Lanthanum carbonate may increase gastrointestinal pH. It is recommended that compounds, which are known to interact with antacids, should not be taken within 2 hours of dosing with FOSRENOL (e.g. chloroquine, hydroxychloroquine and ketoconazole).
In healthy subjects, the absorption and pharmacokinetics of lanthanum were not affected by co-administration of citrate.
Serum levels of fat-soluble vitamins A, D, E and K, were not affected by FOSRENOL administration in clinical studies.
Human volunteer studies have shown that co-administration of FOSRENOL with digoxin, warfarin or metoprolol does not produce clinically-relevant changes in the pharmacokinetic profiles of these drugs. Potential pharmacodynamic interactions between lanthanum and these drugs (e.g. bleeding time or prothrombin time) were not evaluated. None of the drug interaction studies were done at the maximum recommended therapeutic dose of lanthanum carbonate. No drug interaction studies assessed the effects of drugs on phosphate binding by lanthanum carbonate.
In simulated gastric juice, lanthanum carbonate did not form insoluble complexes with warfarin, digoxin, frusemide, phenytoin, metoprolol or enalapril, suggesting a low potential to affect the absorption of these drugs.
Lanthanum carbonate is not a substrate for cytochrome P450. In vitro tests indicate that no significant inhibition of the activities of the major human cytochrome P450 isoenzymes, CYP1A2, CYP2D6, CYP3A4, CYP2C9 or CYP2C19 is expected at therapeutic concentrations. Lanthanum is extensively bound in human plasma and isolated human plasma protein preparations, including albumin, transferrin and alpha-1-acid glycoprotein (99.7 to >99.9%).
No evidence of complexiometric interactions has been observed with FOSRENOL. However, such interaction with drugs such as tetracycline, and doxycycline are theoretically possible and if these compounds are to be co-administered, it is recommended that they are not to be taken within 2 hours of dosing with FOSRENOL.
The bioavailability of oral ciprofloxacin was decreased by approximately 50% when taken with FOSRENOL in a single dose study in healthy volunteers. It is recommended that oral floxacin formulations are taken at least 2 hours before or 4 hours after FOSRENOL.
Phosphate binders (including FOSRENOL) have been shown to reduce the absorption of levothyroxine. Consequently, thyroid hormone replacement therapy should not be taken within 2 hours of dosing with FOSRENOL and closer monitoring of TSH levels is recommended in patients receiving both medicinal products.
In Vitro-Interactions with other Medicines: Gastric Fluid: The potential for a physico-chemical interaction (precipitation) between lanthanum and six commonly used medications (warfarin, digoxin, furosemide, phenytoin, metoprolol, and enalapril) was investigated in simulated gastric fluid. The results suggest that precipitation in the stomach of insoluble complexes of these drugs with lanthanum is unlikely.
The therapeutic activity of FOSRENOL depends on the acidity of the gastric environment. The potential for drugs which alter gastric acidity (for example proton-pump inhibitors) to alter the therapeutic activity of FOSRENOL has not been examined in trials but should be considered.
In Vivo-Interactions with other Medicines: Lanthanum carbonate is neither a substrate nor an inhibitor of CYP450 enzymes.
The absorption of a single dose of 1000 mg of FOSRENOL is unaffected by co-administration of citrate. No effects of lanthanum were found on the absorption of digoxin (0.5 mg), metoprolol (100 mg), or warfarin (10 mg) in healthy subjects co-administered lanthanum carbonate (three doses of 1000 mg on the day prior to exposure and one dose of 1000 mg on the day of coadministration). Potential pharmacodynamic interactions between lanthanum and these drugs (e.g. bleeding time or prothrombin time) were not evaluated. None of the drug interaction studies was done with the maximum recommended therapeutic dose of lanthanum carbonate. No drug interaction studies assessed the effects of drugs on phosphate binding by lanthanum carbonate.