Interaction of Methadon and Antiretrovirals: a serial case study

EndahWarrozaPutri*, LuhNyoman Alit Aryani **, AnakAyu Sri Wahyuni**

*Psychiatry Resident, Faculty of Medicine Udayana University/Sanglah General Hospital
Bali
**Lecturer staff, Psychiatry Department, Faculty of Medicine Udayana University/Sanglah
General Hospital Bali

Abstract
Introduction: Better adherence to antiretroviral (ARV) therapy has been demonstrated
among people with HIV/AIDS who had ceased injecting opioid and has simultaneously
received opioid agonist therapy including methadone. However, drug interactions involving
methadone and antiretrovirals might affect the course of therapy, hence the necessity to
conduct this study to provide better understanding of this particular topic.
Methods: serial case study
Results: Analysis was conducted for 3 cases of male patients in Bali who simultaneously
received methadone and antiretrovirals: 1) MS, 45 years old, married, Balinese. He initially
received 60 mgmethadone daily. Following the commencement of ARV
Efavirenz/Lamivudine and Duviral/Zidovudine, for the first time he presented complaints
including pain, nausea and sleeplessness. Improvement was reported after he had received
175 mg methadone daily. 2) WS, 48-year-old, married, Balinese, who initially received 40
mg of methadone daily. His commencement of ARV therapy (Nevirapine and Duviral) was
followed by first-time complaints of insomnia and hallucinations. His symptoms improved
after his methadone dose was increased to 95 mg daily. 3). IS, 39 years old, married,
Javanese who initially received 25 mg of methadone daily. Following ARV therapy
Efavirenz/Lamivudine and Duviral/Zidovudine, for the first time he developed pain and
sleeplessness, but his symptoms improved by the time he had 90 mg of methadone daily. In
all three cases, increased methadone dose was needed following the commencement of ARV
therapy.
Discussions: Methadone undergoes biotransformation in the liver by cytochrome P450
enzymes especially CYP3A4 N-demethylation, CYP2B6, and CYP2C19.Efavirenz and
nevirapine also interact consistently by inducing CYP3A4. Studies on methadone
maintenance patients had demonstrated that plasma methadone level decreased following the
commencement of ARV and resulted in withdrawal symptoms including muscle pain, nausea,
insomnia and hallucinations, hence the necessity of higher methadone dose.
Conclusions: This serial case added to the previous findings that antiretrovirals decreases the
plasma methadone level plasma which results in withdrawal symptoms. Among patients who
simultaneously received antiretrovirals and methadone, this interaction should be considered
in determining the optimum methadone dose.
Keywords: Antiretrovirals, methadone, interaction

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