At least one death, believed to be the result of a ritonavir/MDMA mix, has been reported thus far. The case discussed by Dr. Pau involved a 32-year-old HIV-positive British male with a history of alcohol-related liver disease, who died of an MDMA overdose on October 6, 1996. He had been taking a standard dose of ritonavir (600 mg BID) for approximately two weeks. On the night of his death, he had taken two and a half MDMA tablets (150 mg in total) and had consumed four beers. Soon after taking the extra half tablet, he became hypertonic; his respiratory rate peaked at 45 and his heart rate exceeded 140 bpm. He then became cyanotic, experienced a tonic-clonic seizure and vomiting, went into cardiac arrest, and died later that night.
The concentration of MDMA in his blood was 3.56 mg/L—the equivalent of taking 22 ecstasy tablets. Following additional toxicological investigations, it was concluded that inhibition of CYP2D6 by ritonavir and alcohol ingestion contributed to the high MDMA levels and his unfortunate death. However, some experts note that there is no way to say with certainty if this was truly a drug-drug interaction; other possibilities include abnormal CYP2D6 function or self-administration of a large MDMA dose.
On the topic of MDMA-related death, it appears that even normal metabolisers may be at risk from persisting MDMA concentration in the blood if taken in combination with inhibitors such as Ritonavir (which inhibits 3A4 and 2D6) or substances that compete for metabolism such as DXM. (ie. When you inhibit the major enzymes responsible for metabolising MDMA, you run into trouble).
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