IMITREX spray warnings and precautions

# Warnings and Precautions

### Myocardial Ischemia, Myocardial Infarction, and Prinzmetals Angina
The use of IMITREX Nasal Spray 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 IMITREX Nasal Spray. Some of these reactions occurred in patients without known CAD. IMITREX Nasal Spray may cause coronary artery vasospasm (Prinzmetals angina), even in patients without a history of CAD.
Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving IMITREX Nasal Spray. If there is evidence of CAD or coronary artery vasospasm, IMITREX Nasal Spray is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of IMITREX Nasal Spray in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of IMITREX Nasal Spray. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of IMITREX Nasal Spray.

### Arrhythmias
Life-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 IMITREX Nasal Spray if these disturbances occur. IMITREX Nasal Spray 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/Pressure
Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw may occur after treatment with IMITREX Nasal Spray and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of IMITREX Nasal Spray is contraindicated in patients with CAD and those with Prinzmetals variant angina.

### Cerebrovascular Events
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, 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. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue IMITREX Nasal Spray 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. IMITREX Nasal Spray is contraindicated in patients with a history of stroke or TIA.

### Other Vasospasm Reactions
IMITREX Nasal Spray 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 Raynauds syndrome. In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before using additional IMITREX Nasal Spray.
Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5HT1 agonists. 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 Headache
Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination 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 Syndrome
Serotonin syndrome may occur with IMITREX Nasal Spray, 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 aberrations (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 IMITREX Nasal Spray if serotonin syndrome is suspected.

### Increase in Blood Pressure
Significant 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 IMITREX. IMITREX Nasal Spray is contraindicated in patients with uncontrolled hypertension.

### Local Irritation
Local irritative symptoms such as burning, numbness, paresthesia, discharge, and pain or soreness were reported in approximately 5% of patients in controlled clinical trials and were noted to be severe in about 1%. The symptoms were transient and generally 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 Imitrex Nasal Spray on the nasal and/or respiratory mucosa have not been systematically evaluated in patients.

### Anaphylactic/Anaphylactoid Reactions
Anaphylactic/anaphylactoid reactions have occurred in patients receiving IMITREX. 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. IMITREX Nasal Spray is contraindicated in patients with a history of hypersensitivity reaction to IMITREX.

### Seizures
Seizures have been reported following administration of IMITREX. 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. IMITREX Nasal Spray should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.