NARATRIPTAN Drug Interactions: What You Need to Know

INTERACTIONS

7.1 Ergot-Containing Drugs Ergot-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 naratriptan tablets within 24 hours of each other is contraindicated.

7.2 Other 5-HT 1 Agonists Concomitant use of other 5-HT 1B/1D agonists (including triptans) within 24 hours of treatment with naratriptan tablets is contraindicated because the risk of vasospastic reactions may be additive.

7.3 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors <span class="opacity-50 text-xs">[see Warnings and Precautions (5.7)]</span> .

Naratriptan is contraindicated in patients with:

• Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal’s angina [see Warnings and Precautions ( 5.1 )]
• Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions ( 5.2 )]
• History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because such patients are at a higher risk of stroke [see Warnings and Precautions ( 5.4 )]
• Peripheral vascular disease [see Warnings and Precautions ( 5.5 )]
• Ischemic bowel disease [see Warnings and Precautions ( 5.5 )]
• Uncontrolled hypertension [see Warnings and Precautions ( 5.8 )]
• Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions ( 7.1 , 7.2 )]
• Hypersensitivity to naratriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions ( 5.9 )]
• Severe renal or hepatic impairment [see Use in Specific Populations ( 8.6 , 8.7 ), Clinical Pharmacology ( 12.3 )]
• History of coronary artery disease or coronary artery vasospasm ( 4 )
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders ( 4 )
• History of stroke, transient ischemic attack, or hemiplegic or basilar migraine ( 4 )
• Peripheral vascular disease ( 4 )
• Ischemic bowel disease ( 4 )
• Uncontrolled hypertension ( 4 )
• Recent (within 24 hours) use of another 5-HT 1 agonist (e.g., another triptan) or an ergotamine-containing medication ( 4 )
• Hypersensitivity to naratriptan (angioedema and anaphylaxis seen) ( 4 )
• Severe renal or hepatic impairment ( 4 )

AND PRECAUTIONS Myocardial ischemia/infarction and Prinzmetal’s angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. (5.1) Arrhythmias: Discontinue naratriptan tablets if occurs. (5.2) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for CAD in patients at high risk. (5.3) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue naratriptan tablets if occurs. (5.4) Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue naratriptan tablets if occurs. (5.5) Medication overuse headache: Detoxification may be necessary. (5.6) Serotonin syndrome: Discontinue naratriptan tablets if occurs. (5.7)

5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina Naratriptan tablets are 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 naratriptan tablets. Some of these reactions occurred in patients without known CAD. Naratriptan tablets may cause coronary artery vasospasm (Prinzmetal’s 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 naratriptan tablets. If there is evidence of CAD or coronary artery vasospasm, naratriptan tablets are contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of naratriptan tablets in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of naratriptan tablets. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of naratriptan tablets.

5.2 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-HT 1 agonists. Discontinue naratriptan tablets if these disturbances occur. Naratriptan tablets are contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure Sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw commonly occur after treatment with naratriptan tablets and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. 5-HT 1 agonists, including naratriptan tablets, are contraindicated in patients with CAD and those with Prinzmetal’s variant angina.

5.4 Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT 1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1 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 naratriptan tablets if a cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine, exclude other potentially serious neurological conditions. Naratriptan tablets are contraindicated in patients with a history of stroke or TIA.

5.5 Other Vasospasm Reactions Naratriptan tablets 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 non-coronary vasospasm reaction following the use of any 5-HT 1 agonist, rule out a vasospastic reaction before receiving additional doses of naratriptan tablets. Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists have not been clearly established.

5.6 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.

5.7 Serotonin Syndrome Serotonin syndrome may occur with naratriptan tablets, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors <span class="opacity-50 text-xs">[see Drug Interactions (7.3)]</span>. 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 naratriptan tablets if serotonin syndrome is suspected.

5.8 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-HT 1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with naratriptan tablets. Naratriptan tablets are contraindicated in patients with uncontrolled hypertension.

5.9 Anaphylactic Reactions There have been reports of anaphylaxis and hypersensitivity reactions, including angioedema, in patients receiving naratriptan tablets. 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. Naratriptan tablets are contraindicated in patients with a history of hypersensitivity reaction to naratriptan tablets.