İHALE DÜNYASI
İHALE DÜNYASI
Sumatriptan Nasal Spray contains sumatriptan, a selective 5-hydroxytryptamine 1 receptor subtype agonist. Sumatriptan is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide, and it has the following structure: The empirical formula is C 14 H 21 N 3 O 2 S, representing a molecular weight of 295.4. Sumatriptan is a white to off-white powder that is readily soluble in water and in saline. Each Sumatriptan Nasal Spray contains 5 or 20 mg of sumatriptan in a 100-?L unit dose aqueous buffered solution containing monobasic potassium phosphate NF, anhydrous dibasic sodium phosphate USP, sulfuric acid NF, sodium hydroxide NF, and purified water USP. The pH of the solution is approximately 5.5. The osmolality of the solution is 372 or 742 mOsmol for the 5- and 20-mg Sumatriptan Nasal Spray, respectively. Chemical structure
Sumatriptan Nasal Spray is indicated for the acute treatment of migraine attacks with or without aura in adults. Sumatriptan Nasal Spray is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see CONTRAINDICATIONS). Safety and effectiveness of sumatriptan nasal spray have not been established for cluster headache, which is present in an older, predominantly male population.
In controlled clinical trials, single doses of 5, 10, or 20 mg of sumatriptan nasal spray administered into 1 nostril were effective for the acute treatment of migraine in adults. A greater proportion of patients had headache response following a 20-mg dose than following a 5- or 10-mg dose (see CLINICAL TRIALS). Individuals may vary in response to doses of Sumatriptan Nasal Spray. The choice of dose should therefore be made on an individual basis, weighing the possible benefit of the 20-mg dose with the potential for a greater risk of adverse events. A 10-mg dose may be achieved by the administration of a single 5-mg dose in each nostril. There is evidence that doses above 20 mg do not provide a greater effect than 20 mg. If the headache returns, the dose may be repeated once after 2 hours, not to exceed a total daily dose of 40 mg. The safety of treating an average of more than 4 headaches in a 30-day period has not been established.
Sumatriptan Nasal Spray should not be given to patients with history, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes. In addition, patients with other significant underlying cardiovascular diseases should not receive Sumatriptan Nasal Spray. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable angina of effort, vasospastic forms of angina such as the Prinzmetal variant), all forms of myocardial infarction, and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease (see WARNINGS). Because Sumatriptan Nasal Spray may increase blood pressure, it should not be given to patients with uncontrolled hypertension. Concurrent administration of MAO-A inhibitors or use within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated (see CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions). Sumatriptan Nasal Spray and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should Sumatriptan Nasal Spray and another 5-HT 1 agonist. Sumatriptan Nasal Spray should not be administered to patients with hemiplegic or basilar migraine. Sumatriptan Nasal Spray is contraindicated in patients with hypersensitivity to sumatriptan or any of its components. Sumatriptan Nasal Spray is contraindicated in patients with severe hepatic impairment.
Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan injection or tablets. These events are extremely rare and most have been reported in patients with risk factors predictive of CAD. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS). Significant hypertensive episodes, including hypertensive crises, have been reported on rare occasions in patients with or without a history of hypertension (see WARNINGS). Incidence in Controlled Clinical Trials Among 3,653 patients treated with sumatriptan nasal spray in active- and placebo-controlled clinical trials, less than 0.4% of patients withdrew for reasons related to adverse events. Table 2 lists adverse events that occurred in worldwide placebo-controlled clinical trials in 3,419 migraineurs. The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ. Only events that occurred at a frequency of 1% or more in the sumatriptan nasal spray 20-mg treatment group and were more frequent in that group than in the placebo group are included in Table 2. Table 2. Treatment-Emergent Adverse Events Reported by at Least 1% of Patients in Controlled Migraine Trials Adverse Event Type Percent of Patients Reporting Placebo (n = 704) Sumatriptan 5 mg (n = 496) Sumatriptan 10 mg (n = 1,007) Sumatriptan 20 mg (n = 1,212) Atypical sensations Burning sensation 0.1% 0.4% 0.6% 1.4% Ear, nose, and throat Disorder/discomfort of nasal cavity/sinuses 2.4% 2.8% 2.5% 3.8% Throat discomfort 0.9% 0.8% 1.8% 2.4% Gastrointestinal Nausea and/or vomiting 11.3% 12.2% 11.0% 13.5% Neurological Bad/unusual taste 1.7% 13.5% 19.3% 24.5% Dizziness/vertigo 0.9% 1.0% 1.7% 1.4% Phonophobia also occurred in more than 1% of patients but was more frequent on placebo. Sumatriptan nasal spray is generally well tolerated. Across all doses, most adverse reactions were mild and transient and did not lead to long-lasting effects. The incidence of adverse events in controlled clinical trials was not affected by gender, weight, or age of the patients; use of prophylactic medications; or presence of aura. There were insufficient data to assess the impact of race on the incidence of adverse events. Other Events Observed in Association With the Administration of Sumatriptan Nasal Spray In the paragraphs that follow, the frequencies of less commonly reported adverse clinical events are presented. Because the reports include events observed in open and uncontrolled studies, the role of sumatriptan nasal spray in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, etc., limit the value of the quantitative frequency estimates provided. Event frequencies are calculated as the number of patients who used sumatriptan nasal spray (5, 10, or 20 mg in controlled and uncontrolled trials) and reported an event divided by the total number of patients (N = 3,711) exposed to sumatriptan nasal spray. All reported events are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: infrequent adverse events are those occurring in 1/100 to 1/1,000 patients and rare adverse events are those occurring in fewer than 1/1,000 patients. Atypical Sensations: Infrequent were tingling, warm/hot sensation, numbness, pressure sensation, feeling strange, feeling of heaviness, feeling of tightness, paresthesia, cold sensation, and tight feeling in head. Rare were dysesthesia and prickling sensation. Cardiovascular: Infrequent were flushing and hypertension (see WARNINGS), palpitations, tachycardia, changes in ECG, and arrhythmia (see WARNINGS and PRECAUTIONS). Rare were abdominal aortic aneurysm, hypotension, bradycardia, pallor, and phlebitis. Chest Symptoms: Infrequent were chest tightness, chest discomfort, and chest pressure/heaviness (see PRECAUTIONS: General). Ear, Nose, and Throat: Infrequent were disturbance of hearing and ear infection. Rare were otalgia and Meniere disease. Endocrine and Metabolic: Infrequent was thirst. Rare were galactorrhea, hypothyroidism, and weight loss. Eye: Infrequent were irritation of eyes and visual disturbance. Gastrointestinal: Infrequent were abdominal discomfort, diarrhea, dysphagia, and gastroesophageal reflux. Rare were constipation, flatulence/eructation, hematemesis, intestinal obstruction, melena, gastroenteritis, colitis, hemorrhage of gastrointestinal tract, and pancreatitis. Mouth and Teeth: Infrequent was disorder of mouth and tongue (e.g., burning of tongue, numbness of tongue, dry mouth). Musculoskeletal: Infrequent were neck pain/stiffness, backache, weakness, joint symptoms, arthritis, and myalgia. Rare were muscle cramps, tetany, intervertebral disc disorder, and muscle stiffness. Neurological: Infrequent were drowsiness/sedation, anxiety, sleep disturbances, tremors, syncope, shivers, chills, depression, agitation, sensation of lightness, and mental confusion. Rare were difficulty concentrating, hunger, lacrimation, memory disturbances, monoplegia/diplegia, apathy, disturbance of smell, disturbance of emotions, dysarthria, facial pain, intoxication, stress, decreased appetite, difficulty coordinating, euphoria, and neoplasm of pituitary. Respiratory: Infrequent were dyspnea and lower respiratory tract infection. Rare was asthma. Skin: Infrequent were rash/skin eruption, pruritus, and erythema. Rare were herpes, swelling of face, sweating, and peeling of skin. Urogenital: Infrequent were dysuria, disorder of breasts, and dysmenorrhea. Rare were endometriosis and increased urination. Miscellaneous: Infrequent were cough, edema, and fever. Rare were hypersensitivity, swelling of extremities, voice disturbances, difficulty in walking, and lymphadenopathy. Other Events Observed in the Clinical Development of Sumatriptan The following adverse events occurred in clinical trials with sumatriptan injection and sumatriptan tablets. Because the reports include events observed in open and uncontrolled studies, the role of sumatriptan in their causation cannot be reliably determined. All reported events are included except those already listed, those too general to be informative, and those not reasonably associated with the use of the drug. Breasts: Breast swelling; cysts, lumps, and masses of breasts; nipple discharge; primary malignant breast neoplasm; and tenderness. Cardiovascular: Abnormal pulse, angina, atherosclerosis, cerebral ischemia, cerebrovascular lesion, heart block, peripheral cyanosis, pulsating sensations, Raynaud syndrome, thrombosis, transient myocardial ischemia, various transient ECG changes (nonspecific ST or T wave changes, prolongation of PR or QTc intervals, sinus arrhythmia, nonsustained ventricular premature beats, isolated junctional ectopic beats, atrial ectopic beats, delayed activation of the right ventricle), and vasodilation. Ear, Nose, and Throat: Allergic rhinitis; ear, nose, and throat hemorrhage; external otitis; feeling of fullness in the ear(s); hearing disturbances; hearing loss; nasal inflammation; sensitivity to noise; sinusitis; tinnitus; and upper respiratory inflammation. Endocrine and Metabolic: Dehydration; endocrine cysts, lumps, and masses; elevated thyrotropin stimulating hormone (TSH) levels; fluid disturbances; hyperglycemia; hypoglycemia; polydipsia; and weight gain. Eye: Accommodation disorders, blindness and low vision, conjunctivitis, disorders of sclera, external ocular muscle disorders, eye edema and swelling, eye itching, eye hemorrhage, eye pain, keratitis, mydriasis, and vision alterations. Gastrointestinal: Abdominal distention, dental pain, disturbances of liver function tests, dyspeptic symptoms, feelings of gastrointestinal pressure, gallstones, gastric symptoms, gastritis, gastrointestinal pain, hypersalivation, hyposalivation, oral itching and irritation, peptic ulcer, retching, salivary gland swelling, and swallowing disorders. Hematological Disorders: Anemia. Injection Site Reaction Miscellaneous: Contusions, fluid retention, hematoma, hypersensitivity to various agents, jaw discomfort, miscellaneous laboratory abnormalities, overdose, "serotonin agonist effect," and speech disturbance. Musculoskeletal: Acquired musculoskeletal deformity, arthralgia and articular rheumatitis, muscle atrophy, muscle tiredness, musculoskeletal inflammation, need to flex calf muscles, rigidity, tightness, and various joint disturbances (pain, stiffness, swelling, ache). Neurological: Aggressiveness, bradylogia, cluster headache, convulsions, detachment, disturbances of taste, drug abuse, dystonia, facial paralysis, globus hystericus, hallucinations, headache, heat sensitivity, hyperesthesia, hysteria, increased alertness, malaise/fatigue, migraine, motor dysfunction, myoclonia, neuralgia, neurotic disorders, paralysis, personality change, phobia, photophobia, psychomotor disorders, radiculopathy, raised intracranial pressure, relaxation, stinging sensations, transient hemiplegia, simultaneous hot and cold sensations, suicide, tickling sensations, twitching, and yawning. Pain and Other Pressure Sensations: Chest pain, neck tightness/pressure, throat/jaw pain/tightness/pressure, and pain (location specified). Respiratory: Breathing disorders, bronchitis, diseases of the lower respiratory tract, hiccoughs, and influenza. Skin: Dry/scaly skin, eczema, seborrheic dermatitis, skin nodules, skin tenderness, tightness of skin, and wrinkling of skin. Urogenital: Abortion, abnormal menstrual cycle, bladder inflammation, hematuria, inflammation of fallopian tubes, intermenstrual bleeding, menstruation symptoms, micturition disorders, renal calculus, urethritis, urinary frequency, and urinary infections. Postmarketing Experience (Reports for Subcutaneous or Oral Sumatriptan) The following section enumerates potentially important adverse events that have occurred in clinical practice and that have been reported spontaneously to various surveillance systems. The events enumerated represent reports arising from both domestic and nondomestic use of oral or subcutaneous dosage forms of sumatriptan. The events enumerated include all except those already listed in the ADVERSE REACTIONS section above or those too general to be informative. Because the reports cite events reported spontaneously from worldwide postmarketing experience, frequency of events and the role of sumatriptan in their causation cannot be reliably determined. It is assumed, however, that systemic reactions following sumatriptan use are likely to be similar regardless of route of administration. Blood: Hemolytic anemia, pancytopenia, thrombocytopenia. Cardiovascular: Atrial fibrillation, cardiomyopathy, colonic ischemia (see WARNINGS), Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis. Ear, Nose, and Throat: Deafness. Eye: Ischemic optic neuropathy, retinal artery occlusion, retinal vein thrombosis, loss of vision. Gastrointestinal: Ischemic colitis with rectal bleeding (see WARNINGS), xerostomia. Hepatic: Elevated liver function tests. Neurological: Central nervous system vasculitis, cerebrovascular accident, dysphasia, serotonin syndrome, subarachnoid hemorrhage. Non-Site Specific: Angioneurotic edema, cyanosis, death (see WARNINGS), temporal arteritis. Psychiatry: Panic disorder. Respiratory: Bronchospasm in patients with and without a history of asthma. Skin: Exacerbation of sunburn, hypersensitivity reactions (allergic vasculitis, erythema, pruritus, rash, shortness of breath, urticaria; in addition, severe anaphylaxis/anaphylactoid reactions have been reported [see WARNINGS]), photosensitivity. Urogenital: Acute renal failure.
Sumatriptan Nasal Spray should only be used where a clear diagnosis of migraine headache has been established. Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events Sumatriptan should not be given to patients with documented ischemic or vasospastic coronary artery disease (CAD) (see CONTRAINDICATIONS). It is strongly recommended that sumatriptan not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient's medical history or electrocardiographic investigations reveal findings indicative of, or consistent with, coronary artery vasospasm or myocardial ischemia, sumatriptan should not be administered (see CONTRAINDICATIONS). For patients with risk factors predictive of CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of Sumatriptan Nasal Spray take place in the setting of a physician's office or similar medically staffed and equipped facility unless the patient has previously received sumatriptan. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining an electrocardiogram (ECG) during the interval immediately following the first dose in these patients with risk factors. It is recommended that patients who are intermittent long-term users of sumatriptan and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use sumatriptan. The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to sumatriptan. Drug-Associated Cardiac Events and Fatalities Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported within a few hours following the administration of sumatriptan injection or tablets. Considering the extent of use of sumatriptan in patients with migraine, the incidence of these events is extremely low. The fact that sumatriptan can cause coronary vasospasm, that some of these events have occurred in patients with no prior cardiac disease history and with documented absence of CAD, and the close proximity of the events to sumatriptan use support the conclusion that some of these cases were caused by the drug. In many cases, however, where there has been known underlying coronary artery disease, the relationship is uncertain. Premarketing Experience With Sumatriptan: Among approximately 4,000 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of sumatriptan nasal spray, 1 patient experienced an asymptomatic subendocardial infarction possibly subsequent to a coronary vasospastic event. Of 6,348 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of oral sumatriptan, 2 experienced clinical adverse events shortly after receiving oral sumatriptan that may have reflected coronary vasospasm. Neither of these adverse events was associated with a serious clinical outcome. Among the more than 1,900 patients with migraine who participated in premarketing controlled clinical trials of subcutaneous sumatriptan, there were 8 patients who sustained clinical events during or shortly after receiving sumatriptan that may have reflected coronary artery vasospasm. Six of these 8 patients had ECG changes consistent with transient ischemia, but without accompanying clinical symptoms or signs. Of these 8 patients, 4 had either findings suggestive of CAD or risk factors predictive of CAD prior to study enrollment. Postmarketing Experience With Sumatriptan: Serious cardiovascular events, some resulting in death, have been reported in association with the use of sumatriptan injection or tablets. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively the proportion of the reported cases that were actually caused by sumatriptan or to reliably assess causation in individual cases. On clinical grounds, the longer the latency between the administration of sumatriptan and the onset of the clinical event, the less likely the association is to be causative. Accordingly, interest has focused on events beginning within 1 hour of the administration of sumatriptan. Cardiac events that have been observed to have onset within 1 hour of sumatriptan administration include: coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation, cardiac arrest, and death. Some of these events occurred in patients who had no findings of CAD and appear to represent consequences of coronary artery vasospasm. However, among domestic reports of serious cardiac events within 1 hour of sumatriptan administration, almost all of the patients had risk factors predictive of CAD and the presence of significant underlying CAD was established in most cases (see CONTRAINDICATIONS). Drug-Associated Cerebrovascular Events and Fatalities Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with oral or subcutaneous sumatriptan, and some have resulted in fatalities. The relationship of sumatriptan to these events is uncertain. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. It should also be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., cerebrovascular accident, transient ischemic attack). Other Vasospasm-Related Events Sumatriptan may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported. Very rare reports of transient and permanent blindness and significant partial vision loss have been reported with the use of sumatriptan. Visual disorders may also be part of a migraine attack. Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome may occur with triptans, including treatment with sumatriptan, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (e.g., venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Increase in Blood Pressure Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions in patients with and without a history of hypertension. Sumatriptan is contraindicated in patients with uncontrolled hypertension (see CONTRAINDICATIONS). Sumatriptan should be administered with caution to patients with controlled hypertension as transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients. Local Irritation Of the 3,378 patients using the nasal spray (5-, 10-, or 20-mg doses) on 1 or 2 occasions in controlled clinical studies, approximately 5% noted irritation in the nose and throat. Irritative symptoms such as burning, numbness, paresthesia, discharge, and pain or soreness were noted to be severe in about 1% of patients treated. The symptoms were transient and in approximately 60% of the cases, the symptoms resolved in less than 2 hours. Limited examinations of the nose and throat did not reveal any clinically noticeable injury in these patients. The consequences of extended and repeated use of sumatriptan nasal spray on the nasal and/or respiratory mucosa have not been systematically evaluated in patients. No increase in the incidence of local irritation was observed in patients using sumatriptan nasal spray repeatedly for up to 1 year. In inhalation studies in rats dosed daily for up to 1 month at exposures as low as one half the maximum daily human exposure (based on dose per surface area of nasal cavity), epithelial hyperplasia (with and without keratinization) and squamous metaplasia were observed in the larynx at all doses tested. These changes were partially reversible after a 2-week drug-free period. When dogs were dosed daily with various formulations by intranasal instillation for up to 13 weeks at exposures of 2 to 4 times the maximum daily human exposure (based on dose per surface area of nasal cavity), respiratory and nasal mucosa exhibited evidence of epithelial hyperplasia, focal squamous metaplasia, granulomata, bronchitis, and fibrosing alveolitis. A no-effect dose was not established. The changes observed in both species are not considered to be signs of either preneoplastic or neoplastic transformation. Local effects on nasal and respiratory tissues after chronic intranasal dosing in animals have not been studied. Concomitant Drug Use In patients taking MAO-A inhibitors, sumatriptan plasma levels attained after treatment with recommended doses are 2-fold (following subcutaneous administration) to 7-fold (following oral administration) higher than those obtained under other conditions. Accordingly, the coadministration of sumatriptan and an MAO-A inhibitor is contraindicated (see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS). Hypersensitivity Hypersensitivity (anaphylaxis/anaphylactoid) reactions have occurred on rare occasions in patients receiving sumatriptan. Such reactions can be life threatening or fatal. In general, hypersensitivity reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens (see CONTRAINDICATIONS).
Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported during combined use of SSRIs or SNRIs and triptans (see WARNINGS). Ergot-Containing Drugs: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan within 24 hours of each other should be avoided (see CONTRAINDICATIONS). Monoamine Oxidase-A Inhibitors: MAO-A inhibitors reduce sumatriptan clearance, significantly increasing systemic exposure. Therefore, the use of Sumatriptan Nasal Spray in patients receiving MAO-A inhibitors is contraindicated (see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS).