Drug Interactions of OTC Ibuprofen

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Ibuprofen is an NSAID and it interacts with many drugs. Its major interactions occur with drugs such as Ketorolac, Warfarin, Danaparoid, Heparin, Low molecular weight heparins, Coumarins, Direct thrombin inhibitors, Direct factor Xa inhibitors, Eptifibatide, Antiplatelets, Aspirin, Fondaparinux, SSRIs, SNRIs, Cilostazol, Protein C, Pentoxyfylline, Ginkgo, Medowsweet, Erlotinib, Gossypol, ACEIs, ARBs, Betablockers, Calcium channel blockers, Thiazide diuretics, Loop diuretics, Potassium sparing diuretics, Dabrafenib, Amiodarone, Mifepristone, Cyclosporine, Tacrolimus, Lithium, Methotrexate, Pralatrexate, Fevefew, Beta glucan, Pentosan polysulfate sodium, Voriconazole, Premetrexed, Desipramine, Amikacin, Tacrine, Phenytoin and Fluoroquinolones.

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Drug Interactions of OTC Analgesics (Ibuprofen):

Drug Interactions of OTC Analgesics (Ibuprofen) Dr. P.Naina Mohamed Pharmacologist

Introduction:

Introduction Ibuprofen is a Non Steroidal Anti-inflammatory drug (NSAID). Ibuprofen is used to reduce fever and treat pain or inflammation caused by many conditions such as headache, toothache, back pain, arthritis, menstrual cramps, or minor injury. The FDA warns consumers that all OTC Analgesics (Pain relievers) should be taken carefully to avoid serious problems that may occur with improper usage . Many patients are unaware that over-the-counter (OTC) analgesics can cause potentially serious adverse effects when used in combination with other common medications such as anticoagulants, corticosteroids, or antihypertensive agents. The patients who are on concomitant aspirin, anticoagulant, corticosteroid, or SSRI therapy, can be treated with Acetaminophen an effective alternative to NSAIDs to treat pain or fever.

Ibuprofen and Ketorolac:

Ibuprofen and Ketorolac Ibuprofen + Ketorolac Additive gastrointestinal irritation Cumulative risks of inducing serious NSAID-related adverse events (peptic ulcers, gastrointestinal bleeding and/or perforation ) Contraindication Oral ketorolac is contraindicated in patients currently receiving Ibuprofen or other NSAIDs because of the cumulative risks of inducing serious NSAID-related adverse events (peptic ulcers, gastrointestinal bleeding, and/or perforation).

Ibuprofen and Warfarin:

Ibuprofen and Warfarin Ibuprofen + Warfarin Ibuprofen causes gastric erosion & inhibition of platelet function Increased risk of bleeding The prothrombin time (PT) or international normalized ratio (INR) should be closely monitored during concurrent therapy with ibuprofen and warfarin. Clinicians and patients should be aware of the increased potential for bleeding, especially from the gastrointestinal tract, during concomitant therapy. Adjustments of the warfarin dose may be necessary in order to maintain the desired level of anticoagulation.

Ibuprofen and Danaparoid:

Ibuprofen and Danaparoid Ibuprofen + Danaparoid Decreased platelet function Decreased coagulation Increased risk of bleeding The risk of epidural or spinal hematomas is increased whenever any low-molecular-weight heparin or heparinoid and NSAID are used concurrently in a patient undergoing spinal or epidural punctures . Gastrointestinal bleeding is also a concern with this combination. Patients receiving a low-molecular-weight heparinoid and an NSAID concurrently should be monitored closely for bleeding, which may be serious. NSAID therapy should be discontinued several days prior to surgery. Clinicians should be aware that the increased risk of bleeding with this combination will not be fully reflected by the partial thromboplastin time. In patients requiring analgesia without antiinflammatory action, acetaminophen or a narcotic analgesic would be preferable.

Ibuprofen and Heparin:

Ibuprofen and Heparin Ibuprofen + Heparin Decreased platelet function Increase in the anticoagulant activity of heparin Increased risk of bleeding Use caution and closely monitor the patient for GI bleeding when heparin and an NSAID are coadministered . Acetaminophen , which does not affect platelet function, is a useful alternative for mild analgesic and antipyretic effects.

Ibuprofen and LMWHs:

Ibuprofen and LMWHs Ibuprofen + Low Molecular Weight Heparins (LMWHs) ( Enoxaparin, Dalteparin , Tinzaparin , etc .) Decreased platelet function Decreased coagulation Increased risk of bleeding Concomitant use of low-molecular-weight heparins (LMWH) with NSAIDs may increase the risk of major bleeding events, including epidural or spinal hematomas in patients who are receiving neuraxial anesthesia or undergoing spinal puncture. Discontinuation of an NSAID prior to initiation of LMWH therapy is recommended when possible. If concomitant use of a LMWH and an NSAID is required, use extreme caution and closely monitor the patient for signs and symptoms of bleeding.

Ibuprofen and Coumarins:

Ibuprofen and Coumarins Ibuprofen + Coumarins and other anticoagulants ( Acenocoumarol , Dicumarol , Phenprocoumon , Dabigatran , Anisindione , Phenindione ) Hypoprothrombinemia , inhibition of platelet aggregation, displacement of Coumarins and other anticoagulants from protein binding sites Increased risk of bleeding Use caution with the coadministration of dabigatran and chronic use of an NSAID due to an increased risk of major, life-threatening bleeding. Promptly evaluate any signs or symptoms of bleeding. Discontinue dabigatran with any active bleeding. If concomitant use is required, close monitoring for bleeding may be warranted.

Ibuprofen and Direct Thrombin Inhibitors:

Ibuprofen and Direct Thrombin Inhibitors Ibuprofen + Direct thrombin inhibitors ( Dabigatran , Desirudin , Lepirudin , Bivalirudin , Argatroban ) Additive anticoagulant effects Increased risk of bleeding Concomitant use of desirudin and drugs that affect hemostasis, including NSAIDs, may increase the risk of bleeding. In the presence of spinal or epidural puncture, the combination may result in an increased risk of developing a neuraxial hematoma, which can result in permanent or long-term paralysis. Use caution and closely monitor the patient for bleeding when desirudin and an NSAID are coadministered Promptly evaluate any signs or symptoms of bleeding (such as a drop in hemoglobin and/or hematocrit or hypotension). Discontinue dabigatran with any active bleeding .

Ibuprofen and Direct Factor xa Inhibitors:

Ibuprofen and Direct Factor xa Inhibitors Ibuprofen + Direct factor Xa inhibitors ( Apixaban , Rivaroxaban ) Additive anticoagulant effects Increased risk of bleeding If concomitant apixaban and chronic NSAID therapy is necessary, use caution and monitor the patient closely for bleeding. Monitor for signs and symptoms of blood loss. Closely observe surgical wound drainage and periodically measure hemoglobin levels. If hemoglobin levels fall, or if there is a decrease in blood pressure, bleeding should be suspected. Discontinue apixaban if active pathological bleeding occurs. There is no established reversal therapy or antidote for apixaban -induced bleeding, and its anticoagulation effects usually persist until 24 hours after the last dose .

Ibuprofen and Eptifibatide:

Ibuprofen and Eptifibatide Ibuprofen + Eptifibatide Additive effects on hemostasis Enhanced anticoagulation Increased risk of internal and superficial hemorrhage If concomitant eptifibatide and NSAID therapy is necessary, use caution and monitor the patient closely for bleeding.

Ibuprofen and Antiplatelets:

Ibuprofen and Antiplatelets Ibuprofen + Antiplatelets ( Clopidogrel, Prasugrel , Ticagrelor , Ticlopidine , Dipyridamole , Abciximab , Eptifibatide , Tirofiban ) Additive antiplatelet effects Decreased coagulation Increased risk of bleeding Use caution and closely monitor the patient for bleeding, especially in the gastrointestinal tract, if an Antiplatelet and an NSAID are coadministered . If coadministration cannot be avoided, monitoring of signs and symptoms of active bleeding may be warranted .

Ibuprofen and Aspirin:

Ibuprofen and Aspirin Ibuprofen + Aspirin Ibuprofen competes with aspirin for COX-1 binding site Decreased antiplatelet effect of aspirin Aspirin should be taken at least 30 minutes before the ibuprofen or at least 8 hours after the ibuprofen. Consider switching ibuprofen to acetaminophen, or a COX-2 inhibitor is recommended in patients at high-risk for cardiovascular events.

Ibuprofen and Fondaparinux:

Ibuprofen and Fondaparinux Ibuprofen + Fondaparinux Decreased platelet function Decreased coagulation Increased risk of gastrointestinal bleeding Concomitant use of fondaparinux , an anticoagulant, with an NSAID increases the risk of gastrointestinal (GI) bleeding. Use caution and closely monitor the patient for GI bleeding when fondaparinux and an NSAID are coadministered .

Ibuprofen and SSRIs:

Ibuprofen and SSRIs Ibuprofen + Selective serotonin reuptake inhibitors ( SSRIs ) ( Escitalopram , Fluvoxamine, Paroxetine, Vortioxetine , Sertraline, Nefazodone , vilazodone ) SSRIs block uptake of serotonin by platelets Decreased function of platelets Increased risk of Bleeding Serotonin is essential in initiating the hemostatic response of platelets to vascular injury. Monitor patient for signs of increased bleeding when Selective serotonin reuptake inhibitors and an antiplatelet agent are given concurrently. Bleeding events reported have included epistaxis, ecchymosis, hematoma, petechiae , and life-threatening hemorrhages .

Ibuprofen and SNRIs:

Ibuprofen and SNRIs Ibuprofen + Selective serotonin and norepinephrine reuptake inhibitors ( SNRIs ) ( Venlafaxine, Desvenlafaxine , Duloxetine, Milnacipran , Levomilnacipran , Sibutramine ) SNRIs block uptake of serotonin by platelets Decreased function of platelets Increased risk of Bleeding Serotonin is essential in initiating the hemostatic response of platelets to vascular injury. Monitor patient for signs of increased bleeding when Selective serotonin and norepinephrine reuptake inhibitors and an antiplatelet agent are given concurrently. Bleeding events reported have included epistaxis, ecchymosis, hematoma, petechiae , and life-threatening hemorrhages .

Ibuprofen and Cilostazol:

Ibuprofen and Cilostazol Ibuprofen + Cilostazol Cilostazol inhibits platelet aggregation Additive Antiplatelet activity Increased risk of bleeding Use caution with the coadministration of cilostazol and an antiplatelet agent due to an increased risk of bleeding. If concomitant use is required, close monitoring for bleeding may be warranted.

Ibuprofen and Protein C:

Ibuprofen and Protein C Ibuprofen + Protein C Increased risk of gastrointestinal bleeding Decreased platelet function Decreased coagulation Concomitant use of protein C, an anticoagulant, with an NSAID increases the risk of gastrointestinal (GI) bleeding. Use caution and closely monitor the patient for GI bleeding when protein C and an NSAID are coadministered .

Ibuprofen and Pentoxyfylline:

Ibuprofen and Pentoxyfylline Ibuprofen + Pentoxyfilline Increased risk of bleeding Coadministration of pentoxifylline and NSAIDs, such as ibuprofen, naproxen, or indomethacin, should be undertaken with caution due to an increased risk of bleeding. Periodic monitoring of patients at increased risk of complications from bleeding ( eg , recent surgery, peptic ulceration) is recommended if pentoxifylline and an NSAID are coadministered .

Ibuprofen and Ginkgo:

Ibuprofen and Ginkgo Ibuprofen + Ginkgo Ginkgolide B may inhibit platelet activating factor (PAF) induced platelet aggregation Increased risk of bleeding Avoid concomitant use of ginkgo with any medicine that can inhibit platelet aggregation or coagulation, including NSAIDs. If both agents are taken together, frequently monitor the patient for bleeding time and signs and symptoms of excessive bleeding to determine if platelet function has been adversely affected by ginkgo. The gastrointestinal effects of NSAIDs may increase the risk of gastrointestinal bleeding if ginkgo is taken concomitantly.

Ibuprofen and Meadowsweet:

Ibuprofen and Meadowsweet Ibuprofen + Meadowsweet Salicylates in meadowsweet may additively inhibit platelet function Increased risk of bleeding Caution is advised if meadowsweet is taken with an NSAID . Monitor the patient closely for signs and symptoms of bleeding.

Ibuprofen and Erlotinib:

Ibuprofen and Erlotinib Ibuprofen + Erlotinib Increased risk of gastrointestinal bleeding and perforation Cases of gastrointestinal bleeding and perforation (both resulting in fatal outcomes) have been reported in patients receiving erlotinib . Patients receiving concomitant NSAIDs, such as ibuprofen, are at increased risk for these events. Caution is advised if these agents are used concurrently. It is recommended that erlotinib be permanently discontinued in patients who develop gastrointestinal perforation.

Ibuprofen and Gossypol:

Ibuprofen and Gossypol Ibuprofen + Gossypol Gossypol may cause tissue congestion, mucosal sloughing, mucosal necrosis, and intestinal wall hemorrhage Increased risk of adverse gastrointestinal effects ( stomach bleeding and irritation) Avoid concomitant use of gossypol and NSAIDs, take the compounds at different times of the day, and/or accompany their use by food and water. Anorexia , nausea, diarrhea, and weight loss have been associated with gossypol intake.

Ibuprofen and ACEIs:

Ibuprofen and ACEIs Ibuprofen + ACE Inhibitors ( Captopril, Enalapril , Imidapril , Temocapril , Delapril , Ramipril, Perindopril, Cilazapril ) Ibuprofen blocks cycloxygenase and decreases the production of vasodilator and natriuretic prostaglandin Decreased antihypertensive effects of ACE Inhibitors Use caution if ACE inhibitors and NSAIDs are coadministered . When concomitant use is required, monitor the patient for ACE inhibitor antihypertensive efficacy and renal function periodically for signs of renal failure.

Ibuprofen and ARBs:

Ibuprofen and ARBs Ibuprofen + Angiotensin II receptor blockers (ARBs) ( Losartan, Valsartan, Telmisartan ) NSAIDs block cycloxygenase and decreases the production of vasodilator and natriuretic prostaglandin Decreased antihypertensive effects of ARBs and an increased risk of renal impairment The antihypertensive effects of angiotensin II receptor blockers (ARB) may be decreased if administered concurrently with an NSAID. Additionally, renal deterioration and acute renal failure may result, especially in volume-depleted patients (including those receiving diuretic therapy), elderly patients, and those with renal impairment. Monitor renal function periodically .

Ibuprofen and Beta blockers:

Ibuprofen and Beta blockers Ibuprofen + Beta adrenergic blockers NSAIDs decrease the production of vasodilating and renal prostaglandins Decreased antihypertensive effect Use caution if an NSAID and a beta-adrenergic blocker are coadministered . If concurrent therapy is required, monitor the patient's blood pressure carefully and assess the need for a dosage adjustment of the beta-blocker.

Ibuprofen and Calcium Channel Blockers:

Ibuprofen and Calcium Channel Blockers Ibuprofen + Calcium Channel Blockers Additive effects of bleeding & decreased renal prostaglandin Increased risk of gastrointestinal hemorrhage and/or antagonism of hypotensive effect Caution is advised if calcium channel blockers and NSAIDs are used concomitantly. Monitor for signs and symptoms of gastrointestinal hemorrhage, such as weakness, nausea, and blood in the stool. The antihypertensive effects of calcium channel blockers may be antagonized by concomitant administration of NSAIDs.

Ibuprofen and Thiazide Diuretics:

Ibuprofen and Thiazide Diuretics Ibuprofen + Thiazide Diuretics Decreased renal prostaglandin production Removal of direct vasodilatory influence and also increased vascular response to vasoconstrictor stimuli Decreased diuretic, natriuretic and antihypertensive efficacy Monitor the patient for desired diuretic effects. Monitor blood pressure, weight, and for signs of renal failure, including decreases in urine output and increased edema.

Ibuprofen and Loop Diuretics:

Ibuprofen and Loop Diuretics Ibuprofen + Loop Diuretics Decreased renal prostaglandin production Decreased renal blood flow Decreased diuretic, natriuretic and antihypertensive efficacy Monitor the patient for desired diuretic effects. Monitor blood pressure, weight, and for signs of renal failure, including decreases in urine output and increased edema.

Ibuprofen and Potassium sparing Diuretics:

Ibuprofen and Potassium sparing Diuretics Ibuprofen + Potassium sparing Diuretics NSAID decreases renal prostaglandin synthesis Hyporeninemic hypoaldosteronism Reduced diuretic effectiveness, hyperkalemia, or possible nephrotoxicity When coadministering NSAIDs and potassium-sparing diuretics, monitor the patient for decreased effectiveness of the diuretic and hyperkalemia. Monitor blood pressure, weight changes, urine output, potassium levels, and creatinine levels.

Ibuprofen and Dabrafenib:

Ibuprofen and Dabrafenib Ibuprofen + Dabrafenib Dabrafenib induces CYP2C9 Increased CYP2C9 mediated metabolism of Ibuprofen Reduced Ibuprofen serum concentrations If possible, substitute the use of CYP2C9 substrates during dabrafenib therapy. If concomitant use of dabrafenib and a CYP2C9 substrate is required, monitor patients for loss of efficacy.

Ibuprofen and Amiodarone:

Ibuprofen and Amiodarone Ibuprofen + Amiodarone Amiodarone inhibits CYP2C9-mediated ibuprofen metabolism Increased plasma levels of ibuprofen Use caution with the concomitant use of amiodarone (a CYP2C9 inhibitor) and ibuprofen (a CYP2C9 substrate). Frequent monitoring for NSAID-related adverse effects is recommended during coadministration . Dosage adjustment of ibuprofen may be necessary.

Ibuprofen and Voriconazole:

Ibuprofen and Voriconazole Ibuprofen + Voriconazole Voriconazole inhibits CYP2C9-mediated ibuprofen metabolism Increased ibuprofen exposure and plasma concentration Use caution with the coadministration of ibuprofen and voriconazole as this may result in increased ibuprofen exposure and plasma concentration. Close monitoring for NSAID-related adverse events is recommended and dosage reduction of ibuprofen may be warranted.

Ibuprofen and Mifepristone:

Ibuprofen and Mifepristone Ibuprofen + Mifepristone Mifepristone inhibits CYP2C9 mediated NSAIDs metabolism Increased serum levels of NSAIDs When using mifepristone together with an NSAID, use the lowest possible dose of the NSAID and monitor the patient closely for adverse effects. Due to the long terminal half-life of mifepristone after reaching steady state, allow at least 2 weeks following cessation of mifepristone before increasing the NSAID dose. The lowest dose of the NSAID should be used when given concomitantly with mifepristone and patients should be monitored closely for NSAID adverse effects.

Ibuprofen and Cyclosporine:

Ibuprofen and Cyclosporine Ibuprofen + Cyclosporine Ibuprofen decreases renal prostacyclin synthesis Increased risk of cyclosporine nephrotoxicity Concomitant use of cyclosporine with an NSAID may potentiate cyclosporine-related renal dysfunction, especially in dehydrated patients. Additionally , cyclosporine may decrease the clearance of the NSAID. Use caution when coadministering an NSAID with cyclosporine, and closely monitor renal function including serum creatinine. In patients with rheumatoid arthritis, monitoring of serum creatinine and blood pressure is recommended after initiation of a new NSAID or an NSAID dose increase.

Ibuprofen and Tacrolimus:

Ibuprofen and Tacrolimus Ibuprofen + Tacrolimus Ibuprofen inhibits the synthesis of renal prostaglandins Acute renal failure (Anuria or Oliguria ) Concomitant administration of NSAIDs and tacrolimus should be avoided, particularly in patients with liver dysfunction. If used concurrently, monitor serum creatinine and urine output.

Ibuprofen and Lithium:

Ibuprofen and Lithium Ibuprofen + Lithium Ibuprofen inhibits renal prostaglandin synthesis Decreased lithium clearance Elevated lithium serum levels Increased risk of lithium toxicity (weakness, tremor, excessive thirst, confusion ) Due to the potential for increased serum lithium levels, patients should be monitored for signs of lithium toxicity. A reduction in lithium dosage may be necessary.

Ibuprofen and Methotrexate:

Ibuprofen and Methotrexate Ibuprofen + Methotrexate Decreased methotrexate clearance Increase methotrexate levels Increased risk of methotrexate toxicity (leukopenia, thrombocytopenia, anemia, nephrotoxicity, mucosal ulcerations ) Deaths from severe hematologic and gastrointestinal toxicity In general, do not administer NSAIDS within 10 days of high-dose methotrexate ( ie , doses used in cancer therapy). If concomitant administration is necessary, monitor closely for toxicity, especially myelosuppression and gastrointestinal toxicity. Concomitant administration of low-dose methotrexate ( ie , doses used for arthritis, 7.5 mg to 15 mg per week) and NSAIDS has been well tolerated in many patients; however, caution is advised. Preexisting renal dysfunction (or NSAID-induced renal dysfunction) also increases the risk of adverse reactions.

Ibuprofen and Pralatrexate:

Ibuprofen and Pralatrexate Ibuprofen + Pralatrexate Decreased renal clearance of Pralatrexate Increased serum concentrations of Pralatrexate Caution is warranted with the concomitant use of P ralatrexate and NSAIDs. Monitor the patient for systemic toxicity due to increased drug exposure.

Ibuprofen and Premetrexed:

Ibuprofen and Premetrexed Ibuprofen + Premetrexed Decreased clearance of pemetrexed Pemetrexed toxicity ( myelosuppression , renal toxicity, and gastrointestinal toxicity ) Concomitant administration of NSAIDs and pemetrexed could potentially decrease the clearance of pemetrexed . Caution should be used when ibuprofen and pemetrexed are coadministered to patients with mild to moderate renal insufficiency. Patients with mild to moderate renal insufficiency should avoid taking NSAIDs with short elimination half-lives for a period of 2 days before, the day of, and 2 days following administration of pemetrexed . All patients taking NSAIDs with longer half-lives should interrupt dosing for at least 5 days before, the day of, and 2 days following administration of pemetrexed . If concomitant administration of an NSAID is necessary, monitor the patient for toxicity, especially myelosuppression , renal toxicity, and gastrointestinal toxicity.

Ibuprofen and Feverfew:

Ibuprofen and Feverfew Ibuprofen + Feverfew Feverfew inhibits prostaglandin synthesis and supresses thromboxane synthesis Additive prostaglandin and thromboxane inhibition Increased risk of NSAID associated adverse effects ( ie , gastrointestinal, renal effects). Avoid concomitant use of feverfew with NSAIDs. There is insufficient benefit to offset perceived risk in combining these 2 agents.

Ibuprofen and Betaglucan:

Ibuprofen and Betaglucan Ibuprofen + Beta Glucan Possibly alteration of the cytokine network Acute inflammation (Enteric-induced bacterial peritonitis ) Severe gastrointestinal damage Concomitant use of therapeutic doses of beta glucan and NSAIDs is not recommended.

Ibuprofen and Pentosan Polysulfate Sodium:

Ibuprofen and Pentosan Polysulfate Sodium Ibuprofen + Pentosan Polysulfate Sodium Additive effects Increased risk of bleeding Concomitant use of pentosan polysulfate sodium therapy with NSAIDs increases the risk of bleeding. If concomitant pentosan polysulfate sodium and NSAID therapy is necessary, monitor the patient closely for bleeding complications and use with caution.

Ibuprofen and Desipramine:

Ibuprofen and Desipramine Ibuprofen + Desipramine Ibuprofen inhibits Desipramine metabolism Increased risk of tricyclic toxicity (drowsiness, hypotension, akathisia ). Monitor desipramine plasma concentrations in patients prescribed chronic doses of ibuprofen. Also monitor the patient for signs of tricyclic toxicity (alterations of consciousness, seizure activity, cardiac arrhythmias).

Ibuprofen and Amikacin:

Ibuprofen and Amikacin Ibuprofen + Amikacin Increased amikacin serum levels Concurrent use of amikacin and ibuprofen may result in increased amikacin half-life and decreased amikacin clearance. The dosing interval of amikacin may have to be increased when amikacin is coadministered with ibuprofen lysine.

Ibuprofen and Tacrine:

Ibuprofen and Tacrine Ibuprofen + Tacrine Symptoms of delirium (delusions, hallucinations, confusion, insomnia, tremor) Clinicians should be aware of a potential interaction between ibuprofen and tacrine . If these drugs are used concurrently, monitor patients for signs and symptoms of delirium (delusions, hallucinations, confusion, insomnia, tremor).

Ibuprofen and Phenytoin:

Ibuprofen and Phenytoin Ibuprofen + Phenytoin Altered metabolism of Phenytoin Increased free phenytoin serum concentrations Increased risk of phenytoin toxicity (ataxia, hyperreflexia , nystagmus , tremor ) Monitor patients receiving combined phenytoin and ibuprofen for signs and symptoms of phenytoin toxicity (ataxia, nystagmus , tremor, hyperreflexia ). Phenytoin serum concentrations need to be monitored if this combination of agents is administered to patients with renal impairment. Combined ibuprofen and phenytoin therapy may be safe and efficacious in patients with normal renal function. Because of the narrow therapeutic window of phenytoin, caution should be used when combining ibuprofen and phenytoin therapy. Onset: Delayed Severity: Moderate Documentation: Good Probable Mechanism: increased free phenytoin serum concentrations and/or altered metabolism of either agent Summary: Combined ibuprofen and phenytoin therapy may be safe and efficacious in patients with normal renal function ( Dasgupta & Timmerman, 1996; Bachmann et al, 1986), although 1 case has been reported of therapeutic levels of ibuprofen causing apparent phenytoin toxicity in a patient with no known renal impairment ( Sandyk , 1982). The mechanism of that possible interaction was thought to be inhibition by ibuprofen of hepatic cytochrome P450 metabolism of phenytoin. Literature : A 38-year-old woman had been taking phenytoin 300 mg daily for 5 years and developed a toxic phenytoin level after 1 week of concurrent use of ibuprofen 400 mg 4 times daily for degenerative rheumatoid disease. The patient was admitted with symptoms of severe frontal headache, nausea, and difficulty maintaining balance. On examination, she exhibited truncal ataxia, vertical and horizontal nystagmus , tremor of the tongue, asterixis , titubation of the head and trunk, and generalized brisk tendon jerks. The blood phenytoin level on admission was 101 mmol /L (therapeutic 40 to 70 mmol /L). Ibuprofen was withdrawn and all symptoms resolved within 5 weeks. A baseline phenytoin serum level was not stated in this report ( Sandyk , 1982). In a controlled pharmacokinetic study, 10 healthy male volunteers were given a single dose of phenytoin 300 mg orally following a 1 week-course of ibuprofen 400 mg 4 times daily. Free unbound phenytoin increased slightly (p less than 0.001), while the total clearance and intrinsic unbound clearance of phenytoin was not significantly affected. It was concluded that no important changes would occur in phenytoin pharmacokinetics when ibuprofen is given concomitantly (Bachmann et al, 1986). Nonsteroidal antiinflammatory drugs, including ibuprofen, influences protein binding displacement of phenytoin in vitro. Phenytoin is 90% bound to serum albumin, and ibuprofen is 98% to 99% bound to serum protein. A significant increase (46.7%) in free serum phenytoin occurred only at above-therapeutic concentrations of ibuprofen (75 mcg/mL) in a normal serum pool with albumin 3.7 g/ dL . Using a serum pool of uremic patients where the albumin concentration was 2.9 g/ dL , significant phenytoin displacement occurred with high therapeutic serum concentrations of ibuprofen (30 mcg/mL) ( Dasgupta & Timmerman, 1996). A study evaluating substrate structure-activity relationship of hepatic cytochrome isoenzymes CYP2D6, CYP3A4, and CYP2C9 demonstrated that CYP2C9 metabolized both phenytoin and ibuprofen. Thus, it may be theoretically possible that the combination of phenytoin and ibuprofen in vivo produces competitive inhibition of metabolism of either or both agents. Because P450 metabolism and protein binding issues are involved, further controlled studies of coadministered phenytoin and ibuprofen are needed (Smith & Jones, 1992).

Ibuprofen and Fluoroquinolones:

Ibuprofen and Fluoroquinolones Ibuprofen + Fluoroquinolones ( Ofloxacin , Levofloxacin, Norfloxacin ) Inhibition of gamma aminobutyric acid (GABA ) Central nervous system stimulation Increased risk of seizures Fluoroquinolones should be used cautiously in patients receiving other medications that may lower the seizure threshold, including NSAIDs. Alternative therapy should be considered, especially in patients who are predisposed to seizure activity.

Ibuprofen and Pregnancy & Breast Feeding:

Ibuprofen and Pregnancy & Breast Feeding Pregnancy: There are no adequate or well-controlled studies evaluating the use of ibuprofen in pregnant women . Due to the lack of human safety information, ibuprofen should be used in pregnant women prior to 30 weeks gestation only if the potential benefit outweighs the potential risk to the fetus. Ibuprofen should be avoided after 30 weeks gestation because of the effects of NSAID-related prostaglandin inhibition on the fetal cardiovascular system (closure of ductus arteriosus ). Breast Feeding: It is not known if ibuprofen is excreted in human milk. Due to the potential for adverse events in the nursing infant, a decision should be made to either discontinue nursing or discontinue ibuprofen therapy.

Tips for patients to avoid OTC Drug interactions:

Tips for patients to avoid OTC Drug interactions Patients should thoroughly read the labels of all over-the-counter and prescription medicines. Patients should make sure that they know the benefits as well as the potential risks of both prescription and over-the-counter medications they are taking. They should look specifically for the section called "Warnings" on the labels of over-the-counter medicines. Patients should talk to their doctor or pharmacist before taking any new prescription or over the counter medication. Patients should maintain a record containing the list of prescription or over the counter medications and share it with their doctors and their pharmacist. Patients should use one pharmacy for all of their family's prescription and over-the-counter medication needs . By filling all prescriptions at one pharmacy, all the important information about (what and when the patients take) could be found in a central location. The pharmacist can help the patients by retrieving all the informations about possible drug interactions from any OTC, prescription or herbal medications. Learning about interactions with commonly used OTC remedies can also assure smart choices. Talk to doctor or pharmacist if you have any medical conditions or take other medications. They can help explain what risks you may have and what precautions to take.

Conclusion:

Conclusion Physicians should be aware of potential drug interactions with OTC medicines when prescribing new medications. Pharmacists can be instrumental in assisting patients with using OTC medications safely and effectively. To achieve maximum efficacy of a medication, drug-drug interactions, drug-disease interactions, and the timing of administration with respect to food should be examined thoroughly before co-administration of multiple medications. Physicians and Pharmacists should make patients aware of the potential for toxicity and adverse drug interactions associated with the long-term and inappropriate use of OTC analgesics. They should advise Patients to use OTC analgesics not in higher-than-recommended doses or not in combinations that magnify the risk of adverse interactions. Patients should be notified that OTC analgesics are also found in many common cough, cold, or flu medications. Pharmacists may provide educational materials to patients so that they may learn to recognize the generic names of OTC medications. Pharmacists should warn consumers of the risks of misusing OTC pain relievers.

References:

References Stockley’s Drug Interactions, 9e Karen Baxter http :// www.micromedexsolutions.com http :// www.ncbi.nlm.nih.gov/pmc/articles/PMC2257951/ http :// www.sciencedirect.com/science/article/pii/S0149291807003712 http :// www.researchgate.net/publication/5684542_Adverse_drug_interactions_involving_common_prescription_and_over-the-counter_analgesic_agents http :// www.fda.gov/ohrms/dockets/dailys/02/Aug02/082202/80022395.pdf

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