Consider the following scenarios:
A 65-year-old woman with osteoporotic compression fractures is prescribed acetaminophen with codeine, 30 mg. She has filled two prescriptions for 30 tablets in the last 6 months and is requesting a refill. The PDMP report is consistent with your medical records. Prior to refilling the prescription you order a urine drug test. The results were negative for codeine, but positive for morphine and low levels of hydrocodone.
A 35-year-old man with sickle cell disease presents with acute bronchitis and a severe cough. He is being prescribed hydrocodone by a pain management physician. Prior to prescribing a cough syrup containing codeine, you obtain a urine drug test. The screening test is positive for opioids and amphetamines. A confirmatory test is performed that shows the presence of hydrocodone as well as low levels of hydromorphone and methamphetamine.
If you are not certain how to proceed in these cases, then read on.
Drug testing of patients receiving opioids for treatment of pain is not only an important clinical tool to assure patient safety, it is also required by state regulations under certain circumstances. The conditions under which Georgia physicians are required to perform drug testing in order to satisfy the minimum standards of medical practice for licensure are contained in Georgia Composite Medical Board Rule 360-3-.06 and summarized below. Patients receiving opioids for chronic pain under those conditions are required to sign an agreement that includes consent for drug testing as a condition for continued treatment.
Drug testing is required when:
- Prescribing a Schedule II or III controlled substance for 90 consecutive days or greater in a given year for the treatment of chronic pain
- The condition is not terminal
- The patient is not in a hospice, hospital or nursing home
Frequency of drug testing:
- Morphine equivalent dose 30 mg/day or less – at least once a year
- Morphine equivalent dose greater than 30 mg/day – at least every three months on a random basis
- If the physician determines there is a substantial hardship for the patient, the frequency of testing may be reduced to once a year regardless of dose. The hardship must be documented in the patient’s record.
Types of Drug Testing
Drug testing may be performed on urine, sweat, serum, saliva or hair. Urine is the most common medium for testing due to the ease of collection, storage and analysis; however, patients who are unable to provide a urine sample when requested should be tested using other means. Tests fall into two broad categories: Screening and Confirmatory.1
Screening tests may be performed in the office, with the results available at the time of the patient’s visit. This may be accomplished with dipstick-type devices or an automated multi-channel analyzer employing enzyme immunoassay (EIA). The results of these tests indicate the presence of drugs in certain broad categories such as opioids, benzodiazepines, THC, cocaine and methadone. Unexpected results on screening tests require further analysis.
The most common form of confirmatory testing is performed using a liquid or gas chromatograph column that is coupled to a mass spectrometer (LC/MS or GC/MS). Due to the time required to prepare and calibrate this equipment, the testing is performed on batches of samples, with a turnaround time of several days. The tests are highly sensitive and are capable of identifying specific drug molecules and their relative concentrations within the sample.
Strict chain of custody, required for forensic testing, is not necessary for clinical purposes. Nonetheless, the samples should be analyzed for temperature, creatinine concentration and the presence of adulterants to detect substitution, dilution or other forms of tampering.
Understanding the Results
Clinical interpretation of the test results requires a basic understanding of drug metabolism. Concentrations of the parent drug are highest shortly following administration, with concentration of metabolites peaking later. Most drugs or their metabolites may be detected in the urine up to 72 hours following ingestion. In patients who take medications intermittently, it is not unusual to detect only the metabolites if it has been 24 hours or more since the drug was last taken. Heavy or chronic use may result in drugs being detected for a much longer time.
There are several drugs whose metabolites are themselves commonly prescribed drugs.2 For example, codeine is metabolized to morphine and hydrocodone (Lortab, Vicodin), and hydrocodone is metabolized to hydromorphone (Dilaudid). Diazepam (Valium) is metabolized to two other prescription sedatives, temazepam (Restoril) and oxazepam (Serax).
Significant levels of the metabolites may remain after the parent drug can no longer be detected. Knowing the relative levels of the detected drugs as well as the history of the time since ingestion is helpful in determining whether the results are consistent with normal metabolism or indicative of abuse. An interesting sidelight is that genetic variations in levels of activity of some of the Cytochrome P450 enzymes (especially CYP2D6) may create unexpected results. Enzyme activity can be assessed using pharmaco-genetic testing.
Commonly Prescribed Drugs and their Metabolites
Drug – Metabolite(s)
morphine – hydromorphone
codeine – morphine, hydrocodone
hydrocodone – hydromorphone
oxycodone – oxymorphone
fentanyl – norfentanyl
tramadol – O-desmethyltramadol
diazepam – Nordiazepam, oxazepam, temazepam
Drugs of Abuse
Proper monitoring of patients who are prescribed opioids requires screening for evidence of concurrent drug abuse. Most clinical panels will test for the following substances:
Alcohol. Ethyl alcohol itself is detectable in the urine only for 1-2 hours after it is last detectable in blood. Its metabolite, ethyl glucuronide, can be detected up to 80 hours after alcohol ingestion.
Amphetamines. A confirmatory test is required to differentiate between prescription amphetamines and methamphetamine. A positive result for methamphetamine on a confirmatory test should be followed by yet another test to evaluate which stereoisomers are present; d-methamphetamine is the psychoactive form of the drug, while l-methamphetamine is an ingredient in some over-the-counter cold medications.
Cocaine. Rapidly metabolized by plasma esterases, cocaine is only detectable for about five hours after use. Its metabolite, benzoylecgonine can be detected for up to four days.
Heroin. Since heroin is rapidly metabolized, testing for its metabolite, 6-monoacetylmorphine, can detect its use.
THC. Can be detected for up to 30 days in heavy users.
Acting on the Test Results
Any unexpected test result requires follow-up. An abnormal screening test should be followed by a confirmatory test. The best course of action should be determined after assessment of all relevant clinical information and review of the PDMP database.
Rule 360-3-.06 does not cover all possible clinical situations, but does require the following:
- The physician shall respond to any abnormal result of any monitoring, and such response shall be recorded in patient’s record.
- When a physician determines that a patient for whom he/she is prescribing controlled scheduled substances is abusing the medication, then the physician shall make an appropriate referral for treatment for substance abuse.
- When a physician determines that a new medical condition exists that is beyond their scope of training, he/she shall make a referral to the appropriate practitioner.
Both of the clinical scenarios at the beginning of the article require additional action by the physician. In each instance, the test results (not just the fact that testing was done) should be noted in the patient’s record.
In the first scenario, an explanation to the effect that morphine and hydromorphone were expected metabolites of codeine and that the results were consistent with intermittent use of the medication would be appropriate, along with a notation that a review of the PDMP showed no other opioid prescriptions.
In the second case, again the note should contain an explanation that hydromorphone is an expected metabolite of hydrocodone. In addition, the presence of methamphetamine needs to be addressed and requires that a third test be performed to assess the relative concentrations of the d and l stereoisomers. The presence of greater than 20 percent d-methamphetamine indicates illegal drug use. Less than 20 percent d-methamphetamine would be consistent with use of an over-the-counter decongestant. If further information supports the diagnosis of drug abuse, the record would also need to indicate that a referral was made to an appropriate specialist or treatment program.
2. Milone, MC (2012) Laboratory testing for prescription opioids. J. Med Toxicol. (2012) 8:408-416
3. Smith, HS (2009) Opioid metabolism. Mayo Clin Proc. (2009) 84(7):613-624