that occurred at a frequency greater than the placebo group are included in Table 1.
Table 1: Adverse Reactions Reported by at Least 2% of
Patients in 2 Controlled Migraine Trials
| Adverse Reaction | Percent of Patients Reporting | |
| ONZETRA N=151 |
Placebo N=150 |
|
| Abnormal Taste | 20 | 3 |
| Nasal Discomfort | 11a | 1 |
| Rhinorrhea | 5 | 2 |
| Rhinitis | 2 | 0 |
| a Limited examinations of the nose and throat did not reveal any clinically noticeable injury in these patients. |
There is insufficient data with ONZETRA Xsail to assess the impact of age, gender, and race on adverse effects.
ONZETRA™ Xsail™ is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of UseSignificant elevation in blood pressure, including hypertensive crisis, has been reported in patients treated with sumatriptan, with and without a history of hypertension.
Peripheral (Small) ArteriesIn healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan injection on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance.
Heart RateTransient increases in blood pressure observed in some patients in clinical studies carried out during development of sumatriptan as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.
The mean maximum concentration (Cmax) following a 22 mg nasal dose of ONZETRA Xsail was 21 ng/mL (range: 9 to 61 ng/mL), and the AUC0-∞ was 65 ng•hr/ml (range: 40 to 107 ng/mL). Peak plasma concentration (Tmax) was achieved on average 45 minutes (range: 10 minutes to 2 hours) following ONZETRA Xsail administration. The bioavailability of ONZETRA relative to subcutaneous injection was approximately 19%, primarily due to pre-systemic metabolism and partly due to incomplete absorption. Sumatriptan bioavailability following liquid nasal spray administration is 14%, similar to that after oral administration (15%).
DistributionProtein binding of sumatriptan, determined by equilibrium dialysis over the concentration range of 10 to 1000 ng/mL, is approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated. The apparent volume of distribution is 2.7 L/kg.
MetabolismIn vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO (predominately A isoenzyme). Most of a radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive.
EliminationThe elimination half-life of sumatriptan administered as a nasal powder by the Xsail device is approximately 3 hours, similar to the half-life seen with sumatriptan nasal spray. Only 3% of a nasal spray dose is excreted in the urine as unchanged sumatriptan; 42% of a nasal spray dose is excreted as the major metabolite, the indole acetic acid analogue of sumatriptan. The total plasma clearance of the nasal spray is approximately 1200 mL/min.
There are no adequate and well-controlled trials in pregnant women. In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal. Developmental toxicity studies of sumatriptan by the intranasal route have not been conducted. ONZETRA Xsail should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 and 0.75 mg/kg/day, respectively.
Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day.
ONZETRA Xsail is supplied as a disposable nosepiece containing a capsule and a reusable delivery device body. Each capsule contains 11 mg sumatriptan base (equivalent to 15.4 mg of sumatriptan succinate nasal powder) in a clear, hypromellose capsule with 825 printed on one side.
ONZETRA Xsail is supplied as a disposable nosepiece containing a capsule and a reusable breath-powered delivery device body. Each capsule contains 11 mg sumatriptan base (equivalent to 15.4 mg of sumatriptan succinate nasal powder) in a clear, hypromellose capsule with 825 printed on one side.
ONZETRA Xsail is available in kits containing 8 doses.
The following table provides a description of the packaging configurations:
| Description | Contents | NDC Code |
| 8 Dose Kit | 8 pouches containing 2 nosepieces (22 mg sumatriptan) per pouch. Each nosepiece contains 11 mg sumatriptan 2 breath-powered delivery system bodies | 64597-311-08 |
Store at room temperature between 20° C to 25° C (68° F to 77° F), with excursions permitted between 15° C to 30° C (59° F to 86° F). Do not store in the refrigerator or freezer. Use nosepiece immediately after removing from foil pouch.
Manufactured for: Avanir Pharmaceuticals, Inc., Aliso Viejo, CA 92656, 1-844-ONZETRA (669-3872). Revised: January 2016
Included as part of the PRECAUTIONS section.
PRECAUTIONS Myocardial Ischemia, Myocardial Infarction, And Prinzmetal's AnginaThe use of ONZETRA Xsail is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of sumatriptan. Some of these reactions occurred in patients without known CAD. 5-HT1 agonists, including ONZETRA Xsail, may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD.
Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving ONZETRA Xsail. If there is evidence of CAD or coronary artery vasospasm, ONZETRA Xsail is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of ONZETRA Xsail in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of ONZETRA Xsail. For such patients, consider periodic cardiovascular evaluation in intermittent longterm users of ONZETRA Xsail.
ArrhythmiasLife-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue ONZETRA Xsail if these disturbances occur. ONZETRA Xsail is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.
Chest, Throat, Neck, And/Or Jaw Pain/Tightness/PressureSensations of tightness, pain, pressure, and heaviness in the chest, throat, neck, and jaw commonly occur after treatment with 5-HT1 agonists including other products containing sumatriptan and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of ONZETRA Xsail is contraindicated in patients with known CAD and those with Prinzmetal's variant angina.
Cerebrovascular EventsCerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have occurred in patients treated with 5-HT1 agonists including other products containing sumatriptan, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). ONZETRA Xsail is contraindicated in patients with a history of stroke or TIA. Discontinue ONZETRA Xsail if a cerebrovascular event occurs.
Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, exclude other potentially serious neurological conditions.
Other Vasospasm Reactions5-HT1 agonists, including ONZETRA Xsail, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of a non-coronary vasospastic reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before using ONZETRA Xsail.
Transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists including sumatriptan. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.
Medication Overuse HeadacheOveruse of acute migraine drugs (e.g., ergotamine, triptans, opioids, nonsteroidal anti-inflammatory drugs or combinations of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
Serotonin SyndromeSerotonin syndrome may occur with triptans, including ONZETRA Xsail, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue ONZETRA Xsail if serotonin syndrome is suspected.
Increase In Blood PressureSignificant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with ONZETRA Xsail. ONZETRA Xsail is contraindicated in patients with uncontrolled hypertension.
Anaphylactic ReactionsAnaphylactic reactions have occurred in patients receiving sumatriptan. Such reactions can be life-threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. ONZETRA Xsail is contraindicated in patients with a history of hypersensitivity reaction to sumatriptan.
SeizuresSeizures have been reported following administration of sumatriptan. Some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures. There are also reports in patients where no such predisposing factors are apparent. ONZETRA Xsail should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.
Patient Counseling InformationAdvise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use).
Only patients who are able to understand and follow the instructions should use ONZETRA Xsail.
Instructions on the proper use of ONZETRA Xsail from a physician or healthcare professional prior to administration for the first time may be helpful. For support, healthcare professionals and patients can call 1-844-ONZETRA or see www.ONZETRA.com.
Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm-Related Events, Arrhythmias, andCerebrovascular EventsInform patients that triptan medications, including ONZETRA Xsail, may cause serious cardiovascular side effects such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech and should ask for medical advice if any indicative signs or symptoms are observed. Apprise patients of the importance of this follow-up.
Anaphylactic ReactionsInform patients that anaphylactic reactions have occurred in patients receiving sumatriptan. Such reactions can be life-threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens.
Concomitant Use with Other Triptans and Ergot MedicationsInform patients that use of ONZETRA Xsail within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated.
Serotonin SyndromeCaution patients about the risk of serotonin syndrome with the use of ONZETRA Xsail or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors.
Medication Overuse HeadacheInform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary).
PregnancyInform patients that ONZETRA Xsail should not be used during pregnancy unless the potential benefit justifies thepotential risk to the fetus.
Nursing MothersAdvise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed.
Ability To Perform Complex TasksTreatment with sumatriptan may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks during migraine attacks and after administration of ONZETRA Xsail.
Local IrritationInform patients that they may experience local irritation of their nose and throat. The symptoms will generally resolve in less than 2 hours.
How to Use ONZETRA Xsail with the breath powered deviceProvide patients with instructions on the proper use of ONZETRA Xsail with the breath powered device.
Advise patients that use of the breath powered device is for ONZETRA Xsail only. No other product or substance is approved for use in the breath powered device.
Advise patients to remove a disposable nosepiece from the foil pouch, remove the clear device cap from the reusable device, and click the nosepiece into the device body.
Advise the patient to fully press and release the white piercing button on the device body to pierce the capsule inside the nosepiece. Instruct the patient to press the white piercing button only once.
Advise the patient to insert the nosepiece into the nostril so that it makes a tight seal. The device is then rotated and the mouthpiece inserted between the lips.
Instruct the patient to blow forcefully through the mouthpiece to deliver the sumatriptan powder into the nasal cavity. Vibration (e.g., a rattling noise) may occur, and indicates that the patient is blowing forcefully, as directed.
Advise the patient to remove and discard the nosepiece in the trash once the medication has been administered.
Instruct the patient to follow the same process using a second nosepiece in the other nostril to administer the remainder of the total recommended dose.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility CarcinogenesisIn carcinogenicity studies in mouse and rat in which sumatriptan was administered orally for 78 weeks and 104 weeks, respectively, there was no evidence in either species of an increase in tumors related to sumatriptan administration.
Carcinogenicity studies of sumatriptan using the nasal route have not been conducted.
MutagenesisSumatriptan was negative in in vitro (bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays.
Impairment of FertilityWhen sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses of up to 60 mg/kg/day. When sumatriptan (5, 50, or 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than 5 mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.
Fertility studies of sumatriptan using the intranasal route have not been conducted.
Use In Specific Populations Pregnancy Pregnancy Category CThere are no adequate and well-controlled trials in pregnant women. In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal. Developmental toxicity studies of sumatriptan by the intranasal route have not been conducted. ONZETRA Xsail should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 and 0.75 mg/kg/day, respectively.
Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day.
Nursing MothersSumatriptan is excreted in human milk following subcutaneous administration. Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with ONZETRA Xsail.
Pediatric UseSafety and effectiveness has not been established in pediatric patients younger than 18 years of age.
Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 adolescent migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.
Five controlled clinical trials (2 single-attack studies, 3 multiple-attack studies) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 adolescent migraineurs. These studies did not establish the efficacy of oral sumatriptan compared to placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older adolescents.
Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or nasal sumatriptan are not presently available.
Geriatric UseClinical trials of ONZETRA Xsail did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with subcutaneous, oral, and liquid nasal spray sumatriptan has not identified differences in responses between the elderly and younger patients. In general, treatment for an elderly patient should be cautious, reflecting the greater frequency of decreased or abnormal hepatic function, renal function, or cardiac function, more pronounced blood pressure increases, higher risks for unrecognized CAD, and/or concomitant disease or other drug therapy.
A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving ONZETRA Xsail.
Hepatic ImpairmentThe clearance of oral sumatriptan was reduced in patients with moderate hepatic impairment. Similar changes can be expected following intranasal administration. The effect of severe hepatic impairment was NOT evaluated using oral formulation. The use of ONZETRA Xsail in patients with severe hepatic impairment is contraindicated.
The recommended dosage of ONZETRA is 22 mg of sumatriptan nasal powder (2 nosepieces), administered using the Xsail breath-powered delivery device. If the migraine has not resolved by 2 hours after taking ONZETRA Xsail, or returns after a transient improvement, a second dose of 22 mg may be administered at least 2 hours after the first dose. The maximum recommended dose that may be given in 24 hours is two doses of ONZETRA Xsail (44 mg/4 nosepieces) or one dose of ONZETRA Xsail and one dose of another sumatriptan product, separated by at least 2 hours. The safety of treating an average of more than 4 headaches in a 30 day period has not been established.
Administration InstructionsThe recommended dose of 22 mg is administered by using one 11 mg nosepiece in each nostril. For administration of ONZETRA Xsail, the patient removes the clear device cap from the reusable delivery device, then removes a disposable nosepiece from its foil pouch and clicks the nosepiece into the device body. The patient then fully presses and promptly releases the white piercing button on the device body to pierce the capsule inside the nosepiece. The white piercing button should only be pressed once and released prior to administration to each nostril. The nosepiece is then inserted into the nostril so that it makes a tight seal. Keeping the nosepiece in the nose, the device is rotated to place the mouthpiece into the mouth. The patient blows forcefully through the mouthpiece to deliver the sumatriptan powder into the nasal cavity. Vibration (e.g., a rattling noise) may occur, and indicates that the patient is blowing forcefully, as directed. Once the medication in the first nosepiece has been administered, the patient removes and discards the nosepiece. The same process must then be repeated using a second 11 mg nosepiece into the other nostril to administer the remainder of the total recommended 22 mg dose.
The following serious adverse reactions are discussed in more detail in other sections of the prescribing information:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug, and may not reflect the rates observed in practice.
Table 1 lists adverse reactions that occurred in 2 placebo-controlled clinical trials in 301 patients with migraine who took at least 1 dose of ONZETRA Xsail or placebo. Only adverse reactions that occurred at a frequency of 2% or more with ONZETRA Xsail and that occurred at a frequency greater than the placebo group are included in Table 1.
Table 1: Adverse Reactions Reported by at Least 2% of
Patients in 2 Controlled Migraine Trials
| Adverse Reaction | Percent of Patients Reporting | |
| ONZETRA N=151 |
Placebo N=150 |
|
| Abnormal Taste | 20 | 3 |
| Nasal Discomfort | 11a | 1 |
| Rhinorrhea | 5 | 2 |
| Rhinitis | 2 | 0 |
| a Limited examinations of the nose and throat did not reveal any clinically noticeable injury in these patients. |
There is insufficient data with ONZETRA Xsail to assess the impact of age, gender, and race on adverse effects.
DRUG INTERACTIONS Ergot-Containing DrugsErgot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine containing or ergot-type medications (like dihydroergotamine or methysergide) and ONZETRA Xsail within 24 hours of each other is contraindicated.
Monoamine Oxidase InhibitorsMAO-A inhibitors increase systemic exposure by up to 7-fold. Therefore, the use of ONZETRA Xsail in patients receiving MAO-A inhibitors is contraindicated.
Other 5-HT1 AgonistsBecause their vasospastic effects may be additive, co-administration of ONZETRA Xsail and other 5-HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.
Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors And Serotonin SyndromeCases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors.
