DEXTROMETORPHAN + QUINIDINE

• Cytochrome P450 enzyme substrate: CYP2D6 and CYP3A4
• Action to be taken: Caution with close monitoring for signs of toxicity.
• Rationale: The co-administration of NUEDEXTA with drugs that undergo extensive CYP2D6 metabolism may
  result in altered drug effects, due to accumulation of parent drug and/or failure of metabolite formation
  Therapy with medications that are primarily metabolized by CYP2D6 and that have a relatively narrow therapeutic
  index should be initiated at a low dose if a patient is receiving NUEDEXTA concurrently. Quinidine is eliminated via hepatic metabolism through CYP3A4 isoenzyme. Cimetidine(CYP3A4 inhibitor)can inhibit metabolism and produce quinidine toxicity. Quinidine concentrations should be monitored closely after addition of cimetidine; choose an alternate therapy if possible. In vitro studies have shown that cannabis is a weak inhibitor of CYP2D6 and CYP3A4, thus concomitant administration with dextrometorphan and quinidine may lead to increased serum concentrations of these drugs.
  

MEMANTINE

• Action to be taken: No action needed
• Rationale:Memantine undergoes partial hepatic metabolism. The hepatic microsomal CYP450 enzyme system does not play a significant role in the metabolism of memantine.Memantine is predominantly renally eliminated, and drugs that are substrates and/or inhibitors of the CYP450 system are not expected to alter the metabolism of memantine.

References

1. Neudexta (dextrometorphan/quinidine) package insert.  Avanir Pharmaceuticals, Inc. Aliso Viejo, CA 2010
   
2. Watanabe K, Yamaori S, Funahashi T, et al. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80:1415-1419.
3. Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46:86-95.​​
4. Namenda (memantine) package insert. Allergan USA, Inc. Irvine, CA 2016