Effect of buprenorphine and antiretroviral agents on the QT interval in opioid-dependent patients.
BACKGROUND
Cardiac arrhythmias have been linked to treatment with methadone and levacetylmethadol. HIV-positive patients often have conditions that place them at risk for QT interval prolongation including HIV-associated dilated cardiomyopathy, coronary artery disease as a consequence of highly active antiretroviral (ARV) therapy-associated metabolic syndrome, and uncorrected electrolyte abnormalities. As of February 14, 2006, no cases of adverse events related to QT interval prolongation have been reported in patients receiving buprenorphine, an opioid partial agonist and the newest drug approved for the treatment of opioid dependence.


OBJECTIVE
To evaluate the effects of buprenorphine/naloxone alone and in combination with 1 of 5 ARV agents (efavirenz, nelfinavir, delavirdine, ritonavir, lopinavir/ritonavir) on the QT interval.


METHODS
This study was prospective, open-label, and within-subject in design, with subjects serving as their own controls. In 50 HIV-negative, opioid-dependent subjects, electrocardiogram recordings were obtained at baseline, after receiving buprenorphine/naloxone for 2 weeks, and then following buprenorphine/naloxone plus ARV administration for 5-15 days at steady-state. QTc interval measurements were compared using mixed-model, repeated-measures ANOVA. Recent cocaine use and gender were considered covariates.


RESULTS
Buprenorphine/naloxone alone and often in the presence of evidence for recent use of cocaine did not significantly alter the QT interval (p = 0.612). Buprenorphine/naloxone in combination with ARVs caused a statistically, but not clinically, significant increase (p = 0.005) in the QT interval. Subjects receiving buprenorphine/naloxone in combination with either delavirdine or ritonavir had the greatest increase in QTc intervals.


CONCLUSIONS
Prolonged QT intervals were not observed in opioid-dependent subjects receiving buprenorphine/naloxone alone. QT interval increases were observed with buprenorphine/naloxone in combination with either delavirdine or ritonavir, which inhibit CYP3A4.
Baker
Jennifer R
JR
Addiction Psychiatry, Virginia Commonwealth University, Richmond, 23298, USA.
Best
Al M
AM
Pade
Patricia A
PA
McCance-Katz
Elinore F
EF
D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D002047:Buprenorphine / Q000009:adverse effects* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000009:adverse effects / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000150:complications / Q000503:physiopathology* / Q000534:rehabilitation; D011446:Prospective Studies
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human