Ritonavir Ecstasy

A fatal interaction between ritonavir and MDMA (methylenedioxymethamphetamine, ecstasy) has been reported in an HIV-positive man (see Henry et ah, 1998). The patient had allegedly taken MDMA on several occasions without untoward effects. However, several weeks after ritonavir was added to his regular medication with zidovudine and lamivudine, he took some MDMA for recreational purposes and died of a cardiorespiratory arrest within hours. Toxicology showed that the plasma MDMA concentration was about ten times that expected from the ingested dose. Inhibition of CYP2D6, the principal pathway for MDMA metabolism, by ritonavir was thought to be the most likely cause. 

A 32-year-old HIV-positive man, who added ritonavir 600 mg bd to his antiretroviral regimen of zidovudine and lamivudine, became unwell within hours after having taken two and a half tablets of ecstasy, estimated to contain 180 mg of MDMA. He was hypertonic, sweating profusely, tachypneic, tachycardic, and cyanosed. Shortly after he had a tonic-clonic seizure and a cardiorespiratory arrest. Attempts at resuscitation were unsuccessful. Blood concentrations obtained post-mortem showed an MDMA concentration of 4.56 mg/1, in the range of that reported in a patient with a life-threatening illness and symptoms similar to this patient after an overdose of 18 tablets of MDMA. 

Ritonavir can interact with methylenedioxymetamfeta-mine (MDMA, ecstasy) (23). 

A patient infected with HIV-1 who was taking ritonavir and saquinavir had a prolonged effect from a small dose of methylenedioxymetamfetamine (MDMA, ecstasy) and a near-fatal reaction from a small dose of gammahydrox-ybutyrate (45). 

A man taking ritonavir suffered a fatal serotonergic reaction after taking ecstasy (MDMA, methylenedioxymethamfetamine). A simitar fatat reaction occurred with metamfetamine and ritona-... 

Ritonavir inhibits the cytochrome P450 isoenzyme CYP2D6, which is responsible for the demethylenation of ecstasy, so concurrent use leads to a sharp rise in ecstasy plasma levels. Poor liver function (due to alcoholism) may have been a contributory factor in one patient, and further CYP inhibition by nitric oxide (the metabolite of amyl nitrate) may have contributed to another case. An additional factor is that ecstasy may show non-linear pharmacokinetics. Metamfetamine is also metabolised by CYP2D6 and its levels would therefore similarly be raised by ritonavir. 

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