treximet

Adults Recommended dosage: 1 tablet of 85/500 mg. ( 2.1 ) Maximum dosage in a 24-hour period: 2 tablets of 85/500 mg; separate doses by at least 2 hours. ( 2.1 ) Pediatric Patients 12 to 17 years of Age Recommended dosage: 1 tablet of 10/60 mg. ( 2.2 ) Maximum dosage in a 24-hour period: 1 tablet of 85/500 mg. Mild to Moderate Hepatic Impairment Recommended dosage: 1 tablet of 10/60 mg. ( 2.3 , 8.7 ) 2.1 Dosage in Adults The recommended dosage for adults is 1 tablet of TREXIMET 85/500 mg. TREXIMET 85/500 mg contains a dose of sumatriptan higher than the lowest effective dose. The choice of the dose of sumatriptan, and of the use of a fixed combination such as in TREXIMET 85/500 mg should be made on an individual basis, weighing the possible benefit of a higher dose of sumatriptan with the potential for a greater risk of adverse reactions. The maximum recommended dosage in a 24-hour period is 2 tablets, taken at least 2 hours apart. The safety of treating an average of more than 5 migraine headaches in adults in a 30-day period has not been established. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5) ] . 2.2 Dosage in Pediatric Patients 12 to 17 Years of Age The recommended dosage for pediatric patients 12 to 17 years of age is 1 tablet of TREXIMET 10/60 mg. The maximum recommended…

The following serious adverse reactions are described below and elsewhere in labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1) ] GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2) ] Arrhythmias [see Warnings and Precautions (5.3) ] Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure [see Warnings and Precautions (5.4) ] Cerebrovascular Events [see Warnings and Precautions (5.5) ] Other Vasospasm Reactions [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.7) ] Hypertension [see Warnings and Precautions (5.8) ] Heart Failure and Edema [see Warnings and Precautions (5.9) ] Medication Overuse Headache [see Warnings and Precautions (5.10) ] Serotonin Syndrome [see Warnings and Precautions (5.11) ] Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.12) ] Anaphylactic Reactions [see Warnings and Precautions (5.13) ] Serious Skin Reactions [see Warnings and Precautions (5.14) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.15) ] Hematological Toxicity [see Warnings and Precautions (5.17) ] Exacerbation Asthma Related to Aspirin Sensitivity [see Warnings and Precautions (5.18) ] Seizures [see Warnings and Precautions (5.19) ] The most common adverse reactions (incidence ≥2%) were: Adults: Dizziness, somnolence, nausea, chest…

TREXIMET is contraindicated in the following patients: Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina [see Warnings and Precautions (5.1) ]. In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1) ] . Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.3) ] . History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [s ee Warnings and Precautions (5.5) ]. Peripheral vascular disease [see Warnings and Precautions (5.6) ]. Ischemic bowel disease [see Warnings and Precautions (5.6) ]. Uncontrolled hypertension [see Warnings and Precautions (5.8) ]. Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine 1 (5-HT 1 ) agonist [see Drug Interactions (7) ]. Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor [see Drug Interactions (7) , Clinical Pharmacology (12.3) ]. History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.13 , 5.14 , 5.18) ] . Known hypersensitivity (e.g., anaphylactic reactions, angioedema, and serious skin reactions) to sumatriptan, naproxen, or any components of TREXIMET [see Warnings and Precautions (5.14) ]. Severe hepatic impairment [see Warnings and Precautions (5.7) , Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ]. History of coronary artery disease or coronary vasospasm. ( 4 ) In the setting of CABG surgery. ( 4 ) Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders. ( 4 ) History of stroke, transient ischemic attack, or hemiplegic or basilar migraine. ( 4 ) Peripheral vascular disease. ( 4 ) Ischemic bowel disease. ( 4 ) Uncontrolled hypertension. ( 4 ) Recent (within 24 hours) use of another 5-HT 1 agonist (e.g., another triptan) or of ergotamine-containing medication. ( 4 ) Concurrent or recent (past 2 weeks) use of monoamine oxidase-A inhibitor. ( 4 ) History of asthma, urticaria, other allergic type reactions, rhinitis, or nasal polyps syndrome after taking aspirin or other NSAID/analgesic drugs. ( 4 ) Known hypersensitivity to sumatriptan, naproxen, or any components of TREXIMET (angioedema and anaphylaxis seen). ( 4 ) Severe hepatic impairment. ( 4 )

Patients (N = 670) have received single oral doses of 140 to 300 mg of sumatriptan without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 to 400 mg without serious adverse events. Overdose of sumatriptan in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation. Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting and epigastric pain. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions (5.1 , 5.2) ] . Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding. It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Drugs that Interfere with Hemostasis (e.g. warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking TREXIMET with drugs that interfere with hemostasis. Concomitant use of TREXIMET and analgesic doses of aspirin is not generally recommended. ( 7.1 ) ACE Inhibitors and ARBs: Concomitant use with TREXIMET in elderly, volume depleted, or those with renal impairment may result in deterioration of renal function. In such high risk patients, monitor for signs of worsening renal function. ( 7.1 ) Diuretics: NSAIDs can reduce natriuretic effect of loop and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects. ( 7.1 ) Digoxin: Concomitant use with TREXIMET can increase serum concentration and prolong half-life of digoxin. Monitor serum digoxin levels. ( 7.1 ) Lithium: Increases lithium plasma levels. ( 7.1 ) Methotrexate: Increases methotrexate plasma levels. ( 7.1 ) 7.1 Clinically Significant Drug Interactions with TREXIMET See Table 3 for clinically significant drug interactions with NSAIDs or Sumatriptan. Table 3. Clinically Significant Drug Interactions with Naproxen or Sumatriptan Ergot-Containing Drugs Clinical Impact: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Intervention: Because these effects may be additive, coadministration of TREXIMET and ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) within 24 hours of each other is contraindicated. Monoamine Oxidase-A Inhibitors Clinical Impact: MAO-A inhibitors increase systemic exposure of orally administered sumatriptan by 7-fold. Intervention: The use of TREXIMET in patients receiving MAO-A inhibitors is contraindicated. Other 5-HT 1 Agonists Clinical Impact: 5-HT 1 agonist drugs can cause vasospastic effects. Intervention: Because these effects may be additive, coadministration of TREXIMET and other 5 HT 1 agonists (e.g., triptans) within 24 hours of each other is contraindicated. Drugs That Interfere with Hemostasis Clinical Impact: Naproxen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of naproxen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of TREXIMET with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see Warnings and Precautions (5.17) ] . Aspirin Clinical Impact: A pharmacodynamic (PD) study has demonstrated an interaction in which lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen [see Clinical Pharmacology (12.2) ] . There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the PD study due to the longer washout period. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . Intervention: Because there may be an increased risk of cardiovascular events following discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics where appropriate. Concomitant use of TREXIMET and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions (5.17) ] . Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome Clinical Impact: Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.11) ] . Intervention: Discontinue TREXIMET if serotonin syndrome is suspected. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-blockers Clinical Impact: NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention: During concomitant use of TREXIMET and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained [see Warnings and Precautions (5.8) ] . During concomitant use of TREXIMET and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [see Warnings and Precautions (5.8) ]. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of TREXIMET with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.8 , 5.12) ] . Digoxin Clinical Impact: The concomitant use of naproxen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Intervention: During concomitant use of TREXIMET and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance . The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of TREXIMET and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinical Impact: Concomitant administration of some NSAIDs with high-dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity. Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of TREXIMET and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact: Concomitant use of NSAIDs and cyclosporine may increase cyclosporine's nephrotoxicity. Intervention: During concomitant use of TREXIMET and cyclosporine, monitor patients for signs of worsening renal function. NSAIDs and Salicylates Clinical Impact: Concomitant use of naproxen with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [see Warnings and Precautions (5.2) ]. Intervention: The concomitant use of naproxen with other NSAIDs or salicylates is not recommended. Pemetrexed Clinical Impact: Concomitant use of NSAIDs and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). Intervention: During concomitant use of TREXIMET and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration. Probenecid Clinical Impact: Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly. The clinical significance of this is unknown. Intervention: Reduce the frequency of administration of Treximet when given concurrently with probenecid. 7.2 Drug/Laboratory Test Interactions Blood Tests Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined. Urine Tests The administration of naproxen sodium may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artificially altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used. Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).