Migraine and headache:
Indications for: TREXIMET
Acute treatment of migraine with or without aura in adults and children ≥12yrs old.
Limitations of Use:
Use only if clear diagnosis of migraine. Not indicated for prevention of migraine attacks. Safety and effectiveness not established for cluster headache.
Clinical Trials:
Adults
In 2 randomized, double-blind, multicenter, parallel-group trials (Study 1 and Study 2), the efficacy of Treximet 85/500 mg (sumatriptan and naproxen sodium) was evaluated for the acute treatment of migraine with or without aura in adults. Patients were randomly assigned to receive either placebo or each individual active component of Treximet as comparison treatments (Study 1 and Study 2). Patients were instructed to treat a migraine of moderate to severe pain with 1 tablet. No rescue medication was allowed within 2 hours postdose.
Headache relief was defined as a reduction in headache severity from moderate or severe pain to mild or no pain. Sustained pain free was defined as a reduction in headache severity from moderate or severe pain to no pain at 2 hours postdose without a return of mild, moderate, or severe pain and no use of rescue medication for 24 hours postdose.
Results from Study 1 and Study 2 showed that 65% and 57% of patients treated with Treximet, respectively, achieved headache pain relief 2 hours postdose compared with 28% and 29% of those treated with placebo (P <.05). Moreover, in Study 1 and 2, a significantly greater proportion of patients treated with Treximet 85/500 mg (25% and 23%) remained pain free without the use of other medications for 24 hours postdose compared with those treated with placebo (8% and 9%) or either sumatriptan (16% and 14%) or naproxen sodium (10%) alone (all P <.01).
There was a decreased incidence of photophobia, phonophobia, and nausea 2 hours after the administration of Treximet 85/500 mg compared with placebo. Regardless of the presence of aura, Treximet 85/500 mg was more effective than placebo for: duration of headache prior to treatment; gender, age, or weight of the subject; or concomitant use of oral contraceptives or common migraine prophylactic drugs (e.g., beta-blockers, anti-epileptic drugs, tricyclic antidepressants).
Pediatric Patients 12 to 17 Years of Age
In a randomized, double-blind, multicenter, parallel-group, placebo-controlled, multicenter trial (Study 3), the efficacy of Treximet was evaluated for the acute treatment of migraine with or without aura in pediatric patients 12 to 17 years of age. Eligible patients included thos with at least a 6-month history of migraine attacks with or without aura usually lasting 3 hours or more when untreated. Following a single-blind, placebo run-in phase, placebo nonresponders were randomly assigned to receive a single dose of either Treximet 10/60 mg, 30/180 mg, 85/500 mg, or placebo. Patients were instructed to treat a single migraine attack with headache pain of moderate to severe intensity. No rescue medication was allowed within 2 hours postdose. Two-hour pain free was defined as a reduction in headache severity from moderate or severe pain to no pain at 2 hours postdose.
Results showed that a significantly greater proportion of patients who received Treximet 10/60 mg (29%), 30/180 mg (27%), 85/500 mg (24%) were pain free at 2 hours postdose compared with placebo (10%) (all P <.01).
A significantly greater percentage of pediatric patients remained pain free without use of other medications 2 through 24 hours postdose after administration of a single dose of Treximet 85/500 mg compared with placebo. A greater percentage of pediatric patients who received a single dose of 10/60 mg or 30/180 mg remained pain free 2 through 24 hours postdose compared with placebo.
There was a significant decrease in the incidence of photophobia and phonophobia 2 hours after the administration of a single dose of 85/500 mg compared with placebo, whereas the incidence of nausea was comparable. There was also a decreased incidence of photophobia, phonophobia, and nausea 2 hours after single-dose administration of 10/60 mg or 30/180 mg compared with placebo.
Adult Dosage:
Use lowest effective dose for shortest duration. Swallow whole. 1 tab (85/500mg) once; may repeat once after 2 hours; max 2 tabs/day. Mild to moderate hepatic impairment: 1 tab (10/60mg)/day. The safety of treating an average of more than 5 migraines in a 30-day period has not been established.
Children Dosage:
<12yrs: not established. Use lowest effective dose for shortest duration. Swallow whole. 12–17yrs: 1 tab (10/60mg) once; max 1 tab (85/500mg)/day. Mild to moderate hepatic impairment: 1 tab (10/60mg)/day. The safety of treating an average of more than 2 migraines in a 30-day period has not been established.
TREXIMET Contraindications:
Ischemic coronary artery disease (CAD) (eg, angina pectoris, MI, silent ischemia). Coronary artery vasospasm (including Prinzmetal's angina). Coronary artery bypass graft surgery. Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders. History of stroke or TIA. History of hemiplegic or basilar migraine. Peripheral vascular disease. Ischemic bowel disease. Uncontrolled hypertension (HTN). Within 24hrs of ergot-type drugs (eg, methysergide, dihydroergotamine) or other 5-HT1 agonists. During or within 2 weeks after discontinuing MAO-type A inhibitors. Aspirin allergy. Severe hepatic impairment.
Boxed Warning:
Risk of serious cardiovascular and gastrointestinal events.
TREXIMET Warnings/Precautions:
Increased risk of serious cardiovascular events (including MI, stroke). Exclude cardiovascular disease in patients with multiple risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) before initiating; if negative, supervise 1st dose, consider monitoring ECG. Avoid in severe heart failure; if necessary, monitor. Increased risk of serious GI adverse events (including inflammation, bleeding, ulceration, perforation). History of ulcer disease and/or GI bleeding. Discontinue if serious arrhythmias or cerebrovascular events occur or if serotonin syndrome is suspected. Peripheral or GI vascular ischemia and infarction following other 5-HT1 agonists. Hypertension; monitor BP closely. Hepatic impairment. Discontinue if signs/symptoms of liver or renal disease develop, or if abnormal LFTs persist or worsen. Severe renal impairment (CrCl<30mL/min): not recommended; monitor in mild or moderate impairment, pre-existing kidney disease, dehydration. Hypovolemia. Hyperkalemia. Coagulation disorders. Monitor CBCs, blood chemistry, hepatic, and renal function in long-term therapy. Pre-existing asthma. Seizure disorders. May mask signs of infection or fever. Discontinue at 1st sign of rash or any other hypersensitivity. Elderly. Debilitated. Labor & delivery. May be associated with a reversible delay in ovulation in females of reproductive potential. Pregnancy (avoid during ≥30 weeks gestation): increased risk of premature closure of the fetal ductus arteriosus; (20–30 weeks gestation): may cause fetal renal dysfunction/oligohydramnios; if treatment needed, limit dose and duration of use. Nursing mothers: minimize infant exposure by avoiding breastfeeding for 12hrs after dose.
TREXIMET Classification:
Selective 5-HT1B/1D receptor agonist + NSAID.
TREXIMET Interactions:
See Contraindications. Concomitant aspirin, salicylates (eg, diflunisal, salsalate) or other NSAIDs: not recommended. Increased risk of GI bleed with anticoagulants, antiplatelets, oral corticosteroids, SSRIs, SNRIs, smoking, alcohol, or prolonged NSAID therapy; monitor. May antagonize, or increase risk of renal failure with diuretics (eg, loop or thiazides), ACE inhibitors, ARBs, or β-blockers; monitor closely. Potentiates digoxin; monitor levels. May potentiate lithium, methotrexate, cyclosporine; monitor for toxicity. Concomitant with pemetrexed may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity. Serum levels increased by probenecid. Risk of serotonin syndrome with concomitant SSRIs, SNRIs, TCAs, MAOIs. May interfere with 5HIAA urinary assays or Porter-Silber tests.
Adverse Reactions:
Dizziness, somnolence, nausea, chest or neck/throat/jaw discomfort/pain, paresthesia, dyspepsia, dry mouth; cardiovascular thrombotic events, GI ulcer/bleed, hepatotoxicity, renal toxicity, hypersensitivity reactions, serious skin reactions (eg, exfoliative dermatitis, Stevens-Johnson Syndrome, toxic epidermal necrolysis), Drug Reaction with Eosinophilia and Systemic Symptoms (discontinue if occurs), anemia. Children: hot flush, muscle tightness.
Drug Elimination:
The elimination half-life of sumatriptan is approximately 2 hours. Radiolabeled 14C-sumatriptan administered orally is largely renally excreted (about 60%), with about 40% found in the feces.
The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen (less than 1%), 6-0-desmethyl naproxen (less than 1%), or their conjugates (66% to 92%). The plasma half-life of the naproxen anion in humans is approximately 19 hours. The corresponding half-lives of both metabolites and conjugates of naproxen are shorter than 12 hours, and their rates of excretion have been found to coincide closely with the rate of naproxen disappearance from the plasma. In patients with renal failure, metabolites may accumulate.
Generic Drug Availability:
YES
How Supplied:
Tabs—9
