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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TREXIMET (TREXIMET).
| Breastfeeding | Sumatriptan excreted in human milk in low amounts (M/P ratio 2.1 based on AUC). Naproxen excreted in milk (M/P ratio 0.10-0.20). Potential adverse effects in infant (drowsiness, gastrointestinal effects). American Academy of Pediatrics recommends caution; consider immediate-release sumatriptan alone if breastfeeding. |
| 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. |
■ 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 |
Hypersensitivity to sumatriptan, naproxen, or any component; history of coronary artery disease, cerebrovascular disease, peripheral vascular disease; uncontrolled hypertension; hemiplegic or basilar migraine; within 24 hours of ergotamine derivatives or 5-HT1 agonists; within 24 hours of MAO-A inhibitors; severe hepatic impairment; active gastrointestinal bleeding; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; third trimester of pregnancy; peri-operative pain in CABG surgery.
| 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. |
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| 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. |