Entacapone

• Action to be taken: Caution. Monitor CNS depressant effects
• Rationale:  Entacapone is almost completely metabolized prior to excretion, with only a very small amount (0.2% of dose) found unchanged in urine. The main metabolic pathway is isomerization to the cis-isomer, followed by direct glucuronidation to an inactive metabolite. In vitro studies of human CYP enzymes showed that entacapone inhibited the CYP enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A only at very high concentrations, therefore these enzymes not be expected to be inhibited in clinical setting.  The risk of somnolence was increased in controlled studies. It has been reported that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence. Adding ethanol to both high and low doses of THC increased impairment on several measures, as well as adding to subjective experiences . In a study by Johnstone et al. THC potentiated the sedative and respiratory depressant effects of the opioid oxymorphone.  A second study in man confirmed an additive effect when THC was combined with secobarbital.  

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Tolcapone 

• Action to be taken: Caution. Monitor CNS depressant effects
• Rationale: In vitro studies of human CYP enzymes showed that tolcapone does not interact with the following CYP450 enzymes CYP1A2, CYP2A6, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. However it was found that tolcapone has affinity for CYP2C9 and therefore may interfere with drugs who's metabolism depends on CYP2C9. In an in vivo interaction study, tolcapone did not change the pharmacokinetics of tolbutamide. Therefore, clinically relevant interactions involving cytochrome P450 2C9 appear unlikely. The most commonly observed adverse reactions in the double-blind, placebo-controlled trials  were dyskinesia, nausea, diarrhea, anorexia, sleep disorder, vomiting, urine discoloration, somnolence, hallucination, dystonia, and sweating. Adding ethanol to both high and low doses of THC increased impairment on several measures, as well as adding to subjective experiences . In a study by Johnstone et al. THC potentiated the sedative and respiratory depressant effects of the opioid oxymorphone.  A second study in man confirmed an additive effect when THC was combined with secobarbital. ​
  

References

1. Comtan(entacapone) package insert, Novartis Pharmaceuticals Corporation,East Hanover, NJ 2016
   
2. ​Hollister LE. Interactions of cannabis with other drugs in man. NIDA Res Monogr. 1986;68:110-116
3. Johnstone RE, Lief PL, Kulp RA, Smith TC. Combination of delta9-tetrahydrocannabinol with oxymorphone or pentobarbital: Effects on ventilatory control and cardiovascular dynamics. Anesthesiology. 1975;42(6):674-684.
   
4. Tasmar(tolcapone) package insert, Valiant Pharmaceuticals North America LLC, Bridgewater, NJ2013