September 9, 2013

Methadone Linked to Prolonged QTc Interval

September 5, 2013

Keith Henry, MD reviewing Vallecillo G et al. Clin Infect Dis 2013 Aug 14. Keith Henry, MD

A prolonged QTc interval in HIV-infected patients on methadone was associated with higher methadone doses, hepatitis C liver disease, and ART-naive status. Keith Henry, MD

Illicit opioid use is associated with increased risk for HIV infection. Methadone is an effective drug for the long-term management of opioid-dependent HIV-infected patients, although safety concerns have been identified (i.e., cardiac arrhythmias such as prolonged QTc interval and torsades de pointes).

In a cross-sectional study, HIV-infected patients on methadone maintenance therapy followed at a single outpatient clinic in Spain underwent 12-lead electrocardiography 24 hours after supervised methadone administration. Individuals with known cardiac disease, drug-positive urine tests, electrolyte abnormalities, or changes in antiretroviral therapy (ART) regimen or methadone dose in the preceding 2 months were excluded.

Of the 91 study participants (64% men; 100% white; median age, 44.5), 68 (75%) were on ART; the regimen for 56 of them included a boosted protease inhibitor. The median nadir and current CD4 counts were 232 and 438 cells/mm3, respectively. The median methadone dose was 70 mg/day, and the mean QTc interval was 438 milliseconds. A prolonged QTc interval (>450 ms) was documented in 33 participants (36%), including 3 with intervals >500 milliseconds. On multiple linear regression analysis, higher methadone dose, chronic hepatitis C–induced cirrhosis, and ART-naive state were associated with a prolonged QTc interval.


In a cross-sectional study without a control population, it is difficult to fully assess the clinical risk posed by the reported QTc abnormalities.

A prolonged QTc interval was associated with being antiretroviral-naive, but was not observed with use of protease inhibitors (which have been linked in other studies to QTc prolongation). Complicating the situation was the common use of other QTc-prolonging drugs (58% of the participants were taking antipsychotics, antidepressants, antiepileptics, or antibiotics). The study findings remind clinicians of the possible effects of drugs on cardiac conduction and the need to be diligent in monitoring for potential problems (often including input from an HIV-savvy pharmacist, as well as baseline and follow-up electrocardiograms).


Vallecillo G et al. Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. Clin Infect Dis 2013 Aug 14; [e-pub ahead of print]. (


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