TREXIMET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TREXIMET (TREXIMET).
Treximet is a combination of sumatriptan (5-HT1B/1D receptor agonist) and naproxen sodium (NSAID). Sumatriptan causes vasoconstriction of cranial blood vessels and inhibits trigeminal nerve transmission; naproxen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
| Metabolism | Sumatriptan: primarily metabolized by monoamine oxidase A (MAO-A). Naproxen: metabolized by CYP2C9 and glucuronidation. |
| Excretion | Renal: sumatriptan (22% unchanged, 38% as metabolites), naproxen (95% as naproxen and conjugates); fecal: ~5% for sumatriptan. |
| Half-life | Sumatriptan: 2–2.5 h; Naproxen: 12–17 h (terminal); clinical context: twice-daily dosing for migraine. |
| Protein binding | Sumatriptan: 14–21%; Naproxen: >99% (albumin). |
| Volume of Distribution | Sumatriptan: 2.4 L/kg (extensive tissue distribution); Naproxen: 0.16 L/kg (limited to extracellular fluid). |
| Bioavailability | Oral sumatriptan: 15% (due to first-pass metabolism), naproxen: 95%. |
| Onset of Action | Oral: sumatriptan 30–60 min, naproxen 1–2 h. |
| Duration of Action | Sumatriptan: 2–4 h; Naproxen: 8–12 h; combination provides sustained relief for up to 24 h in some patients. |
| Molecular Weight | Sumatriptan: 295.4 Da; Naproxen: 230.3 Da |
TREXIMET (sumatriptan 85 mg / naproxen sodium 500 mg) orally as a single tablet at onset of migraine headache. Maximum dose is one tablet in 24 hours.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). No dose adjustment required for mild to moderate impairment (CrCl ≥30 mL/min). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). No dose adjustment for mild to moderate impairment (Child-Pugh class A or B). |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years. Not recommended. |
| Geriatric use | Use with caution due to age-related renal function decline and increased risk of cardiovascular events. Consider lower starting doses; however, no specific dose adjustment recommendations exist. |
| 1st trimester | Sumatriptan/naproxen sodium: Avoid in first trimester unless benefit outweighs risk. Sumatriptan is pregnancy category C; naproxen is category D after 30 weeks. Limited human data show no major teratogenic risk for sumatriptan; naproxen is associated with adverse fetal effects (premature closure of ductus arteriosus, oligohydramnios) particularly in third trimester. |
| 2nd trimester | Use only if clearly needed. Sumatriptan crosses placenta; naproxen may cause fetal renal impairment and oligohydramnios. No specific data for combination in second trimester. |
| 3rd trimester | Contraindicated after 30 weeks due to naproxen's risk of premature ductus arteriosus closure and persistent pulmonary hypertension in newborn. Sumatriptan may cause uterine contractions and reduced placental blood flow. |
Clinical note
Comprehensive clinical and safety monograph for TREXIMET (TREXIMET).
| Placental transfer | Sumatriptan crosses the placenta with a cord-to-maternal plasma ratio of 0.19-0.55. Naproxen crosses the placenta; fetal levels reach 1% of maternal levels. Both drugs appear to have limited placental transfer, but naproxen can accumulate in fetal tissues due to reduced clearance. |
■ FDA Black Box Warning
NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Cardiovascular risk is greater in patients with known cardiovascular disease or risk factors. NSAIDs are contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
Prinzmetal's anginaCoronary artery disease, history of myocardial infarction, or silent ischemiaUncontrolled hypertensionHemiplegic or basilar migraineUse within 24 hours of ergotamine-containing medications or other triptansSevere hepatic impairmentActive peptic ulcer disease or gastrointestinal bleedingHypersensitivity to sumatriptan, naproxen, or any componentThird trimester of pregnancy (after 30 weeks)
| Precautions | Cardiovascular events, gastrointestinal bleeding/ulceration, serotonin syndrome (especially with SSRIs/SNRIs), hypertension, anaphylactic reactions, renal toxicity, hepatotoxicity, risk of asthma exacerbation, hematologic toxicity, ocular effects, and increased risk of myocardial ischemia/infarction. |
| Food/Dietary |
Loading safety data…
| Breastfeeding | Sumatriptan is excreted into breast milk in small amounts (4.3% of maternal dose) with an estimated infant dose of 3-5% of maternal weight-adjusted dose. Naproxen is excreted in breast milk at low levels (1% of maternal dose). Both are considered compatible with breastfeeding by the AAP, but observe infant for potential adverse effects (diarrhea, drowsiness). Avoid in breastfeeding mothers of infants with known sensitivity to NSAIDs or sumatriptan. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Pregnancy Category C. First trimester: No adequate studies; potential risk based on animal data (skeletal and visceral malformations at supratherapeutic doses). Second and third trimesters: Known risk of premature closure of ductus arteriosus and oligohydramnios due to NSAID component (sumatriptan 85mg/naproxen sodium 500mg). Use avoided, especially after 30 weeks gestation. |
| Fetal Monitoring | Monitor fetal heart rate and uterine contractility if used during labor. Assess amniotic fluid volume via ultrasound if prolonged use (oligohydramnios risk). Monitor for signs of premature ductus arteriosus closure (fetal echocardiography if used near term). Maternal blood pressure monitoring due to potential vasospasm. |
| Fertility Effects | NSAID component may impair female fertility via inhibition of prostaglandin synthesis, affecting ovulation (reversible upon discontinuation). No data on male fertility. Sumatriptan not associated with fertility impairment in animals. |
| No significant food interactions reported. However, alcohol may increase the risk of gastrointestinal bleeding from the naproxen component. Avoid high-fat meals as they may delay absorption, potentially reducing the onset of action. |
| Clinical Pearls | TREXIMET (sumatriptan/naproxen sodium) is a fixed-dose combination for acute migraine. Naproxen enhances sumatriptan efficacy and reduces recurrence. Avoid within 24 hours of ergotamines or other 5-HT1 agonists due to additive vasospasm risk. Contraindicated in patients with a history of coronary artery disease, cerebrovascular disease, or hemiplegic/basilar migraine. Use with caution in patients with risk factors for cardiovascular disease, and consider first dose in a monitored setting for such patients. The naproxen component may cause gastrointestinal bleeding, especially in elderly or those with a history of ulcers. Do not use for migraine prophylaxis. |
| Patient Advice | Take one tablet at the first sign of migraine headache; do not use for prevention. · Do not exceed one tablet in 24 hours unless directed by your doctor. · Seek emergency medical attention if you experience chest pain, shortness of breath, sudden numbness or weakness, or severe abdominal pain. · Avoid alcohol while taking this medication as it may increase risk of stomach bleeding. · Inform your doctor if you are pregnant or breastfeeding before use. · Do not take with other NSAIDs or triptans within 24 hours. |