Naratriptan (Page 2 of 6)

5.7 Serotonin Syndrome

Serotonin syndrome may occur with naratriptan, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors [see Drug Interactions (7.3)]. 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 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. Naratriptan is 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 is contraindicated in patients with a history of hypersensitivity reaction to naratriptan.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the prescribing information:

• Myocardial ischemia, myocardial infarction, and Prinzmetal’s angina [see Warnings and Precautions (5.1 )]
• Arrhythmias [see Warnings and Precautions (5.2) ]
• Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3) ]
• Cerebrovascular events [see Warnings and Precautions (5.4) ]
• Other vasospasm reactions [s ee Warnings and Precautions (5.5) ]
• Medication overuse headache [see Warnings and Precautions (5.6) ]
• Serotonin syndrome [see Warnings and Precautions (5.7) ]
• Increase in blood pressure [see Warnings and Precautions (5.8) ]
• Hypersensitivity reactions [see Contraindications (4) , Warnings and Precautions (5.9) ]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a long-term open-label trial where patients were allowed to treat multiple migraine attacks for up to 1 year, 15 patients (3.6%) discontinued treatment due to adverse reactions.

In controlled clinical trials, the most common adverse reactions were paresthesias, dizziness, drowsiness, malaise/fatigue, and throat/neck symptoms, which occurred at a rate of 2% and at least 2 times placebo rate.

Table 1 lists the adverse reactions that occurred in 5 placebo-controlled clinical trials of approximately 1,752 exposures to placebo and naratriptan tablets in adult patients with migraine. Only reactions that occurred at a frequency of 2% or more in groups treated with naratriptan tablets 2.5 mg and that occurred at a frequency greater than the placebo group in the 5 pooled trials are included in Table 1.

Table 1. Adverse Reactions Reported by at Least 2% of Patients Treated With Naratriptan Tablets and at a Frequency Greater Than Placebo

Adverse Reaction	Percent of Patients Reporting
	Naratriptan Tablets 1 mg (n = 627)	Naratriptan Tablets 2.5 mg (n = 627)	Placebo (n = 498)
Atypical sensation	2	4	1
Paresthesias (all types)	1	2	<1
Gastrointestinal	6	7	5
Nausea	4	5	4
Neurological	4	7	3
Dizziness	1	2	1
Drowsiness	1	2	<1
Malaise/fatigue	2	2	1
Pain and pressure sensation	2	4	2
Throat/neck symptoms	1	2	1

The incidence of adverse reactions in controlled clinical trials was not affected by age or weight of the patients, duration of headache prior to treatment, presence of aura, use of prophylactic medications, or tobacco use. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

7 DRUG 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 within 24 hours of each other is contraindicated.