.png?width=200&height=94&name=PDR_stacked_purple%20(002).png)
Naprelan
Classes
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Administration
For storage information, see specific product information within the How Suppled section.
Administer with milk, food, or antacids (preferably aluminum and magnesium hydroxide containing antacids) to minimize GI irritation. For self-medication, administer with a full glass of water or other liquid.
EC-Naprosyn delayed-release tablets: Do not break, crush, or chew.
Oral suspension: Shake well before use. Administer using the measuring cup provided or other calibrated device appropriate for accurate administration of liquid medications.
Adverse Reactions
peptic ulcer / Delayed / 0-10.0
GI bleeding / Delayed / 0-10.0
GI perforation / Delayed / 0-10.0
visual impairment / Early / 0-3.0
cholecystitis / Delayed / 0-1.0
hematemesis / Delayed / 0-1.0
esophageal ulceration / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
hemolytic anemia / Delayed / 0-1.0
agranulocytosis / Delayed / 0-1.0
pancytopenia / Delayed / 0-1.0
muscle paralysis / Delayed / 0-1.0
coma / Early / 0-1.0
keratoconjunctivitis / Early / 0-1.0
hearing loss / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
hepatic necrosis / Delayed / 0-1.0
aseptic meningitis / Delayed / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
glomerulonephritis / Delayed / 0-1.0
azotemia / Delayed / 0-1.0
hyperkalemia / Delayed / 0-1.0
interstitial nephritis / Delayed / 0-1.0
renal papillary necrosis / Delayed / 0-1.0
nephrotic syndrome / Delayed / 0-1.0
oliguria / Early / 0-1.0
proteinuria / Delayed / 0-1.0
heart failure / Delayed / 0-1.0
myocardial infarction / Delayed / 0-1.0
arrhythmia exacerbation / Early / 0-1.0
vasculitis / Delayed / 0-1.0
pulmonary edema / Early / 0-1.0
erythema multiforme / Delayed / 0-1.0
erythema nodosum / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
anaphylactic shock / Rapid / 0-1.0
eczema vaccinatum / Delayed / 0-1.0
skin necrosis / Early / 0-1.0
angioedema / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
bone fractures / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
odynophagia / Delayed / Incidence not known
esophageal stricture / Delayed / Incidence not known
seizures / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
corneal opacification / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
stroke / Early / Incidence not known
thromboembolism / Delayed / Incidence not known
pseudoporphyria / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / 0-15.0
constipation / Delayed / 3.0-9.0
edema / Delayed / 0-9.0
dyspnea / Early / 3.0-9.0
gastritis / Delayed / 0-3.0
stomatitis / Delayed / 0-3.0
anemia / Delayed / 0-3.0
peripheral edema / Delayed / 0-3.0
hypertension / Early / 0-3.0
palpitations / Early / 0-3.0
hyperglycemia / Delayed / 0-3.0
cystitis / Delayed / 0-3.0
chest pain (unspecified) / Early / 0-3.0
glossitis / Early / 0-1.0
colitis / Delayed / 0-1.0
cholelithiasis / Delayed / 0-1.0
melena / Delayed / 0-1.0
oral ulceration / Delayed / 0-1.0
esophagitis / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
eosinophilia / Delayed / 0-1.0
prolonged bleeding time / Delayed / 0-1.0
lymphadenopathy / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
depression / Delayed / 0-1.0
hallucinations / Early / 0-1.0
subdural hematoma / Early / 0-1.0
myasthenia / Delayed / 0-1.0
amnesia / Delayed / 0-1.0
neuritis / Delayed / 0-1.0
confusion / Early / 0-1.0
hypertonia / Delayed / 0-1.0
amblyopia / Delayed / 0-1.0
blurred vision / Early / 0-1.0
conjunctivitis / Delayed / 0-1.0
hepatomegaly / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
splenomegaly / Delayed / 0-1.0
vaginitis / Delayed / 0-1.0
pyuria / Delayed / 0-1.0
flank pain / Delayed / 0-1.0
glycosuria / Early / 0-1.0
urinary retention / Early / 0-1.0
urinary incontinence / Early / 0-1.0
dysuria / Early / 0-1.0
hematuria / Delayed / 0-1.0
peripheral vasodilation / Rapid / 0-1.0
bundle-branch block / Early / 0-1.0
phlebitis / Rapid / 0-1.0
migraine / Early / 0-1.0
hypotension / Rapid / 0-1.0
angina / Early / 0-1.0
bleeding / Early / 0-1.0
sinus tachycardia / Rapid / 0-1.0
contact dermatitis / Delayed / 0-1.0
skin ulcer / Delayed / 0-1.0
pneumonitis / Delayed / 0-1.0
bullous rash / Early / 0-1.0
bone pain / Delayed / 0-1.0
dehydration / Delayed / 0-1.0
hypoglycemia / Early / 0-1.0
metabolic alkalosis / Delayed / 0-1.0
hypokalemia / Delayed / 0-1.0
hyperuricemia / Delayed / 0-1.0
respiratory depression / Rapid / 0-1.0
dysphagia / Delayed / Incidence not known
platelet dysfunction / Delayed / Incidence not known
medication overuse headache / Delayed / Incidence not known
withdrawal / Early / Incidence not known
hepatitis / Delayed / Incidence not known
photophobia / Early / Incidence not known
hyponatremia / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
infertility / Delayed / Incidence not known
headache / Early / 3.0-15.0
dyspepsia / Early / 0-14.0
vomiting / Early / 0-10.0
flatulence / Early / 0-10.0
influenza / Delayed / 10.0-10.0
diarrhea / Early / 0-9.0
pyrosis (heartburn) / Early / 3.0-9.0
abdominal pain / Early / 3.0-9.0
nausea / Early / 3.0-9.0
drowsiness / Early / 3.0-9.0
dizziness / Early / 0-9.0
tinnitus / Delayed / 3.0-9.0
rash / Early / 0-9.0
ecchymosis / Delayed / 3.0-9.0
pruritus / Rapid / 0-9.0
back pain / Delayed / 3.0-9.0
infection / Delayed / 0-9.0
sinusitis / Delayed / 3.0-9.0
rhinitis / Early / 3.0-9.0
pharyngitis / Delayed / 3.0-9.0
asthenia / Delayed / 0-3.0
paresthesias / Delayed / 0-3.0
insomnia / Early / 0-3.0
vertigo / Early / 0-3.0
diaphoresis / Early / 0-3.0
purpura / Delayed / 0-3.0
myalgia / Early / 0-3.0
arthralgia / Delayed / 0-3.0
muscle cramps / Delayed / 0-3.0
cough / Delayed / 0-3.0
fever / Early / 0-3.0
weight loss / Delayed / 0-1.0
xerostomia / Early / 0-1.0
anorexia / Delayed / 0-1.0
eructation / Early / 0-1.0
anxiety / Delayed / 0-1.0
tremor / Early / 0-1.0
diplopia / Early / 0-1.0
emotional lability / Early / 0-1.0
malaise / Early / 0-1.0
ocular pain / Early / 0-1.0
lacrimation / Early / 0-1.0
nocturia / Early / 0-1.0
increased urinary frequency / Early / 0-1.0
polyuria / Early / 0-1.0
dysmenorrhea / Delayed / 0-1.0
menorrhagia / Delayed / 0-1.0
syncope / Early / 0-1.0
acne vulgaris / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
photosensitivity / Delayed / 0-1.0
xerosis / Delayed / 0-1.0
alopecia / Delayed / 0-1.0
chills / Rapid / 0-1.0
ptosis / Delayed / 0-1.0
epistaxis / Delayed / 0-1.0
pelvic pain / Delayed / 0-1.0
lichen planus-like eruption / Delayed / Incidence not known
Boxed Warning
NSAIDs, including naproxen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and GI perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a more than 10-fold increased risk for developing a GI bleed compared to patients without risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy, concomitant oral corticosteroids, anticoagulant therapy, aspirin, or selective serotonin reuptake inhibitors (SSRIs), tobacco smoking, ethanol ingestion, older age, and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease or coagulopathy are at increased risk for GI bleeding. To minimize GI risks in NSAID-treated patients, use the lowest effective dosage for the shortest possible duration, and avoid administration of more than 1 NSAID at a time. In the setting of concomitant low-dose aspirin use for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding. Avoid NSAID use in higher risk populations unless the benefits are expected to outweigh the risks of bleeding; consider alternate therapy other than NSAIDs in higher risk patients as well as those with active GI bleeding. Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.[32122]
Naproxen is contraindicated in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of thromboembolism, including myocardial infarction or stroke, was found through analysis of data regarding the use of a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) for the treatment of pain in the first 10 to 14 days after CABG surgery. Naproxen, like all NSAIDs, may exacerbate heart failure and hypertension and may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Avoid the use of naproxen in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If naproxen is used in patients with severe heart failure, monitor for signs of worsening heart failure. Trials demonstrated an approximately doubling of hospitalizations for heart failure in patients treated with selective and nonselective NSAIDs compared to placebo-treated patients. Additionally, fluid retention and edema have been observed with NSAID use. Consider the sodium content of naproxen sodium in patients requiring severe sodium restriction.[32122] Caution is recommended when administering naproxen to patients with cardiac disease, cardiomyopathy, cardiac arrhythmias (e.g., tachycardia), significant coronary artery disease (including acute myocardial infarction, angina, or history of myocardial infarction), peripheral vascular disease, cerebrovascular disease (e.g., stroke, transient ischemic attack), hypertension, pre-existing renal disease, or fluid retention.[59937] Closely monitor blood pressure during naproxen receipt. Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse cardiovascular event. Inform patients to seek immediate medical attention if they experience any signs or symptoms of a cardiovascular thrombotic event. Myocardial infarction or stroke can occur as early as the first weeks of using a NSAID, and risk may increase with higher doses and longer duration of use. NSAIDs may increase the risk of a cardiovascular thrombotic event in patients with or without underlying heart disease or risk factors for heart disease. Patients with known heart disease or risk factors appear to have a greater likelihood of an event after NSAID use, likely due to a higher baseline risk.[32122] While comprehensive data regarding relative cardiovascular safety of any particular NSAID compared to other NSAIDs is not available, celecoxib 100 mg twice daily was shown to be non-inferior to ibuprofen 600 to 800 mg 3 times daily or naproxen 375 to 500 mg twice daily for the composite endpoint of cardiovascular death, nonfatal MI, and nonfatal stroke in osteoarthritis or rheumatoid arthritis adult patients with or at high risk for cardiovascular disease. Celecoxib had negligible effect on average 24-hour systolic blood pressure, while average 24-hour systolic pressures increased by 3.7 mmHg and 1.6 mmHg in patients taking ibuprofen and naproxen, respectively. There is no consistent evidence that concomitant use of aspirin mitigates the increased risk for cardiovascular thrombotic events.[32122] Guidelines state NSAIDs should not be administered to patients presenting with and hospitalized for ST-elevation myocardial infarction (STEMI) due to increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use. Observational data from a national registry demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, cardiovascular-related death, and all-cause mortality beginning the first week of treatment. An increased relative risk of death in NSAID users continued during the follow-up period of 4 years. Data demonstrate that patients treated with NSAIDs were more likely to die in the first year following a myocardial infarction compared to those not treated with NSAIDs.[32122]
Common Brand Names
Aflaxen, Aleve, Aleve Arthritis, All Day Pain Relief, All Day Relief, Anaprox, Anaprox DS, EC-Naprosyn, Naprelan, Naprosyn, Walgreens Naproxen Sodium
Dea Class
OTC, Rx
Description
Propionic acid NSAID; has antipyretic and analgesic properties; used for OA, RA, mild to moderate pain, and migraine; all formulations liberate naproxen as the active drug; increases risk of serious GI events; may increase CV events; use lowest effective dose for shortest possible duration.
Dosage And Indications
250 or 500 mg PO twice daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods of up to 6 months.
275 or 550 mg PO twice daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods of up to 6 months.
375 or 500 mg PO twice daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods of up to 6 months.
750 or 1,000 mg PO once daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods.
5 mg/kg/dose (Max: 500 mg/dose) PO twice daily.
5 mg/kg/dose (Max: 500 mg/dose) PO twice daily.
NOTE: Delayed-release naproxen is not recommended for the treatment of acute gout because of the absorption delay as compared to other naproxen formulations.
Oral dosage (naproxen tablets or suspension) Adults
750 mg PO once, then 250 mg PO every 8 hours as needed until the attack has subsided.
825 mg PO once, then 275 mg PO every 8 hours as needed until the attack has subsided.
1,000 to 1,500 mg PO once, then 1,000 mg PO once daily as needed until the attack has subsided.
NOTE: Delayed-release naproxen is not recommended for the initial treatment of pain because the absorption is delayed as compared to other naproxen formulations.
NOTE: Naproxen sodium may be preferred to naproxen when fast-onset pain relief is needed. For the treatment of mild to moderate pain. Oral dosage (naproxen tablets or suspension) Adults
500 mg PO once, then 250 mg PO every 6 to 8 hours as needed. Max: 1,250 mg/day.
550 mg PO once, then 550 mg PO every 12 hours or 275 mg PO every 6 to 8 hours as needed. Max: 1,375 mg on day 1, then 1,100 mg/day.
1,000 or 1,500 mg PO once daily. Usual Max: 1,000 mg/day.
440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day.
440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day.
500 mg PO once, then 250 mg PO every 6 to 8 hours as needed. Max: 1,250 mg/day.
550 mg PO once, then 550 mg PO every 12 hours or 275 mg PO every 6 to 8 hours as needed. Max: 1,375 mg on day 1, then 1,100 mg/day.
1,000 or 1,500 mg PO once daily. Usual Max: 1,000 mg/day.
440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if pain gets worse or lasts for more than 10 days.
440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if pain gets worse or lasts for more than 10 days.
440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if fever gets worse or lasts for more than 3 days.
440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if fever gets worse or lasts for more than 3 days.
500 mg PO once, then 250 mg PO every 6 to 8 hours as needed. Max: 1,250 mg/day.
550 mg PO once, then 550 mg PO every 12 hours or 275 mg PO every 6 to 8 hours as needed. Max: 1,375 mg on day 1, then 1,100 mg/day.
1,000 or 1,500 mg PO once daily. Usual Max: 1,000 mg/day.
500 mg PO as a single dose. Guidelines classify naproxen as having established efficacy for the treatment of acute migraine.
550 mg PO as a single dose. Guidelines classify naproxen as having established efficacy for the treatment of acute migraine.
500 or 550 mg PO once or twice daily for 6 days starting 2 to 7 days before the expected onset of menses and repeated monthly with each menstrual cycle.
250 mg PO 3 times daily for 6 weeks or 500 mg PO twice daily for 7 days after total hip arthroplasty.
NOTE: Dosage expressed as naproxen base (200 mg naproxen base is equivalent to 220 mg naproxen sodium).
For the treatment of acute pericarditis†. Oral dosage (naproxen tablets or suspension) Adults
250 to 500 mg PO every 12 hours, initially; may increase dose up to 1,500 mg/day if tolerated and needed and continue for 1 to 2 weeks, then decrease dose by 125 to 250 mg/day every 1 to 2 weeks in combination with colchicine.
5 mg/kg/dose PO every 12 hours for 1 to 4 weeks; up to 15 mg/kg/day has been tolerated. Consider tapering dose gradually every 1 to 2 weeks.
250 to 500 mg PO every 12 hours, initially; may increase dose up to 1,500 mg/day if tolerated and needed and continue for at least 2 to 4 weeks, then decrease dose by 125 to 250 mg/day every 1 to 2 weeks in combination with colchicine.
5 mg/kg/dose PO every 12 hours for at least 2 to 4 weeks in combination with colchicine; up to 15 mg/kg/day has been tolerated. Consider tapering dose gradually every 1 to 2 weeks.
†Indicates off-label use
Dosing Considerations
Although specific guidelines are not available, dosage reduction may be necessary in patients with hepatic dysfunction.
Renal ImpairmentCrCl >= 30 ml/min: No dosage adjustment needed.
CrCl < 30 ml/min: Not recommended.
Drug Interactions
Abciximab: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Acebutolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Acetaminophen; Aspirin: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Acetaminophen; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Acyclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of acyclovir and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as nonsteroidal antiinflammatory drugs may increase the risk of developing nephrotoxicity even in patients who have normal renal function. The use of adefovir with NSAIDs may be done cautiously. As stated in the current adefovir prescribing information, 'Ibuprofen (800 mg PO three times daily), when given concomitantly with adefovir dipivoxil, increased the adefovir Cmax by 33% and AUC by 23%, as well as urinary recovery. The increase appears to be due to higher oral bioavailability, not a reduction in renal clearance of adefovir.' In an in vitro investigation, the antiviral effect of adefovir was unaltered and the renal proximal tubule accumulation of adefovir was inhibited by the presence of a NSAID. Adefovir is efficiently transported by the human renal organic anion transporter 1, and the presence of this transporter appears to mediate the accumulation of the drug in renal proximal tubules. The in vitro study suggests that the use of a NSAID with adefovir may potentially reduce the nephrotoxic potential of adefovir. Of course, NSAIDs are associated with nephrotoxicity of their own; therefore, further data on the interaction between NSAIDs and adefovir in humans are needed.
Albuterol; Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Aldesleukin, IL-2: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Alendronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Alendronate; Cholecalciferol: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aliskiren: (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of vasodilatory prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further deterioration of renal function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and renal function should be monitored closely when an NSAID is administered to a patient taking aliskiren.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of vasodilatory prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further deterioration of renal function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and renal function should be monitored closely when an NSAID is administered to a patient taking aliskiren.
Alpha-blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Alteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Altretamine: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Amikacin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
Amiloride: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Aminolevulinic Acid: (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and during photodynamic therapy may be advisable.
Aminosalicylate sodium, Aminosalicylic acid: (Major) Avoid concomitant use of naproxen with aminosalicylic acid due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Amiodarone: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including naproxen. The metabolism of naproxen may be decreased.
Amlodipine; Benazepril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amlodipine; Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Amlodipine; Olmesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amlodipine; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amphotericin B lipid complex (ABLC): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B liposomal (LAmB): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Anagrelide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Angiotensin II receptor antagonists: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Antacids: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Antithrombin III: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Apixaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Aprepitant, Fosaprepitant: (Minor) Use caution if naproxen and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of naproxen. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Naproxen is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as NSAIDs, as the risk of renal impairment may be increased.
Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Aspirin, ASA: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Carisoprodol: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Aspirin, ASA; Dipyridamole: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Aspirin, ASA; Omeprazole: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Atazanavir: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
Atazanavir; Cobicistat: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
Atenolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Azathioprine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Azelastine; Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Azilsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Bacitracin: (Major) Avoid concurrent use of bacitracin with nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Beclomethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Benazepril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid concomitant use of naproxen with phenyl salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Beta-blockers: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Betamethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Betaxolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and nonsteroidal antiinflammatory drugs (NSAIDs) are used concomitantly. Coadministration of betrixaban and NSAIDs may increase the risk of bleeding.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Bismuth Subsalicylate: (Major) Avoid concomitant use of naproxen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Avoid concomitant use of naproxen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Bisoprolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Bivalirudin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Brimonidine; Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Budesonide; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Bumetanide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Bupivacaine; Meloxicam: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Busulfan: (Major) Due to the thrombocytopenic effects of busulfan, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection.
Calcium Chloride: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Calcium-channel blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Candesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Cannabidiol: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Capreomycin: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory dru
Captopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Carmustine, BCNU: (Major) Due to the thrombocytopenic effects of carmustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Carteolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Carvedilol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Celecoxib; Tramadol: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Chlorambucil: (Major) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Chlorpropamide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Cholestyramine: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered.
Choline Salicylate; Magnesium Salicylate: (Major) Avoid concomitant use of naproxen with choline salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. (Major) Avoid concomitant use of naproxen with magnesium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Cholinesterase inhibitors: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ciclesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Cidofovir: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Cilostazol: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Citalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Cladribine: (Major) Due to the thrombocytopenic effects of cladribine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Clofarabine: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Clopidogrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Colistimethate, Colistin, Polymyxin E: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
Colistin: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
Corticosteroids: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Cortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Cyclosporine: (Moderate) Serum creatinine ,potassium concentrations, and cyclosporine concentrations should be closely monitored when systemic cyclosporine is given with nonsteroidal antiinflammatory drugs (NSAIDs). Renal dysfunction associated with cyclosporine may be potentiated by concurrent usage of NSAIDs. The effects of NSAIDs on the production of renal prostaglandins may cause changes in the elimination of cyclosporine. Potentiation of renal dysfunction may especially occur in a dehydrated patient. Patients should be monitored for signs and symptoms of cyclosporine toxicity and infection, as NSAIDs may mask fever, pain, or swelling. Increased tear production was not seen in patients receiving ophthalmic NSAIDs or using punctual plugs concurrently with cyclosporine ophthalmic emulsion.
Cytarabine, ARA-C: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Dabigatran: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Dabrafenib: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was decreased by 37%.
Dacarbazine, DTIC: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Dasatinib: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Deflazacort: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Desirudin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia.
Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by desvenlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be monitored for signs and symptoms of bleeding while taking desvenlafaxine with NSAIDs.
Dexamethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Diclofenac: (Major) Avoid concomitant use of diclofenac with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Diclofenac; Misoprostol: (Major) Avoid concomitant use of diclofenac with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Diflunisal: (Major) Avoid concomitant use of diflunisal with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. Additionally, concomitant administration of naproxen and diflunisal significantly decreased the urinary excretion of naproxen and its glucuronide metabolite; naproxen and diflunisal plasma concentrations were unaffected.
Digoxin: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Diphenhydramine; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Dipyridamole: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Docetaxel: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Donepezil: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Donepezil; Memantine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Dorzolamide; Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Doxazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Drospirenone: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Estetrol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Ethinyl Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
Duloxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant duloxetine and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Edoxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Elexacaftor; tezacaftor; ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Eltrombopag: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Emtricitabine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Enalapril, Enalaprilat: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Enoxaparin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Entecavir: (Moderate) The manufacturer of entecavir recommends monitoring for adverse effects when coadministered with NSAIDs. Entecavir is primarily eliminated by the kidneys; NSAIDs can affect renal function. Concurrent administration may increase the serum concentrations of entecavir and adverse events.
Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating coadministration of eplerenone and nonsteroidal antiinflammatory drugs (NSAIDs), and monitor blood pressure. The concomitant use of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Patients who develop hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium concentrations.
Epoprostenol: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.
Eprosartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Eptifibatide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with nonsteroidal antiinflammatory drugs (NSAIDs) is necessary. Permanently discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib ranged from 0.1% to 0.4%, including fatal cases. Patients receiving concomitant NSAIDs may be at increased risk of perforation.
Escitalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Esmolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Ethacrynic Acid: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Ethanol: (Major) Advise patients to avoid alcohol and alcohol-containing products while taking NSAIDs. Concomitant ingestion of alcohol with NSAIDs increases the risk of developing gastric irritation and GI mucosal bleeding. Alcohol is a mucosal irritant and NSAIDs decrease platelet aggregation. Routine ingestion of alcohol and NSAIDs can cause significant GI bleeding, which may or may not be overt. Even occasional concomitant use of NSAIDs and alcohol should be avoided. Chronic alcohol ingestion is often associated with hypoprothrombinemia and this condition increases the risk of bleeding.
Ethiodized Oil: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ethotoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug.
Etidronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Etodolac: (Major) Avoid concomitant use of etodolac with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid.
Fenoprofen: (Major) Avoid concomitant use of fenoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Flavocoxid, Flavocoxid; Citrated Zinc Bisglycinate: (Major) Flavocoxid exerts similar pharmacologic characteristics to other systemic NSAIDs. Additive pharmacodynamic effects, including a potential for additive adverse cardiac and GI effects, may be seen if flavocoxid is used with NSAIDs. In general, the concurrent use of flavocoxid and NSAIDs should be avoided.
Floxuridine: (Major) Due to the thrombocytopenic effects of floxuridine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fludrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Flunisolide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluorouracil, 5-FU: (Major) Due to the thrombocytopenic effects of fluorouracil, 5-FU, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fluoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Flurbiprofen: (Major) Avoid concomitant use of flurbiprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluticasone; Salmeterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluticasone; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluvoxamine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Fondaparinux: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Formoterol; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Foscarnet: (Minor) The risk of renal toxicity may be increased if foscarnet is used in conjuction with other nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor renal function carefully during concurrent therapy.
Fosinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Fosphenytoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug.
Furosemide: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Galantamine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ganciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Garlic, Allium sativum: (Minor) Garlic, Allium sativum may produce clinically-significant antiplatelet effects; until more data are available, garlic should be used cautiously in patients receiving drugs with a known potential risk for bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs).
Gemfibrozil: (Moderate) Use naproxen and gemfibrozil together with caution. Naproxen is a substrate of CYP2C8, and gemfibrozil is a strong CYP2C8 inhibitor. Coadministration may result in a significant increase in naproxen exposure. A dose reduction of naproxen may be required if used concomitantly with gemfibrozil.
Gentamicin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as gentamicin.
Ginger, Zingiber officinale: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and NSAIDs as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glipizide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glipizide; Metformin: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glyburide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glyburide; Metformin: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Gold: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Guanfacine: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.
H2-blockers: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Heparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydantoins: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Hydrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid concomitant use of naproxen with phenyl salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Ibandronate: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate, respectively, and nonsteroidal antiinflammatory drugs. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as nonsteroidal antiinflammatory drugs (NSAIDs); the risk of bleeding may be increased. If coadministration with NSAIDs is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Ibuprofen lysine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Ibuprofen: rong> (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ibuprofen; Famotidine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ibuprofen; Oxycodone: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Iloprost: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indapamide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Indomethacin: (Major) Avoid concomitant use of indomethacin with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and nonsteroidal antiinflammatory drugs (NSAIDs) due to the risk of glomerulonephritis and nephrotoxicity as well as the potential risk of bleeding from thrombocytopenia. Consider discontinuation of NSAIDs in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Iodipamide Meglumine: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iodixanol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iohexol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iomeprol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iopamidol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iopromide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ioversol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ioxaglate Meglumine; Ioxaglate Sodium: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Irbesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Isosulfan Blue: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Ketoprofen: (Major) Avoid concomitant use of ketoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ketorolac: (Contraindicated) Concomitant use of ketorolac with another NSAID is contraindicated. Increased adverse gastrointestinal effects are possible if ketorolac is used with other systemic nonsteroidal antiinflammatory drugs (NSAIDs).
Labetalol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Leflunomide: (Moderate) In vitro studies indicate that the M1 metabolite of leflunomide inhibits cytochrome P450 2C9, the enzyme responsible for the metabolism of many NSAIDs. Leflunomide altered protein binding and thus, increased the free fraction of ibuprofen by 13% to 50%. The clinical significance of the interactions with NSAIDs is unknown. There was extensive concomitant use of NSAIDs in phase III clinical studies of leflunomide in the treatment of rheumatoid arthritis, and no clinical differential effects were observed. However, because some NSAIDs have been reported to cause hepatotoxic effects, some caution may be warranted in their use with leflunomide.
Levobunolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Levomefolate: (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
Levomilnacipran: (Moderate) Platelet aggregation may be impaired by SNRIs such as levomilnacipran due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and symptoms of bleeding in patients taking levomilnacipran and NSAIDs.
Lisinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Lithium: (Moderate) Monitor serum lithium concentrations during concomitant nonsteroidal anti-inflammatory (NSAID) use; reduce the lithium dose based on serum lithium concentrations and clinical response. NSAIDs decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations.
Lomustine, CCNU: (Major) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Losartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Lumacaftor; Ivacaftor: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of naproxen and lumacaftor; ivacaftor may alter naproxen exposure; caution and monitoring are advised if these drugs are administered together. Naproxen is a substrate of CYP2C9 (primary) and CYP2C8. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Lumacaftor; Ivacaftor: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of naproxen and lumacaftor; ivacaftor may alter naproxen exposure; caution and monitoring are advised if these drugs are administered together. Naproxen is a substrate of CYP2C9 (primary) and CYP2C8. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events.
Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as nonsteroidal antiinflammatory drugs (NSAIDs). Healthcare providers are advised to discontinue NSAID therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Mafenide: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Magnesium Salicylate: (Major) Avoid concomitant use of naproxen with magnesium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Mannitol: (Major) Avoid use of mannitol and nonsteroidal anti-inflammatory drugs (NSAIDs), if possible. If use together is necessary, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Concomitant administration of nephrotoxic drugs, such as NSAIDs, increases the risk of renal failure after administration of mannitol. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Mecamylamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Mechlorethamine, Nitrogen Mustard: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meclofenamate Sodium: (Major) Avoid concomitant use of meclofenamate sodium with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Mefenamic Acid: (Major) Avoid concomitant use of mefenamic acid with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Meloxicam: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Mesalamine, 5-ASA: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Methenamine; Sodium Salicylate: (Major) Avoid concomitant use of naproxen with sodium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Methotrexate: (Major) Do not administer nonsteroidal anti-inflammatory drugs (NSAIDs) before or concomitantly with high doses of methotrexate, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate concentrations, resulting in deaths from severe hematologic and gastrointestinal toxicity. Use caution when NSAIDs are administered concomitantly with lower doses of methotrexate as they have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity. Despite potential interactions, patients with rheumatoid arthritis (RA) are often receiving concurrent treatment with NSAIDs without apparent problems. However, these doses are lower than those used in psoriasis or malignancy; higher methotrexate doses may lead to unexpected toxicity in combination with NSAIDs. NSAIDs may be continued in patients with RA receiving treatment with methotrexate, although the possibility of increased toxicity has not been fully explored.
Methoxsalen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable.
Methyldopa: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Methylprednisolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Methylsulfonylmethane, MSM: (Moderate) Patients taking methylsulfonylmethane, MSM have reported increased bruising or blood in the stool. These effects have not been confirmed in published medical literature or during clinical studies. Use methylsulfonylmethane, MSM with caution in patients who are taking drugs with the potential for additive bleeding, including nonsteroidal antiinflammatory drugs (NSAIDs). During an available, published clinical trials in patients with osteoarthritis, patients with bleeding disorders or using anticoagulants or platelet inhibiting drugs were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving NSAIDs should be observed for potential bleeding.
Metoprolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Mifepristone: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Milnacipran: (Moderate) Platelet aggregation may be impaired by milnacipran due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and symptoms of bleeding in patients taking milnacipran and NSAIDs.
Mitoxantrone: (Major) Due to the thrombocytopenic effects of mitoxantrone, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Nabumetone: (Major) Avoid concomitant use of nabumetone with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Nadolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Nebivolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Nebivolol; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Nelarabine: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Neomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, such as aminoglycosides.
Neostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Neostigmine; Glycopyrrolate: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Non-Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Olmesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olopatadine; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and nonsteroidal antiinflammatory drugs (NSAIDs) when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding.
Omeprazole; Sodium Bicarbonate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Oritavancin: (Moderate) Naproxen is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated naproxen plasma concentrations. If these drugs are administered concurrently, monitor patients for NSAID-induced toxicity, such as nausea, GI bleeding, or renal dysfunction.
Oxaprozin: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Paclitaxel: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Pamidronate: (Moderate) Monitor renal function during concomitant pamidronate and nonsteroidal antiinflammatory drug use due to risk for additive nephrotoxicity.
Paroxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Pentamidine: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
Pentosan: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Pentostatin: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Perindopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Perindopril; Amlodipine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Phenoxybenzamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Phentolamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Phenytoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug.
Photosensitizing agents (topical): (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and during photodynamic therapy may be advisable.
Physostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Pindolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Pioglitazone; Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Piroxicam: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Platelet Inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Pneumococcal Vaccine, Polyvalent: (Moderate) Concomitant administration of antipyretics, such as nonsteroidal antiinflammatory drugs (NSAIDS), may decrease an individual's immunological response to the pneumococcal vaccine. A post-marketing study conducted in Poland using a non-US vaccination schedule (2, 3, 4, and 12 months of age) evaluated the impact of prophylactic oral acetaminophen on antibody responses to Prevnar 13. Data show that acetaminophen, given at the time of vaccination and then dosed at 6 to 8 hour intervals for 3 doses on a scheduled basis, reduced the antibody response to some serotypes after the third dose of Prevnar 13 when compared to the antibody responses of infants who only received antipyretics 'as needed' for treatment. However, reduced antibody responses were not observed after the fourth dose of Prevnar 13 with prophylactic acetaminophen.
Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Polymyxin B: (Major) The chronic coadministration of systemic polymyxins may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since Polymyxin B is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Pralatrexate: (Major) Renal elimination accounts for approximately 34% of the overall clearance of pralatrexate. Concomitant administration of drugs that undergo substantial renal clearance, such as nonsteroidal antiinflammatory drugs (NSAIDs), may result in delayed clearance of pralatrexate.
Prasugrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Prazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Prednisolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Prednisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Probenecid: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Probenecid; Colchicine: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Procarbazine: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Propranolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Pyridostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Quinapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Quinolones: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ramipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Reteplase, r-PA: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Risedronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Rivaroxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Rivastigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Sacubitril; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Salsalate: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Selective serotonin reuptake inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Sertraline: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Sodium Bicarbonate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Sotalol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Sparsentan: (Moderate) Monitor for worsening renal function during concomitant use of sparsentan and nonsteroidal antiinflammatory drugs (NSAIDs), including selective cyclooxygenase (COX-2) inhibitors. Concomitant use increases the risk for nephrotoxicity, especially in patients with additional risk factors such as hypovolemia and chronic renal impairment.
Spironolactone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Streptomycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as streptomycin.
Sucralfate: (Moderate) Separate sucralfate and naproxen administration by at least 2 hours. Concomitant administration of sucralfate and enteric-coated or delayed-release naproxen tablets can delay the absorption of naproxen.
Sulfadiazine: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Sulfasalazine: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Sulfonamides: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug.
Sulfonylureas: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Sulindac: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Tacrine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Tacrolimus: (Moderate) Monitor patients for signs of worsening renal function during coadministration of tacrolimus and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Telavancin: (Minor) Concurrent or sequential use of telavancin with drugs that inhibit renal prostaglandins such as nonsteroidal antiinflammatory drugs (NSAIDS) may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Telmisartan; Amlodipine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Temozolomide: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tenecteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacody namic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Teniposide: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Terazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Teriflunomide: (Moderate) Increased monitoring is recommended if teriflunomide is administered concurrently with CYP2C8 substrates, such as naproxen. In vivo studies demonstrated that teriflunomide is an inhibitor of CYP2C8. Coadministration may lead to increased exposure to CYP2C8 substrates; however, the clinical impact of this has not yet been determined. Monitor for increased adverse effects, including additive hepatotoxicity.
Tezacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Thiazide diuretics: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Thioguanine, 6-TG: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Thrombolytic Agents: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Ticagrelor: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ticlopidine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Tirofiban: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant use of NSAIDs with tobacco smoking may enhance the risk of gastrointestinal side effects, including peptic ulcer and GI bleeding. Patients using tobacco and NSAIDs concurrently should be monitored closely for GI adverse reactions.
Tobramycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as tobramycin.
Tolazamide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Tolbutamide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Tolmetin: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Torsemide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Tositumomab: (Major) The tositumomab therapeutic regimen frequently causes severe and prolonged thrombocytopenia. The potential benefits of medications that interfere with platelet function and/or anticoagulation should be weighed against the potential increased risk of bleeding and hemorrhage. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Trandolapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with medications that impair platelet function and to promptly report any bleeding events to the practitioner.
Treprostinil: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.
Triamcinolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Triamterene: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant triamterene and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant triamterene and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Urea: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Valacyclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of valacyclovir and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Valganciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Vancomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Vemurafenib: (Minor) Concomitant use of vemurafenib and naproxen may result in increased naproxen concentrations. Vemurafenib is a CYP2C9 and CYP1A2 inhibitor and naproxen is a CYP2C9 and CYP1A2 substrate. Patients should be monitored for toxicity.
Venlafaxine: (Moderate) Platelet aggregation may be impaired by venlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor patients for signs and symptoms of bleeding when coadministering venlafaxine with NSAIDs.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with nonsteroidal anti-inflammatory drugs is necessary due to the risk of decreased verteporfin efficacy. Oxaprozin may additionally worsen photosensitivity. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation like nonsteroidal anti-inflammatory drugs could decrease the efficacy of verteporfin therapy.
Vigabatrin: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
Vilazodone: (Moderate) Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with NSAIDs and to promptly report any bleeding events to the practitioner.
Voclosporin: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Vorapaxar: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Voriconazole: (Moderate) The hepatic isoenzyme CYP2C9 is responsible for the metabolism of many NSAIDs. Voriconazole is known to be an inhibitor of CYP2C9 and may lead to increased plasma levels of some NSAIDs, such as naproxen. The clinical significance of this potential interaction is unknown. Monitor for NSAID-related side-effects, such as fluid retention or GI irritation, and adjust the dose of the NSAID if needed.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with medications which impair platelet function and to promptly report any bleeding events to the practitioner.
Warfarin: (Moderate) Monitor patients for signs or symptoms of bleeding during concurrent use of warfarin and nonsteroidal antiinflammatory drugs (NSAIDs). To minimize the potential for GI bleeding, use the lowest effective NSAID dose for the shortest possible duration. If signs or symptoms of bleeding occur, promptly evaluate and treat. Systemic hematological effects may also occur with the use of topical NSAIDs. NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients.
Zoledronic Acid: (Moderate) Monitor renal function during concomitant zoledronic acid and nonsteroidal antiinflammatory drug use due to risk for additive nephrotoxicity.
How Supplied
Aflaxen/Aleve/Aleve Arthritis/All Day Pain Relief/All Day Relief/Anaprox/Anaprox DS/Naprosyn/Naproxen/Naproxen Sodium Oral Tab: 220mg, 250mg, 275mg, 375mg, 500mg, 550mg
Aleve/Aleve Arthritis/Naproxen/Naproxen Sodium/Walgreens Naproxen Sodium Oral Cap: 220mg
EC-Naprosyn/Naproxen Oral Tab DR: 375mg, 500mg
Naprelan/Naproxen Oral Tab ER: 375mg, 500mg, 750mg
Naprosyn/Naproxen Oral Susp: 5mL, 125mg
Maximum Dosage
Naproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day PO.
GeriatricNaproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day PO.
AdolescentsNaproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day PO.
Children>= 12 years: In clinical practice, 20 mg/kg/day PO not to exceed 1000 mg/day PO; for non-prescription use, 660 mg/day PO.
2 to < 12 years: In clinical practice, 20 mg/kg/day PO not to exceed 1000 mg/day PO; non-prescription (self medication) use is not recommended.
< 2 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Mechanism of Action: Naproxen competitively inhibits both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, by blocking arachidonate binding resulting in analgesic, antipyretic, and anti-inflammatory pharmacologic effects. The enzymes COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin G2 (PGG2), the first step of the synthesis prostaglandins and thromboxanes that are involved in rapid physiological responses. COX isoenzymes are also responsible for a peroxidase reaction, which is not affected by NSAIDs. In addition, NSAIDs do not suppress leukotriene synthesis by lipoxygenase pathways. COX-1 is constitutively expressed in almost all tissues, while COX-2 appears to only be constitutively expressed in the brain, kidney, bones, reproductive organs, and some neoplasms (e.g., colon and prostate cancers). COX-1 is responsible for prostaglandin synthesis in response to stimulation by circulating hormones, as well as maintenance of normal renal function, gastric mucosal integrity, and hemostasis. However, COX-2 is inducible in many cells in response to certain mediators of inflammation (e.g., interleukin-1, tumor necrosis factor, lipopolysaccharide, mitogens, and reactive oxygen intermediates).•Anti-inflammatory Activity: The anti-inflammatory mechanism of naproxen is due to decreased prostaglandin synthesis via inhibition of COX-1 and COX-2. It appears that the anti-inflammatory effects may be primarily due to inhibition of the COX-2 isoenzyme. However, COX-1 is expressed at some sites of inflammation. COX-1 is expressed in the joints of rheumatoid arthritis or osteoarthritis patients, especially the synovial lining, and it is the primary enzyme of prostaglandin synthesis in human bursitis. Naproxen is slightly more selective for COX-1 than COX-2.•Analgesic Activity: Naproxen is effective in cases where inflammation has caused sensitivity of pain receptors (hyperalgesia). It appears prostaglandins, specifically prostaglandins E and F, are responsible for sensitizing the pain receptors; therefore, naproxen has an indirect analgesic effect by inhibiting the production of further prostaglandins and does not directly affect hyperalgesia or the pain threshold.•Antipyretic Activity: Naproxen promotes a return to a normal body temperature set point in the hypothalamus by suppressing the synthesis of prostaglandins, specifically PGE2, in circumventricular organs in and near the hypothalamus. Naproxen may mask fever in some patients, especially with high or chronic dosing.•GI Effects: Gastrointestinal side effects of naproxen are primarily contributed to COX-1 inhibition; however, potential role of COX-2 inhibition in the GI tract has not been fully elucidated.•Platelet Effects: The inhibition of platelet aggregation seen with naproxen is due to dose-dependent inhibition of COX-1 in platelets leading to decreased levels of platelet thromboxane A2 and an increase in bleeding time (see Adverse Reactions). The inhibition of platelet aggregation is reversible upon discontinuation of naproxen. This differs from aspirin, which irreversibly binds to COX-1 in platelets inhibiting this enzyme for the life of the cell. In an in vitro study, naproxen inhibited thromboxane production and platelet aggregation by 88% for up to 8 hours. Naproxen inhibited COX-1 (measured as thromboxane B2 generation in clotting whole blood) to a greater extent as compared to ibuprofen, diclofenac, or meloxicam (94.9%, 88.7%, 49.5%, and 53.3%, respectively). Clinically, naproxen may provide some cardioprotection benefits. However, naproxen produces less consistent inhibition of thromboxane A2 than low-dose aspirin, and in clinical trials, the cardioprotective effects of naproxen have been inconsistent.•Renal Effects: In the kidney, prostaglandins, produced by both COX-1 and COX-2, are important regulators of sodium and water reabsorption through PGE2 and of renal function and hemodynamics via PGI2 in response to vasoconstrictive factors (e.g., endothelin-1, a factor that increases peripheral vascular resistance) and through effects on the renin-angiotensin system. In conditions where renal blood flow is dependent upon prostaglandin synthesis, administration of NSAIDs can result in significant decreases in renal blood flow leading to acute renal failure. In addition, alterations in sodium and water reabsorption may worsen increased blood pressure, which can be significant in selected individuals.•Bone Effects: Nonsteroidal anti-inflammatory drugs appear to suppress bone formation via inhibition of COX-2. In vivo data from rabbits revealed a significant reduction of bone growth with both naproxen and rofecoxib as compared with placebo. Bone resorption does not appear to be a mechanism that leads to decreased net bone formation, as the number of CD51 positive osteoclast-like cells per section was decreased with either NSAID as compared with drinking water alone. As determined from in vitro data, NSAIDs appear to arrest the osteoblast cell cycle at the G(0)/G(1) phase and induce cytotoxicity and cell death of osteoblasts primarily by apoptosis rather than by necrosis.
Pharmacokinetics
Naproxen is administered orally. It is more than 99% bound to albumin. At doses more than 500 mg/day, a less than proportional increase in plasma concentrations occurs due to increased clearance because of saturation of plasma protein binding. It is extensively metabolized in the liver to 6-O-desmethyl naproxen. Both naproxen and 6-O-desmethyl naproxen are further metabolized to their respective acylglucoronide conjugated metabolites. Urinary excretion is the predominant elimination pathway. Approximately 95% of naproxen is excreted in the urine with less than 1% as unchanged drug, less than 1% as 6-O-desmethyl naproxen, and 66% to 92% as their conjugates. Small amounts, 3% or less of an administered dose, is excreted in the feces. The naproxen anion has a plasma half-life of 12 to 17 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2C8, CYP2C9
Naproxen is a substrate of the hepatic cytochrome isoenzymes CYP1A2, CYP2C8, and CYP2C9; CYP2C9 appears to be the main substrate pathway.
The different dosage forms of naproxen are bioequivalent in terms of extent of absorption (AUC) and peak concentration; however, the products do differ in their pattern of absorption. Naproxen and naproxen sodium are rapidly and completely absorbed from the GI tract. Onset of pain relief can be within 1 hour in patients taking naproxen and 30 minutes in patients taking naproxen sodium. The analgesic effect has been found to last for up to 12 hours. Peak plasma concentrations of naproxen are achieved 2 to 4 hours and 1 to 2 hours after ingestion of naproxen and naproxen sodium, respectively. The difference in rates between the 2 products is due to the increased aqueous solubility of the sodium salt of naproxen. The enteric polymer coating for enteric-coated naproxen dissolves above pH 6. Enteric-coated naproxen dissolves primarily in the small intestine rather than in the stomach, so the absorption of the drug is delayed until the stomach is emptied. When enteric-coated naproxen was given to fasted subjects, peak plasma concentrations were achieved about 4 to 6 hours after the first dose (range: 2 to 12 hours). When enteric-coated naproxen was given with food, peak plasma concentrations were achieved in about 12 hours (range: 4 to 24 hours). The presence of food prolonged the time the tablets remained in the stomach, time to first detectable serum naproxen concentrations, and time to maximal naproxen concentrations, but did not affect peak naproxen concentrations. The elimination half-life of naproxen is unchanged across products ranging from 12 to 17 hours. Steady-state concentrations are reached in 4 to 5 days.
Pregnancy And Lactation
Naproxen is excreted into breast milk in concentrations approximately equivalent to 1% of the maximal maternal plasma concentrations. Consider the developmental and health benefits of breast-feeding along with the need for naproxen and any potential adverse effects on the breastfed infant from naproxen or the underlying condition. Naproxen use is usually considered compatible with breast-feeding; other alternative analgesic and antiinflammatory drugs considered to be usually compatible with breast-feeding include acetaminophen and ibuprofen.