Memantine drug interactions

Micuda S, Mundlova L, Anzenbacherova E, Anzenbacher P, Chladek J, Fuksa L et al (2004) Inhibitory effects of memantine on human cytochrome P450 activities Prediction of in vivo drug interactions. Eur J Clin Pharmacol 60 583-589... 

In vitro studies have shown that memantine produces minimal inhibition of CYP450 enzymes CYP1A2, 2A6, 2C9,2D6, 2E1, and 3A4. These data indicate that no pharmacokinetic interactions with drugs metabolized by these enzymes should be expected.38... 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

Drugs that make the urine alkaline (e.g. sodium bicarbonate, carbonic anhydrase inhibitors) will reduce the elimination of memantine. Memantine should be used with caution with other NMDA antagonists, such as amantadine, ketamine and dextromethorphan, or concurrent use should be avoided, because of the theoretical increased risk of adverse effects. Memantine is predicted to interact with other drugs eliminated by the same renal secretion mechanism, but no important interaction was seen with glibenclamide, hydrochlorothiazide, metformin or triamterene. 

The results of in vitro studies indicate that memantine is not likely to cause interactions via induction or inhibition of the major cytochrome P450 isoenzymes involved in drug metabolism (CYP1A2, CYP2C9, CYP3A4). In addition, memantine is not metabolised by this enzyme system, and is therefore not expected to undergo interactions via this mechanism. ... 

Memantine is predicted to interact with other drugs that use the same renal cationic transport system leading to increased levels of memantine and/or the other drug. The manufacturer lists cimetidine, ranitidine, hydrochlorothiazide, metformin, procainamide, qninidine, qninine and triamterene as possible examples. However, in an interaction study, the concurrent use of memantine and hydrochlorothiazide/triamterene did not result in any change in the steady-state AUC of memantine or triamterene, and the AUC of hydrochlorothiazide showed a modest reduction of about 20%. This degree of change is unlikely to be clinically relevant. Therefore, whether any clinically important interactions occur via this mechanism remains to be established. 

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