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Ibuprofen: Coumarin-type anticoagulants: Several short-term controlled studies failed to show that ibuprofen significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on coumarin-type anticoagulants. However, because bleeding has been reported when ibuprofen and other non-steroidal anti-inflammatory agents have been administered to patients on coumarin-type anticoagulants, the physician should be cautious when administering ibuprofen to patients on anticoagulants.
Warfarin: Concurrent use of NSAIDs and warfarin has been associated with severe sometimes fatal haemorrhage. The mechanism of this interaction is not known but may involve increased bleeding from NSAID-induced gastrointestinal ulceration or an additive effect of NSAID inhibition of platelet function with the anticoagulant effect of warfarin.
Ibuprofen should only be used in patients taking warfarin if absolutely necessary. Patients taking this combination must be closely monitored.
Aspirin: Animal studies show that aspirin given with non-steroidal anti-inflammatory agents, including ibuprofen, yields a net decrease in anti-inflammatory activity with lowered blood levels of the non-aspirin drug. Single dose bioavailability studies in normal volunteers have failed to show an effect of aspirin on ibuprofen blood levels. Correlative clinical studies have not been done.
Methotrexate: NSAIDs inhibit tubular secretion of methotrexate in animals. As a result, reduction of clearance of methotrexate may occur. Use of high doses of methotrexate concomitant with NSAIDs should be avoided. At low doses of methotrexate caution should be used if ibuprofen is administered concomitantly.
H-2 Antagonists: In studies with human volunteers, co administration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.
Diuretics: Clinical studies, as well as random observations, have shown that ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with ibuprofen, the patient should be observed closely for signs of renal failure (see PRECAUTIONS), as well as to assure diuretic efficacy.
Lithium: Ibuprofen produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of eleven normal volunteers. The mean minimum lithium concentration increased 15% and the renal clearance of lithium was decreased by 19% during this period of concomitant drug administration. This effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. Thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparation before use of such concurrent therapy.)
Antihypertensive: Ibuprofen like other NSAIDs can reduce the antihypertensive effect of ACE inhibitors and beta-blockers with possible loss of blood pressure control and can attenuate the natriuretic effects of thiazide diuretics and furosemide.
Glycosides: NSAIDs may increase plasma cardiac glycoside levels. Care should therefore be taken in patients treated with cardiac glycosides.
Alcohol or corticosteroids or chronic therapeutic use of corticotrophin or potassium supplements: Concurrent use with ibuprofen may increase the risk of gastrointestinal side effects, including ulceration or haemorrhage.
Oral antidiabetic agents or insulin: Ibuprofen may increase the hypoglycemic effect of these medications because prostaglandins are directly involved in regulatory mechanisms of glucose metabolism and possibly because of displacement of the oral anti-diabetics from serum proteins. Hence, dosage adjustments of anti-diabetic agent may be necessary.
Bone marrow depressants: Leukopenic and/or thrombocytopenic effects of these medications may be increased with concurrent or recent therapy; dosage adjustment of the bone marrow depressant, if necessary, should be based on blood counts.
Cefamandole or cefoperazone or cefotetan or plicamycin or valproic acid: These medications may cause hypoprothrombinemia; in addition, plicamycin or valproic acid may inhibit platelet aggregation; concurrent use with ibuprofen may increase the risk of bleeding because of additive interferences with platelet function and/or the potential occurrence of ibuprofen-induced gastro-intestinal ulceration or hemorrhage.
Cyclosporine or gold compounds and other nephrotoxic compounds: Inhibition of renal prostaglandin activity by ibuprofen may increase the plasma concentration of cyclosporine and/or the risk of cyclosporine induced nephrotoxicity; patients should be carefully monitored during concurrent use.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.
Laboratory Tests: Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should follow chronically treated patients for the signs and symptoms of ulcerations and bleeding and should inform them of the importance of this follow-up (see Risk of GI Ulceration, Bleeding and Perforation with Non-steroidal Anti-inflammatory Therapy under WARNINGS).
Paracetamol: Alcohol and Hepatic Enzyme Inducers: Risk of hepatotoxicity with single toxic dose or prolonged use of high dose of Paracetamol may be increased in alcoholics or in patients regularly taking other hepatotoxic medications or hepatic enzyme inducers.
Barbiturates and Antidepressants: Concomitant barbiturates and tricyclic antidepressants may increase the hepatotoxicity of Paracetamol particularly after overdose. Chronic use of barbiturates (except Butalbital) or primidone has been reported to decrease the therapeutic effects of acetaminophen, probably because of increased metabolism resulting from induction of hepatic microsomal enzyme activity; the possibility should be considered that similar effects may occur with other hepatic enzyme inducers.
Anti-convulsant: Anti-convulsant or oral steroid contraceptives have the ability to reduce serum levels of Paracetamol by liver enzyme induction.
Metoclopramide: The rate absorption of Paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
Anti-inflammatory drugs (NSAIDs): Prolonged concurrent use of acetaminophen and a salicylate is not recommended because recent evidence suggests that chronic high-dose administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, end stage renal disease and cancer of the kidney or urinary bladder, also, it is recommended that for short-term use, the combined dose of acetaminophen plus salicylate given alone.
Prolonged concurrent use of acetaminophen and NSAID other than aspirin may also increase the risk of adverse renal effects; it is recommended that patients be under close medical supervision while receiving such combined therapy.
Anti-coagulants, coumarin or indandione derivatives: Concurrent chronic, high dose administration of acetaminophen may increase the anticoagulant effect, possible by decreasing hepatic synthesis of procoagulant factors; anticoagulant dosage adjustment based on increased monitoring of prothrombin time may be necessary when chronic; high dose acetaminophen therapy is initiated or discontinued; however, this does not apply to occasional use, or to chronic use of doses below 2 grams per day, of acetaminophen.
Cholestyramine: The absorption of Paracetamol is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour if maximal is analgesia.
Chloramphenicol: Increased plasma concentration of chloramphenicol has been reported.
