Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Ibuprofen (like other NSAIDs) should be used with caution in combination with: 
Other NSAIDs including salicylates
Concomitant administration of several NSAIDs may increase the risk of gastrointestinal ulceration and haemorrhage due to synergistic effects. Therefore, concomitant use of ibuprofen with other NSAIDs should be avoided (see section 4.4).

Aspirin (acetylsalicylic acid)
Due to the potential for increased undesirable effects, concomitant use of ibuprofen with aspirin is generally not recommended.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose aspirin on platelet aggregation when they are administered concomitantly. Although there are uncertainties regarding extrapolation of these data to the clinical situation, it cannot be 
ruled out that regular long-term ibuprofen use can diminish the cardioprotective effect of low doses of aspirin. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

Digoxin, phenytoin, lithium
Concomitant use of Ibufen 600 with digoxin, phenytoin or lithium preparations may increase the serum level of these medicines. Surveillance of the serum lithium level is necessary, surveillance of the serum digoxin level and the serum phenytoin level is recommended.

Diuretics, ACE inhibitors, beta-adrenergic antagonists and angiotensin II receptor antagonists
NSAIDs may diminish the effect of diuretics and antihypertensive drugs. In patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function), concomitant use of an ACE inhibitor, a beta-blocker or an angiotensin II receptor antagonist with a cyclooxygenase inhibitor may lead to further deterioration of the renal function, including a possibly acute renal failure, which is usually reversible.
This combination should thus be chosen only with great caution, especially in elderly patients. Patients must be encouraged to an adequate intake of fluid and regular surveillance of renal parameters should be considered after initiation of a combination therapy.
Concomitant administration of Ibufen 600 and potassium-sparing diuretics may cause hyperkalaemia.

Glucocorticoids
Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Anti-platelet agents and selective serotonin re-uptake inhibitors (SSRIs) Increased risk of gastrointestinal bleeding (see section 4.4).

Methotrexate
Administration of Ibufen 600 within 24 hours before or after administration of methotrexate may lead to an increased methotrexate concentration and to an increase of its toxic effect.

Ciclosporin
Increased risk of nephrotoxicity of ciclosporin in concomitant use with certain NSAIDs.
This effect cannot be ruled out either for a combination of ciclosporin with ibuprofen.

Anticoagulants
NSAIDs may enhance the effects of anticoagulants such as warfarin (see section 4.4).
Sulfonylurea
Clinical trials have shown interaction between NSAIDs and oral anti-diabetic medication (sulfonylurea). When Ibuprofen is used concomitantly with sulfonylurea, surveillance of blood glucose levels is recommended as a precaution.

Tacrolimus
Increased risk of nephrotoxicity when ibuprofen is administered with tacrolimus.

Zidovudine
There is evidence of an increased risk of haemarthroses and haematoma in HIV positive haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Probenecid and sulfinpyrazone
Medicinal products containing probenecid or sulfinpyrazone may retard ibuprofen excretion.

Quinolone antibiotics
Experimental data from animal studies suggest that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. In patients receiving concomitant treatment with NSAIDs and quinolone, there may be an increased risk of developing seizures.

CYP2C9 inhibitors
Concomitant use of ibuprofen and CYP2C9 inhibitors may increase exposure to ibuprofen (CYP2C9 substrate). In a study involving voriconazole and fluconazole (CYP2C9 inhibitors), the exposure was approximately 80-100% higher compared to (S)- (+)-Ibuprofen. Reducing the ibuprofen dose should be considered when potent CYP2C9 inhibitors are used concomitantly, especially if high doses of ibuprofen are administered with either voriconazole or fluconazole.

Ginkgo biloba
Ginkgo biloba may increase the NSAID-related risk of haemorrhage.

Mifepristone
NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.