AIDS TREATMENT NEWS Issue #265, February 21, 1997
Bruce Mirken
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 Jan. 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 2-3 fold 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 5-10 fold," though in these individuals such levels could also occur without ritonavir.
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 AIDS TREATMENT NEWS with 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 <=50%).
"***Methadone: A large increase in the concentration of methadone (AUC increase >3-fold) likely. A reduction in dose of >=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 2-3 fold 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."
970221
ATN26503
Copyright © 1997 - AIDS Treatment News. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. Subscription lists are kept confidential. AIDS Treatment News, Subscription and Editorial Office: 1233 Locust St., 5th floor Philadelphia, PA 19107 800/TREAT-1-2 toll-free email: aidsnews@critpath.org http://www.aidsnews.org
Subscription Information: Call 800/TREAT-1-2: Businesses, Institutions, Professionals: $270/year. Includes early delivery of an extra copy by email. Nonprofit organizations: $135/year. Includes early delivery of an extra copy by email. Individuals: $120/year, or $70 for six months. Special discount for persons with financial difficulties: $54/year, or $30 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U.S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207
ÆGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.
ÆGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1990, 2000. ÆGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on ÆGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ÆGIS and the Sisters of Saint. Elizabeth of Hungary, or the party credited as the provider of the content.