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Concurrent administration of either calcium carbonate or aluminium and magnesium-hydroxide containing antacids do not affect the systemic exposure of raloxifene.
Co-administration of raloxifene and warfarin or other coumarin derivatives does not alter the pharmacokinetics of either compound. However, modest decreases in the prothrombin time have been observed, and if raloxifene is given concurrently with warfarin or other coumarin derivatives, the prothrombin time should be monitored. Effects on prothrombin time may develop over several weeks if CELVISTA treatment is started in patients who are already on coumarin anticoagulant therapy.
Raloxifene has no effect on the pharmacokinetics of methylprednisolone given as a single dose.
Raloxifene does not affect the steady-state AUC of digoxin. The Cmax of digoxin increased by less than 5%.
The influence of concomitant medication on raloxifene plasma concentrations was evaluated in the prevention and treatment trials. Frequently co-administered medicinal products included: paracetamol, nonsteroidal anti-inflammatory drugs (such as acetylsalicylic acid, ibuprofen, and naproxen), oral antibiotics, H1 and H2 antagonists, and benzodiazepines. No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.
Concomitant use of vaginal estrogen preparations was commonplace in the clinical trial programme. No interaction was noted and compared to placebo there was no increased use in CELVISTA treated patients.
In vitro, raloxifene did not interact with the binding of warfarin, phenytoin or tamoxifen.
Raloxifene should not be co-administered with cholestyramine (or other anion exchange resins), which significantly reduces the absorption and enterohepatic cycling of raloxifene.
Peak concentrations of raloxifene are reduced with co-administration with ampicillin. However, since the overall extent of absorption and the elimination rate of raloxifene are not affected, raloxifene can be concurrently administered with ampicillin.
Raloxifene modestly increases hormone-binding globulin concentrations, including sex steroid binding globulins (SHBG), thyroxine binding globulin (TBG) and corticosteroid binding globulin (CBG), with corresponding increases in total hormone concentrations. These changes do not affect concentrations of free hormones.
