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Sumatriptan and Naproxen

Pronunciation

(soo ma TRIP tan & na PROKS en)

Index Terms

  • Naproxen and Sumatriptan
  • Naproxen Sodium and Sumatriptan
  • Naproxen Sodium and Sumatriptan Succinate
  • Sumatriptan Succ/Naproxen Sod
  • Sumatriptan Succinate and Naproxen
  • Sumatriptan Succinate and Naproxen Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Treximet 10/60: Sumatriptan 10 mg and naproxen sodium 60 mg [contains sodium ~20 mg/tablet]

Treximet 85/500: Sumatriptan 85 mg and naproxen sodium 500 mg [contains sodium ~60 mg/tablet]

Brand Names: U.S.

  • Treximet

Pharmacologic Category

  • Analgesic, Nonopioid
  • Antimigraine Agent
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Oral
  • Serotonin 5-HT1B, 1D Receptor Agonist

Pharmacology

Sumatriptan: Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) on intracranial blood vessels and sensory nerves of the trigeminal system; causes vasoconstriction and reduces neurogenic inflammation associated with antidromic neuronal transmission correlating with relief of migraine

Naproxen: Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which result in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties

Use: Labeled Indications

Migraine headache: Acute treatment of migraine attacks with or without aura in adults and pediatric patients ≥12 years

Contraindications

Hypersensitivity to sumatriptan, naproxen, or any component of the formulation; asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; ischemic coronary artery disease (angina pectoris, history of myocardial infarction, documented silent ischemia), coronary artery vasospasm, including Prinzmetal’s angina, history of coronary artery bypass (CABG) surgery; Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders; history of stroke or transient ischemic attack (TIA); history of hemiplegic or basilar migraine (higher risk of stroke); peripheral vascular disease; ischemic bowel disease; uncontrolled hypertension; use within 24 hours of ergotamine-containing medication, ergot-type medication (eg, dihydroergotamine, methysergide); or another 5-HT1 agonist; concurrent administration or within 2 weeks of a monoamine oxidase (MAO)-A inhibitor; third trimester of pregnancy; severe hepatic impairment

Dosing: Adult

Note: Use care when prescribing; there are 2 different Treximet tablet strengths available.

Migraine headache: Oral: Sumatriptan 85 mg/naproxen 500 mg. If a satisfactory response has not been obtained at 2 hours, a second dose may be administered (maximum: Sumatriptan 170 mg/naproxen 1,000 mg in 24 hours). Note: The safety of treating an average of >5 migraine headaches in a 30-day period has not been established.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Use care when prescribing; there are 2 different Treximet tablet strengths available.

Migraine headache: Children and Adolescents ≥12 to 17 years: Sumatriptan 10 mg/naproxen 60 mg; maximum: Sumatriptan 85 mg/naproxen 500 mg (adult dose) in 24 hours. Note: The safety of treating an average of >2 migraine headaches in a 30-day period has not been established.

Dosing: Renal Impairment

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution and monitor renal function.

CrCl <30 mL/minute: Use not recommended.

Dosing: Hepatic Impairment

Mild to moderate impairment: Sumatriptan 10 mg/naproxen 60 mg in 24 hours.

Severe impairment: Use is contraindicated.

Administration

Oral: May be administered with or without food. Swallow tablet whole; tablet should not be divided, crushed, or chewed.

Dietary Considerations

Some products may contain a significant amount of sodium.

Storage

Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Store in original container.

Drug Interactions

5-ASA Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-ASA Derivatives. Monitor therapy

ACE Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Monitor therapy

Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Monitor therapy

Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy

Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Apixaban: Naproxen may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Naproxen may increase the serum concentration of Apixaban. Consider therapy modification

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Consider therapy modification

Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (Nonselective). Monitor therapy

CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Specifically, elevated diclofenac concentrations have been reported. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (e.g., hypertension) during concomitant therapy with NSAIDs. Consider therapy modification

Dabigatran Etexilate: NSAID (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy

Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Diclofenac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs. Consider therapy modification

Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Monitor therapy

Drospirenone: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone. Monitor therapy

Droxidopa: Serotonin 5-HT1D Receptor Agonists may enhance the hypertensive effect of Droxidopa. Monitor therapy

Edoxaban: NSAID (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification

Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Ergot Derivatives: Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Exceptions: Nicergoline. Avoid combination

Floctafenine: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. Consider therapy modification

HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Monitor therapy

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Ketorolac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Consider therapy modification

Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Consider therapy modification

MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. Consider therapy modification

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy

Morniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Monitor therapy

NSAID (COX-2 Inhibitor): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Avoid combination

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Pelubiprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

PEMEtrexed: NSAID (Nonselective) may increase the serum concentration of PEMEtrexed. Management: Patients with mild-to-moderate renal insufficiency (estimated creatinine clearance 45-79 mL/min) should avoid NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. Consider therapy modification

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Monitor therapy

Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Monitor therapy

Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Monitor therapy

Rivaroxaban: NSAID (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification

Salicylates: NSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification

Serotonin 5-HT1D Receptor Agonists: May enhance the adverse/toxic effect of SUMAtriptan. Avoid combination

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy

Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Monitor therapy

Talniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Vitamin K Antagonists (eg, warfarin): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification

Test Interactions

See individual agents.

Adverse Reactions

>1% to 10%:

Cardiovascular: Chest pain/discomfort (3%), palpitation (>1%)

Central nervous system: Dizziness (4%), somnolence (3%), fatigue (≥1%)

Gastrointestinal: Nausea (3%), dyspepsia (2%), xerostomia (2%), abdominal pain (≥1%)

Neuromuscular & skeletal: Neck, throat, and jaw pain/tightness/pressure (3%), paresthesia (2%), weakness (≥1%), muscle tightness (>1%)

Miscellaneous: Feeling hot (>1%)

≤1% (Limited to important or life-threatening): Abdominal distention, acute coronary syndrome, ambulation difficulties, anemia, anxiety, aphasia, arthralgia, asthma, attention disturbances, back pain, biliary colic, bruising, burning, cardiac flutter, cataract, CHF, colitis, conjunctival hemorrhage, conjunctivitis, constipation, cough, depression, diabetes mellitus, diarrhea, disorientation, diverticulitis, dysgeusia, dysphagia, dyspnea, ear pain, epistaxis, facial edema, facial palsy, fever, flatulence, flushing, gastric ulcer, gastritis, gastroesophageal reflux, goiter, heaviness sensation, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperhidrosis, hypertension, hypoglycemia, hypothyroidism, infection (various), insomnia, irritability, irritable bowel syndrome, jittery, lethargy, leukopenia, lymphadenopathy, malaise, mental impairment, motion sickness, myalgia, nephrolithiasis, nervousness, oral mucosal blistering, oropharyngeal edema, panic attacks, peripheral coldness, peripheral edema, pleurisy, pruritus, psychomotor impairment, rash, renal insufficiency, right ventricular failure, sedation, systemic lupus erythematosus, tachycardia, temperature intolerance, thirst, tinnitus, tongue edema, tremor, urticaria, ventricular extrasystoles, vertigo, viral myocarditis, visual disturbance, vomiting

ALERT: U.S. Boxed Warning

Cardiovascular thrombotic events:

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Sumatriptan/naproxen is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal bleeding, ulceration, and perforation:

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis with or without nasal polyps) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.

• Cardiovascular events: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may occur early during treatment and may increase with duration of use. Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of cardiovascular events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors. New onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema. Avoid use in patients with heart failure (ACCF/AHA [Yancy 2013]). Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk. Coronary artery vasospasm, transient ischemia, myocardial infarction, life-threatening disturbances of cardiac rhythm, including ventricular tachycardia/fibrillation leading to death, have been reported with 5-HT1 agonist administration; some events have occurred within a few hours of administration. Discontinue if these events occur. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal angina before receiving additional doses; if dosing is resumed and similar symptoms recur, monitor with ECG. Tightness, pain, pressure, and heaviness in the chest, jaw/neck/throat, commonly occur after treatment with sumatriptan and is usually noncardiac in origin, cardiac evaluation recommended for patients at high cardiac risk. Use is contraindicated in patients with ischemic or vasospastic CAD and Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

• Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke (may be fatal) have been reported with 5-HT1 agonist administration; discontinue use if a cerebrovascular event occurs. Use is contraindicated in patients with a history of stroke or transient ischemic attack (TIA).

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long term therapy.

• Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has also been reported on rare occasions in patients with and without a history of hypertension, monitor blood pressure; contraindicated in patients with uncontrolled hypertension.

• Gastrointestinal events: [US Boxed Warning]: NSAIDs cause an increased risk of serious gastrointestinal inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. Avoid use in patients with active GI bleeding. Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt 2008).

• Headaches: Acute migraine agents (eg, triptans, opioids, ergotamine, or a combination of the agents) used for 10 or more days per month may lead to worsening of headaches (medication overuse headache); withdrawal treatment may be necessary in the setting of overuse.

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatotoxicity: Elevated liver enzymes and severe hepatic reactions (eg, jaundice, fatal fulminant hepatitis, liver necrosis, liver failure) have occurred with NSAID use. Closely monitor patients with any abnormal LFT; discontinue if signs or symptoms of liver disease develop, if systemic manifestations (eg, eosinophilia, rash) occur, or if abnormal liver tests persist or worsen.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.

• Renal toxicity: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation. Patients with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) which can be fatal; discontinue use at first sign of skin rash or hypersensitivity.

• Vasospasm-related events: Non-coronary vasospastic reactions, such as peripheral vascular ischemia, GI vascular ischemia and infarction (with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud syndrome have been reported with 5-HT1 agonist.

• Visual effects: Transient and permanent blindness and significant partial vision loss have been reported rarely with use of 5-HT1 agonists; a causal relationship between these events and 5-HT1 agonist administration has not been clearly determined.

Disease-related concerns:

• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.

• Coronary artery disease: Should not be given to patients with documented CAD (contraindicated), history of CABG (contraindicated), or who have multiple risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) without adequate cardiac evaluation. Patients with suspected CAD should have cardiovascular evaluation to rule out CAD before considering use; if cardiovascular evaluation is "satisfactory," first dose should be given in the healthcare provider's office (consider ECG monitoring). Periodic evaluation of cardiovascular status should be done in all patients.

• Heart failure/edema: Use caution in patients with fluid retention or heart failure; fluid retention, edema, and peripheral edema have occurred in patients receiving NSAIDs.

• Hepatic function impairment: Use is contraindicated in patients with severe hepatic impairment; dosage reduction recommended in patients with mild to moderate hepatic impairment.

• Renal impairment: Not recommended for use in patients with severe renal impairment (CrCl <30 mL/minute); monitor renal function in patients with mild to moderate impairment, preexisting kidney disease, or dehydration.

• Seizure disorders: Use with caution in patients with history of seizure disorder or in patients with a lowered seizure threshold; seizures have been reported in patients receiving sumatriptan with or without a history of seizures.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce sumatriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended. If concomitant administration with SSRIs is warranted, monitor closely, especially at initiation and with dose increases.

Special populations:

• Elderly: Elderly patients are more likely to have underlying cardiovascular disease and renal impairment and blood pressure increases may be more pronounced; use with caution. Perform a cardiovascular evaluation prior to initiation of therapy in elderly patients with cardiovascular risk factors (eg, diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) and periodically during intermittent long-term use.

Other warnings/precautions:

• Appropriate use: Only indicated for treatment of acute migraine; if a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered; rule out underlying neurologic disease in patients with atypical headache and in patients with no prior history of migraine; not indicated for prevention of migraine attacks; safety and effectiveness have not been established for cluster headache.

Monitoring Parameters

Migraine relief; occult blood loss; periodic liver function test, hematocrit and hemoglobin (in patients with signs or symptoms suggestive of anemia); platelets and bleeding time (in patients who may be affected by changes in platelet function), urine output; blood pressure; renal function (in patients with dehydration, mild to moderate renal impairment, or preexisting kidney disease), signs/symptoms suggestive of angina; perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD), monitor ECG with first dose in patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation and consider periodic cardiovascular evaluation in such patients if they are intermittent long-term users; signs/symptoms of serotonin syndrome and hypersensitivity reactions.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Refer to individual agents.

Very limited pregnancy outcome information for this combination is available from a pregnancy registry sponsored by GlaxoSmithKline. The pregnancy registry was closed due to low enrollment in January, 2012. Additional information may be obtained from the manufacturer (800-336-2176).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience heartburn, nausea, vomiting, constipation, flatulence, fatigue, or flushing. Have patient report immediately to prescriber signs of abdominal ulcers (severe abdominal or back pain; black, tarry, or bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or abnormal swelling), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of a heart attack (angina; pain in arms, back, neck, jaw, or stomach; shortness of breath; cold sweats; severe dizziness; passing out; severe nausea or vomiting), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling), severe headache, severe dizziness, passing out, severe abdominal pain, bloody diarrhea, vision changes, eye pain, severe eye irritation, blindness, shortness of breath, excessive weight gain, swelling of arms or legs, severe loss of strength and energy, seizures, burning or numbness feeling, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, severe diarrhea), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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