Gerald Aronoff, MD, medical director, Carolina Pain Associates, and medical director, North American Pain & Disability Group, Charlotte, North Carolina, doesn’t prescribe opiates to his patients until he first screens them for any illegal substance, including tetrahydrocannabinol (THC), a psychoactive ingredient in cannabis.

And he recommends other doctors do the same.

“I will not write a prescription for opiates until the patient has clearly negative urine drug screens,” Dr Aronoff told Medscape Medical News.

At a session here during the American Academy of Pain Medicine (AAPM) 2016 Annual Meeting, Dr Aronoff discussed issues related to marijuana and motor vehicle accidents, and legal decisions that appear to protect employers wanting a drug-free workplace. These, along with the problems of diversion, abuse, and misuse of controlled substances, might affect prescribing physicians, he said.

Chances are that some patients in any pain medicine practice are using marijuana. Dr Aronoff described what might be a typical pain patient: That patient has back pain, has undergone multiple back surgeries, has been prescribed oxycodone and other pain medicine, and has numerous comorbidities.

“In addition to the medications you’re prescribing, there are multiple other physicians involved, treating the diabetes” and other disorders, said Dr Aronoff. “The patient then decides he’s going to add marijuana. So you have some decisions to make,” and you have to determine which are wise ones, he said.

Dr Aronoff stressed that the potency of the marijuana available today “is magnitudes stronger” than that available back in the 1960s and 1970s.

Along with fellow session speakers, Dr Aronoff outlined extensive research on the physical and neuropsychological effects of marijuana. These include dizziness, drowsiness, psychomotor and perception alterations, and orthostatic hypotension.

In a driving situation, cannabinoids can affect reaction time, vision, and attention. Syeda Sabah A. Kareem, PharmD, St. Joseph’s Hospital, Tampa, Florida, pointed out that simulated and on-road studies have shown effects on perceptual processes, maintaining speed, response to stimuli, and estimation of time and distance.

More Accidents

These factors might explain the increase in motor vehicle collisions related to marijuana use. Dr Aronoff referred to 2014 statistics from Seattle, Washington, showing a tripling of fatal motor vehicle accidents involving marijuana.

These statistics also showed that drugged driving was involved in more than 28% of deaths and that combining alcohol and marijuana increases the chances of a fatality by 24%.

Functional MRI data also show decreased psychomotor function and a significant level of driving impairment, even in patients with relatively low (1.5 ng/mL) THC concentrations, said Dr Aronoff.

Dr Kareem noted that the National Highway Traffic Safety Administration issued a statement in 2014 that said “psychomotor impairment can persist even after the perceived high has dissipated.”

Are physicians who prescribe medical marijuana to patients who are in an accident liable? Maybe, said Dr Aronoff.

He used the hypothetical situation of a physician who writes a prescription for medical marijuana for a patient who, with a high plasma concentration of THC, gets into a car accident that involves a death.

In this scenario, a physician might be brought in for a wrongful death case and on the witness stand be asked to respond to articles outlining various factors related to marijuana intoxication. “You’re asked, one by one, are you aware of the potential to have impaired reaction time, to have a lapse of concentration, to have sensory changes, to have perceptual changes, et cetera, and of course, you need to acknowledge that you are aware,” said Dr Aronoff.

“The question is, are you in a defensible position, having written the prescription knowing the risks?”

Dr Aronoff suggests noting in a patient’s records any concerns and recommendations about driving.

In addition to drug screening, Dr Aronoff might also carry out what some of his colleagues have dubbed the “Aronoff” test. When patients aren’t expecting it, he throws a sponge rubber ball at their head. If they reach up to block the ball, it’s an indication that their concentration and attention are intact.

Workplace Risks

Impairments related to marijuana use may extend to the workplace. Statistics from the National Institute on Drug Abuse show that compared with nonusers, marijuana users have 85% more work-related injuries and 78% greater work absenteeism, and their chance of an industrial accident is increased by 55%, Dr Aronoff noted.

“Drugged employees increase medical costs by 300%,” he told delegates.

Dr Aronoff discussed several court cases concerning use of marijuana and the workplace. One involved an employee in Colorado, a state that allows medical marijuana, who had a prescription for it to treat his back spasms. His employer, which maintained a drug-free work zone and instituted random drug tests, terminated this worker’s employment when he tested positive.

Last year, the state’s Supreme Court upheld the decision in this case to terminate the employee. The court indicated that medical marijuana use is unlawful under federal law and that the employee can’t seek protection under Colorado’s lawful off-duty activities statute.

On the basis of the available data, Dr Aronoff does not recommend prescribing medical marijuana. “Even if I could, I wouldn’t,” he told Medscape Medical News. His state, North Carolina, does not have legalized marijuana.

“I’m interested in functional restoration, meaning getting people back to work, and being able to drive safely, and until there’s evidence that there is a form of marijuana that does not increase risks for driving accidents or work accidents, I won’t prescribe it.”

Having a card allowing a patient access to medical marijuana “means nothing” as such cards are relatively easy to acquire, he said.

On the other hand, emerging research shows that patients who are on “stable doses of sustained-acting, time-release opiates” generally don’t pose hazards on the road or on the job, noted Dr Aronoff.

Another speaker, Alfonso Romero-Sandoval, MD, PhD, director of research, and associate professor of pharmaceutical sciences, Presbyterian College School of Pharmacy, Clinton, South Carolina, said there are no guidelines for using opiates and marijuana together.

“We know the risk factors to consider before prescribing opioids, but we don’t have a list for medical cannabis,” he said.

There could be potential additive effects for using both, such as sedation, hypotension, and motor impairment, said Dr Romero-Sandoval.

American Academy of Pain Medicine (AAPM) 2016 Annual Meeting. Concurrent session. Presented February 21, 2016.

The move, announced at press briefing Tuesday, is part of a handful of changes that the agency hopes will curb an ongoing prescription painkiller epidemic, including a label clarification about the risks of abuse and death with the drugs, a requirement for additional postmarketing studies, and a boxed warning about the risks of neonatal opioid withdrawal syndrome.

“Opioids are important pain relieving medications that provide significant benefits when used appropriately,” Douglas Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research (CDER), said during a press briefing. “But they have significant risks associated with inappropriate patient selection and improper use, whether accidental or intentional.”

The announcement is the culmination of a series of agency meetings and research on opioid safety that were prompted in large part by a Citizen’s Petition from the groups Physicians for Responsible Opioid Prescribing (PROP) and Public Citizen.

The petition was signed by nearly 40 doctors, researchers, and public health officials, and aimed to make it more difficult for drug companies to market opioids for chronic, noncancer pain. Among other criteria, it asked FDA to strike the word “moderate” from opioid labels in chronic pain.

Throckmorton said changing the indication to “pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate” will further discussions between clinicians and patients about their eligibility for the drugs.

“The change reflects a departure from an indication that was based on a severity scale and transitions to a more specific use,” Throckmorton said. “Patients in pain will not only be assessed by a rating on a pain scale, but a more thoughtful determination of pain.”

Greg Anderson, MD, a primary care physician at the Mayo Clinic in Rochester, Minnesota welcomed the FDA action.

“In the absence of malignancy related pain, examples where long acting opioids can be justified are relatively few and far between,” Anderson, wrote in an email.

James A. McGowan, MD, of the center for interventional pain medicine at Mercy Medical Center in Baltimore, said chronic pain treatment is challenging but he warned that “too often these medications are prescribed without adequate thought being given to their serious side effects, their marginal effectiveness in treating long term pain, and the fact that these medications often end up doing more harm than good.”

In an email, McGowan acknowledged that “small subsets of patients may benefit from chronic opiate use” but he added that the new labels would serve as a necessary reminder “to both patients and physicians that the use of these medications must be done very cautiously and only after carefully weighing the potential risks and benefits.”

Randy Wexler, MD, MPH, of Ohio State University, said the changes were “appropriate” adding that he only “rarely” prescribes long-acting opioids for chronic pain.

“This will have no impact on my practice other than as support for my discussion with patients as to why such medications are often not indicated,” Wexler said in an email to MedPage Today.

Kevin Hill, MD, MPH, psychiatrist-in-charge at McLean Hospital’s alcohol and drug abuse program in Belmont, Massachusetts, wrote that he has experience treating opioid addiction. “I’ve seen patients that have been prescribed long-acting opioids inappropriately on an “as-needed” basis, and inappropriate prescribing can have the unintended effect of starting someone on a path to addiction,” Hill wrote in an email to MedPage Today. “Opioid addiction is very difficult to treat, so I appreciate the FDA’s effort to limit the risk associated with these medications.”

The updated label will further clarify that the drugs should be used as a last resort in patients who have no other options, due to their risk of addiction, abuse, and misuse even at recommended doses, as well as greater risk of overdose and death.

The FDA is also requiring postmarketing studies to further assess those risks. Throckmorton said the agency expects companies to collaborate on the requisite trials in order to get more information as efficiently as possible.

He added that it became apparent through earlier meetingson the issue that there were not enough data available on the risks of long-term opioid use, as earlier trials had only been completed through 12 weeks.

Additionally, the agency will now require long-acting opioids to carry a boxed warning describing the risk of neonatal opioid withdrawal syndrome with chronic use during pregnancy.

“By exercising our legal and regulatory authority to take action, the FDA will ensure that the benefits of long-acting opioids will continue to outweigh the risks,” FDA Commissioner Margaret Hamburg, MD, said during the briefing.

Michael Von Korff, ScD, of Group Health Research Institute in Seattle, who is also a member of PROP, said the move is a step in the right direction, but said that overall the agency’s actions on the opioid epidemic leave something to be desired.

“It is not clear to me why the FDA’s actions apply only to long-acting opioids when similar cautions apply to short-acting opioids, like Vicodin,” Von Korff said in an email.

Von Korff added that the label now appropriately places “increased emphasis on the risks of chronic opioid therapy. But the current FDA label does not adequately reflect that data are lacking to establish the effectiveness — and long-term safety — of long-term or high-dose opioid therapy for chronic pain.”

“Prescribing opioids for longer than 90 days for chronic pain should remain an option for physicians and patients, but it should be an off-label use, because there is almost no research establishing that this use is either safe or effective,” Von Korff said.

Under the proposed label changes, opioids would no longer be indicated for moderate noncancer pain. The petition notes that moderate to severe pain is the FDA-approved indication for nearly all instant-release opioids as well as extended-release versions when 24/7 pain relief is needed for a long stretch of time. Such “overly broad indications” imply that the FDA has established that long-term use of opioids is safe and effective, the petition states. “An increasing body of medical literature suggests that long-term use of opioids may be neither safe nor effective for many patients, especially when prescribed in high doses.”

In addition, the maximum daily dose would be the equivalent of 100 mg of morphine, and the maximum duration for continuous daily use would be 90 days under the proposed label changes. Both limits would apply to noncancer pain.

One of the petitioners, Andrew Kolodny, MD, president of Physicians for Responsible Opioid Prescribing, told Medscape Medical News that the label changes would not prevent physicians from prescribing opioids at doses and durations that they deem appropriate for patients on a case-by-case basis. However, the changes would limit claims that drug companies can make about their products.

“Right now, drug companies are promoting long-term opioids as proven safe and effective for chronic pain,” he said. “They’ll promote [them] for lower back pain, fibromyalgia, osteoarthritis, whatever they want…because the current label is like a blank check.”

“By prohibiting the aggressive marketing, we can reduce the overprescribing,” said Dr. Kolodny. Physicians who understand that opioids are not necessarily safe and effective long term may resort to other treatments such as behavior modification, physical therapy, and weight loss, he added.

Other physicians signing the petition include

• Roger Chou, MD, Associate Professor of Medicine, Oregon Health & Science University
• Edward Covington, MD, Director, Neurological Center for Pain, Cleveland Clinic
• Stuart Gitlow, MD, MPH, Acting President, American Society of Addiction Medicine
• Elinore McCance-Katz, MD, PhD, Professor, Department of Psychiatry, University of California–San Francisco
• Nirav Shah, MD, MPH, Commissioner, New York State Department of Health
• Sidney Wolfe, MD, Director, Health Research Group at Public Citizen

Label Change Called Necessary for Effective REMS

The petition to revise the label of opioid analgesics comes on the heels of a new FDA initiative to help turn the tide of the prescription painkiller epidemic, which is causing more fatal overdoses than cocaine and heroin combined, according to the US Centers for Disease Control and Prevention. Earlier this month, the FDA approved a Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting opioids prescribed for moderate to severe chronic pain. More than 20 opioid manufacturers must make available to prescribers continuing education programs on the proper use of these drugs. This education will be funded through grants from manufacturers to continuing medical education providers, who will develop the training based on a blueprint for content provided by the FDA and will deliver the training.

Dr. Kolodny told Medscape Medical News that the REMS for opioids “isn’t going to help and could potentially make things worse.”

Without the label change sought by his coalition, he said, the REMS curriculum would still leave doctors “with the false impression that long-term opioid therapy was proven safe and effective.”

One company that would be affected by the envisioned label change is Purdue Pharma, the maker of controlled-release oxycodone (OxyContin), which is indicated for moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period. When asked to comment on the petition to the FDA, Purdue Pharma issued a statement saying, “[The] FDA, its advisory committees, and numerous medical experts maintain that the current indications for long-acting opioids are appropriate.

“We agree with the FDA that prescribing information for any medication should be subject to ongoing review and modification to the extent that compelling medical evidence emerges,” the company added.

Ensure Opioid Availability for Legitimate Need, Cautions Pain Expert

One pain expert interviewed by Medscape Medical News sounded a cautionary note about the petition submitted to the FDA about revising opioid labels.

“I share the concern of this group,” said Charles Argoff, MD, a professor in the neurology department at Albany Medical College and director of the Comprehensive Pain Program at Albany Medical Center in New York. “However, we need to establish prospectively whether this approach accomplishes what this petition suggests it would. This group has yet to prove that the recommendations in the petition are appropriate recommendations.”

Any changes to opioid labeling must be anchored “in the highest-quality medical evidence,” said Dr. Argoff, a member of the editorial advisory board for Medscape Neurology. Otherwise, patients could suffer harm.

“We have a prescription drug abuse crisis…that we must combat,” he said. “But [the petition] does not address the millions and millions of people who have been appropriately prescribed this medication, who have been appropriately monitored, and who have lived a more functional life as a consequence. We need to ensure the availability of these drugs for patients who can benefit from them and establish concrete approaches to limiting the abuses and misuses.”

Dr. Argoff has spoken out in the past on the problem of “allowing physicians with insufficient training to prescribe medications that can kill people.” He reiterated that concern in his remarks on the opioid-labeling petition.

“To demonize the drug is ignoring the responsibility of the prescriber,” he said. (Robert Lowes)