Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Ibuprofen should be avoided in combination with:
Other NSAIDs including cyclooxygenase-2 selective inhibitors: concomitant use of two or more NSAIDs should be avoided as this may increase the risk of adverse effects (see section 4.4).

Acetylsalicylic acid:
Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly.
Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

Ibuprofen should be used with caution in combination with:
Antihypertensives (ACE inhibitors, betareceptor blocking medicinal products and angiotensin-II antagonists) and diuretics:
NSAIDs may reduce the effect of these medicinal products. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor, betareceptor blocking medicinal product or angiotensin-II antagonists and medicinal product that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides: e.g. Digoxin: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels. The concomitant use of ibuprofen with medicinal products containing digoxin may increase serum level of digoxin. A check of serum digoxin is not as a rule required on correct use (maximum over 3 days).

Lithium: There is evidence for the potential increase in plasma levels of lithium. A check of serum lithium is not as a rule required on correct use (maximum over 3 days).

Potassium sparing diuretics: The concomitant administration of ibuprofen and potassium-sparing diuretics may lead to hyperkalaemia. (check of serum potassium is recommended).

Phenytoin:
The concomitant use of ibuprofen with phenytoin preparations may increase serum level of phenytoin. A check of serum-phenytoin levels is not as a rule required on correct use (maximum over 3 days).

Methotrexate. There is evidence for the potential increase in plasma levels of methotrexate. The administration of ibuprofen within 24 hours before or after administration of methotrexate may lead to elevated concentrations of methotrexate and an increase in its toxic effect.

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Ciclosporin: Increased risk of nephrotoxicity.

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (See section 4.4).

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4).

Anti-platelet medicinal products and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).

Sulphonylureas:
Clinical investigations have shown interactions between NSAIDs and antidiabetics (sulphonylureas). Although interactions between ibuprofen and sulphonylureas have not been described to date, a check of blood-glucose values is recommended as a precaution on concomitant intake.

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

Probenecid and sulfinpyrazone:
Medicinal products that contain probenecid or sulfinpyrazone may delay the excretion of ibuprofen.

Baclofen:
Baclofen toxicity may develop after starting ibuprofen.

Ritonavir:
Ritonavir may increase the plasma concentrations of NSAIDs.
Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

CYP2C9 inhibitors: Concomitant administration of Ibuprofen with CYP2C9 inhibitors may increase the exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors) an increased S (+) ibuprofen exposure by approximately 80-100% has been shown. Reduction of ibuprofen dose should be considered when potent CYP2C9 inhibitors are administered concomitantly, particularly when high-dose ibuprofen is administered with either voriconazole or fluconazole.

Captopril: Experimental studies indicate that ibuprofen inhibits the sodium excretion effect of captopril.

Cholestyramine: At concomitant administration of ibuprofen and cholestyramine the absorption of ibuprofen is delayed and decreased (25%). The medicinal products should be administered with a few hours interval.