Drug-Food Interactions: Products containing calcium and other multivalent cations (such as aluminium, magnesium, iron), including milk and food, are likely to interfere with absorption of Bonviva which is consistent with findings in animal studies. Therefore, with such products, including food, intake must be delayed for 60 minutes following oral administration.
Drug-Drug Interactions: It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Bonviva. Therefore, patients must wait 60 minutes after taking Bonviva before taking other oral medications.
Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma.
In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Bonviva is administered with H2-antagonists or other drugs which increase gastric pH.
In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs.
Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs.
In a one-year study in postmenopausal women with osteoporosis (BM16549), the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Bonviva 2.5 mg daily or 150 mg once monthly.
Of over 1,500 patients enrolled in study BM16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Bonviva 150 mg once monthly was similar to that in patients treated with Bonviva 2.5 mg daily.