Leg Ischemia in a Patient Receiving Ritonavir and Ergotamine
Authors: Antonio Montero
Journal: Annals of Internal Medicine (1999)

Letters16 February 1999Leg Ischemia in a Patient Receiving Ritonavir and ErgotamineAntonio Montero, Adria G. Giovannoni, and Pablo L. TvrdeAntonio MonteroHospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Montero)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Giovannoni)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Tvrde)Search for more papers by this author, Adria G. GiovannoniHospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Montero)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Giovannoni)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Tvrde)Search for more papers by this author, and Pablo L. TvrdeHospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Montero)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Giovannoni)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Tvrde)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-4-199902160-00102 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Ritonavir strongly inhibits the P450-cytochrome isoenzymes CYP3A4, CYP3D6, and CYP2C9 (1) and increases plasma concentrations of drugs sharing this metabolic pathway (2-4). A 40-year-old HIV-infected woman receiving ritonavir, lamivudine, and stavudine self-administrated one antimigraine pill consisting of ergotamine-tartrate, 1 mg, plus caffeine, 100 mg. Several hours later, nausea, vomiting, markedly cold feet, and leg pain developed. Forty-eight hours later, the patient was referred to our service with severe ischemic signs involving both feet.On admission, the patient showed bilateral and symmetrical cyanosis and lividoreticularis involving both feet, ankles, and distal legs. She was hypotensive, with filiform radial pulses and no posterior-tibial or pedial pulses. Her hands and legs were cool to touch. A vascular Doppler examination showed a flow-wave typical of high vascular impedance. Ritonavir therapy was discontinued, and nifedipine plus dextran was given as a circulatory-supporting measure. The patient did not respond, and sodium nitroprusside was given. Ischemic signs quickly regressed and resolved in 24 hours, although pain persisted for several days.Acute ergotamine toxicity may develop with 26 mg of the drug given orally. However, acute toxicity at doses as low as 1 mg has been associated only with parenteral administration; this indicates that toxicity is closely linked to peak serum levels (5). Our case suggests that ergotamine, 1 mg orally, may trigger full-blown ergotism in patients receiving ritonavir. Interactions of ritonavir with otherwise banal prescriptions may be life-threatening, and providers should counsel patients to avoid nonprescribed drugs. Although ergotamine is a widely used antimigraine agent, it is not currently included among drugs with potential interactions listed by the ritonavir manufacturer.We reported this case to the manufacturer and to the Argentine Drug Administration (ANMAT) but not to the U.S. Food and Drug Administration. Neither the manufacturer nor ANMAT had knowledge of previous similar reports.References1. Kempf DJ, Marsh KC, Denissen JF, McDonald E, Vasavanonda S, Flentge CA, et al . ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral availability in humans. Prot Natl Acad Sci U S A. 1995;92:2484-8. CrossrefMedlineGoogle Scholar2. Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, et al . A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group. N Engl J Med. 1995;333:1528-33. CrossrefMedlineGoogle Scholar3. Piscitelli SC, Flexner C, Minor JR, Polis MA, Masur H. Drug interactions in patients infected with human immunodeficiency virus. Clin Infect Dis. 1996;23:685-93. CrossrefMedlineGoogle Scholar4. Bartlett JG. Antiretroviral therapy. In: Bartlett JG. The John Hopkins Hospital 1997 Guide to Medical Care of Patients with HIV Infection. 7th ed. Baltimore: Williams & Wilkins; 1997:63-89. Google Scholar5. Rall TW, Schleifer LS. Oxitocina, prostaglandinas, alcaloides del cornezuelo de centeno y otras drogas; agentes tocolíticos. In: Goodman Gilman A, Goodman LS, Rall TW, Murad F. Las bases farmacológicas de la terapéutica. 7th ed. Buenos Aires: Panamericana Eds; 1986:890-902. Google Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Montero)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Giovannoni)Hospital de Emergencias Dr. Clemente Alvarez; Rosario, Argentina (Tvrde) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInhaled drug therapy development for the treatment of migraineLopinavirANTIVIRAL DRUGS, INCLUDING IMMUNOGLOBULINS AND INTERFERONSThe role of cytochrome P450 in antiretroviral drug interactionsLopinavir and ritonavirTwenty-eight Year Old HIV Positive Male Patient with Ergotism. Interaction of Ergot-alkaloids and Protease-inhibitorsDrug Interactions with Medications Used for HIV/AIDSIrreversible Coma, Ergotamine, and RitonavirErgotism associated with HIV antiviral protease inhibitor therapyDrug Interactions Between Antiretroviral Drugs and Comedicated AgentsAntiviral drugsClinically Significant Drug Interactions with Agents Specific For Migraine AttacksRational Psychopharmacology for Patients With HIV Infection and AIDSDrugs acting on the cerebral and peripheral circulationsIschaemic peripheral neuritis secondary to ergotism associated with ritonavir therapyErgotamine interaction 16 February 1999Volume 130, Issue 4_Part_1Page: 329-330KeywordsDrug interactionsDrugsFood and Drug AdministrationIschemiaMetabolic pathwaysNauseaSodiumTouchToxicityVomiting ePublished: 15 August 2000 Issue Published: 16 February 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...