Methadone and buprenorphine for the management of opioid dependence in pregnancy.

Filed under: Methadone Side Effects

Drugs. 2012 Apr 16; 72(6): 747-57
Jones HE, Finnegan LP, Kaltenbach K

This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk?:?benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient’s opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying multifaceted complexities of their patient’s lives.
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Treatment of hepatitis C as prevention: a modeling case study in Vietnam.

Filed under: Methadone Side Effects

PLoS One. 2012; 7(4): e34548
Durier N, Nguyen C, White LJ

Treatment of hepatitis C (HCV) is very effective, achieving a cure in 50-90% of patients. Besides its own good for individuals, this most likely translates in reduced transmission, but this phenomenon has yet to be fully explored.In this mathematical modeling study done in the context of Vietnam, we estimated the public health benefit that HCV therapy for injecting drug users (IDUs) may achieve. Treatment coverage of 25, 50 and 75% of chronically HCV-infected IDUs (4 years into infection) is predicted to reduce the chronic HCV viremia prevalence respectively by 21, 37 and 50%, 11 years after full scale up to the intended coverage. At a constant 50% coverage level, earlier treatment, 3, 2, and 1 year into infection is predicted to reduce the chronic HCV viremia prevalence by 46, 60 and 85%. In these later 3 scenarios, for every 100 treatment courses provided, a total of respectively 50, 61 and 94 new infections could be averted. These benefits were projected in the context of current low coverage of methadone maintenance therapy and needles/syringes exchange programs, and these services expansion showed complementary preventive benefits to HCV therapy. The program treatment commitment associated with the various scenarios is deemed reasonable. Our model projections are robust under adjustment for uncertainty in the model parameter values.In this case study in Vietnam, we project that treatment of HCV for injecting drug users will have a preventative herd effect in addition to curing patients in need for therapy, achieving a substantial reduction in HCV transmission and prevalence.
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Evaluating the Relationship of Methadone Concentrations and EDDP Formation in Chronic Pain Patients.

Filed under: Methadone Side Effects

J Anal Toxicol. 2012 May; 36(4): 239-49
Leimanis E, Best BM, Atayee RS, Pesce AJ

Methadone is used to treat moderate to severe pain in patients not responsive to non-narcotic analgesics and for maintenance treatment of opioid addiction. Methadone is primarily metabolized by N-demethylation to an inactive metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) by CYP3A4 and CYP2B6. Establishing expected concentrations for metabolism of methadone to EDDP using urine excretion data may be useful for monitoring “medications” and toxicity. Urine specimens from chronic pain patients were collected during routine clinic visits. Methadone and EDDP were quantified by liquid chromatography-tandem mass spectrometry. Approximately 8,000 subjects who reported taking methadone had creatinine concentrations ?20 mg/dL, and excreted concentrations of methadone and EDDP above ?100 ng/mL were selected. The median methadone urine concentration was 3.03 mg/g cr. Ninety-five percent of the population had concentrations between 0.175 and 20.9 mg/g cr. EDDP was, on average, twice the methadone concentration. The wide variance in relationship of methadone to its metabolite was not concentration-dependent. Variability between subjects was larger than variability within subjects. As the urinary pH increased, the proportion of excreted EDDP increased, implying a preferred excretion of EDDP.
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