Version July 2025
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 during the perioperative setting of coronary artery bypass graft (CABG) surgery.
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.
Migraine, moderate to severe, acute treatment:
Note: Safety: Use the lowest effective dose for the shortest duration of time. Avoid or use with caution in patients at risk for or with existing cardiovascular disease, GI disease, kidney impairment, chronic liver disease, or a bleeding diathesis due to greater risk for adverse events. Consider administering in combination with a proton-pump inhibitor in patients at risk for GI bleeding (eg, taking dual antiplatelet therapy or an anticoagulant, ≥60 years of age) (Ref). Do not use within 24 hours of an ergotamine preparation or a different triptan. Use: Limit use to <10 days per month to avoid medication overuse headache. Administration early in the course of a migraine attack, at the first sign of pain, may improve response to treatment. When attack is complicated by severe nausea or vomiting, a nonoral medication may be more effective (Ref).
Oral: Sumatriptan 85 mg/naproxen 500 mg as a single dose; if symptoms persist or return, may repeat dose after ≥2 hours. Maximum: Sumatriptan 85 mg/naproxen 500 mg per dose; sumatriptan 170 mg/naproxen 1 g per 24 hours (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Mild to moderate impairment: The manufacturer’s labeling recommends sumatriptan 10 mg/naproxen 60 mg as a single dose; however, a tablet containing these amounts of sumatriptan and naproxen is no longer available.
Severe impairment: Use is contraindicated.
Note: Unless alternative agents are ineffective and a gastroprotective agent can be administered, avoid short-term scheduled use of naproxen in combination with corticosteroids, anticoagulants, or antiplatelet agents or chronic use with or without medications that increase risk for bleeding (Ref).
Refer to adult dosing.
(For additional information see "Sumatriptan and naproxen: Pediatric drug information")
Migraine: Children ≥12 years and Adolescents <18 years: Limited data available: Oral: Sumatriptan 85 mg/naproxen 500 mg once at onset of mild to moderate pain; dose has been evaluated in over 600 pediatric patients accounting for over 12,000 doses; the pain free response at 2 hours postdose was shown to be consistent and higher than placebo; in a long-term (12 month) open-label trial, patients were exposed to an average 2.5 doses/month (Ref). Note: Although an initial dose of sumatriptan 10 mg/naproxen 60 mg is described in manufacturer's labeling, a dosage form is no longer available.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥12 years and Adolescents:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in manufacturer's labeling (has not been studied). Use with caution.
CrCl <30 mL/minute: Use not recommended.
Children ≥12 years and Adolescents:
Mild to moderate impairment: The manufacturer's labeling recommends sumatriptan 10 mg/naproxen 60 mg as a single dose; however, a tablet containing these amounts of sumatriptan and naproxen is no longer available.
Severe impairment: Use is contraindicated.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported in adults, unless otherwise noted. Also see individual agents.
1% to 10%:
Cardiovascular: Chest discomfort (≤3%), chest pain (≤3%)
Endocrine & metabolic: Hot flash (adolescents: ≤2%)
Gastrointestinal: Dyspepsia (2%), nausea (3%), xerostomia (2%)
Nervous system: Dizziness (4%), drowsiness (3%), hypertonia (adolescents: 2%), paresthesia (2%)
Neuromuscular & skeletal: Jaw pain (≤3%), jaw pressure (≤3%), jaw tightness (≤3%), neck pain (≤3%), neck pressure (≤3%), neck tightness (≤3%)
Respiratory: Pharyngeal edema (≤3%; tightness and pressure), pharyngitis (≤3%)
<1%: Gastrointestinal: Gastrointestinal ulcer
Frequency not defined:
Cardiovascular: Acute myocardial infraction, coronary thrombosis
Gastrointestinal: Gastrointestinal hemorrhage, gastrointestinal perforation
Nervous system: Cerebrovascular accident
Postmarketing: Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms
Hypersensitivity (eg, anaphylactic reactions, angioedema, serious skin reactions) to sumatriptan, naproxen, or any component of the formulation; asthma, urticaria, or allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs; ischemic coronary artery disease (angina pectoris, history of myocardial infarction, documented silent ischemia), coronary artery vasospasm, including Prinzmetal angina, history of coronary artery bypass surgery; Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders; history of stroke or transient ischemic attack; 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-A inhibitor; severe hepatic impairment.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in the US labeling): Ophthalmoplegic migraine; breastfeeding; moderate hepatic impairment; active liver disease; severe, uncontrolled heart failure; active GI ulcer (gastric, duodenal, peptic); active GI bleeding; cerebrovascular bleeding or other bleeding disorders; inflammatory bowel disease; severe renal impairment (<30 mL/minute) or deteriorating renal disease; known hyperkalemia; pregnancy (third trimester).
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 nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.
• Cardiovascular events: 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 when possible (Heidenreich 2022). 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.
• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.
• GI events: Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis (Strate 2016). 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 GI 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 (sometimes fatal), including exfoliative dermatitis, fixed drug eruption (including generalized bullous fixed drug eruption), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) may occur without warning; discontinue use at first sign of skin rash (or any other 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.
• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur (Bhangu 2014; Mechanick 2020). Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain (Chou 2016; Horsley 2019; Thorell 2016).
• 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 health care 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. Patients with advanced hepatic disease are at an increased risk of GI bleeding and kidney failure with NSAIDs (AASLD [Biggins 2021]; AASLD [Runyon 2013]).
• 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:
• 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:
• Older adult: Older adult 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 older adult 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.
Serious adverse effects, such as MI, stroke, visual loss, and death, have been reported in pediatric patients after sumatriptan use by the oral, intranasal, and/or SubQ routes; frequency of such adverse effects cannot currently be determined, monitor patients closely. Pseudoporphyria (ie, increased skin fragility and blistering with scarring in sun-exposed skin) has been reported in naproxen-treated children with JIA (reported incidence, 12%); discontinue therapy if this occurs.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Treximet: Sumatriptan 85 mg and naproxen sodium 500 mg [contains sodium ~60 mg/tablet]
Generic: Sumatriptan 85 mg and naproxen sodium 500 mg
No
Tablets (SUMAtriptan-Naproxen Sodium Oral)
85-500 mg (per each): $93.87 - $100.10
Tablets (Treximet Oral)
85-500 mg (per each): $168.20
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Suvexx: Sumatriptan 85 mg and naproxen sodium 500 mg
Oral: May be administered with or without food. Swallow tablet whole; tablet should not be divided, crushed, or chewed.
Oral: May be administered with or without food. Swallow tablet whole; tablet should not be divided, crushed, or chewed.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Treximet: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021926s019lbl.pdf#page=32
NSAIDs Class Medication Guide
Migraine, moderate to severe, acute treatment: Acute treatment of migraine attacks with or without aura in adults and pediatric patients ≥12 years of age.
Naproxen may be confused with Natacyn, Nebcin, neomycin, niacin
SUMAtriptan may be confused with somatropin, ZOLMitriptan
Treximet may be confused with Trexall
Beers Criteria: Naproxen is identified in the Beers Criteria as a potentially inappropriate medication to be avoided for chronic use in patients 65 years and older (unless alternative agents ineffective and patient can receive concomitant gastroprotective agent) due to increased risk of GI bleeding and peptic ulcer disease in older adults in high-risk category (eg, older than 75 years of age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents). In addition, avoid for short-term scheduled use in combination with oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents unless alternatives are ineffective and patient can receive concomitant gastroprotective agent (Beers Criteria [AGS 2023]).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Acemetacin: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Alcohol (Ethyl): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Aliskiren. Risk C: Monitor
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor
Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid
Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor
Anagrelide: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Angiotensin II Receptor Blockers may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Anticoagulants (Miscellaneous Agents): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Apixaban: Naproxen may increase adverse/toxic effects of Apixaban. Specifically, the risk for bleeding may be increased. Naproxen may increase serum concentration of Apixaban. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and naproxen. If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Aspirin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Aspirin. Aspirin may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Specifically, the risk for bleeding may be increased. Aspirin may decrease serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: In general, avoid regular, frequent use of NSAIDs with aspirin whenever possible. If combined, monitor for increased bleeding and a reduced cardioprotective effect of aspirin. Risk D: Consider Therapy Modification
Bemiparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Bemiparin. Management: Avoid this combination if possible, due to an increased risk of bleeding. If coadministration cannot be avoided, monitor patients closely for clinical and laboratory evidence of bleeding. Risk D: Consider Therapy Modification
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Beta-Blockers. Risk C: Monitor
Bile Acid Sequestrants: May decrease absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor
Bromocriptine: May increase adverse/toxic effects of Serotonin 5-HT1D Receptor Agonists (Triptans). Management: Consider alternatives to this combination when possible. If combined, monitor for increased bromocriptine and triptan toxicities. Risk D: Consider Therapy Modification
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Cardiac Glycosides: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Cardiac Glycosides. Risk C: Monitor
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
Corticosteroids (Systemic): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor
CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider Therapy Modification
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desirudin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Desirudin. Risk C: Monitor
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Diflunisal: May increase antiplatelet effects of Naproxen. Diflunisal may increase adverse/toxic effects of Naproxen. Specifically, the risk for gastrointestinal toxicity may be increased. Diflunisal may decrease excretion of Naproxen. Risk X: Avoid
Direct Oral Anticoagulants (DOACs): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Drospirenone-Containing Products: May increase hyperkalemic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Droxidopa: Serotonin 5-HT1D Receptor Agonists (Triptans) may increase hypertensive effects of Droxidopa. Risk C: Monitor
Enoxaparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Enoxaparin. Management: Discontinue nonselective NSAIDs prior to initiation of enoxaparin whenever possible. If coadministration cannot be avoided, monitor patients closely for clinical and laboratory evidence of bleeding. Risk D: Consider Therapy Modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Eplerenone. Risk C: Monitor
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Serotonin 5-HT1D Receptor Agonists (Triptans) may increase vasoconstricting effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid
Fondaparinux: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Fondaparinux. Management: Discontinue nonselective nonsteroidal anti-inflammatory agents prior to the initiation of fondaparinux, if possible. If coadministration is required, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Heparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Heparin. Risk C: Monitor
Heparins (Low Molecular Weight): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of HydrALAZINE. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Ketorolac (Nasal): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Ketorolac (Systemic). Risk X: Avoid
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider Therapy Modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may decrease diuretic effects of Loop Diuretics. Loop Diuretics may increase nephrotoxic effects 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. Risk D: Consider Therapy Modification
Macimorelin: Coadministration of Nonsteroidal Anti-Inflammatory Agents and Macimorelin may alter diagnostic results. Risk X: Avoid
MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of MetFORMIN. Risk C: Monitor
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Methotrexate. Management: Avoid coadministration of higher dose methotrexate (such as that used for the treatment of oncologic conditions) and NSAIDs. Use caution if coadministering lower dose methotrexate and NSAIDs. Risk D: Consider Therapy Modification
Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor
Methoxyflurane: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Methoxyflurane. Risk X: Avoid
Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Mifamurtide. Risk X: Avoid
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Monoamine Oxidase Inhibitors: Serotonin 5-HT1D Receptor Agonists (Triptans) may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid
Nadroparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Nadroparin. Management: Coadministration of NSAIDs and nadroparin is not recommended due to an increased risk of bleeding. If coadministration is required, monitor patients closely for clinical and laboratory signs of bleeding. Risk D: Consider Therapy Modification
Naftazone: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): Nonsteroidal Anti-Inflammatory Agents (Topical) may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider Therapy Modification
Nonsteroidal Anti-Inflammatory Agents: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased. Risk X: Avoid
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Phenylbutazone: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid
Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Potassium Salts. Risk C: Monitor
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Potassium-Sparing Diuretics. Risk C: Monitor
PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider Therapy Modification
Probenecid: May increase serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor
Quinolones: Nonsteroidal Anti-Inflammatory Agents may increase neuroexcitatory and/or seizure-potentiating effects of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Quinolones. Risk C: Monitor
Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase adverse/toxic effects of Salicylates. An increased risk of bleeding may be associated with use of this combination. Risk X: Avoid
Selective Serotonin Reuptake Inhibitor: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider Therapy Modification
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Serotonergic Agents (High Risk): Serotonin 5-HT1D Receptor Agonists (Triptans) may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonin 5-HT1D Receptor Agonists (Triptans): May increase vasoconstricting effects of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid
Serotonin/Norepinephrine Reuptake Inhibitor: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification
Sodium Phosphates: May increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Sulprostone: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Sulprostone. Risk X: Avoid
Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Tacrolimus (Systemic). Risk C: Monitor
Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects 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 due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider Therapy Modification
Tenoxicam: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Thiazide and Thiazide-Like Diuretics. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Tolperisone: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may increase therapeutic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Tricyclic Antidepressants: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Tricyclic Antidepressants may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Risk C: Monitor
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Vancomycin. Risk C: Monitor
Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider Therapy Modification
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Nonsteroidal anti-inflammatory drugs may delay or prevent rupture of ovarian follicles. This may be associated with infertility that is reversible upon discontinuation of the medication.
Refer to the naproxen monograph for additional information.
Maternal use of nonsteroidal anti-inflammatory drugs may be associated with adverse pregnancy outcomes.
Limited pregnancy outcome data for sumatriptan/naproxen are available from a pregnancy registry sponsored by GlaxoSmithKline. As of September 2012, data were available for only 6 pregnancies exposed to sumatriptan/naproxen (5 with first trimester exposure to this combination). The pregnancy registry was closed to enrollment in January 2012 (Ephross 2014). Data from the pregnancy registry were compared to data obtained from an insurance claims database. Between 1996 and 2012, the database recorded 371 pregnancies exposed to sumatriptan/naproxen (296 with first trimester exposure) (Yusuf 2018).
Refer to individual monographs for additional information.
Sumatriptan and naproxen are present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Refer to individual monographs for additional information.
Some products may contain a significant amount of sodium.
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.
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
See individual agents.
