AMERGE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMERGE (AMERGE).
Selective serotonin 5-HT1B/1D receptor agonist; binds to 5-HT1B and 5-HT1D receptors on cranial blood vessels and trigeminal nerve endings, causing vasoconstriction and inhibition of pro-inflammatory neuropeptide release.
| Metabolism | Primarily hepatic via CYP1A2 isoenzyme; minor pathways include flavin monooxygenase and other CYP enzymes. |
| Excretion | Renal excretion accounts for approximately 50% of the dose, with about 40% as unchanged drug and 10% as metabolites. Fecal excretion accounts for 30% of the dose. The remainder is unknown. |
| Half-life | Terminal elimination half-life is approximately 26 hours (range 13-40 hours). This long half-life allows for once-daily dosing for prophylaxis, but may prolong the duration of adverse effects. |
| Protein binding | Approximately 60% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 3.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 60%, with no significant food effect. |
| Onset of Action | Oral: Onset of action for acute migraine treatment occurs within 2-4 hours after a single dose. |
| Duration of Action | Clinical duration of action for migraine relief is up to 24 hours with a single 6.25 mg or 12.5 mg oral dose. For prophylaxis, effects are seen with continued daily dosing. |
2.5 mg orally at onset of migraine; may repeat after 4 hours if needed, maximum 5 mg in 24 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl <15 mL/min: not recommended; CrCl 15-30 mL/min: use with caution, maximum 2.5 mg in 24 hours; CrCl >30 mL/min: no adjustment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: not recommended; Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established in patients <18 years; not recommended. |
| Geriatric use | Use with caution due to potential for reduced hepatic/renal function; initial dose 2.5 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMERGE (AMERGE).
| Breastfeeding | Excreted in breast milk; M/P ratio unknown. Avoid use during breastfeeding due to potential adverse effects on infant, including vasospasm and gastrointestinal disturbances. |
| Teratogenic Risk | Pregnancy Category X. First trimester: No adequate studies; contraindicated due to risk of uterine contractions and reduced placental blood flow. Second and third trimesters: Avoid; may cause fetal hypoxia, bradycardia, or preterm labor. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
History of ischemic heart disease, coronary artery vasospasm (including Prinzmetal's angina), other significant cardiovascular disease; cerebrovascular disease (e.g., stroke, TIA); peripheral vascular disease; uncontrolled hypertension; hemiplegic or basilar migraine; within 24 hours of another triptan or ergotamine-containing drug; concomitant use with MAO-A inhibitors; severe hepatic impairment; hypersensitivity to naratriptan or any component.
| Precautions | Risk of myocardial ischemia, infarction, and coronary artery vasospasm; cerebrovascular events; serious cardiac arrhythmias; increased blood pressure; serotonin syndrome (especially with concomitant serotonergic drugs); medication overuse headache; severe hepatic impairment; anaphylaxis/anaphylactoid reactions. |
| Food/Dietary | No clinically significant food interactions. Grapefruit juice does not affect naratriptan metabolism. Avoid alcohol as it may exacerbate migraine symptoms or cause drowsiness. |
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| Monitor maternal blood pressure, heart rate, and signs of ischemia. Fetal heart rate monitoring if inadvertent exposure in later pregnancy. |
| Fertility Effects | No known effects on fertility in animal studies; human data insufficient. |
| Clinical Pearls | Amerge (naratriptan) has a longer half-life (5-6 hours) than sumatriptan, which may be advantageous for patients with prolonged migraines or those who experience headache recurrence. It has the highest oral bioavailability among triptans (70%) and fewer drug interactions due to minimal CYP450 metabolism. It is contraindicated in patients with a history of ischemic heart disease, cerebrovascular disease, or uncontrolled hypertension. Use with caution in patients with liver or kidney impairment, as dose adjustment is required (maximum 2.5 mg in 24 hours for severe impairment). |
| Patient Advice | Take Amerge at the first sign of a migraine headache, not for prevention of migraines. · Do not exceed 2 tablets (2.5 mg each) in 24 hours, with at least 4 hours between doses. · Seek emergency care if you experience chest pain, shortness of breath, or signs of an allergic reaction. · Avoid using Amerge within 24 hours of another triptan or ergotamine-containing medication. · Report any history of heart disease, stroke, or uncontrolled blood pressure to your doctor before use. |