ArticleClinical pharmacology and therapeutics2022
Identifying Clinically Relevant Drug-Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal Detection.
Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 3 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Pooled it
- Clinical outcomes associated with drug-drug interactions involving buprenorphine: a systematic review.Addiction science & clinical practice · 2026Pooled it
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy.Clinical pharmacology and therapeutics · 2024Guideline
- Signals of Venous Thromboembolism Risk from Drug-Drug Interactions Involving Benzodiazepines and Other Sedative Hypnotics: Self-Controlled Case Series Analyses.Clinical drug investigation · 2026Article
- Can Buprenorphine Be Overdosed? The Ceiling Effect and Its Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Medications Associated with Increased Risk of Hypoglycemia in Older Adults on Sulfonylureas: A High-Throughput Case-Crossover-Based Screening Study.Drug safety · 2026Article
- Absence of pharmacovigilance signals for bleeding events associated with warfarin-SSRI drug interactions: a comparative analysis of FAERS and CVARD databases.Therapeutic advances in drug safety · 2026Article
- Risk of opioid overdose associated with concurrent use of hydrocodone and CYP3A4-inhibiting calcium channel blockers: a population-based cohort study.American journal of epidemiology · 2025Article
- ABCB1, SLC22A1, COMT, and OPRM1 genotypes: Study of their influence on plasma methadone levels and clinical response to methadone maintenance treatment in opioid use disorder.Fundamental & clinical pharmacology · 2025Article
- The recent trend of twin epidemic in the United States: a 10-year longitudinal cohort study of co-prescriptions of opioids and stimulants.Lancet regional health. Americas · 2025Article
- Improving the Working Models for Drug-Drug Interactions: Impact on Preclinical and Clinical Drug Development.Pharmaceutics · 2025Article
- Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.Pharmacoepidemiology and drug safety · 2025Review
- Methadone for Chronic Pain: A Review of Pharmacology, Efficacy, and Safety Concerns.Health psychology research · 2025Article
- Thinking Three-Dimensionally: A Self- and Externally-Controlled Approach to Screening for Drug-Drug-Drug Interactions Among High-Risk Populations.Clinical pharmacology and therapeutics · 2024Article
- Natural Products Inhibition of Cytochrome P450 2B6 Activity and Methadone Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Cytochrome P450-2D6 activity in people with codeine use disorder.The pharmacogenomics journal · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs). We performed high-throughput screening for clinically relevant DDIs with methadone or buprenorphine by combining pharmacoepidemiologic and pharmacokinetic approaches. We conducted pharmacoepidemiologic screening via a series of self-controlled case series studies (SCCS) in Optum claims data from 2000 to 2019. We included persons 18 years or older who experienced an outcome of interest during target drug treatment. Exposures were all overlapping medications (i.e., the candidate precipitants) during target drug treatment. Outcomes were opioid overdose, non-overdose adverse effects, and cardiac arrest. We used conditional Poisson regression to calculate rate ratios, accounting for multiple comparisons with semi-Bayes shrinkage. We explored the impact of key study design choices in analyses that varied the exposure definitions of the target drugs and the candidate precipitant drugs. Pharmacokinetic screening was conducted by incorporating published data on CYP enzyme metabolism into an equation-based static model. In SCCS analysis, 1,432 events were included from 248,069 new users of methadone or buprenorphine. In the primary analysis, statistically significant DDIs included gabapentinoids with either methadone or buprenorphine; baclofen with methadone; and benzodiazepines with methadone. In sensitivity analysis, additional statistically significant DDIs included methocarbamol, quetiapine, or simvastatin with methadone. Pharmacokinetic screening identified two moderate-to-strong potential DDIs (clonidine and fluconazole with buprenorphine). The combination of clonidine and buprenorphine was also associated with a significantly increased risk of opioid overdose in pharmacoepidemiologic screening. These DDI signals may be the most important targets for future confirmation studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.