Being Alive 1997 Apr 5: 10
Abbott Laboratories has acknowledge potentially dangerous
interactions between its protease inhibitor ritonavir (Norvir)
and certain recreational drugs. This came in the aftermath of
the death of a British PWA who died after using MDMA, commonly
known as "ecstasy," while taking ritonavir.
According to the coroner's report, Phillip Kay's death on
October 6, 1996, was caused by an MDMA overdose, with a blood
level of 4.56 mg/liter, "nearly ten times that at which we
would expect to see serious toxic effects"-roughly the level
that would be expected after taking 22 MDMA tablets. That led
his partner, Jim Lumb, certain that Kay would not have taken
such an excessive dose, to suspect a drug interaction. He
contacted the company requesting data about such interactions,
and asked that a warning be issued.
In a letter to Lumb dated January 27, 1997, Dr. P. Kon of
Abbott's British division wrote that "Abbott has not conducted,
and does not plan on conducting any drug-drug interaction
studies between ritonavir and any illegal substances, including
ecstasy," but noted that the company's scientists had evaluated
the theoretical interaction between the two drugs. Because
MDMA's metabolism is mediated by the P450 2D6 isoform, which is
partially inhibited by ritonavir, use of the two drugs together
could result in "a two-threefold increase" in MDMA levels,
according to Kon. He added that between 3 and 10 percent of
individuals are poor metabolizers of this particular isoform
and could see MDMA levels increase "as high as five-tenfold,"
though in these individuals such levels could also occur
Kon declined Lumb's request to issue a warning, writing,
"Illegal/recreational drugs are never safe to use, therefore,
Abbott will not condone their use under any circumstances."
Lumb provided a fact sheet which Abbott has made available to
British physicians who request it. In addition to MDMA it also
lists the following interactions (all are predictions based on
known drug metabolism routes and have not been verified by
human or animal studies):
Heroin: A moderate decrease in heroin concentration (AUC
decrease less than 50%).
Methadone: A large increase in the concentration of methadone
(AUC increase greater than threefold) likely. A reduction in
dose of greater than 50% is likely to be necessary. Methadone
is metabolized by CYP3A, an isoform known to be potentially
inhibited by ritonavir.
Cocaine: Interaction unlikely (minimal change in AUC expected)
because drug is metabolized by a pathway not known to be
affected by ritonavir.
Amphetamine: An increase in concentration of two-threefold
could be expected.
U.S. Abbott spokeswoman Kim Modory said that American doctors
can call the company's medical department at 800.633.9110 for
information, and reiterated that the company has no plans to
issue a general alert: "Abbott is responding to inquiries, but
has no plans to issue an alert or recommendations in the U.S.
at this time."
This article is reprinted from AIDS Treatment News. For copies
and subscription information, write P.O. Box 411256, San
Francisco, CA 94141 or call 800.treat.1.2.