Is a low EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) level of 3.829 nanograms per milliliter and a methadone level of 320 nanograms per milliliter in a patient chronically taking methadone (Dolophine) 100 milligrams a concern for diversion?

From the Guidelines

The presence of both methadone (320 ng/ml) and its metabolite EDDP (3.829 ng/ml) in the oral swab does not necessarily indicate diversion in a patient chronically taking 100 mg of methadone. This result is likely not concerning because methadone is primarily excreted in urine, with only small amounts appearing in oral fluid 1. The detection of both the parent drug and its metabolite (EDDP) actually supports appropriate medication use rather than diversion. The ratio between methadone and EDDP can vary widely based on individual metabolism, time since last dose, oral pH, and other factors. While the EDDP level appears low, its presence is significant as it indicates the patient is metabolizing the methadone rather than just briefly holding it in their mouth for testing purposes (which would show methadone but little to no EDDP). For more accurate assessment of adherence, urine testing would be more appropriate as it provides better detection of methadone and its metabolites due to their primary excretion route. If diversion remains a clinical concern, consider implementing more frequent monitoring, directly observed therapy, or additional urine drug screens to establish a clearer pattern of medication use, as suggested by the use of prescription drug monitoring programs to curb prescription opioid misuse 1. Some key points to consider in assessing diversion include:

• The use of a state prescription monitoring program may help identify patients who are at high risk for prescription opioid diversion or doctor shopping 1
• Prescription drug monitoring programs ideally serve multiple functions, including identifying patients who engage in doctor shopping, and patients, providers, or pharmacies who engage in diversion of controlled substances 1
• The detection of methadone and its metabolite in oral fluid, although not the primary route of excretion, can still provide valuable information about medication use and adherence. However, it is essential to consider the limitations and variability of oral fluid testing in assessing medication adherence and diversion. In clinical practice, a comprehensive approach to monitoring and managing patients on methadone, including regular urine drug screens, prescription monitoring, and directly observed therapy, can help minimize the risk of diversion and ensure optimal patient outcomes.

From the FDA Drug Label

Methadone, like morphine and other opioids used for analgesia, has the potential for being abused and is subject to criminal diversion. Methadone can be abused in a manner similar to other opioid agonists, legal or illicit This should be considered when dispensing Methadone Hydrochloride Oral Concentrate in situations where the clinician is concerned about an increased risk of misuse, abuse, or diversion.

The presence of low Eddp and methadone in an oral swab drug screen may indicate diversion or abuse, as methadone has a high potential for abuse and is subject to criminal diversion 2, 2. However, the concentration of methadone in the oral swab is 320 ng/ml, which may be consistent with therapeutic use, especially considering the patient is on chronic methadone 100 mg therapy.

• The EDDP level is low, which could suggest that the methadone is not being fully metabolized, or that the patient is not taking the medication as prescribed.
• The methadone level is detectable, which could indicate that the patient is taking the medication, but the level may not be consistent with the prescribed dose. It is essential to consider the patient's medical history, treatment plan, and other factors to determine whether the results indicate diversion or abuse. Key points to consider:
• Methadone abuse potential: Methadone has a high potential for abuse and is subject to criminal diversion.
• Therapeutic use: The patient is on chronic methadone 100 mg therapy, which may be consistent with the detectable methadone level.
• EDDP level: The low EDDP level may suggest that the methadone is not being fully metabolized or that the patient is not taking the medication as prescribed.

From the Research

Methadone and EDDP Detection

• The oral swab drug screen shows low EDDP (3.829 ng/ml) and methadone (320 ng/ml) detection in a patient on methadone 100 mg chronically 3, 4.
• Methadone is metabolized to EDDP, which is then excreted in the urine 4, 5.
• The concentration of methadone and EDDP in urine can vary depending on several factors, including urine pH 4, 5.

Concern for Diversion

• A low EDDP level in the oral swab drug screen may not necessarily indicate diversion, as EDDP is primarily excreted in the urine 4, 5.
• However, the presence of methadone in the oral swab drug screen at a concentration of 320 ng/ml may suggest that the patient is taking the medication as prescribed 3, 5.
• It is essential to consider the patient's medical history, treatment plan, and other factors before making any conclusions about diversion 6, 7.

Urine vs. Plasma Samples

• Urine samples are often used to monitor methadone treatment, as they provide a more accurate reflection of the patient's methadone levels over time 3, 4, 5.
• Plasma samples can also be used to monitor methadone levels, but they may not provide as complete a picture of the patient's treatment adherence 3, 5.
• The choice of sample type (urine or plasma) may depend on the specific clinical context and the goals of the testing 3, 4, 5.