Is it time to drug test your chronic pain patient?

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Applied Evidence

Is it time to drug test your chronic pain patient?

J Fam Pract. 2010 November;59(11):628-633

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References

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Lab variability and technical limitations. Some urine drug panels may not have a lower limit sufficient to detect small quantities of opioids. Others may not detect certain substances, notably the semisynthetic and synthetic opioids (TABLE 3).¹⁹ Oxycodone is a prime example of a commonly prescribed semisynthetic opioid that does not appear on many urine test panels.⁸

In addition, individual drugs within a class may not be identified on UDT panels. When confirmation of a specific drug or metabolite is needed, serum testing must be performed.⁸

TABLE 3
Classifying opioids¹⁹

Natural	Semisynthetic	Synthetic
Codeine	Hydrocodone	Fentanyl
Morphine	Hydromorphone	Meperidine
	Oxycodone	Methadone
		Propoxyphene

Differences in metabolism. Genetic differences in metabolism can also skew the results of UDT. Codeine, which relies on hepatic metabolism via cytochrome P450 2D6 for conversion to morphine, is the classic example; cytochrome P450 2D6 is a polymorphic enzyme, meaning that it manifests with different activity levels in different people. Patients who are poor metabolizers (an estimated 5%-10% of Caucasians, 1%-5% of Asians, 2%-7% of African Americans, and 2%-6% of Hispanics²⁰) will convert very little codeine to morphine; conversely, those who are rapid metabolizers will convert extensive amounts. A rapid metabolizer taking codeine as prescribed may therefore have a negative UDT; in an average metabolizer taking the same dose, both codeine and morphine will be detected.²⁰

FAST TRACK

Individual drugs within a class may not be identified on urine drug panels, so serum testing must be performed if confirmation of a particular agent is needed.

Drugs’ half-lives. Opioids with a short half-life (TABLE 4)^9,21 may not appear in the urine if the test is done several hours after the last dose. On the other hand, some opioids may have an extended half-life in patients with liver or kidney disease, and may appear in the urine longer than would be expected.⁹

False-positive results. Substances that may cause false positives for opioids on a urine test include dextromethorphan, papaverine, poppy seeds and oil, quinine, quinolones, rifampin, and verapamil.¹⁰

FAST TRACK

Synthetic and semisynthetic opioids, such as fentanyl and oxycodone, may go undetected in urine drug testing.

False-negative results. Many of the problems already discussed can lead to false-negative results, including the panel’s failure to detect semisynthetic and synthetic opioids, rapid metabolism (most notably, of codeine), the timing of the test relative to the dose, and adulteration of the specimen. Thus, a negative test result in a patient on opioid therapy does not necessarily mean that he or she is noncompliant—and certainly is not proof of diversion.

Because of the variables that affect UDT outcomes, unanticipated results should be reviewed with the patient and possibly, with the lab, and viewed within the therapeutic context. When more definitive information is needed, serum testing may be performed as follow-up. While serum testing can detect drugs and their metabolites ingested within hours, it is not widely used on initial screening because it is a more invasive procedure with higher associated costs.¹³

CASE 2 Upon further discussion with Don F, the physician orders a serum oxycodone test, which shows a level of 10 ng/mL. The physician notes that serum testing is more appropriate than UDT for Don because of the inconsistent detection of oxycodone in urine.

TABLE 4
Pharmacokinetics of common opioids: Time detectable in urine^9,21

Drug (half-life)	Time detectable in urine	Comment
Codeine (2.5-3 h)	48 h	Pharmacogenetic-dependent effects may affect detection
Fentanyl Transdermal (17 h) Submucosal (7 h)	Not usually detected in urine (lack of metabolites)	Excretion of transdermal fentanyl can last days
Hydromorphone IR (2.3 h) ER (18.6 h)	2-4 d	Significant interpatient variability
Methadone (8-59 h)	3 d
Morphine (1.5-2 h)	48-72 h	90% eliminated within 24 h
Oxycodone IR (3.2 h) ER (4.5 h)	Often not detected in urine	High-fat meals may increase serum concentrations of ER formulation
Propoxyphene Parent drug (6-12 h) Metabolite (30-36 h)	6-48 h
ER, extended release; IR, immediate release.

CORRESPONDENCE Sarah McBane, PharmD, CDC, BCPS, University of California, San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, 9500 Gilman Drive, La Jolla, CA 92023; smcbane@ucsd.edu