Document 0487
 DOCN  M9440487
 TI    Incidence of cardiac arrhythmias during intravenous pentamidine therapy
       in HIV-infected patients.
 DT    9404
 AU    Eisenhauer MD; Eliasson AH; Taylor AJ; Coyne PE Jr; Wortham DC;
       Department of Medicine, Walter Reed Army Medical Center,; Washington,
       DC.
 SO    Chest. 1994 Feb;105(2):389-95. Unique Identifier : AIDSLINE MED/94139390
 AB    STUDY OBJECTIVE: There have been 15 published cases of probable
       pentamidine-induced torsade de pointes (TdP). A prospective analysis of
       this complication of therapy is valuable considering the high frequency
       of Pneumocystis carinii pneumonia in the AIDS population, and the role
       of pentamidine in its therapy. DESIGN: Open, nonrandomized, prospective
       study of HIV-infected patients receiving intravenous pentamidine in a
       12-month period. SETTING: Walter Reed Army Medical Center, a tertiary
       care, referral-based facility in Washington, DC. PATIENTS: Eighteen
       HIV-infected patients were enrolled with informed consent; four were
       withdrawn from statistical analysis after receiving only one or two
       doses of empiric intravenously administered pentamidine. MEASUREMENTS
       AND RESULTS: Daily 12-lead electrocardiography, echocardiography, weekly
       signal-averaged electrocardiography, and weekly 24-h ambulatory
       electrocardiography were performed on each patient. Of the 14 subjects,
       3 developed TdP. These 3 patients and 2 others developed a prolonged
       rate corrected, QT interval (QTc) to greater than 0.48 s (max QTc mean,
       0.55 s, mean increase, 0.12 s). The QTc prolongation was noted in all
       five patients by the fourth daily dose (4 mg/kg/d) of pentamidine. The
       other 9 patients developed minimal change in QTc intervals throughout
       therapy (max QTc mean, 0.45 s; mean increase, 0.03 s). The maximum QTc
       increase was significantly different between these two cohorts (p <
       0.03). The occurrence of TdP in the subgroup of patients developing
       prolonged QTc intervals to greater than 0.48 s (3 of 5 patients), or a
       change in QTc of greater than 0.08 s (3 of 4 patients) over individual
       baseline also was significant (p = 0.03 and p = 0.01, respectively). No
       baseline clinical variables associated with TdP or QTc prolongation were
       identified. CONCLUSION: Intravenously administered pentamidine
       frequently results in QTc prolongation with a subsequent risk of TdP in
       HIV-infected patients. All patients treated with intravenously
       administered pentamidine should be evaluated with baseline and daily
       ECGs, at least during the first week of therapy, and should be closely
       monitored for a change in the QT interval. An increase in QTc to above
       0.48 s or greater than 0.08 s above baseline carries a significant risk
       for proarrhythmia, and in this instance, continuous electrocardiographic
       monitoring or an alternative antibiotic regimen should be considered.
 DE    Adult  Aged  Arrhythmia/*CHEMICALLY INDUCED  AIDS-Related Opportunistic
       Infections/*DRUG THERAPY  Cohort Studies  Dose-Response Relationship,
       Drug  Electrocardiography/DRUG EFFECTS  Female  Forecasting  Human  *HIV
       Infections  Incidence  Injections, Intravenous  Male  Middle Age
       Pentamidine/ADMINISTRATION & DOSAGE/*ADVERSE EFFECTS  Pneumonia,
       Pneumocystis carinii/*DRUG THERAPY  Prospective Studies  Risk Factors
       Support, Non-U.S. Gov't  Torsades de Pointes/CHEMICALLY INDUCED  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).