Ibuprofen + Paracetamol interactions

Food & lifestyle

• alcohol

  Major

  Metabolism

  Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

  What to do: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

  12 sources

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical (2002):

  Show all 12 sourcesShow fewer sources

  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73

• alcohol

  Moderate

  Synergy

  The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

  What to do: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

  1 source

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):

Conditions

Conditions in which Ibuprofen + Paracetamol needs care, as documented in this source.

• Alcoholism

  Major

  Chronic alcohol abusers may be at increased risk of hepatotoxicity during treatment with acetaminophen (APAP). Severe liver injury, including cases of acute liver failure resulting in liver transplant and death, has been reported in patients using acetaminophen. Therapy with acetaminophen should be administered cautiously, if at all, in patients who consume three or more alcoholic drinks a day. In general, patients should avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure. They should also be advised to seek medical attention if they experience signs and symptoms of liver injury such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.

  11 sources

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  5. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  6. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  7. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical (2002):
  8. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50

  Show all 11 sourcesShow fewer sources

  9. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  10. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73

• Asthma

  Major

  Nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated in patients with history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps, severe potentially fatal bronchospasm, and/or intolerance to aspirin and other NSAIDs. Since cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, therapy with any NSAID should be avoided in patients with this form of aspirin sensitivity. NSAIDs should be used with caution in patients with preexisting asthma (without known aspirin sensitivity), and these patients should be monitored for changes in the signs and symptoms of asthma.

  15 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  6. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  7. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):
  8. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):

  Show all 15 sourcesShow fewer sources

  9. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  10. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  11. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  12. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Daypro (oxaprozin)." Searle (2001):
  14. "Product Information. Celebrex (celecoxib)." Searle (2001):
  15. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):

• Exanthema

  Major

  Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious skin adverse reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis), which can be fatal. These serious events may occur without warning. Patients should be advised to discontinue the NSAID and seek medical attention promptly at the first sign of skin rash or any other sign of hypersensitivity. NSAIDs are contraindicated in patients with previous serious skin reactions to these drugs.

  16 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  6. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  7. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):
  8. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  10. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  11. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  12. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Daypro (oxaprozin)." Searle (2001):
  14. "Product Information. Celebrex (celecoxib)." Searle (2001):
  15. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):
  16. "Product Information. Meclofenamate Sodium (meclofenamate)." Mylan Pharmaceuticals Inc (2012):

• Kidney Diseases

  Major

  Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion: in such patients, NSAIDs may cause a dose-dependent reduction in prostaglandin synthesis and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk for this reaction include the elderly, those with impaired renal function, dehydration, hypovolemia, heart failure, or liver dysfunction, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; discontinuation of NSAID therapy will usually lead to recovery to the pretreatment state. No information is available regarding use NSAIDs in patients with advanced renal disease; the renal effects of NSAIDs may hasten the progression of renal dysfunction in patients with preexisting renal disease. Volume status should be corrected in dehydrated or hypovolemic patients prior to initiating treatment. Renal function should be monitored during therapy in patients with renal or liver dysfunction, heart failure, dehydration, or hypovolemia. NSAIDs should be avoided in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if an NSAID is used in such patients, they should be monitored for signs of worsening renal function.

  16 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  6. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  7. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):
  8. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  10. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  11. "Product Information. Dolobid (diflunisal)." Merck & Co., Inc (2001):
  12. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  13. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Daypro (oxaprozin)." Searle (2001):
  15. "Product Information. Celebrex (celecoxib)." Searle (2001):
  16. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):

• Liver Diseases

  Major

  Acetaminophen is primarily metabolized in the liver to inactive forms. However, small quantities are converted by minor pathways to metabolites that can cause hepatotoxicity or methemoglobinemia. Patients with hepatic impairment may be at increased risk of toxicity due to increased minor metabolic pathway activity. Likewise, chronic or overuse of acetaminophen can saturate the primary hepatic enzymes and lead to increased metabolism by minor pathways. Severe liver injury, including cases of acute liver failure resulting in liver transplant and death, has been reported in patients using acetaminophen. Therapy with acetaminophen should be administered cautiously in patients with hepatic insufficiency. Clinical monitoring of hepatic function is recommended. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.

  6 sources

  1. Gillette JR "An integrated approach to the study of chemically reactive metabolites of acetaminophen." Arch Intern Med 141 (1981): 375-9
  2. Arnman R, Olsson R "Elimination of paracetamol in chronic liver disease." Acta Hepatogastroenterol (Stuttg) 25 (1978): 283-6
  3. Clements JA, Critchley JA, Prescott LF "The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man." Br J Clin Pharmacol 18 (1984): 481-5
  4. Forrest JA, Adriaenssens P, Finlayson ND, Prescott LF "Paracetamol metabolism in chronic liver disease." Eur J Clin Pharmacol 15 (1979): 427-31
  5. Venkataramanan R, Kalp K, Rabinovitch M, et al. "Conjugative drug metabolism in liver transplant patients." Transplant Proc 21 (1989): 2455
  6. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical (2002):

• Peptic Ulcer

  Major

  Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can develop at any time, with or without warning symptoms. Only 1 in 5 patients who develop a serious upper GI side effect on NSAIDs is symptomatic. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating elderly or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.

  16 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  6. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  7. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):
  8. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  10. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  11. "Product Information. Dolobid (diflunisal)." Merck & Co., Inc (2001):
  12. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  13. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Daypro (oxaprozin)." Searle (2001):
  15. "Product Information. Celebrex (celecoxib)." Searle (2001):
  16. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):

• Thrombosis

  Major

  Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to 3 years duration have supported this increased risk. It is unclear from available data if the risk for cardiovascular thrombotic events is similar for all NSAIDs. Therapy with NSAIDs should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease. Patients should be treated with the lowest effective dosage for the shortest duration necessary. Appropriate antiplatelet therapy should be administered to patients requiring cardioprotection; however, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use, while the risk of serious gastrointestinal events is increased. Physicians and patients should remain alert for the development of adverse cardiovascular events throughout the entire duration of therapy, even without prior cardiovascular symptoms. Patients should be advised to promptly seek medical attention if they experience symptoms of cardiovascular thrombotic events (including chest pain, shortness of breath, weakness, or slurring of speech).NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Two large clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.The use of NSAIDs should be avoided in patients with a recent myocardial infarction unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. If an NSAID is used in patients with a recent myocardial infarction, they should be monitored for signs of cardiac ischemia.

  8 sources

  1. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  2. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  3. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):
  4. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  5. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  6. "Product Information. Celebrex (celecoxib)." Searle (2001):
  7. "Product Information. Ponstel (mefenamic acid)." Pfizer U.S. Pharmaceuticals Group (2006):
  8. "Product Information. Meclofenamate Sodium (meclofenamate)." Mylan Pharmaceuticals Inc (2012):

• Water-Electrolyte Imbalance

  Major

  Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Therapy with NSAIDs should be administered cautiously in patients with preexisting fluid retention, hypertension, or a history of heart failure. Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

  14 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  6. "Product Information. Anaprox (naproxen)." Roche Laboratories (2006):
  7. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  8. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  10. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  11. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  12. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Daypro (oxaprozin)." Searle (2001):
  14. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):

• Anemia

  Moderate

  Anemia has been reported in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). This may be due to fluid retention, occult/gross blood loss, or an incompletely described effect on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients with any signs/symptoms of anemia or blood loss, especially during long-term therapy. NSAIDs may increase risk of bleeding events; comorbid conditions (e.g., coagulation disorders; concomitant use of warfarin/other anticoagulants, antiplatelet agents, serotonin/serotonin norepinephrine reuptake inhibitors) may increase this risk, and patients with these conditions should be monitored for signs of bleeding. Therapy with NSAIDs should be administered cautiously in patients with or predisposed to anemia. Clinical monitoring of hematopoietic function may be appropriate, particularly during chronic therapy.

  17 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Toradol (ketorolac)." Roche Laboratories (2002):
  6. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  7. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  8. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):

  Show all 17 sourcesShow fewer sources

  9. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):
  10. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  11. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  12. "Product Information. Dolobid (diflunisal)." Merck & Co., Inc (2001):
  13. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  14. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  15. "Product Information. Daypro (oxaprozin)." Searle (2001):
  16. "Product Information. Celebrex (celecoxib)." Searle (2001):
  17. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):

• Blood Platelet Disorders

  Moderate

  Nonsteroidal anti-inflammatory drugs (NSAIDs) reversibly inhibit platelet adhesion and aggregation and may prolong bleeding time in some patients. With the exception of aspirin, the platelet effects seen with most NSAIDs at usual recommended dosages are generally slight and of relatively short duration but may be more pronounced in patients with underlying hemostatic abnormalities. Thrombocytopenia has also been reported rarely during NSAID use. Therapy with NSAIDs should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. NSAIDs that selectively inhibit cyclooxygenase-2 (i.e., COX-2 inhibitors) do not appear to affect platelet function or bleeding time at indicated dosages and may be preferable if risk of bleeding is a concern.

  16 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  6. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  7. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):
  8. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  10. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  11. "Product Information. Dolobid (diflunisal)." Merck & Co., Inc (2001):
  12. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  13. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Daypro (oxaprozin)." Searle (2001):
  15. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):
  16. "Product Information. Flector Patch (diclofenac topical)." Actavis U.S. (Alpharma USPD) (2016):

• Heart Failure

  Moderate

  Fluid retention and edema have been observed in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), including some topical formulations. These drugs should be avoided in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If an NSAID is used in patients with severe heart failure, they should be monitored for signs of worsening heart failure.

  12 sources

  1. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  2. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  3. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):
  4. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  5. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Dolobid (diflunisal)." Merck & Co., Inc (2001):
  7. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  8. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Daypro (oxaprozin)." Searle (2001):
  10. "Product Information. Celebrex (celecoxib)." Searle (2001):
  11. "Product Information. Meclofenamate Sodium (meclofenamate)." Mylan Pharmaceuticals Inc (2012):
  12. "Product Information. Flector Patch (diclofenac topical)." Actavis U.S. (Alpharma USPD) (2016):

• Hyperkalemia

  Moderate

  Increases in serum potassium concentration (including hyperkalemia) have been reported with use of nonsteroidal anti-inflammatory drugs (NSAIDs), even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. Caution is advised in patients with hyperkalemia.

  3 sources

  1. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  2. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Celebrex (celecoxib)." Searle (2001):

• Hypertension

  Moderate

  Nonsteroidal anti-inflammatory drugs (NSAIDs), including topicals, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events. NSAIDs should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the course of therapy.

  12 sources

  1. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  2. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  3. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):
  4. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  5. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Dolobid (diflunisal)." Merck & Co., Inc (2001):
  7. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  8. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Daypro (oxaprozin)." Searle (2001):
  10. "Product Information. Celebrex (celecoxib)." Searle (2001):
  11. "Product Information. Meclofenamate Sodium (meclofenamate)." Mylan Pharmaceuticals Inc (2012):
  12. "Product Information. Flector Patch (diclofenac topical)." Actavis U.S. (Alpharma USPD) (2016):

• Liver Diseases

  Moderate

  Borderline elevations of 1 or more liver tests may occur in up to 15% of patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). These laboratory abnormalities may progress, remain unchanged, or regress with continuing therapy. Elevations of ALT or AST (at least 3 times the upper limit of normal) have been reported in about 1% of patients in clinical trials. In addition, rare (sometimes fatal) cases of severe hepatotoxicity, including liver necrosis, hepatic failure, jaundice, and fulminant hepatitis have been reported. Therapy with NSAIDs should be administered cautiously in patients with preexisting liver disease. Periodic monitoring of liver function is recommended during prolonged therapy. NSAIDs are also highly protein-bound and some are extensively metabolized by the liver. Metabolic activity and/or plasma protein binding may be altered in patients with hepatic impairment. A dosage reduction may be required in some cases.

  17 sources

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):
  2. "Product Information. Nalfon (fenoprofen)." Xspire Pharma (2002):
  3. "Product Information. Indocin (indomethacin)." Merck & Co., Inc (2002):
  4. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories (2002):
  5. "Product Information. Toradol (ketorolac)." Roche Laboratories (2002):
  6. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc (2002):
  7. "Product Information. Clinoril (sulindac)." Merck & Co., Inc (2001):
  8. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical (2001):

  Show all 17 sourcesShow fewer sources

  9. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals (2001):
  10. "Product Information. Relafen (nabumetone)." SmithKline Beecham (2001):
  11. "Product Information. Feldene (piroxicam)." Pfizer U.S. Pharmaceuticals (2001):
  12. "Product Information. Dolobid (diflunisal)." Merck & Co., Inc (2001):
  13. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn (2001):
  14. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories (2001):
  15. "Product Information. Daypro (oxaprozin)." Searle (2001):
  16. "Product Information. Celebrex (celecoxib)." Searle (2001):
  17. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim (2001):

• Phenylketonurias

  Moderate

  Several oral acetaminophen and acetaminophen-combination products, particularly flavored chewable tablets, contain the artificial sweetener, aspartame (NutraSweet). Aspartame is converted to phenylalanine in the gastrointestinal tract following ingestion. Chewable and effervescent formulations of acetaminophen products may also contain phenylalanine. The aspartame/phenylalanine content should be considered when these products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).

  1 source

  1. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical (2002):

• Phenylketonurias

  Moderate

  Chewable products frequently may contain aspartame, which is metabolized in the gastrointestinal tract to phenylalanine. Motrin (brand of ibuprofen) chewable 50 mg and 100 mg tablets provide the equivalent of 3 mg and 6 mg of phenylalanine each, respectively. The aspartame/phenylalanine content should be considered when these and similar products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).

  1 source

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):

Therapeutic duplication

Drug classes that overlap with Ibuprofen + Paracetamol, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Consensi

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Synalgos-dc

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Diphenhydramine/naproxen

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Esomeprazole/naproxen

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Phosphasal

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Treximet

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Orphengesic forte

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Diclofenac/misoprostol

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/citric acid/sodium bicarbonate

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Soma compound with codeine

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Stanback

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/methocarbamol

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/butalbital/caffeine/codeine

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/carisoprodol

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Micrainin

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/chlorpheniramine/dextromethorphan/phenylpropanolamine

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Zynrelef

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Seglentis

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Percodan

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/omeprazole

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/dipyridamole

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Migraine relief

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/chlorpheniramine/phenylephrine

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Aspirin/hydrocodone

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Laniroif

• nonsteroidal anti-inflammatories

  The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category.

  Example product in the source data (US market): Naproxen/pseudoephedrine