NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)









Aspirin | Acetylsalicylic acid | ASA

Dosage form
  • Aspirin is available over-the-counter in many different brands (e.g. Bayer®, St. Joseph®, Bufferin®, etc.)
  • Aspirin comes in tablets, caplets, buffered forms, enteric-coated forms, and chewable pills
  • Most common dosage forms are 81, 325, and 500 mg

Dosing - Adults
Analgesic/antipyretic
  • 325 - 1000 mg every 6 hours as needed
  • Do not exceed 4000 mg/day
Acute heart attack
  • 162 - 325 mg of non-enteric coated aspirin, chewed or swallowed
  • AHA recommendation
Secondary prevention of coronary artery disease
Primary prevention of cardiovascular disease and colorectal cancer
  • 81 mg once daily
  • See aspirin for more
  • USPSTF recommendation
Dual antiplatelet therapy (with P2Y12 inhibitor)

Dosing - Children
  • With a few exceptions, aspirin is not recommended in children and teenagers because of the risk of Reye's syndrome

Other
  • See aspirin for a comprehensive review of aspirin including its use in cardiovascular disease and other disease prevention

Generic / Price - YES/$

Diflunisal (Dolobid®)

Dosage form
Tablet
  • 500 mg

Dosing
Mild to moderate pain
  • Initial dose of 1000 mg followed by 500 mg every 12 hours as needed
  • Some patients may require 500 mg every 8 hours
  • Do not exceed 1500 mg/day
Osteoarthritis
  • 500 -1000 mg/day given in two divided doses
  • Do not exceed 1500 mg/day
Rheumatoid arthritis
  • 500 -1000 mg/day given in two divided doses
  • Do not exceed 1500 mg/day

Other
  • Half-life: 8 - 12 hours

Generic / Price - YES/$

Fenoprofen (Nalfon®)

Dosage form
Tablet
  • 600 mg

Dosing
Mild to moderate pain
  • 200 mg every 4 - 6 hours as needed
Osteoarthritis
  • 400 - 600 mg three to four times a day as needed
  • Do not exceed 3200 mg/day
Rheumatoid arthritis
  • 400 - 600 mg three to four times a day as needed
  • Do not exceed 3200 mg/day

Other
  • Half-life: 3 hours
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.

Generic / Price - YES/$$

Flurbiprofen (Ansaid®)

Dosage form
Tablet
  • 50 mg
  • 100 mg

Dosing
Osteoarthritis
  • 50 - 100 mg two to four times a day as needed
  • Recommended starting dose is 200 - 300 mg/day
Rheumatoid arthritis
  • 50 - 100 mg two to four times a day as needed
  • Recommended starting dose is 200 - 300 mg/day
Other
  • Half-life: 5.7 hours
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.

Generic / Price - YES/$

Ibuprofen | Advil® | Motrin®

Dosage form
Tablet
  • 200 mg (OTC)
  • 400 mg
  • 600 mg
  • 800 mg
Suspension (Children's Motrin®)
  • 100 mg/5 ml (OTC)
Drops (Infants' Motrin®)
  • 50 mg/1.25ml (OTC)

Dosing - Infants (6 months - 2 years)
Pain/fever
  • Dosing based on infant drops (50 mg/1.25ml)
  • May repeat dose every 6 - 8 hours
  • Do not give more than 4 doses a day

Weight (lbs) Weight (kg) Age (months) Dose
Under 6 months Not well studied
12 - 17 5.4 - 8.1 6 - 11 1.25 ml (50 mg)
18 - 23 8.2 - 10.8 12 - 23 1.875 ml (75 mg)
Alternative: 5 - 10 mg/kg/dose


Dosing - Children (2 - 11 years)
Pain/fever
  • May repeat dose every 6 - 8 hours
  • Do not give more than 4 doses a day

Weight (lbs) Weight (kg) Age (years) Dose (mg)
24 - 35 10.9 - 16.3 2 - 3 100
36 - 47 16.4 - 21.7 4 - 5 150
48 - 59 21.8 - 27.2 6 - 8 200
60 - 71 27.3 - 32.6 9 - 10 250
72 - 95 32.7 - 43.2 11 300
Alternative: 5 - 10 mg/kg/dose (max 400 mg)


Dosing - Adults
Mild to moderate pain
  • 400 mg every 4 - 6 hours as needed
  • In trials, doses above 400 mg were not more effective than 400 mg
Dysmenorrhea
  • 400 mg every 4 hours as needed
Osteoarthritis
  • 400 - 800 mg three to four times a day
  • In trials, daily doses above 2400 mg were not more effective than 2400 mg/day
Rheumatoid arthritis
  • 400 - 800 mg three to four times a day
  • In trials, daily doses above 2400 mg were not more effective than 2400 mg/day

Efficacy
Other
  • Half-life: 2.2 hours
  • Taking after a meal may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.

Generic / Price - YES/$ (all forms)

Ibuprofen + Famotidine (Duexis®)

Dosage form
Tablet
  • Famotidine : Ibuprofen
    • 26.6 mg : 800 mg

Dosing
Osteoarthritis
  • 1 tablet three times a day as needed
Rheumatoid arthritis
  • 1 tablet three times a day as needed

Other
  • Ibuprofen half-life: 2.2 hours
  • Food may delay absorption
  • Famotidine (Pepcid) is a H2 blocker that may help prevent NSAID-induced peptic ulcers
  • Do not cut or crush tablets

Generic / Price - NO/$$$$

Indomethacin IR (Indocin®)

Dosage form
Capsule
  • 25 mg
  • 50 mg
Suspension
  • 25 mg/5 ml
  • Comes in bottles of 237 ml
Suppository
  • 50 mg
  • Comes in box of 30

Dosing
Acute gout
  • 50 mg three times a day until pain is tolerable then taper
Osteoarthritis
  • Starting: 25 mg two to three times a day
  • Increase daily dose by 25 - 50 mg at weekly intervals to a maximum of 200 mg/day
Rheumatoid arthritis
  • Starting: 25 mg two to three times a day
  • Increase daily dose by 25 - 50 mg at weekly intervals to a maximum of 200 mg/day
Ankylosing spondylitis
  • Starting: 25 mg two to three times a day
  • Increase daily dose by 25 - 50 mg at weekly intervals to a maximum of 200 mg/day
Painful shoulder
  • 75 - 150 mg/day given in 3 - 4 divided doses

Other
  • Half-life: 4.5 hours
  • Suppositories should be refrigerated

Generic / Price
  • Capsule (#30) - YES/$
  • Suspension (#30) - NO/$$$$
  • Suppository (#30) - NO/$$$$

Indomethacin ER (Indocin SR®)

Dosage form
Capsule, extended-release
  • 75 mg

Dosing
Osteoarthritis
  • Starting: 75 mg once daily
  • May increase to 75 mg twice a day if necessary
Rheumatoid arthritis
  • Starting: 75 mg once daily
  • May increase to 75 mg twice a day if necessary
Ankylosing spondylitis
  • Starting: 75 mg once daily
  • May increase to 75 mg twice a day if necessary
Painful shoulder
  • 75 mg given once or twice a day as needed

Other
  • Give capsules with food to decrease gastric irritation
  • Extended-release capsules are not recommended for acute gout

Generic / Price - YES/$

Ketoprofen (Orudis®)

Dosage form
Capsule
  • 25 mg
  • 50 mg
  • 75 mg

Dosing
Mild to moderate pain
  • 25 - 50 mg every 6 - 8 hours as needed
  • Do not exceed 300 mg/day
Osteoarthritis
  • 75 mg three times a day as needed or 50 mg four times a day as needed
  • Do not exceed 300 mg/day
Rheumatoid arthritis
  • 75 mg three times a day as needed or 50 mg four times a day as needed
  • Do not exceed 300 mg/day
Dysmenorrhea
  • 25 - 50 mg every 6 - 8 hours as needed
  • Do not exceed 300 mg/day

Other
  • Half-life: 2 hours
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.
  • Doses above 200 mg/day have not been shown to increase effectiveness
  • Dose should be reduced in kidney and liver disease. See precautions below.
  • Use lower doses in patients ≥ 75 years
  • Use lower doses in smaller individuals

Generic / Price - YES/$

Ketoprofen ER (Oruvail®)

Dosage form
Capsule, extended-release
  • 100 mg
  • 150 mg
  • 200 mg

Dosing
Osteoarthritis
  • 200 mg once daily day as needed
  • Do not exceed 200 mg/day
Rheumatoid arthritis
  • 200 mg once daily day as needed
  • Do not exceed 200 mg/day

Other
  • Half-life: 5.4 hours
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.
  • Dose should be reduced in kidney and liver disease. See precautions below.
  • Use lower doses in patients ≥ 75 years
  • Use lower doses in smaller individuals

Generic / Price - YES/$$$ (30 capsules)

Ketorolac tromethamine (Toradol®)

Dosage form
Tablet
  • 10 mg

Dosing
Moderate to severe pain
  • Ketorolac tablets are only recommended as continuation therapy after ketorolac has been started by the IV or IM route
  • Total course of therapy (parenteral + oral) should not exceed 5 days
  • The total daily dose should not exceed 40 mg in any patient

Patients Recommended dose
Age 17 - 64 years
  • 20 mg once, then 10 mg every 4 - 6 hours as needed
Any of the following:
  • Age ≥ 65 years
  • Renal impairment
  • Weight < 50 kg (110 lbs)
  • 10 mg once, then 10 mg every 4 - 6 hours as needed


Other
  • Half-life: 5 - 6 hours

Generic / Price - YES/$

Ketorolac (Sprix®)

Dosage form
Nasal spray
  • Comes in single-day sprayer that delivers 8 sprays
  • Each spray delivers 15.75 mg of ketorolac
  • Comes in box of 5 sprayers

Dosing
Moderate to severe pain
  • Sprix may be initiated without prior parenteral ketorolac therapy
  • Total course of therapy (parenteral + oral + spray) should not exceed 5 days

Patients Recommended dose
Age 18 - 64 years
  • One spray in each nostril (31.5 mg total) every 6 - 8 hours as needed
  • Do not exceed 4 doses/day (126 mg)
Any of the following:
  • Age ≥ 65 years
  • Renal impairment
  • Weight < 50 kg (110 lbs)
  • One spray in one nostril (15.75 mg) every 6 - 8 hours as needed
  • Do not exceed 4 doses/day (63 mg)


Other
  • Half-life: 5 - 6 hours
  • Do not use one spray bottle for more than 24 hours. After 24 hours, it will not deliver intended dose.
  • Keep unopened sprayers refrigerated
  • Open sprayers may be kept at room temperature. Protect from sunlight.

Generic / Price - NO/$$$$ (5 bottles)

Meclofenamate

Dosage form
Capsule (Meclodium®)
  • 50 mg
  • 100 mg

Dosing
Mild to moderate pain
  • 50 - 100 mg every 4 - 6 hours as needed
  • Do not exceed 400 mg/day
Osteoarthritis
  • 200 - 400 mg/day given in 3 -4 equal doses
  • Do not exceed 400 mg/day
Rheumatoid arthritis
  • 200 - 400 mg/day given in 3 -4 equal doses
  • Do not exceed 400 mg/day
Dysmenorrhea and excessive menstrual blood loss
  • 100 mg three times a day for up to 6 days
  • Should be given at start of menstrual flow

Other
  • Half-life: Parent compound - 1.3 hours | Active metabolite - 15 hours
  • Food decreases the rate and extent of absorption

Generic / Price - YES/$$-$$$$ (30 capsules)

Mefenamic acid (Ponstel®)

Dosage form
Capsule
  • 250 mg

Dosing - Adults and adolescents (≥ 14 years)
Acute pain
  • Give 500 mg initially followed by 250 mg every 6 hours as needed
  • Therapy should not typically exceed a week
Dysmenorrhea
  • Give 500 mg initially followed by 250 mg every 6 hours as needed
  • Begin treatment with start of menses and take for 2 - 3 days

Other
  • Half-life: 2 hours

Generic / Price - YES/$$$ (30 capsules)

Nabumetone (Relafen®)

Dosage form
Tablet
  • 500 mg
  • 750 mg

Dosing
Osteoarthritis
  • 1000 mg once daily as needed
  • May increase dose up to 2000 mg/day if necessary
  • Daily dose may be given in one or two divided doses
  • Do not exceed 2000 mg/day
Rheumatoid arthritis
  • 1000 mg once daily as needed
  • May increase dose up to 2000 mg/day if necessary
  • Daily dose may be given in one or two divided doses
  • Do not exceed 2000 mg/day

Other
  • Half-life: 24 hours
  • The manufacturer states that in trials, nabumetone had little effect on collagen-induced platelet aggregation and no effect on bleeding time
  • May take with or without food
  • Patients who weigh < 50 kg (110 lbs) may respond to lower doses

Generic / Price - YES/$

Naproxen IR | Naprosyn® | Aleve® | Anaprox®

Dosage form
Tablets, gelcaps, caplets (Aleve®, Anaprox®)
  • Naproxen : Sodium
    • 200 mg : 20 mg (OTC)
    • 250 mg : 25 mg
    • 500 mg : 50 mg
Tablet (Naprosyn®)
  • 250 mg
  • 375 mg
  • 500 mg
Tablet, enteric-coated(EC-Naprosyn®)
  • 375 mg
  • 500 mg
Suspension (Naprosyn®)
  • 25 mg/ml

Dosing - Children (≥ 2 years)
NOTE: Dosing based on naproxen component
Juvenile arthritis
  • 5 mg/kg/dose twice a day as needed
Other (pain, fever, etc.)
  • 2.5 - 5 mg/kg/dose two to three times a day as needed
  • Do not exceed 15 mg/kg/day

Dosing - Adults
Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis
  • 250 - 500 mg twice daily as needed
Pain, Dysmenorrhea, Tendonitis, Bursitis
  • 500 mg initially followed by 500 mg every 12 hours as needed or 250 mg every 6 - 8 hours as needed
Acute gout
  • 750 mg initially followed by 250 mg every 8 hours until pain subsides

Efficacy
Other
  • Half-life: 12 - 17 hours
  • May take with or without food
  • Naproxen sodium has a quicker onset of action (30 minutes) than naproxen (1 hour)
  • Enteric-coated naprosyn is not recommended in gout or acute pain because of delayed absorption

Generic / Price - YES/$ (all forms)

Naproxen ER (Naprelan®)

Dosage form
Tablets, extended-release
  • 375 mg
  • 500 mg
  • 750 mg
  • Strength based on naproxen component
  • Contains naproxen sodium

Dosing
Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis
  • 750 - 1000 mg once daily as needed
  • Maximum dose is 1500 once daily
Pain, Dysmenorrhea, Tendonitis, Bursitis
  • 1000 mg once daily as needed
  • May increase to 1500 mg once daily for short period if necessary
Acute gout
  • 1000 - 1500 mg once daily on Day 1, then 1000 mg once daily until attack resolves

Other
  • Half-life: 15 hours
  • May take with or without food
  • For patients taking standard-release naproxen, the total daily dose of standard-release naproxen may be given as a once daily dose of extended-release naproxen

Generic / Price - YES/$$$$ (60 tablets)

Naproxen + Esomeprazole (Vimovo®)

Dosage form
Tablets, enteric-coated
  • Naproxen : Esomeprazole
    • 375 mg : 20 mg
    • 500 mg : 20 mg

Dosing
Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis
  • 375 - 500 mg twice a day as needed

Other
  • Half-life (naproxen): 15 hours
  • Take at least 30 minutes before meals
  • Do not crush, cut, or chew tablets
  • Vimovo is not recommended for acute pain because absorption is delayed
  • Esomeprazole is a proton pump inhibitor (Nexium) that protects against gastrointestinal irritation
  • See the Nexium PI for precautions, warnings, and drug interactions regarding esomeprazole

Generic / Price - NO/$$$$

Oxaprozin (Daypro®)

Dosage form
Tablet
  • 600 mg

Dosing - Children (6 - 16 years old)
Juvenile rheumatoid arthritis
  • Give as once daily dose

Body weight (kg) Body weight (lbs) Daily dose
22 - 31 48 - 68 600 mg
32 - 54 69 - 119 900 mg
≥ 55 ≥ 120 1200 mg


Dosing - Adults
Osteoarthritis
  • 1200 mg once daily as needed
  • Maximum dose is 1800 mg/day or 26 mg/kg/day, whichever is lower. Give in divided doses.
  • Patients with lower body weight should start with 600 mg once daily
  • A one-time loading dose of 1200 - 1800 mg (not to exceed 26 mg/kg) may be given when a quicker onset of action is desired
Rheumatoid arthritis
  • 1200 mg once daily as needed
  • Maximum dose is 1800 mg/day or 26 mg/kg/day, whichever is lower. Give in divided doses.
  • Patients with lower body weight should start with 600 mg once daily
  • A one-time loading dose of 1200 - 1800 mg (not to exceed 26 mg/kg) may be given when a quicker onset of action is desired

Other
  • Half-life: 55 hours (single dose) | 41 hours (multiple doses)
  • Food may decrease the rate of absorption. Extent of absorption is not affected.

Generic / Price - YES/$$ (60 tablets)

Sulindac (Clinoril®)

Dosage form
Tablet
  • 150 mg
  • 200 mg

Dosing
Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis
  • 150 - 200 mg twice a day as needed
  • Do not exceed 400 mg/day
Painful shoulder, Tendonitis, Bursitis
  • 200 mg twice a day as needed
  • Do not exceed 400 mg/day
Acute gout
  • 200 mg twice a day until satisfactory response, then taper
  • Do not exceed 400 mg/day

Other
  • Half-life: 16.4 hours
  • Take with food

Generic / Price - YES/$

Tolmetin (Tolectin®)

Dosage form
Tablet
  • 200 mg
  • 600 mg
Capsule
  • 400 mg

Dosing - Children (≥ 2 years old)
Juvenile rheumatoid arthritis
  • 20 mg/kg/day given in three or four divided doses
  • Usual dosage range is 15 - 30 mg/kg/day
  • Do not exceed 30 mg/kg/day

Dosing - Adults
Osteoarthritis
  • 400 mg three times a day as needed
  • May increase to 600 mg three times a day
  • Do not exceed 1800 mg/day
Rheumatoid arthritis
  • 400 mg three times a day as needed
  • May increase to 600 mg three times a day
  • Do not exceed 1800 mg/day

Other
  • Half-life: 5 hours
  • Food decreases bioavailability
  • Do not give with sodium bicarbonate antacids

Generic / Price
  • Generic (60 tablets) - $$$$
  • Generic (60 capsules) - $$-$$$


Diclofenac potassium IR (Cataflam®)

Dosage form
Tablet
  • 50 mg

Dosing
Pain or primary dysmenorrhea
  • 50 mg three times a day as needed
  • Initial dose of 100 mg may be given
Osteoarthritis
  • 50 mg two to three times a day as needed
Rheumatoid arthritis
  • 50 mg three to four times a day as needed

Other
  • Half-life: 1.9 hours
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.
  • Cataflam is diclofenac potassium. Cataflam is not bioequivalent with diclofenac sodium on a mg-to-mg basis

Generic / Price - YES/$

Diclofenac sodium EC (Voltaren®)

Dosage
Tablet, delayed-release
  • 25 mg
  • 50 mg
  • 75 mg
  • Tablets are enteric-coated

Dosing
Osteoarthritis
  • 50 mg two to three times a day as needed or 75 mg two times a day as needed
Rheumatoid arthritis
  • 50 mg three to four times a day as needed or 75 mg two times a day as needed
  • Do not exceed 225 mg/day
Ankylosing spondylitis
  • 25 mg four times a day with an extra 25 mg at bedtime if necessary

Other
  • Half-life: 2 hours
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.
  • Voltaren is diclofenac sodium. Voltaren is not bioequivalent with diclofenac potassium on a mg-to-mg basis
  • Tablets are enteric-coated
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$

Diclofenac sodium ER (Voltaren XR®)

Dosage form
Tablet, extended-release
  • 100 mg

Dosing
Osteoarthritis
  • 100 mg once daily as needed
Rheumatoid arthritis
  • 100 mg once daily as needed
  • In rare cases, 100 mg twice a day may be used

Other
  • Taking with food may delay absorption and increase peak plasma levels. Extent of absorption is not affected.
  • Voltaren is not bioequivalent with diclofenac potassium on a mg-to-mg basis
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$

Diclofenac sodium (Voltaren® Gel)

Dosage form
Gel
  • 1%
  • Comes in 100 gram tube

Dosing
Osteoarthritis of knees, ankles, and feet
  • Apply 4 grams to affected joint 4 times a day as needed
Osteoarthritis of elbows, wrists, and hands
  • Apply 2 grams to affected joint 4 times a day as needed

Other
  • Comes with dosing card for measuring and application
  • Total dose should not exceed 32 g per day, over all affected joints
  • Avoid bathing for at least 1 hour after application
  • Avoid sunlight/heat exposure to treated joints
  • Avoid clothing over treated joints for 10 minutes after applying
  • Systemic exposure from gel is ∼ 6% of that seen with the oral form of diclofenac
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$ (100g tube)

Diclofenac potassium (Zipsor®)

Dosage form
Capsule, liquid filled
  • 25 mg
  • Diclofenac potassium

Dosing
Mild to moderate acute pain
  • 25 mg four times a day as needed

Other
  • Half-life: 1 hour
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.
  • Zipsor is diclofenac potassium. Zipsor is not bioequivalent with other diclofenac preparations on a mg-to-mg basis
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - NO/$$$$

Diclofenac (Zorvolex®)

Dosage form
Capsule
  • 18 mg
  • 35 mg

Dosing
Acute pain
  • 18 - 35 mg three times a day as needed
Osteoarthritis
  • 35 mg three times a day as needed

Other
  • Half-life: 2 hours
  • Taking with food may decrease absorption and lower effectiveness
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - NO/$$$$

Diclofenac potassium (Cambia®)

Dosage form
Powder for solution
  • 50 mg packet of powder
  • Comes in box of 9 packets

Dosing
Acute migraine with or without aura
  • 50 mg (one packet) with start of acute migraine
  • Safety and effectiveness of second dose has not been established

Other
Other
  • Half-life: 2 hours
  • Mix contents of packet with 30 - 60 mls of water
  • Only mix with water. Drink immediately.
  • Taking with food may decrease absorption and lower effectiveness
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - NO/$$$$ (9 packets)

Diclofenac + Misoprostol (Arthrotec®)

Dosage form
Tablet
  • Diclofenac : Misoprostol
    • 50 mg : 200 mcg
    • 75 mg : 200 mcg
    • Contains diclofenac sodium

Dosing
Osteoarthritis
  • 50 mg two to three times a day as needed or 75 mg twice a day as needed
Rheumatoid arthritis
  • 50 mg two to four times a day as needed or 75 mg twice a day as needed

Other
  • Half-life: 2 hours
  • DO NOT GIVE to pregnant women
  • Misoprostol is a synthetic prostaglandin E1 analog with gastric antisecretory and mucosal protective properties
  • Misoprostol may cause diarrhea, abdominal pain, nausea, and flatulence
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$-$$ (30 tablets)

Diclofenac (Flector®)

Dosage form
Patch
  • 1.3% patch
  • Patch is 10 X 14 cm (3.9" X 5.5")
  • Each patch contains 180 mg of diclofenac
  • Comes in box of 30 patches

Dosing
Local acute pain due to strains, sprains, and contusions
  • 1 patch to most painful area twice a day

Other
  • Do not wear when bathing or showering. Do not place on non-intact or damaged skin.
  • May wear mesh sleeve over patch to hold in place
  • Systemic exposure to diclofenac after repeated patch use for four days was lower (< 1%) than that of a single oral 50 mg diclofenac sodium tablet
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - NO/$$$$ (30 patches)

Diclofenac (Pennsaid®)

Dosage form
Solution
  • 16.05 mg/ml (1.5%)
  • Comes in 150 ml bottle

Dosing
Osteoarthritis of the knee
  • Apply 40 drops to affected knee 4 times a day as needed

Other
  • Avoid bathing for at least 30 minutes after application
  • Avoid sunlight/heat exposure to treated joints
  • Avoid clothing over treated joint until it is dry
  • Systemic exposure does occur, but is much less than with oral forms
  • Diclofenac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$ (150 ml)

Etodolac IR (Lodine®)

Dosage form
Capsule
  • 200 mg
  • 300 mg
Tablet
  • 400 mg
  • 500 mg

Dosing
Acute pain
  • 200 - 400 mg every 6 - 8 hours as needed
  • Doses above 1000 mg/day have not been studied
Osteoarthritis
  • 300 - 500 mg twice a day as needed or 300 mg three times a day as needed
  • Doses above 1000 mg/day have not been studied
Rheumatoid arthritis
  • 300 - 500 mg twice a day as needed or 300 mg three times a day as needed
  • Doses above 1000 mg/day have not been studied

Other
  • Half-life 6.4 hours
  • Taking with food may delay absorption and decrease peak plasma levels. Extent of absorption is not affected.
  • Etodolac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$

Etodolac ER (Lodine XL®)

Dosage form
Tablet, extended-release
  • 400 mg
  • 500 mg
  • 600 mg

Dosing - Children (6 - 16 years)
Juvenile rheumatoid arthritis
  • 20 - 30 kg: 400 mg once daily
  • 31 - 45 kg: 600 mg once daily
  • 46 - 60 kg: 800 mg once daily
  • > 60 kg: 1000 mg once daily

Dosing - Adults
Osteoarthritis
  • 400 - 1000 mg once daily as needed
Rheumatoid arthritis
  • 400 - 1000 mg once daily as needed

Other
  • Half-life: 8.4 hours
  • Food may increase the rate of absorption. Extent of absorption is not affected.
  • Etodolac is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$ (30 tablets)

Meloxicam (Mobic®)

Dosage form
Tablet
  • 7.5 mg
  • 15 mg
Suspension
  • 7.5 mg/5 ml
  • Comes in 100 ml bottle

Dosing - Children ≥ 2 years old
Juvenile rheumatoid arthritis
  • 0.125 mg/kg once daily
  • Do not exceed 7.5 mg/day

Dosing - Adults
Osteoarthritis
  • 7.5 - 15 mg once daily
Rheumatoid arthritis
  • 7.5 - 15 mg once daily

Other
  • Half-life: 15 - 20 hours
  • May take with or without food
  • Meloxicam is partially COX-2 selective. See COX selectivity for more.

Generic / Price
  • 30 tablets - YES/$
  • Solution 100 ml - YES/$$

Meloxicam (Vivlodex®)

Dosage form
Capsule
  • 5 mg
  • 10 mg

Dosing
Osteoarthritis
  • 5 - 10 mg once daily
  • Do not exceed 10 mg/day

Other
  • Half-life: 22 hours
  • Food may decrease rate of absorption, but extent of absorption is not affected. May take without regard to meals.

Generic / Price - NO/$$$$

Piroxicam (Feldene®)

Dosage form
Capsule
  • 10 mg
  • 20 mg

Dosing
Osteoarthritis
  • 20 mg once daily as needed
  • Dose may be divided if desired
Rheumatoid arthritis
  • 20 mg once daily as needed
  • Dose may be divided if desired

Other
  • Half-life: 50 hours
  • Food may decrease the rate of absorption. Extent of absorption is not affected.
  • Piroxicam has a long half-life (50 hours), therefore, the full effect of the drug may not be seen for 7 - 12 days
  • Piroxicam is partially COX-2 selective. See COX selectivity for more.

Generic / Price - YES/$



Celecoxib (Celebrex®)

Dosage form
Capsule
  • 50 mg
  • 100 mg
  • 200 mg
  • 400 mg

Dosing - Children (≥ 2 years)
Juvenile rheumatoid arthritis
  • Weight ≥ 10 kg - ≤ 25 kg: 50 mg twice a day
  • Weight > 25 kg: 100 mg twice a day

Dosing - Adults
Osteoarthritis
  • 200 mg once daily as needed or 100 mg twice a day as needed
Rheumatoid arthritis
  • 100 - 200 mg twice a day as needed
Acute pain and dysmenorrhea
  • 400 mg initially followed by an additional 200 mg on the first day if needed. On subsequent days, 200 mg twice a day as needed.
Ankylosing spondylitis
  • 200 mg once daily as needed or 100 mg twice a day as needed
  • If necessary, may increase to 400 mg/day after 6 weeks

Efficacy
Other
  • Half-life: 11 hours
  • The manufacturer states that in trials, celecoxib had no effect on reduction of platelet aggregation or increase in bleeding time
  • For doses up to 200 mg twice a day, celecoxib may be taken without regard to food. For doses ≥ 400 mg twice a day, celecoxib should be taken with food to improve absorption.
  • Capsules may be opened and sprinkled on applesauce
  • Celecoxib is a COX-2 selective NSAID

Generic / Price - YES/$ (60 capsules)










  • References: 1 - PMID 20214589, 2 - Anaphylaxis and Hypersensitivity Reactions, 2011, pp 107-125, ISBN 978-1-60327-951-2
Salicylates Propionic acids
  • Aspirin
  • Salsalate
  • Diflunisal
  • Ibuprofen (Motrin®, Advil®)
  • Naproxen (Naprosyn®, Aleve®)
  • Ketoprofen
  • Flurbiprofen (Ansaid®)
  • Fenoprofen (Nalfon®)
  • Oxaprozin (Daypro®)
Enolic acids Acetic acids
  • Meloxicam (Mobic®)
  • Piroxicam (Feldene®)
  • Diclofenac (Voltaren®)
  • Etodolac (Lodine®)
  • Indomethacin (Indocin®)
  • Ketorolac (Toradol®)
  • Sulindac (Clinoril®)
  • Tolmetin
Fenamic acids Nonacidic
  • Meclofenamate
  • Mefenamic acid (Ponstel®)
  • Nabumetone (Relafen®)



Overview
  • In 2004, the COX-2 selective drug Vioxx® was removed from the U.S. market over concerns that the drug increased the risk of cardiovascular events, particularly heart attacks. The following year, another COX-2 selective drug called Bextra® was removed from the market for similar reasons. All NSAIDs currently carry a boxed warning which states that they cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal.
  • The proposed mechanism behind NSAID-induced cardiovascular events is discussed below
  • The problems with Vioxx® and Bextra® increased scrutiny of both selective and nonselective NSAIDs, and studies were conducted to evaluate the association between cardiovascular outcomes and NSAID use. A large, randomized controlled trial (PRECISION Study) that compared the cardiovascular risk of celecoxib to ibuprofen and naproxen is detailed below along with a Lancet meta-analysis that evaluated the risk of a handful of NSAIDs.
Mechanism
  • The proposed mechanism behind the cardiovascular risk seen with NSAIDs has to do with the COX-1 and COX-2 enzymes and their contrasting effects in different cells
  • In platelets, COX-1 is a major enzyme involved in the production of thromboxane A2. Thromboxane A2 promotes platelet activation and thrombosis. COX-1 inhibition thus inhibits thrombosis.
  • In endothelial tissue, COX-2 is a major enzyme involved in the production of prostacyclin. Prostacyclin inhibits platelet aggregation and promotes vasodilation. COX-2 inhibition thus promotes thrombosis.
  • Nonselective NSAIDs inhibit both COX-1 and COX-2 and their overall effect on thrombosis is related to their proportional effects on each enzyme
  • Very low doses of aspirin irreversibly inhibit COX-1 in platelets, and aspirin therefore has the greatest effect on COX-1 of any NSAID. Not surprisingly, aspirin has been proven to prevent thromboembolic events.
  • The selective COX-2 inhibitors Vioxx® and Bextra® inhibit COX-2 in endothelial tissue and smooth muscle cells, but they have no meaningful effect on COX-1 in platelets. This tips the scale in favor of thrombosis, and they were found to increase the risk of cardiovascular events in trials. Contrarily, the COX-2 selective inhibitor celecoxib (Celebrex®) was evaluated in the PRECISION trial (see below), and it was not found to increase the risk of cardiovascular events when compared to ibuprofen and naproxen.
  • The risk of events with nonselective NSAIDs is not well-defined, although a number of observational studies have found that many popular NSAIDs (e.g. ibuprofen) likely increase the risk of cardiovascular events to a small degree. Excluding aspirin, all nonselective NSAIDs reversibly inhibit COX-1 in platelets and this effect does not appear to counterbalance the pro-thrombotic effects of COX-2 inhibition in endothelial cells and smooth muscle. There is also some concern that nonselective NSAIDs may compete with aspirin for COX-1 inhibition and therefore may lower the effectiveness of low-dose daily aspirin. [5,6,8]
PRECISION study - Celecoxib vs Ibuprofen vs Naproxen for Cardiovascular Death, NEJM (2016) [PubMed abstract]
  • The PRECISION study enrolled 24,081 patients with established CVD or risk factors for CVD who required daily treatment with NSAIDs
Main inclusion criteria
  • Any of the following: established CVD, diabetes, three risk factors for CVD
  • Requiring daily treatment with NSAIDs for arthritis pain
Main exclusion criteria
  • CVD event within 3 months of randomization
Baseline characteristics
  • Average age 63 years
  • Female sex - 64%
  • Arthritis diagnosis: Osteoarthritis - 90% | RA - 10%
  • Established CVD - 23%
  • Average creatinine - 0.9 mg/dl
  • Current aspirin use - 46%
  • Smoker - 21%
Randomized treatment groups
  • Group 1 (8072 patients) - Celecoxib 100 mg twice a day
  • Group 2 (7969 patients) - Naproxen 375 mg twice a day
  • Group 3 (8040 patients) - Ibuprofen 600 mg three times a day
  • Patients with RA could have their doses increased if necessary to 200 mg twice a day for celecoxib, 500 mg twice a day for naproxen, and 800 mg three times a day for ibuprofen
  • Patients with OA could have their naproxen and ibuprofen doses increased, but not celecoxib
  • Esomeprazole 20 - 40 mg was provided to all patients for gastric protection
  • Daily aspirin therapy was permitted
Primary outcome: Composite of first occurrence of an adverse event that met Antiplatelet Trialists Collaboration (APTC) criteria (i.e., death from cardiovascular causes, including hemorrhagic death; nonfatal myocardial infarction; or nonfatal stroke)
Results

Duration: Average of 34 months
Outcome Celecoxib Naproxen Ibuprofen Comparisons
Primary outcome 2.3% 2.5% 2.7% 1 vs 2 p=0.45 | 1 vs 3 p=0.12
Death from cardiovascular causes 0.8% 1.1% 1.0% 1 vs 2 p=0.13 | 1 vs 3 p=0.30
Overall mortality 1.6% 2.0% 1.8% 1 vs 2 p=0.052 | 1 vs 3 p=0.49
Serious gastrointestinal events 1.1% 1.5% 1.6% 1 vs 2 p=0.01 | 1 vs 3 p=0.002
Renal events 0.7% 0.9% 1.1% 1 vs 2 p=0.19 | 1 vs 3 p=0.004
Average daily doses 209 mg 852 mg 2045 mg N/A
  • In the subgroup of patients who were taking daily aspirin, no statistical interaction between naproxen or ibuprofen was found
  • Pain relief was slightly better with naproxen when compared to ibuprofen and celecoxib, but the difference was not considered clinically meaningful
  • In the on-treatment analysis, there was no significant difference between the groups for the primary outcome
  • The average length of time that subjects took their NSAID was 20.3 months. 27% of patients were lost to follow-up during the trial.
  • Adherence to esomeprazole therapy was not measured

Findings: At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety
StraightHealthcare analysis
  • The PRECISION study found that celecoxib does not increase the risk of cardiovascular events when compared to naproxen and ibuprofen. This finding is reassuring given the previous history of other COX-2 selective drugs (e.g. Vioxx, Bextra).
  • As expected, celecoxib was associated with significantly fewer gastrointestinal events. A weakness of the study is that esomeprazole adherence was not measured.
  • One unexpected and interesting finding was that celecoxib was associated with significantly fewer renal events than ibuprofen. Celecoxib also had fewer events than naproxen, but the difference was not significant (p=0.19). Renal events were defined as any of the following: Scr ≥ 2 mg/dl with ≥ 0.7 mg/dl increase from baseline, hospitalization for acute renal failure, or initiation of dialysis.
  • No interaction between daily aspirin use and naproxen or ibuprofen was identified. This is an interesting finding since it has been hypothesized that ibuprofen and naproxen may interfere with the antiplatelet activity of aspirin.
Lancet meta-analysis - Vascular and Upper Gastrointestinal Effects of NSAIDs [PubMed abstract]
  • In 2013, a meta-analysis was published in the Lancet that evaluated cardiovascular events among individual NSAIDs. The analysis included 280 randomized controlled trials that compared NSAIDs to placebo and 474 trials that compared NSAIDs to other NSAIDs.
  • Based on their findings, the authors quantified the risk of a major vascular event (defined as nonfatal myocardial infarction, nonfatal stroke, or vascular death) among a handful of popular NSAIDs. Their findings are presented in the table below.

  • *Coxibs are COX-2 selective inhibitors. In this study, primarily celecoxib, rofecoxib, etoricoxib, and lumiracoxib.
  • Major vascular event defined as nonfatal myocardial infarction, nonfatal stroke, or vascular death
  • Reference [6]
Annual risk of major vascular event for patients taking select NSAIDs
Drug Annual excess cases per 1000 patients with 2% baseline annual risk Annual excess cases per 1000 patients with 0.5% baseline annual risk
Ibuprofen 800 mg three times a day 9 2
Diclofenac 75 mg twice a day 8 2
Coxibs* 7 2
Naproxen 500 mg twice a day -1 0



Overview
  • NSAIDs increase the risk of peptic ulcer disease and gastrointestinal bleeding
  • The mechanism of this effect is believed to occur through the inhibition of the COX-1 enzyme which plays an important role in gastric mucosal integrity
  • COX-2 selective NSAIDs (e.g. celecoxib) have been shown to have a lower risk of peptic ulcer disease when compared to nonselective NSAIDs
  • Despite the increased risk, it is often necessary for patients with a history of peptic ulcer/bleeding to receive an NSAID. Recommendations for these patients are detailed below.
Celecoxib studies
  • In the U.S., the only COX-2 selective NSAID available is celecoxib. A handful of other NSAIDs are partially selective for COX-2 (e.g. meloxicam, etodolac, diclofenac), but these medications display a large amount of inter-patient variability in COX-1 inhibition, and this makes it difficult to quantify and predict their associated risks.
  • In trials, the risk of peptic ulcer disease with celecoxib is only slightly higher than placebo and much less that what is seen with nonselective NSAIDs. Three studies are summarized below, and the PRECISION study which also measured gastrointestinal outcomes is reviewed above.
CONCERN trial - Celecoxib vs Naproxen in Patients with History of Upper GI Bleed and CVD, Lancet (2017) [PubMed abstract]
  • Design: Randomized, controlled trial (N=514, length = 18 months) in patients with arthritis, history of upper GI bleed, and CVD
  • Treatment: Celecoxib 100 mg twice a day + esomeprazole 20 mg/day vs Naproxen 500 mg twice a day + esomeprazole 20 mg/day. All patients also received aspirin 80 mg/day.
  • Primary outcome: Recurrent upper gastrointestinal bleeding within 18 months
  • Results:
    • Primary outcome: Celecoxib - 5.6%, Naproxen - 12.3% (p=0.008)
  • Findings: In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety.
Celecoxib vs Naprosyn in RA and OA patients, Am J Gastroenterol (2001) [PubMed abstract]
  • Design: Randomized controlled trial (N=537 | length = 12 weeks) in patients with RA or OA
  • Treatment: Celecoxib 200 mg twice daily vs Naproxen 500 mg twice daily
  • Primary outcome: Gastroduodenal ulcers at 4, 8, and 12 weeks as assessed by endoscopy
  • Results:
    • Primary outcome (cumulative 12 weeks incidence): Group 1 - 9%, Group 2 - 41%
  • Findings: As compared to naproxen (500 mg b.i.d.), use of celecoxib (200 mg b.i.d.), a COX-2 specific agent, at the recommended RA dose and twice the most frequently prescribed OA dose, was associated with lower rates of gastric, duodenal, and gastroduodenal ulcers but had comparable efficacy, in patients with OA and RA.
Celecoxib vs naprosyn in RA patients, JAMA (1999) [PubMed abstract]
  • Design: Randomized controlled trial (N=688 | length = 12 weeks)
  • Treatment: Celecoxib 100 mg twice daily vs Celecoxib 200 mg twice daily vs Celecoxib 400 mg twice daily vs Naproxen 500 mg twice daily vs Placebo
  • Primary outcome: Gastroduodenal ulcers at 12 weeks as assessed by endoscopy before and after treatment
  • Results:
    • Primary outcome: Cel 100 mg - 6%, Cel 200 mg - 4%, Cel 400 mg - 6%, Naproxen - 26%, Placebo - 4% (Cel vs Naproxen p<0.001)
  • Findings: In this study, all dosages of celecoxib were efficacious in the treatment of rheumatoid arthritis and did not affect COX-1 activity in the GI tract mucosa as evidenced by less frequent incidence of endoscopic ulcers compared with naproxen.
Professional guidelines
Low dose daily aspirin for heart disease
NSAIDs for osteoarthritis
  • The American College of Rheumatology published recommendations for NSAID use in osteoarthritis in 2012
  • The guidelines state that in general, NSAIDs should be avoided in patients with a history of GI complications
  • If NSAIDs are still deemed necessary, the following recommendations may help prevent future events:
    • For patients ≥ 75 years, topical NSAIDs are preferred over oral
    • In patients with a history of upper GI ulcer who have not had a GI bleed in the past year, use a COX-2 selective NSAID or a nonselective NSAID with a PPI
    • In patients with a history of upper GI ulcer who have had a GI bleed in the past year, use a COX-2 selective NSAID with a PPI [7]
    • NOTE: Results from the CONCERN trial detailed above support these recommendations




  • Drugs are typically cleared after 4 - 5 half-lives
  • The manufacturer states that in trials, celecoxib had no effect on reduction of platelet aggregation or increase in bleeding time
  • *The manufacturer states that in trials, nabumetone had little effect on collagen-induced platelet aggregation and no effect on bleeding time
  • References [Manufacturer PI]
NSAID half-lives
Drug Half-life
Ibuprofen (Motrin®, Advil®) 2.2 hours
Naproxen (Aleve®, Anaprox®, etc.) 12 - 17 hours
Meloxicam (Mobic®) 15 - 20 hours
Celecoxib (Celebrex®) 11 hours
Indomethacin (Indocin®) 4.5 hours
Ketorolac (Toradol®) 5 - 6 hours
Nabumetone (Relafen®)* 24 hours






NSAID Contraindications / precautions

All NSAIDs
  • Increased risk of thromboembolism - all NSAIDs (except aspirin) may increase the risk of cardiovascular thrombotic events including heart attack and stroke. The risk may be greater with prolonged use. See NSAIDs and cardiovascular risk for more.
  • Coronary Artery Bypass Grafting (CABG) - all NSAIDs (except aspirin) are contraindicated in the perioperative period around CABG surgery. Studies have shown an increased risk of heart attack and stroke in patients who took NSAIDs in the first 10 - 14 days following CABG surgery.
  • Recent myocardial infarction (MI) - observational studies have shown that NSAIDs (excluding aspirin) increase the risk of reinfarction, cardiovascular-related death, and all-cause mortality in patients who have suffered a recent MI. NSAIDs should be avoided in patients with a recent MI unless the benefits outweigh the risks.
  • Gastrointestinal (GI) risk - all NSAIDs increase the risk of gastrointestinal bleeding, ulceration, and perforation. These events can occur at any time during NSAID use. Eighty percent of patients who develop serious upper GI events on NSAIDs are asymptomatic. In patients treated for 3 - 6 months with NSAIDs, 1% will develop serious upper GI events. In patients treated for a year, 2 - 4% will develop serious events. The risk continues to increase with longer durations of use. Patients with a prior history of GI ulcer or bleeding are at greatest risk. Elderly patients are also at increased risk. COX-2 selective NSAIDs (e.g. celecoxib) have a lower risk of GI complications than nonselective NSAIDs. See NSAIDs and peptic ulcers/GI bleeding for more.
  • Hypersensitivity reaction to any NSAID - patients with a history of asthma, urticaria, or other allergic-type reactions to any NSAID may be allergic to all NSAIDs (COX-1 reaction), or they may be allergic to chemically-related NSAIDs. See NSAID allergy for more.
  • Prolonged bleeding - NSAIDs inhibit platelet activation and may prolong bleeding. The effect is greatest with aspirin which irreversibly inhibits platelet function. Other NSAIDs inhibit platelets to a lesser degree, and unlike aspirin, their effect is reversible. COX-2 selective NSAIDs do not inhibit platelets.
  • Asthma - a small subset of asthmatics have "aspirin-exacerbated respiratory disease." These patients may be sensitive to other NSAIDs as well. See NSAID allergy for more.
  • Smoking - smoking can cause gastrointestinal (GI) inflammation and increase the risk for NSAID-induced GI adverse events including ulceration, bleeding, and perforation
  • Elevated liver function tests - borderline elevations (greater than the upper limit of normal [ULN] to 3 X ULN) of liver enzymes may occur in up to 15% of NSAID-treated patients. In trials, severe elevations (> 3 X ULN) have been seen in 1% of NSAID-treated patients. Rare cases of NSAID-induced liver failure have been reported. Patients who develop significant liver disease while taking NSAIDs should discontinue NSAIDs indefinitely.
  • Hypertension - NSAIDs may raise blood pressure through several mechanisms. Patients with uncontrolled hypertension should use caution when taking NSAIDs.
  • Heart failure and edema - NSAIDs may raise blood pressure and promote fluid retention. Patients with heart failure and/or edema should use caution.
  • Kidney disease - long-term NSAID use has been associated with renal papillary necrosis and other kidney diseases. In addition, renal prostaglandins play a compensatory role in maintaining renal perfusion. Prostaglandin inhibition by NSAIDs may decrease renal perfusion and lead to renal decompensation. The risk for NSAID-induced decompensation is greatest in patients with kidney disease, heart failure, liver disease, advanced age, and in those taking diuretics and ACE inhibitors.
  • Serious skin reactions - NSAID use has been associated with serious skin reactions including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN)
  • Pregnancy - NSAIDs should be avoided after 30 weeks of gestation because they may cause premature closure of the ductus arteriosus in the fetus. Safety of use prior to 30 weeks gestation is unknown.
  • Ocular effects - in rare cases, NSAID use has been associated with vision and ocular changes

Diclofenac
  • Bovine protein allergy (Zipsor®) - Zipsor contains gelatin with bovine protein. Do not take if allergic.
  • Phenylketonuria (Cambia®) - Cambia contains aspartame equivalent to phenylalanine 25 mg per packet
  • Pregnancy (Arthrotec®) - misoprostol is contraindicated in pregnancy

Ibuprofen
  • Aseptic meningitis - rare cases of aseptic meningitis have been reported in patients taking ibuprofen. Patients with systemic lupus erythematosus may be at greater risk.

Indomethacin
  • CNS effects - indomethacin may aggravate psychiatric disorders, epilepsy, and parkinsonism. It may also cause drowsiness.

Ketoprofen
  • Kidney disease
    • Mild kidney disease: do not exceed 150 mg/day
    • Severe kidney disease (CrCL < 25 ml/min): do not exceed 100 mg/day
  • Liver disease - ketoprofen is highly protein-bound (> 99%). Starting dose should not exceed 100 mg/day in patients with liver disease or hypoalbuminemia.

Ketorolac
  • Kidney disease - do not use in patients with advanced kidney disease or in patients at risk for kidney failure due to volume depletion

Oxaprozin
  • Photosensitivity - may cause photosensitivity. Avoid sun exposure or wear protection (e.g. sunscreen, clothing)

Sulindac
  • Kidney stones - sulindac metabolites have been found in kidney stones. Use caution in susceptible patients.
  • Pancreatitis - rare cases of pancreatitis have been reported in patients receiving sulindac
  • Aseptic meningitis - sulindac may increase the risk of aseptic meningitis in patients with systemic lupus erythematosus and mixed connective tissue disease


Celecoxib
  • Sulfa allergy - celecoxib contains a sulfonamide group. Patients who are allergic to sulfa drugs may also be allergic celecoxib.
  • CYP2C9 poor metabolizers (e.g. CYP2C9*3/*3) - start therapy at half the recommended daily dose
  • Liver disease
    • Moderate (Child-Pugh B): reduce daily dose by 50%
    • Severe (Child-Pugh C): not recommended



NSAID Drug / lab interactions

All NSAIDs

Diclofenac
  • CYP2C9 inhibitors, inducers, and substrates - diclofenac is primarily metabolized by CYP2C9. Inhibitors, inducers, and other substrates of CYP2C9 may alter diclofenac clearance. Diclofenac may affect the clearance of other CYP2C9 substrates.
  • Antacids (Arthrotec®) - Antacids reduce the bioavailability of misoprostol. Magnesium-containing antacids may exacerbate misoprostol-induced diarrhea.
  • Voriconazole - voriconazole may increase blood levels of diclofenac

Diflunisal
  • Acetaminophen - diflunisal may increase blood levels of acetaminophen by up to 50%
  • Antacids - concomitant antacids may reduce diflunisal levels

Etodolac
  • False-positive urinary bilirubin - etodolac may cause false-positive urinary bilirubin on urine dipsticks

Fenoprofen
  • Highly protein-bound drugs - fenoprofen is highly bound to albumin (99%). It may displace other highly protein-bound drugs and vice versa.

Indomethacin
  • Probenecid - probenecid may raise indomethacin levels. Lower indomethacin doses may be appropriate when given with probenecid.

Ketoprofen
  • Probenecid - probenecid reduces ketoprofen clearance and increases levels. They should not be given together.

Ketorolac
  • Probenecid - probenecid reduces ketorolac clearance and increases levels. They should not be given together.
  • Pentoxifylline - ketorolac should not be given with pentoxifylline because of increased risk of bleeding

Meclofenamate
  • Probenecid - probenecid may increase the half-life of meclofenamate. Lower doses of meclofenamate may be necessary.

Mefenamic acid
  • Antacids - magnesium hydroxide antacids may increase absorption of mefenamic acid
  • CYP2C9 inhibitors, inducers, and substrates - mefenamic acid is a substrate of CYP2C9. Inhibitors, inducers and other substrates of CYP2C9 may alter mefenamic acid clearance. Mefenamic acid may affect the clearance of other CYP2C9 substrates.

Meloxicam
  • Sodium polystyrene sulfonate (Kayexalate®) - meloxicam suspension contains sorbitol. It should not be given with Kayexalate because cases of intestinal necrosis have been reported when kayexalate is given with sorbitol.
  • CYP2C9 inhibitors, inducers, and substrates - meloxicam is a substrate of CYP2C9. Inhibitors, inducers and other substrates of CYP2C9 may alter meloxicam clearance. Meloxicam may affect the clearance of other CYP2C9 substrates.

Naproxen
  • Antacids - concomitant antacids may delay the absorption of naproxen
  • Sucralfate - concomitant sucralfate may delay the absorption of naproxen
  • Cholestyramine - concomitant cholestyramine may delay the absorption of naproxen
  • Probenecid - probenecid reduces naproxen clearance and increases levels
  • Highly protein-bound drugs - naproxen is highly protein-bound and may interact with other highly protein-bound drugs
  • Acid-reducing agents (PPI, H2-blocker, etc.) - acid-reducing agents should not be given with enteric-coated naproxen
  • Urinary 17-ketogenic steroids - naproxen may falsely increase urinary values of 17-ketogenic steroids with some assays
  • Urinary 5-hydroxyindoleacetic acid (5HIAA) - naproxen may interfere with some urinary assays of 5HIAA

Oxaprozin
  • Urine drug screens - false-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking oxaprozin. False-positive results may persist for several days following discontinuation. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish oxaprozin from benzodiazepines

Piroxicam
  • Highly protein-bound drugs - piroxicam is highly protein-bound (99%). It may displace other highly protein-bound drugs and vice versa.

Sulindac
  • Probenecid - probenecid may increase levels of sulindac. Sulindac may cause a modest reduction in the uricosuric effect of probenecid.

Tolmetin
  • Urine proteinuria - tolmetin metabolites have been found to give false-positive results for proteinuria on tests which rely on acid precipitation as their endpoint (e.g. sulfosalicylic acid)

Celecoxib
  • CYP2C9 inhibitors, inducers, and substrates - celecoxib is primarily metabolized by CYP2C9. Inhibitors, inducers and other substrates of CYP2C9 may alter celecoxib clearance. Celecoxib may affect the clearance of other CYP2C9 substrates.
  • CYP2D6 substrates - in vitro studies have shown that celecoxib is an inhibitor of CYP2D6. Celecoxib may inhibit the metabolism of CYP2D6 substrates.



Pricing legend
  • $ = 0 - $50
  • $$ = $51 - $100
  • $$$ = $101 - $150
  • $$$$ = > $151
  • Pricing based on one month of therapy at standard dosing in an adult
  • Pricing based on information from GoodRX.com®
  • Pricing may vary by region and availability