Methadone cardiac arrhythmias

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

P450 enzyme inhibition by SSRIs may also augment effects of alcohol, tramadol, methadone, terfenadine (danger of cardiac arrhythmia), -caine anaesthetics and theophylline. 

Drug-drug interactions Eighteen patients who were given telaprevir and methadone showed no decrease in methadone concentration or any signs of opiate withdraw [55 ]. A meffl-analysis of FAERS from 1997 to 2011 showed increased risk of cardiac arrhythmias in patients on antiretroviral drugs and methadone [43 ]. 

Kao D, Bucher Bartelson B, Khatri V, Dart R, Mehler PS, Katz D, et al. Trends in reporting methadone-associated cardiac arrhythmia, 1997-2011 an analysis of registry data. Annals of internal medicine May 21,2013 158(10) 735-40. 

Deaths, cardiac and resp have been reported during initiation and conversion of pain pts to methadone Tx from Tx w/ other opioids Uses Severe pain detox w/ maint of narcotic addiction Action Narcotic analgesic Dose Adults. 2.5-10 mg IM q3-8h or 5-15 mg PO q8h titrate as needed Feds. 0.7 mg/kg/24 h PO or IM -s- q8h T slowly to avoid resp depression X in renal impair Caution [B/D (prolonged use/high doses at term), + (w/ doses =/> 20 mg/24 h)], severe liver Dz Disp Tabs, inj SE Resp depression, sedation, constipation, urinary retention, T QT interval, arrhythmias Interactions T Effects W/ cimetidine, CNS depressants, protease inhibitors EtOH T effects OF anticoagulants, antihistamines, barbiturates, glutethimide, methocarbamol ... 

Methadone undergoes significant hepatic metabolism by N-demethylation and cycliza-tion to form pyrrolidines and pyrroline (23). Propoxyphene is also hepatically metabolized predominantly by N-demethylation and renally eliminated. The metabolite norpropoxy-phene is cardiotoxic and produces arrhythmias and pulmonary edema that have led to reports of cardiac arrest and death (59). This is especially problematic because of the long half-life of norpropoxyphenethat accumulates with repeated doses of the parent drug. Methadone is excreted in the urine but also in the bile (23). 

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