The opioid use disorder (OUD) epidemic is a major public health crisis in the United States.1 Naltrexone, methadone, and buprenorphine are first-line therapies for OUD and have high success rates.2 While studies have shown that naltrexone is effective, patients must achieve opioid detoxification and maintain 7 to 10 days of total abstinence to avoid a precipitated opioid withdrawal before it can be prescribed.3 Methadone does not require detoxification or a period of complete abstinence, but must be prescribed in special clinics and requires daily observed dosing for the first 90 days,4 though these requirements have been relaxed during the COVID-19 pandemic. In contrast, buprenorphine (with or without naloxone) can be used in office-based settings, which significantly improves the accessibility and availability of treatment for patients with OUD. Clinician knowledge and comfort prescribing buprenorphine are limiting factors to treatment.5 Increasing the number of clinicians proficient with buprenorphine management can improve access to effective treatment and recovery services, which is critical for patients with OUD.
Multiple resources are available for clinicians to learn how to prescribe buprenorphine, but clear guidance on laboratory testing for patients receiving buprenorphine is limited. To safely and effectively prescribe buprenorphine, clinicians need to understand its pharmacology (Box 16-9) and how laboratory testing influences treatment. In an effort to increase clinician knowledge of and proficiency with buprenorphine, this article answers 10 common questions about laboratory monitoring of patients receiving this medication.
For patients with opioid use disorder, buprenorphine is indicated for opioid detoxification and maintenance. Oral formulations of buprenorphine (including tablets and buccal films) have long durations of action, and when dosed daily can prevent opioid withdrawal for at least 48 hours.6 The recommended formulation is a combination of buprenorphine and naloxone, because this formulation is associated with a lower risk of misuse and diversion compared to formulations containing only buprenorphine.7 However, buprenorphine alone can be effective in patients who experience adverse effects from or are unable to tolerate the combination buprenorphine/naloxone formulation.7 Despite the addition of naloxone, buprenorphine prescriptions may still be misused and diverted, so close monitoring is necessary.
Buprenorphine is metabolized by the cytochrome P450 system (CYP) (primarily CYP3A4) to its active metabolite, norbuprenorphine, both of which are primarily excreted in feces.8 However, small quantities of buprenorphine and norbuprenorphine are excreted in the urine,9 which makes urine specimen the best choice to monitor buprenorphine use for therapeutic purposes.
1. Why is laboratory monitoring important?
Proper laboratory monitoring discourages illicit substance use, encourages medication adherence, and influences treatment modifications. Patient self-reporting on medication compliance may be inaccurate or unreliable.10 Patients who relapse or use other illicit substances may also be reluctant to disclose their substance use.11
On the other hand, laboratory tests are objective markers of treatment outcome and adherence, and can verify a patient’s self-report.12 When used appropriately, laboratory monitoring can be therapeutic. It holds patients accountable, especially when used in conjunction with contingency management or other behavioral therapies.13 Laboratory monitoring is the most reliable method of determining if patients are abstaining from opioids and other illicit substances, or if the treatment plan requires revision.
2. Which tests should I order?
When initiating or maintaining a patient on buprenorphine, order a general urine drug screen (UDS), urine opioid screen (availability varies by institution), urine creatinine levels, urine buprenorphine/norbuprenorphine/naloxone/creatinine levels, urine alcohol metabolite levels, and a urine general toxicology test. It is also recommended to obtain a comprehensive metabolic panel (CMP) before starting buprenorphine,14,15 and to monitor CMP values at least once annually following treatment. Patients with a history of IV drug use or other high-risk factors should also be screened for hepatitis B, hepatitis C, and HIV.14,15
A general UDS can determine if opiates, amphetamines, cocaine, marijuana, or other common illicit substances are present to identify additional substance use. The proficiency of a general UDS may vary depending on the panels used at the respective institution. Some clinics use point-of-care UDS as part of their clinical management; these tests are inexpensive and provide immediate results.16 A basic UDS typically does not detect synthetic opioids due to the specificity of conventional immunoassays. As a result, specific tests for opioids such as oxycodone, hydrocodone, hydromorphone, oxymorphone, fentanyl, and methadone should also be considered, depending on their availability. Though buprenorphine treatment may trigger a positive opiate or other opioid screen,17 buprenorphine adherence should be confirmed using several urine tests, including creatinine, buprenorphine, norbuprenorphine, and naloxone urine levels.
In addition to screening for illicit substances and buprenorphine adherence, it is important to also screen for alcohol. Alcohol use disorder (AUD) is highly comorbid with OUD,18 and is associated with worse OUD treatment outcomes.19 Alcohol use may also affect liver function necessary for buprenorphine metabolism,8 so urine alcohol metabolites such as ethyl glucuronide and ethyl sulfate, serum transaminases, and gamma-glutamyl transferase should also be obtained.
Continue to: How frequently should patients be tested?