Ibuprofen Interactions
- Adefovir
- Alendronate
Aminoglycosides
- Amphotericin B
Anticoagulants
Antihypertensive Agents
Antineoplastic Agents
- Antithymocyte Globulin
- Bacitracin
Cholinesterase inhibitors
- Cidofovir
- Cisplatin
Corticosteroids
- Cyclosporine
- Drospirenone; Ethinyl Estradiol
- Entecavir
- Ethanol
- Feverfew, Tanacetum parthenium
- Foscarnet
- Ganciclovir
- Garlic, Allium sativum
- Ginger, Zingiber officinale
- Ginkgo, Ginkgo biloba
Gold compounds
- Ketorolac
- Leflunomide
- Levofloxacin
- Lithium
- Methotrexate
Nonsteroidal antiinflammatory drugs (NSAIDs)
- Ofloxacin
- Pamidronate
- Pemetrexed
- Pentamidine
Photosensitizing Agents
Platelet Inhibitors
Radiopaque Contrast Agents
- Risedronate
Salicylates
Selective serotonin reuptake inhibitors (SSRIs)
- Strontium-89 Chloride
- Sulfinpyrazone
Sulfonylureas
- Tacrolimus
- Tenofovir, PMPA
Thrombolytic Agents
- tobacco
- Tretinoin, ATRA
- Vancomycin
- Voriconazole
- Zoledronic Acid
Ibuprofen Interactions
NOTE: Ibuprofen is a substrate of the hepatic cytochrome isoenzyme CYP2C9.
Ibuprofen may cause hypoglycemia when used concurrently with sulfonylureas. A patient with type 2 diabetes who took glibenclamide 2.5 mg daily (sulfonylurea not available in the U.S.) experienced hypoglycemia symptoms (severe nausea, sweating, and palpitations) on 3 separate occasions about 30 minutes after taking 150 mg of ibuprofen. On the third occasion, his blood glucose concentration was 40 mg/dl. Symptoms were relieved by glucose administration. Although the patient reported no ibuprofen usage before these events, aspirin, acetaminophen, and diclofenac had supposedly been taken without difficulty. A pharmacodynamic (reduced serum glucose concentrations) interaction has been documented during ibuprofen and glyburide therapy. The mechanism of the interaction is unclear but does not appear to be due to additional insulin availability. Due to the potential severity of the interaction, patients who take a sulfonylurea with ibuprofen should carefully monitor their blood glucose concentrations, especially during the first few hours after ibuprofen administration. Avoidance of ibuprofen for patients with hypoglycemia unawareness may be desirable.
Because ibuprofen exerts similar pharmacologic characteristics to other systemic nonsteroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse gastrointestinal (GI) effects, may be seen if ibuprofen is used with other NSAIDs. In general, concurrent use of ibuprofen and another NSAID should be avoided. Concomitant use of ketorolac with ibuprofen is contraindicated.
Concomitant use of ibuprofen with ethanol can enhance the risk of gastrointestinal (GI) side effects. Patients with alcoholism may have an increased risk of GI bleeding with nonsteroidal anti-inflammatory drug usage. Patients using alcohol and ibuprofen concurrently should be monitored closely for bleeding.
Concomitant use of ibuprofen with tobacco may enhance the risk of gastrointestinal (GI) side effects. Patients with tobacco use may have an increased risk of GI bleeding with nonsteroidal anti-inflammatory drug usage. Patients using tobacco and ibuprofen concurrently should be monitored closely for bleeding.
Increased adverse gastrointestinal (GI) effects are possible if ibuprofen is used with corticosteroids. Although some patients may need to be given corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly, which can be done successfully for short periods of time without sequelae, prolonged concomitant administration should be avoided. Concomitant use of corticosteroids appears to increase the risk of adverse GI events due to NSAIDs. NSAIDs may mask fever, pain, swelling and other signs and symptoms of an infection; use NSAIDs with caution in patients receiving immunosuppressant dosages of corticosteroids.
The concomitant administration of ofloxacin or levofloxacin and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of CNS stimulation and convulsive seizures. Patients with CNS disorders that may predispose them to seizure development or patients taking drugs that lower the seizure threshold may not be appropriate candidates for ibuprofen or another NSAID usage if they are also taking levofloxacin or ofloxacin.
Because ibuprofen can cause GI bleeding, inhibit platelet aggregation, and prolong bleeding time, additive pharmacodynamic effects may be seen in patients receiving salicylates (e.g., aspirin) or platelet inhibitors (e.g., aspirin, clopidogrel, ticlopidine). Interesting interactions have been noted between ibuprofen and aspirin, ASA. Concurrent use of chronic ibuprofen therapy (800 mg three times daily) seems to antagonize the inhibition of platelet cyclooxygenase (COX)-1 activity and impairment of platelet aggregation by low-dose aspirin (81 mg once daily) per an ex vivo analysis. Interestingly in this study, diclofenac or rofecoxib therapy, agents with less activity at COX-1 than ibuprofen, did not affect inhibition of platelet aggregation by aspirin. An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs’ ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with regular as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Because ibuprofen can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time, additive pharmacodynamic effects may be seen in patients receiving anticoagulants or thrombolytic agents. Patients treated with anticoagulants may have an increased risk of gastrointestinal (GI) bleeding with nonsteroidal anti-inflammatory drug usage. Ibuprofen does not, however, displace warfarin from protein-binding sites or independently prolong the prothrombin time or INR. Patients receiving any anticoagulant or thrombolytic agent and ibuprofen concurrently should be monitored closely for bleeding.
Nonsteroidal anti-inflammatory drugs (NSAIDs) interfere with lithium excretion and may lead to elevated lithium serum concentrations. With concurrent use, the mean minimum lithium concentration increased 15%, and the renal clearance decreased 19%. It is thought that prostaglandins are involved in the renal clearance of lithium and that NSAIDs interfere with lithium excretion. Typically, increased lithium concentrations develop over 5 - 10 days after adding a NSAID and return to pretreatment levels within 7 days of stopping the NSAID. Lithium concentrations should be monitored when patients initiate or discontinue NSAIDs such as ibuprofen. Observe patients carefully for signs of lithium toxicity.
In general, nonsteroidal anti-inflammatory drug (NSAID) therapy can decrease the clearance of methotrexate, resulting in elevated and prolonged serum methotrexate concentrations. Nonsteroidal anti-inflammatory drugs should not be administered prior to, concomitantly, or following intermediate or high doses of methotrexate. Concomitant administration of NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum concentrations of methotrexate resulting in deaths from severe hematologic and gastrointestinal toxicity. Caution should be used when NSAIDs are administered concurrently with lower doses of methotrexate. In patients with rheumatoid arthritis, methotrexate has been given concurrently with NSAIDs without apparent problems. It should be noted that the doses of methotrexate used for rheumatoid arthritis are lower than those used for psoriasis or malignant disease; these higher doses may lead to unexpected toxicity in combination with NSAIDs. Also, concurrent use of NSAIDs may lead to an increased risk of GI bleeding in patients with methotrexate-induced thrombocytopenia or mask fever, pain, swelling and other signs and symptoms of an infection.
Clinical status and serum creatinine and potassium concentrations should be closely monitored when systemic cyclosporine is given with salicylates or other nonsteroidal antiinflammatory drugs (NSAIDs). Renal dysfunction associated with cyclosporine may be potentiated by concurrent usage of diclofenac, naproxen, or sulindac. The effects of NSAIDs on the production of renal prostaglandins may cause changes in the elimination of cyclosporine. Potentiation of renal dysfunction may especially occur in a dehydrated patient. Serum creatinine, potassium, and cyclosporine concentrations should be closely monitored if cyclosporine is given with salicylates or other NSAIDs. Patients should be monitored for signs and symptoms of cyclosporine toxicity and infection, as NSAIDs may mask fever, pain, or swelling. Increased tear production was not seen in patients receiving ophthalmic NSAIDs or using punctual plugs concurrently with cyclosporine ophthalmic emulsion.
Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease platelet aggregation. Garlic, Allium sativum, ginger, Zingiber officinale, and ginkgo, Ginkgo biloba, also have clinically significant effects on platelet aggregation; concurrent use with a NSAID may lead to a potential increased risk of bleeding. A case of fatal intracerebral bleeding has been reported with the combination of ginkgo and ibuprofen.
An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia. Notable interactions may occur with myelosuppressive antineoplastic agents, antithymocyte globulin and strontium-89 chloride. Patients receiving ibuprofen concurrently with antineoplastic agents, antithymocyte globulin, or strontium-89 chloride should be monitored closely for bleeding.
Preclinical data suggest agents that inhibit prostaglandin synthesis such as ibuprofen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of ibuprofen before and during photodynamic therapy may be advisable (see Pharmacokinetics section for elimination half-life).
Since the use of NSAIDs and aspirin, ASA, is associated with GI irritation, exercise caution when administering these agents with risedronate due to the potential for additive GI toxicity. During clinical trials for osteoporosis, most patients took either NSAIDs or aspirin, and the incidence of adverse upper GI reactions was similar between risedronate-treated (24.5%) and placebo-treated patients (24.8%). Patients using risedronate and ibuprofen concurrently should be monitored closely for gastrointestinal adverse effects including signs and symptoms of bleeding.
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with alendronate has been noted as an independent risk factor for the development of GI adverse reactions with alendronate therapy. In clinical trials, the incidence of upper gastrointestinal adverse events was increased in patients who received aspirin-containing medicines with alendronate 10 mg daily or higher. One patient with a history of peptic ulcer disease and gastrectomy that received alendronate 10 mg daily and aspirin got an anastomotic ulcer with mild hemorrhage. The patient recovered upon alendronate and aspirin discontinuation. Patients using alendronate and ibuprofen concurrently should be monitored closely for gastrointestinal adverse effects including signs and symptoms of bleeding.
In vitro studies indicate that the M1 metabolite of leflunomide inhibits cytochrome P450 2C9, the enzyme responsible for the metabolism of many NSAIDs. Leflunomide altered protein binding and thus, increased the free fraction of ibuprofen by 13 - 50%. The clinical significance of the interactions with NSAIDs is unknown. There was extensive concomitant use of NSAIDs in phase III clinical studies of leflunomide in the treatment of rheumatoid arthritis, and no clinical differential effects were observed. However, because some NSAIDs have been reported to cause hepatotoxic effects, some caution may be warranted in their use with leflunomide.
Nonsteroidal anti-inflammatory drugs (NSAIDs), to varying degrees, have been associated with an elevation in blood pressure (approximately 5 mm Hg) when given over a period of weeks. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways. NSAIDs have been shown to attenuate the effects of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), vasodilators, central alpha-2 agonists, peripheral alpha-1 blockers, and angiotensin II blockers. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. Concomitant volume depletion caused by diuretics and prostaglandin inhibition caused by ibuprofen may increase the risk of renal failure due to inadequate kidney perfusion. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. Also, patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Nonsteroidal anti-inflammatory drugs cause a dose dependent reduction in prostaglandin formation. If ibuprofen and an antihypertensive drug is concurrently used, carefully monitor the patient for signs and symptoms of renal failure and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs.
Due to the inhibition of renal prostaglandins by ibuprofen, concurrent use with other nephrotoxic agents may lead to additive nephrotoxicity. Ibuprofen should be given with caution to patients taking aminoglycosides, amphotericin B, systemic bacitracin, cisplatin, gold compounds, ganciclovir, pamidronate, pentamidine, tacrolimus, tenofovir, PMPA, foscarnet, parenteral vancomycin, or zoledronic acid. Monitor renal function carefully during concurrent therapy.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause additive pharmacodynamic GI effects with cholinesterase inhibitors (e.g., donepezil, galantamine, rivastigmine, or tacrine), leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer’s disease, there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with cholinesterase inhibitors result in synergistic effects in Alzheimer’s disease.
Feverfew appears to inhibit prostaglandin synthesis, reportedly at a different step in the prostaglandin pathway than the nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase. Theoretically, the NSAIDs might decrease the effectiveness of feverfew, Tanacetum parthenium. However, clinical interactions have not been reported.
Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium concentrations. Drugs that may have additive effects on serum potassium with drospirenone; ethinyl estradiol (Yasmin®) include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Voriconazole is a substrate and inhibitor of cytochrome P450 isoenzyme 2C9, which is the isoenzyme responsible for the metabolism of ibuprofen. Thus, increased plasma concentrations of ibuprofen are possible. The clinical significance of this potential interaction is unknown. If voriconazole is administered concurrently with ibuprofen, monitor for NSAID-related side-effects, such as fluid retention or GI irritation, or renal dysfunction and adjust the ibuprofen dose, if needed.
The concomitant administration of cidofovir and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen is contraindicated due to the potential for increased nephrotoxicity. Ibuprofen should be discontinued 7 days prior to beginning cidofovir.
Chronic coadministration of adefovir with nephrotoxic drugs, such as nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. The use of adefovir with NSAIDs may be done cautiously. As stated in the current adefovir prescribing information, ‘Ibuprofen (800 mg PO three times daily), when given concomitantly with adefovir dipivoxil, increased the adefovir Cmax by 33% and AUC by 23%, as well as urinary recovery. The increase appears to be due to higher oral bioavailability, not a reduction in renal clearance of adefovir.’ In an in vitro investigation, the antiviral effect of adefovir was unaltered and the renal proximal tubule accumulation of adefovir was inhibited by the presence of a NSAID. Adefovir is efficiently transported by the human renal organic anion transporter 1, and the presence of this transporter appears to mediate the accumulation of the drug in renal proximal tubules. The in vitro study suggests that the use of a NSAID with adefovir may potentially reduce the nephrotoxic potential of adefovir. Of course, NSAIDs are associated with nephrotoxicity of their own; therefore, further data on the interaction between NSAIDs and adefovir in humans are needed.
Sulfinpyrazone is an inhibitor of CYP2C9 and may lead to increased plasma concentrations of some NSAIDs, including ibuprofen. Sulfinpyrazone and its metabolites inhibit platelet cyclooxygenase leading to decreased platelet aggregation. Sulfinpyrazone has been independently associated with GI bleeding in some cases; concurrent therapy with NSAIDs such as ibuprofen could potentially increase the risk of adverse GI effects. If sulfinpyrazone and ibuprofen are used concurrently, monitor for potential NSAID-induced toxicity such as GI irritation or bleeding.
The clearance of pemetrexed is reduced about 20% in patients with normal renal function that also take ibuprofen 400 mg four times daily. Caution is recommended when ibuprofen and pemetrexed are used together in patients with a creatinine clearance between 45 and 79 ml/minute. Patients with a creatinine clearance between 45 and 79 ml/minute should avoid taking NSAIDs with short elimination half-lives for a period of 2 days before, the day of, and 2 days after pemetrexed administration. Due to an absence of data, NSAIDs with longer half-lives should not be taken by anyone (regardless of renal function status) for a period of 5 days before, the day of, and 2 days after pemetrexed administration. If use of a NSAID is unavoidable, monitor patients for myelosuppression, renal, and gastrointestinal adverse effects from pemetrexed.
Because the use of other nephrotoxic drugs including nonsteroidal anti-inflammatory drugs (NSAIDs) is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, NSAID therapy should be withheld, when possible, during radiopaque contrast agent administration.
The combined use of selective serotonin reuptake inhibitors (SSRIs) with aspirin, ASA or nonsteroidal anti-inflammatory drugs (NSAIDs) may elevate the risk for bleeding including upper gastrointestinal (GI) bleeds. Selective serotonin reuptake inhibitors may inhibit serotonin uptake by platelets, which may augment the antiplatelet effects of aspirin. As determined by analysis of data from >26,000 patients included in a cohort study, SSRI use alone increased the risk for serious GI bleed by 3.6-fold as compared with nonusers of an SSRI. Combined use of an SSRI and NSAIDs increased the risk 12.2-fold whereas use of low-dose aspirin with an SSRI increased the risk 5.2-fold. The absolute risk of GI bleed from concomitant therapy with an NSAID and a SSRI was 17/4107 patients. If the drugs are used concurrently, monitor patients for signs of increased bleeding.
Because entecavir is primarily eliminated by the kidneys and nonsteroidal anti-inflammatory agents (NSAIDs) can affect renal function, concurrent administration with NSAIDs may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
The concomitant use of systemic tretinoin, ATRA and ibuprofen should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
[ Last revised: 5/24/2006 3:43:00 PM ]
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