Non-steroidal anti-inflammatory drugs
Medications listed in the tables and non-FDA approved indications included in these retrospective criteria are not indicative of Texas Vendor Drug Program formulary coverage.
- Revision history
- Revised July 22, 2022; June 2020; June 2018; August 2016; June 2016; October 2014; February 2013; December 2012; March 2011; January 2011; October 2007; January 2006; August 2003; September 2002; August 2001; September 2000; August 2000; November 1999; October 1999; September 1998; September 1997; October 1996; October 1995.
- Initially developed
- January 1994
1. Dosage
Nonselective oral and rectal NSAIDs are FDA-approved for use in rheumatoid arthritis/juvenile rheumatoid arthritis (JRA), osteoarthritis, ankylosing spondylitis, pain management, dysmenorrhea, fever, migraines and cluster headaches. JRA is now also known as juvenile idiopathic arthritis (JIA) or juvenile arthritis (JA). Diclofenac, ibuprofen, and naproxen are also available as combination therapy with gastric acid suppressants to minimize the risk of NSAID-associated gastric ulcer development1-39.
1.1. Adults
Adult maximum daily NSAID dosages as monotherapy and combination therapy are summarized in Tables 1 and 2 and should not exceed these recommended maximum values.
Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Daily Dosage |
---|---|---|---|
aspirin extended-release (ER) (Durlaza®) | 162.5 mg ER capsule | Reduce risk of death and myocardial infarction (MI) in patients with coronary artery disease (CAD) such as patients with a history of MI, unstable angina pectoris, or chronic stable angina | 162.5 mg once daily |
Reduce risk of death and recurrent stroke in patients with previous ischemic stroke or transient ischemic attack (TIA) | 162.5 mg once daily | ||
aspirin (generics) | 81 mg chewable/EC tablets; 325 mg regular/EC tablets | arterial thromboembolism prophylaxis | 325 mg once daily |
81 mg chewable/enteric-coated (EC) tablets; 325 mg, 500 mg regular/EC tablets; 300 mg, 600 mg rectal suppositories | fever, pain (mild to moderate including dysmenorrhea) | 4000 mg/day in divided doses | |
81 mg chewable/EC tablets; 325 mg regular/EC tablets | myocardial infarction | 325 mg x1 dose, chewed | |
81 mg chewable/EC tablets | myocardial infarction prevention | 162 mg once daily | |
325 mg, 500 mg, regular/EC tablets | osteoarthritis | 3000 mg/day in divided doses | |
325 mg, 500 mg, regular/EC tablets | osteoarthritis | 3000 mg/day in divided doses | |
325 mg, 500 mg, regular/EC tablets | rheumatoid arthritis | titrate to a plasma salicylate level between 150- 300 mcg/ mL | |
81 mg chewable/EC tablets; 325 mg regular/EC tablets | stroke prevention in patients with TIA or other stroke risk factors | 325 mg once daily | |
choline magnesium trisalicylate | 500 mg, 750 mg, 1000 mg tablets; 500 mg/5 mL solution | fever, mild/ moderate pain | 3000 mg/day in divided doses |
osteoarthritis, rheumatoid arthritis, or acute painful shoulder | 3000 mg/ day in divided doses | ||
diclofenac potassium (Cambia®) | 50 mg oral powder for solution | acute migraine attack with or without aura | 50 mg (1 packet) as single dose |
diclofenac potassium immediate-release (IR) (Lofena®, Cataflam®, generics) | 25 mg (Lofena®, generics), 50 mg (Cataflam®, generics) IR tablets | osteoarthritis | 150 mg/day in divided doses |
pain (mild to moderate) | 150 mg/day in divided doses | ||
primary dysmenorrhea | 150 mg/day in divided doses | ||
rheumatoid arthritis | 200 mg/day in divided doses | ||
diclofenac sodium delayed- release (DR) (generics) | 25 mg, 50 mg, 75 mg DR tablets | ankylosing spondylitis | 125 mg/day in divided doses |
osteoarthritis | 150 mg/day in divided doses | ||
rheumatoid arthritis | 200 mg/day in divided doses | ||
diclofenac sodium extended-release (ER) (generics) | 100 mg ER tablets | osteoarthritis | 100 mg once daily |
rheumatoid arthritis | 200 mg/day in divided doses | ||
diclofenac potassium (Zipsor®, generics) | 25 mg capsule | pain (mild to moderate) | 100 mg/day in divided doses |
diclofenac (Zorvolex®, generics) | 18 mg, 35 mg (Zorvolex®, generics) capsules | osteoarthritis | 105 mg/day in divided doses |
pain (mild to moderate) | 105 mg/day in divided doses | ||
diflunisal | 500 mg tablets | osteoarthritis | 1500 mg/day in divided doses |
pain (mild to moderate) | 1500 mg/day in divided doses | ||
rheumatoid arthritis | 1500 mg/day in divided doses | ||
etodolac IR (generics) | 200 mg, 300 mg IR capsule; 400 mg, 500 mg IR tablet | acute pain | 1200 mg/day in divided doses |
osteoarthritis | 1200 mg/day in divided doses | ||
rheumatoid arthritis | 1200 mg/day in divided doses | ||
etodolac ER (generics) | 400 mg, 500 mg, 600 mg ER tablets | osteoarthritis | 1200 mg once daily |
rheumatoid arthritis | 1200 mg once daily | ||
fenoprofen capsules (Nalfon®, generics); tablets (Nalfon®, generics) | 200 mg, 400 mg capsules; 600 mg tablets | osteoarthritis | 3200 mg/day in divided doses |
pain (mild to moderate) | 3200 mg/ day in divided doses | ||
rheumatoid arthritis | 3200 mg/day in divided doses | ||
flurbiprofen (generics) | 50 mg, 100 mg tablets | osteoarthritis | 300 mg/day in divided doses |
rheumatoid arthritis | 300 mg/day in divided doses | ||
ibuprofen (Advil®, Motrin®, generics) | 100 mg chewable tablets; 200 mg, 400 mg, 600 mg, 800 mg tablets; 200 mg capsule; 100 mg/5 mL suspension | dysmenorrhea | 3200 mg/day in divided doses |
fever | 3200 mg/day in divided doses | ||
headache | 3200 mg/day in divided doses | ||
migraine | 3200 mg/day in divided doses | ||
osteoarthritis | 3200 mg/day in divided doses | ||
pain (mild to moderate) | 3200 mg/day in divided doses | ||
rheumatoid arthritis | 3200 mg/day in divided doses | ||
indomethacin IR (generics) | 25 mg, 50 mg capsules; 25 mg/5 mL suspension | acute bursitis or tendinitis | 200 mg/day in divided doses |
acute gouty arthritis | 200 mg/day in divided doses | ||
ankylosing spondylitis | 200 mg/day in divided doses | ||
osteoarthritis | 200 mg/day in divided doses | ||
rheumatoid arthritis | 200 mg/day in divided doses | ||
indomethacin ER (generics) | 75 mg ER capsules | acute bursitis or tendinitis | 150 mg/day in divided doses |
ankylosing spondylitis | 150 mg/day in divided doses | ||
osteoarthritis | 150 mg/day in divided doses | ||
rheumatoid arthritis | 150 mg/day in divided doses | ||
indomethacin (Tivorbex®, generics) | 20 mg capsules | acute pain (mild to moderate) | 120 mg/day in divided doses |
indomethacin rectal (Indocin®) | 50 mg rectal suppository | acute bursitis or tendinitis | 150 mg/day in divided doses; no more than 100 mg per dose |
acute gouty arthritis | 150 mg/day in divided doses; no more than 100 mg per dose | ||
ankylosing spondylitis | 200 mg/day in divided doses; no more than 100 mg per dose | ||
osteoarthritis | 200 mg/day in divided doses; no more than 100 mg per dose | ||
rheumatoid arthritis | 200 mg/day in divided doses; no more than 100 mg per dose | ||
ketoprofen IR (generics) | 25 mg, 50 mg, 75 mg IR capsules | osteoarthritis | 300 mg/day in divided doses |
pain (mild/moderate, including acute dysmenorrhea) | 300 mg/day in divided doses | ||
rheumatoid arthritis | 300 mg/day in divided doses | ||
ketoprofen ER (generics) | 200 mg ER capsule | osteoarthritis | 200 mg once daily |
rheumatoid arthritis | 200 mg once daily | ||
ketorolac (generics) | 10mg tablets | acute pain (moderately severe) following IV or IM treatment | 40 mg/day in divided doses |
magnesium salicylate (Doans®, generics) | 580 mg extended-release caplets | pain (mild/moderate) | 4640 mg/day (8 caplets) in divided doses |
meclofenamate (generics) | 50 mg, 100 mg capsules | acute bursitis or tendinitis | 400 mg/day in divided doses |
acute gouty arthritis | 400 mg/day in divided doses | ||
ankylosing spondylitis | 400 mg/day in divided doses | ||
dysmenorrhea and idiopathic heavy menstrual blood loss | 300 mg/day in divided doses | ||
osteoarthritis | 400 mg/day in divided doses | ||
pain (mild/ moderate) | 400 mg/day in divided doses | ||
rheumatoid arthritis | 400 mg/day in divided doses | ||
mefenamic acid (generics) | 250 mg capsules | pain (mild/ moderate including dysmenorrhea) | 1250 mg in divided doses on day 1; 1000 mg/day in divided doses on days 2-7 |
meloxicam (Mobic®, generics) | 7.5 mg, 15 mg tablets, 7.5 mg/ 5 mL suspension | osteoarthritis | 15 mg/day once daily |
rheumatoid arthritis | 15 mg/day once daily | ||
meloxicam (Vivlodex®, generics) | 5 mg, 10 mg capsules | osteoarthritis | 10 mg/day once daily |
nabumetone (generics) | 500 mg, 750 mg tablets | osteoarthritis | 2000 mg/day in single or divided doses |
rheumatoid arthritis | 2000 mg/day in single or divided doses | ||
naproxen IR (Aleve®, Naprosyn®, generics) | 220 mg IR capsule; 220 mg, 250 mg, 275 mg, 375 mg, 500 mg IR tablets; 125 mg/5 mL IR suspension | acute gout | 1500 mg/day in divided doses |
ankylosing spondylitis | 1500 mg/day in divided doses | ||
bursitis/tendinitis | 1500 mg/day in divided doses | ||
osteoarthritis | 1500 mg/day in divided doses | ||
pain (mild/moderate including dysmenorrhea) | 1500 mg/day in divided doses | ||
rheumatoid arthritis | 1500 mg/day in divided doses | ||
naproxen sodium (Anaprox DS®, generics) | 220 mg, 275 mg, 550 mg IR tablets | acute gout | 1650 mg/day in divided doses |
ankylosing spondylitis | 1650 mg/day in divided doses | ||
bursitis/tendinitis | 1650 mg/day in divided doses | ||
osteoarthritis | 1650 mg/day in divided doses | ||
pain (mild/moderate including dysmenorrhea) | 1650 mg/day in divided doses | ||
rheumatoid arthritis | 1650 mg/day in divided doses | ||
naproxen DR (EC-Naprosyn®, generics) | 375 mg, 500 mg DR tablets | ankylosing spondylitis | 1500 mg/day in divided doses |
osteoarthritis | 1500 mg/day in divided doses | ||
rheumatoid arthritis | 1500 mg/day in divided doses | ||
naproxen ER (Naprelan®, generics | 375 mg, 500 mg, 750 mg ER tablets | acute gout | 1500 mg/day in divided doses |
ankylosing spondylitis | 1500 mg/day in divided doses | ||
bursitis/tendinitis | 1500 mg/day in divided doses | ||
osteoarthritis | 1500 mg/day in divided doses | ||
pain (mild/moderate including dysmenorrhea) | 1500 mg/day in divided doses | ||
rheumatoid arthritis | 1500 mg/day in divided doses | ||
oxaprozin (Daypro®, generics) | 600 mg tablets | osteoarthritis | 1800 mg/day (not to exceed 26 mg/kg/day) in divided doses |
rheumatoid arthritis | 1800 mg/day (not to exceed 26 mg/kg/day) in divided doses | ||
piroxicam (Feldene®, generics) | 10 mg, 20 mg capsules | osteoarthritis | 20 mg once daily |
rheumatoid arthritis | 20 mg once daily | ||
salsalate (Disalcid®, generics) | 500 mg, 750 mg tablets | osteoarthritis | 3000 mg/day in divided doses |
rheumatoid arthritis | 3000 mg/day in divided doses | ||
sulindac (generics) | 150 mg, 200 mg tablets | acute gouty arthritis | 400 mg/day in divided doses |
ankylosing spondylitis | 400 mg/day in divided doses | ||
bursitis/tendinitis of shoulder | 400 mg/day in divided doses | ||
osteoarthritis | 400 mg/day in divided doses | ||
rheumatoid arthritis | 400 mg/day in divided doses |
Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Daily Dosage |
---|---|---|---|
acetaminophen/ aspirin/caffeine (Excedrin® Migraine, generics) | 250 mg/250 mg/65 mg tablets | migraine headache | 2 tablets/24 hours |
pain, including headache | 8 tablets/24 hours in divided doses | ||
acetaminophen/aspirin/caffeine (Goody’s®) | 260 mg/520 mg/32.5 mg powders | pain, including headache | 4 powders/24 hours in divided doses |
aspirin/butalbital/caffeine (Fiorinal®, generics) | 325 mg/50 mg/40 mg capsules, tablets | tension or muscle contraction headache | 6 capsules/24 hours in divided doses (1 or 2 every 4 hours) |
diclofenac/misoprostol (Arthrotec®, generics) | 50 mg/200 mcg, 75 mg/200 mcg delayed-release tablet | osteoarthritis in patients at high risk of developing NSAID-induced gastric and duodenal ulcers | 150 mg/600 mcg/day in divided doses |
rheumatoid arthritis in patients at high risk of developing NSAID-induced gastric and duodenal ulcers | 200 mg/800 mcg/day in divided doses | ||
ibuprofen/famotidine (Duexis®, generic) | 800 mg/26.6 mg tablet | pain relief in osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers | 2400 mg/79.8 mg/day in divided doses |
pain relief in rheumatoid arthritis and to decrease the risk of developing upper gastrointestinal ulcers | 2400 mg/79.8 mg/day in divided doses | ||
naproxen/esomeprazole (Vimovo®, generic) | 375 mg/20 mg, 500 mg/20 mg delayed-release tablet | ankylosing spondylitis in patients at risk of developing NSAID-associated ulcers | 1000 mg/40 mg/day in divided doses |
osteoarthritis in patients at risk of developing NSAID-associated ulcers | 1000 mg/40 mg/day in divided doses | ||
rheumatoid arthritis in patients at risk of developing NSAID-associated ulcers | 1000 mg/40 mg/day in divided doses |
1.2. Pediatrics
NSAID safety and efficacy in children have not been established for all available agents. Ibuprofen is FDA-approved for short-term management of fever and mild to moderate pain and long-term management of JRA/JIA/JA in pediatric patients; meloxicam and naproxen are FDA-approved for use in children as young as 2 years of age 1,2,24,25,29,37. Indomethacin is not FDA-approved in those less than 15 years of age, but JRA/JIA/JA patients between 2 and 14 years of age who have experienced toxicity/lack of benefit from other medications, may receive indomethacin up to a maximum dose of 3 mg/kg/day (no more than 200 mg/day orally)1,2,17,38. Aspirin, while FDA-approved for use in fever and pain for adolescents, should not be given for fever and muscle aches seen in viral illness due to the potential for Reye’s syndrome1,2,38. Aspirin in combination with acetaminophen and caffeine is FDA-approved for use in adolescent patients for mild to moderate pain, while naproxen/esomeprazole (Vimovo®) is approved for use in adolescents weighing at least 38 kg diagnosed with juvenile idiopathic arthritis at increased risk for NSAID associated gastric ulcers1,2,36 . NSAID dosages for pediatric indications are summarized in Tables 3 and 4. Dosages exceeding these recommendations will be reviewed.
Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Daily Dosage |
---|---|---|---|
aspirin* | 81 mg chewable/EC tablets; 325 mg, 500 mg regular/EC tablets; 300 mg, 600 mg rectal suppositories | fever/pain |
|
choline magnesium trisalicylate | 500 mg, 750 mg, 1000 mg tablets; 500 mg/5 mL solution | juvenile rheumatoid arthritis (JRA)/ juvenile idiopathic arthritis (JIA) |
|
diflunisal (generics) | 500 mg tablets | osteoarthritis |
|
pain (mild/moderate) |
|
||
rheumatoid arthritis |
|
||
etodolac extended-release (ER) (generics) | 400 mg, 500 mg, 600 mg ER tablets | JIA/JRA |
|
diflunisal (generics) | 500 mg tablets | osteoarthritis |
|
pain (mild/moderate) |
|
||
rheumatoid arthritis |
|
||
etodolac extended-release (ER) (generics) | 400 mg, 500 mg, 600 mg ER tablets | JIA/JRA |
|
ibuprofen (Motrin®, generics) | 50 mg/1.25 ml oral drops | fever, pain (mild to moderate) |
|
ibuprofen (Advil®, Motrin®, generics) | 100 mg/5 ml suspension | fever, pain (mild to moderate) |
|
ibuprofen (Advil®, generics) | 100 mg chewable tablets | fever, pain (mild to moderate) |
|
ibuprofen (Advil®, generics) | 200 mg caplets, capsules, or tablets | fever, pain (mild to moderate) |
|
ibuprofen (Advil®, Motrin®, generics) | chewable tablets, suspension, tablets | JIA/JRA |
|
indomethacin IR+ (generics) | 25 mg, 50 mg IR capsules; 25 mg/5 mL suspension | arthritic disorders |
|
50 mg rectal suppository |
|
||
indomethacin ER+ (generics) | 75 mg ER capsules |
|
|
magnesium salicylate (Doans®, generics) | 580 mg extended-release caplets | pain (mild to moderate) |
|
meclofenamate (generics) | 50 mg, 100 mg capsules | dysmenorrhea |
|
JIA/JRA |
|
||
pain (mild/moderate) |
|
||
mefenamic acid (generics) | 250 mg capsules | pain (mild/moderate, including dysmenorrhea) |
|
meloxicam (Mobic®, generics) | 7.5 mg tablets; 7.5 mg orally disintegrating tablets (ODT) | JIA/JRA |
|
7.5 mg/5 mL suspension |
|
||
naproxen (Aleve®, Naprosyn®, generics) | 220 mg IR capsule; 220 mg, 250 mg, 275 mg, 375 mg, 500 mg IR tablets; 125 mg/5 mL IR suspension | JIA/JRA |
|
pain (mild to moderate including dysmenorrhea) |
|
||
oxaprozin (Daypro®, generics) | 600 mg tablets | JIA/JRA |
|
Legend:
- *Do not use in children less than 12 years of age with flu-like symptoms or chickenpox due to risk of Reye syndrome
- +indomethacin not recommended in pediatric patients 2-14 years of age unless adverse effects/lack of efficacy with other NSAIDs justifies risk; maximum dose is 4 mg/kg/day or 200 mg/day, whichever is less
Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Daily Dosage |
---|---|---|---|
acetaminophen/aspirin/caffeine (Excedrin®, generics) | 250 mg/250 mg/65 mg tablets | pain, including headache | 12-17 years of age: 8 tablets/24 hours in divided doses |
acetaminophen/aspirin/caffeine (Goody’s®) | 260 mg/ 520 mg/ 32.5 mg powders | 12-17 years of age: 4 powders/24 hours in divided doses | |
naproxen/esomeprazole (Vimovo®, generic) | 375 mg/20 mg, 500 mg/20 mg delayed-release tablet | juvenile rheumatoid arthritis/ juvenile idiopathic arthritis in patients at risk of developing NSAID-associated ulcers |
|
2. Duration of Therapy
2.1. Therapy Limits
The duration of therapy derived for NSAIDs may be long-term and indefinite when prescribed for chronic indications; however, the lowest effective dosages for the shortest possible time should be utilized. NSAIDs should be prescribed cautiously, if at all, to patients at high risk for gastrointestinal complications and patients with known cardiovascular disease. High-risk patients include those with a history of peptic ulcer disease or gastrointestinal bleeding, those with concurrent prescriptions for anticoagulants or corticosteroids, those prescribed high NSAID doses, those with a history of alcohol use and/or smoking, and the elderly. High-risk patients unable to discontinue or reduce NSAID use may benefit from adjunctive therapy with gastroprotective agents such as misoprostol, a histamine-2 receptor antagonist, or proton pump inhibitors.
Treatment duration is limited for mefenamic acid to minimize the occurrence of adverse events. Mefenamic acid should be prescribed for no longer than seven days for pain management and no longer than three days for dysmenorrhea to reduce the incidence of diarrhea associated with the use of this drug23.
Treatment duration of ketorolac should not exceed 5 total days due to increased risk of adverse events such as risk of gastric ulceration, bleeding, and perforation37.
Diclofenac powder for oral solution is indicated as a single 50 mg dose to treat acute migraine headache. Safety and efficacy of a second dose for an attack have not been established4.
2.2. NSAID Use in Elderly Patients
Elderly patients frequently utilize prescription and nonprescription NSAIDs to manage acute and chronic pain. Several issues surface with NSAID use in elderly patients, including potential adverse effects and drug interactions. NSAID-induced gastrointestinal and renal toxicity as well as adverse central nervous system effects are more prevalent in elderly patients due to changes in metabolism, underlying disease states, and concurrent drug therapy. The potential for increased cardiovascular risk with NSAID use is also a factor when evaluating NSAID therapy in elderly patients. Elderly patients prescribed NSAIDs, especially those at higher risk, should be evaluated for appropriateness of therapy as well as potential for drug-drug interactions. Appropriate therapy duration as well as appropriate dosages should also be evaluated. Preventive measures such as gastric antisecretory agents should be considered in some individuals to reduce GI complications40. Medication profiles of elderly patients greater than 60 years of age prescribed NSAIDs with increased risk factors for adverse events or drug-drug interactions will be reviewed.
2.3. NSAID Use and Cardiovascular Risk
Some clinical trials have shown that patients prescribed selective and nonselective NSAIDs may be at increased risk for serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, all of which can be fatal. Patients at greater risk are those with known CV disease or risk factors for CV disease. Due to the lack of long-term clinical trial data, CV risks associated with NSAID use remains controversial, especially in high-risk patients. Risk also varies between nonselective NSAIDs and cyclooxygenase-2 (COX-2) inhibitors, as well as between individual NSAIDs. The Center for Drug Evaluation and Research has determined that the increased risk of CV events associated with NSAID use should be considered a class effect for both selective and nonselective NSAIDs until more results are available. Patients should be prescribed the lowest effective NSAID dose for the shortest possible treatment duration to minimize the potential for cardiovascular adverse events41-46.
NSAIDs may induce new onset hypertension or worsen pre-existing hypertension in some patients, which may contribute to the development of cardiovascular adverse events. Blood pressure should be routinely monitored in patients prescribed NSAIDs.
NSAIDs may cause fluid retention or edema in some patients and should be used cautiously in patients with a history of fluid retention or heart failure.
2.4. NSAID Use and Gastrointestinal Risk
All NSAIDs may be associated with an increased risk of serious gastrointestinal (GI) adverse events, including potentially fatal GI bleeding, ulceration, or gastric/intestinal perforation. The risk of NSAID-associated severe GI adverse events increases in patients with a history of peptic ulcer disease, GI bleeding, smoking, alcohol use, concurrent use of anticoagulants or oral corticosteroids, advanced age, poor health and prolonged NSAID use. However, COX-2 inhibitors like celecoxib may be associated with fewer GI adverse events due to selective COX-2 inhibition. Some trials have shown reduced ulcer complications and lower GI bleeding rates with celecoxib compared to nonselective NSAIDs. Further long-term studies are necessary to substantiate the perceived lower GI risk associated with COX-2 inhibitors47,48<./p>
3. Duplicative Therapy
The combination of two or more NSAIDs is not recommended except the use of less than 325 mg daily of aspirin plus another NSAID.
Concurrent administration of an NSAID and ketorolac, another NSAID utilized primarily for pain management with limited treatment duration, is contraindicated due to the potential for increased gastrointestinal adverse events.
The combined use of specific COX-2 inhibitors like celecoxib and nonspecific COX-1/COX-2 inhibitors does not provide additional therapeutic benefit and may result in additive adverse effects, including gastrointestinal toxicity. Concurrent therapy with specific COX-2 inhibitors and nonspecific COX-1/COX-2 inhibitors is not recommended and will be reviewed.
4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically significant for NSAIDs are summarized in Table 5. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
---|---|---|---|---|
NSAIDs | antihypertensive agents (e.g., ACE inhibitors, angiotensin receptor blockers, beta blockers, diuretics) | potential for decreased antihypertensive effects, increased renal impairment risk (especially in patents dependent on renal prostaglandins for perfusion), with combined therapy; increased hyperkalemia risk with potassium-sparing diuretics; NSAIDs may block production of vasodilator and natriuretic prostaglandins | monitor blood pressure, renal function; observe for hyperkalemia with potassium-sparing diuretics; modify therapy as necessary; use combination cautiously in elderly; sulindac, nonacetylated salicylates may be alternative NSAIDS – have less inhibitory effect on prostaglandin synthesis | moderate (DrugReax) 3-moderate (CP) |
NSAIDs | antiplatelet drugs (e.g., clopidogrel, prasugrel) | potential for increased bleeding risk due to additive inhibitory effects on platelet aggregation | administer cautiously together; monitor for increased bleeding, especially gastrointestinal (GI) bleeding | clopidogrel –major; prasugrel - moderate (DrugReax) 3-moderate (CP) |
NSAIDs | aspirin (ASA) | combined therapy may result in reduced ASA antiplatelet/ cardioprotective effects due to competitive inhibition of COX-1 binding site | ASA should be administered at least 30 minutes before or 8 hours after NSAID; NSAID should be given at least 1 hour after enteric-coated ASA | moderate (DrugReax) |
NSAIDs | bisphosphonates | combined therapy may result in additive GI, renal toxicity; NSAIDs also decrease bone mineral density, may attenuate bone mineral stabilizing effects by bisphosphonates | administer combination cautiously; monitor for increased GI/renal adverse effects, reduced bone mineral density | 2-major (CP) |
NSAIDs | corticosteroids | potential for increased GI adverse effects with combined therapy | monitor for adverse effects; avoid prolonged concurrent administration | 3-moderate (CP) |
NSAIDs | cyclosporine | increased risk for additive renal dysfunction with concurrent administration; potential for reduced cyclosporine elimination/ increased pharmacologic and adverse effects due to NSAID effects on renal prostaglandins; NSAIDs may mask signs of infection (e.g., fever, swelling) | use cautiously together; monitor clinical status, renal function, serum potassium concentrations | 3-moderate (CP) |
NSAIDs | fluoroquinolones | increased risk for CNS stimulation and seizures | administer cautiously together; consider alternative therapy in patients with predisposition to seizures | moderate (DrugReax) 3-moderate (CP) |
NSAIDs | lithium | NSAIDs may decrease lithium clearance most likely by blocking renal tubular prostaglandins; may result in increased lithium levels and potential for adverse effects | avoid combination, if possible; if concurrent therapy necessary, monitor lithium levels and signs/symptoms of lithium toxicity; sulindac, aspirin do not affect lithium clearance -may be alternative NSAIDS | moderate (DrugReax) 3-moderate (CP) |
NSAIDs | low molecular weight heparins | potential for additive bleeding adverse effects; NSAIDs inhibit platelet aggregation and have increased GI bleeding risk, prolonged bleeding time | avoid concurrent therapy, if possible; if drug combination necessary, use cautiously, monitor for signs/symptoms of bleeding | major (DrugReax) 2-major (CP) |
NSAIDs | methotrexate (MTX) | potential for increased MTX serum levels, risk of enhanced pharmacologic/toxic effects as NSAIDs can reduce MTX clearance | avoid concurrent NSAIDs within 10 days of high-dose MTX; otherwise, use cautiously together; monitor for increased myelopsuppressive, GI adverse effects; may consider using longer leucovorin rescue | major (DrugReax) 1-severe (CP) |
NSAIDs | phenytoin | NSAIDs may inhibit phenytoin metabolism, with increased risk for enhanced phenytoin pharmacologic/toxic effects (e.g., ataxia, nystagmus, hyperreflexia) | monitor for signs/symptoms of phenytoin toxicity, especially in patients with renal impairment; adjust doses as necessary | moderate (DrugReax) |
NSAIDs | select azole antifungals (e.g., fluconazole, voriconazole) | for NSAIDs metabolized by CYP2C9, increased risk of elevated NSAID plasma levels and potential for enhanced pharmacologic/adverse effects; select antifungals inhibit CYP2C9 | administer cautiously together; monitor for increased NSAID pharmacologic/adverse effects (e.g., bleeding, renal dysfunction); consider reduced NSAID doses, if necessary, or alternate NSAID/antifungal that does not affect metabolism | moderate (DrugReax) 3-moderate (CP) |
NSAIDs | SSRIs/SNRIs (e.g., milnacipran) | increased bleeding risk with combined therapy, especially GI bleeding; SSRIs/SNRIs deplete platelet serotonin, which may impair platelet aggregation | monitor for signs/symptoms of bleeding; may consider lower NSAID doses, shorter treatment durations, adding proton pump inhibitor, or substituting tricyclic antidepressant for SSRI/SNRI | SSRIs –major; SNRIs-moderate (DrugReax) 3-moderate (CP) |
NSAIDs | sulfonylureas | increased risk for additive hypoglycemia | monitor serum glucose concentrations; adjust doses as necessary | moderate (DrugReax) 4-minor (CP) |
NSAIDs | tacrolimus | potential for additive nephrotoxicity with combined therapy due to NSAID inhibitory effects on renal prostaglandins | avoid combination, if possible; if concurrent therapy necessary, closely monitor renal function | major (DrugReax) 3-moderate (CP) |
NSAIDs | warfarin | combined therapy may result in increased INR and increased risk of GI adverse effects, especially in elderly; mechanism unknown | monitor anticoagulant activity, especially in first several days of combination therapy; adjust warfarin doses as necessary | major (DrugReax) 2-major (CP) |
Legend:
- # CP = Clinical Pharmacology
5. References
- IBM Micromedex® DRUGDEX® (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com.libproxy.uthscsa.edu/ (cited: June 20, 2022).
- Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2022. Available at: http://www.clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu. Accessed June 20, 2022.
- Aspirin extended-release capsules (Durlaza®) package insert. New Haven Pharmaceuticals, September 2015.
- Diclofenac potassium powder for solution (Cambia®) package insert. Assertio Therapeutics, Inc. October 2019.
- Diclofenac potassium tablet (Lofena®) package insert. Carwin Pharmaceutical Associates, LLC. November 2021.
- Diclofenac potassium tablet (Cataflam®) package insert. Blucrest Pharmaceuticals, LLC. July 2021.
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