4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for memantine are summarized in Table 3. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
|---|---|---|---|---|
| memantine, memantine/ donepezil | alkalinizing agents (e.g., select carbonic anhydrase inhibitors, sodium bicarbonate) | memantine clearance reduced by about 80% in alkaline conditions (pH greater than or equal to 8); adjunctive administration with alkalinizing agents may decrease memantine elimination and increase memantine serum levels and potential for increased pharmacologic/adverse effects | administer drug combination cautiously together; monitor patients for increased pharmacologic/adverse effects | 3-moderate (CP) |
| memantine, memantine/ donepezil | other drugs excreted by renal tubular secretion (e.g., amiloride, cimetidine, dofetilide, nicotine, quinidine, ranitidine) | memantine eliminated by renal tubular cationic transport; combined administration may result in altered serum levels of both memantine and other drugs excreted by renal tubular secretion due to competition for transport system; elevated dofetilide levels may increase potential for arrhythmias, including torsades de pointes | monitor patient responses, observe for adverse effects or loss of efficacy, and adjust doses as necessary | dofetilide, procainamide, quinidine: 2-major; all other drugs: 3-moderate (CP) |
Legend:
- #CP = Clinical Pharmacology