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The adverse reactions reported below are specific to the clinical trials with TREXIMET. See also the full prescribing information for naproxen and sumatriptan products.
Incidence In Controlled Clinical Trials
Table 2 lists adverse events that occurred in 2 placebo-controlled clinical trials evaluating patients who took at least 1 dose of study drug. Only events that occurred at a frequency of 2% or more with TREXIMET and were more frequent than in the placebo group are included in Table 2. The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.
Table 2: Treatment-Emergent Adverse Events Reported by
at Least 2% of Patients in 2 Controlled Migraine Trialsa
|Adverse Event||Percent of Patients Reporting|
(n = 737)
(n = 752)
|Sumatriptan 85 mg
(n = 735)
|Naproxen Sodium 500 mg
(n = 732)
|Nervous system disorders|
|Paresthesia||2||< 1||2||< 1|
|Dry mouth||2||1||2||< 1|
|Pain and other pressure sensations|
|Chest discomfort/chest pain||3||< 1||2||1|
|a Events that occurred at a frequency of 2% or more in the group treated with TREXIMET and that occurred more frequently in the group treated with TREXIMET than in the placebo group.|
Other events that occurred in more than 1% of patients receiving TREXIMET and occurred at a frequency greater than the placebo group included asthenia, feeling hot, muscle tightness, and palpitations.
TREXIMET was generally well tolerated. Most adverse reactions were mild and transient. The incidence of adverse events in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse events.
Other Events Observed In Migraine Clinical Trials Associated With The Administration Of TREXIMET
The occurrence of less commonly reported adverse clinical events is presented in this section. Because the reports include events observed in an open-label, long-term safety study in which TREXIMET was used as needed for up to 12 months, the role of TREXIMET cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, etc., limit the value of quantitative frequency estimates provided. Event frequencies are calculated as the number of patients who used TREXIMET and reported an event divided by the total number of patients (N = 3,302) exposed to TREXIMET. Events listed in the previous table and text are not included below. Those events described too generally to be informative or those unlikely to be associated with the use of TREXIMET are excluded. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those occurring in at least 1/100 patients, infrequent adverse events are those occurring in 1/100 to 1/1,000 patients, and rare adverse events are those occurring in fewer than 1/1,000 patients.
Gastrointestinal Disorders: Frequent was abdominal pain. Infrequent were abdominal distention, constipation, diarrhea, dysgeusia, dysphagia, flatulence, gastritis, gastroesophageal reflux disease , vomiting. Rare were colitis, diverticulitis, gastric ulcer, irritable bowel syndrome, oral mucosal blistering, swollen tongue.
Nervous System Disorders: Infrequent were burning sensation, disturbance of attention, insomnia, mental impairment, tremor. Rare were aphasia, facial palsy, impairment of psychomotor skills, sedation.
Psychiatric Disorders: Infrequent were anxiety, depression, irritability, nervousness. Rare were disorientation, panic attack.
Renal and Urinary Disorders: Infrequent was nephrolithiasis. Rare was renal insufficiency.
Drug Abuse And Dependence
The potential for abuse with TREXIMET has not been studied.
One clinical study with sumatriptan succinate injection enrolling 12 patients with a history of substance abuse failed to induce subjective behavior and/or physiologic response ordinarily associated with drugs that have an established potential for abuse.
Read the Treximet (sumatriptan and naproxen sodium tablets) Side Effects Center for a complete guide to possible side effects
Monoamine Oxidase-A Inhibitors
The use of TREXIMET in patients receiving MAO-A inhibitors is contraindicated (see CLINICAL PHARMACOLOGY: Drug Interactions and CONTRAINDICATIONS). MAO-A inhibitors reduce sumatriptan clearance, significantly increasing systemic exposure. In patients taking MAO-A inhibitors, sumatriptan plasma levels attained after treatment with recommended doses are 7-fold higher following oral administration than those obtained under other conditions.
Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (e.g., dihydroergotamine, methysergide) and TREXIMET within 24 hours of each other should be avoided (see CONTRAINDICATIONS).
Caution should be used if TREXIMET is administered concomitantly with methotrexate. Naproxen sodium and other NSAIDs have been reported to reduce the tubular secretion of methotrexate in an animal model, possibly increasing the toxicity of methotrexate. 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.
When naproxen is administered with aspirin, its protein binding is reduced, although the clearance of free naproxen is not altered. The clinical significance of this interaction is not known; however, as with other NSAID-containing products, concomitant administration of TREXIMET and aspirin is not generally recommended because of the potential of increased adverse effects.
Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome
Angiotensin-Converting Enzyme Inhibitors
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The use of TREXIMET in patients who are receiving ACE inhibitors may potentiate renal disease states (see WARNINGS: Renal Effects).
Clinical studies, as well as postmarketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS: Renal Effects), as well as to assure diuretic efficacy.
NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when TREXIMET and lithium are administered concurrently, patients should be observed carefully for signs of lithium toxicity.
Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.
Propranolol and Other Beta-Blockers
Propranolol 80 mg given twice daily had no significant effect on sumatriptan pharmacokinetics. Naproxen and other NSAIDs can reduce the antihypertensive effect of propranolol and other beta-blockers.
The effects of warfarin and NSAIDs on gastrointestinal bleeding are synergistic, such that patients taking both drugs have a higher risk of serious gastrointestinal bleeding than patients taking either drug alone.
Drug/Laboratory Test Interactions
The ability of TREXIMET to interfere with commonly employed clinical laboratory tests has not been investigated.
Sumatriptan is not known to interfere with commonly employed clinical laboratory tests. Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined.
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-dinitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter- Silber test) do not appear to be artifactually 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).
Read the Treximet Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 5/30/2014
This monograph has been modified to include the generic and brand name in many instances.
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