Study: Hydrocodone Rescheduling Affects Prescribing

Prescriptions for hydrocodone fixed-dose combination products have plummeted since the opioid was rescheduled from Schedule III to the much more restrictive Schedule II, according to new study results.

The total number of hydrocodone combination tablets prescribed fell by more than 1 billion during the first year after the rescheduling. The rescheduling likely resulted in a variety of costs and inconveniences for patients, as well as in the substitution of less tolerable and/or less efficacious analgesics, according to the study investigators.

The research is part of a soon-to-be published paper, some of which was presented in poster form at PAINWeek 2016 (abstract 101).

In the study, the investigators monitored use of analgesics in the state of Texas during the six-month period before and after the hydrocodone rescheduling. Post-rescheduling, prescriptions for the most commonly prescribed fixed-dose hydrocodone combination products—5 and 10 mg of hydrocodone combined with 325 mg of acetaminophen—fell by 58% and 34%, respectively. Concurrently, prescriptions for Schedule III drugs and combination products rose 597% and 1,056%, respectively, for 300/30 mg and 300/60 mg of acetaminophen-codeine, and |17% for tramadol.

“This suggests that prescribers are unable or unwilling to write for Schedule II opioids if there is an alternative Schedule III that might work,” said Lynn R. Webster, MD, vice president of Scientific Affairs at PRA Health Sciences, in Raleigh, N.C., and immediate past president of the American Academy of Pain Medicine, who was not involved in the research.

Patients May Be Denied Best Meds

That means that patients with chronic pain, postsurgical patients and a variety of other pain patients could be deprived of the most effective pain reliever for their conditions, said co-author Frank Breve, PharmD, MBA, president, CEO and clinical pharmacist consultant at Mid Atlantic PharmaTech Consultants.

Furthermore, those who still receive their hydrocodone prescriptions may be forced to make more frequent clinic and pharmacy visits to obtain their medication, Dr. Breve said. “This can represent a severe hardship for rural patients, those with impaired mobility or patients without a ready means of transportation,” according to the researchers.

An online survey of 6,240 fibromyalgia patients covering the first 100 days after rescheduling showed that 82.5% had been prescribed a hydrocodone product for at least a year; many reported that they were now unable to obtain these drugs.

Eighteen percent reported obtaining them from other sources, while other patients reported substituting marijuana (17.1%), alcohol (13.1%) or illicit drugs (2.3%). Sixty-four percent of these patients reported having to make more frequent provider visits, often resulting in missed work.

The investigators addressed some of the common medical problems that could potentially arise due to the rescheduling. Codeine is often used in hydrocodone’s stead, but some individuals are “poor metabolizers” while others are “ultrarapid metabolizers.” This can reduce effectiveness in some, and “result in morbidity and mortality” in others.

Tramadol’s effectiveness is variable due to cytochrome P450 2D6 gene polymorphisms, and that drug “may also be associated with serotonin syndrome when it is prescribed with certain other drugs, including many antidepressants,” they wrote.

Excess Rx May Lead to Abuse, Tolerance, Overdoses

But Joseph Ranieri, DO, medical director of Seabrook House, a Commission on Accreditation of Rehabilitation Facilities–accredited drug and alcohol addiction treatment facility, noted that primary care providers and dentists routinely prescribe hydrocodone in excess of CDC opioid prescribing guidelines. “Instead of being discarded, [excess pills] are often abused by family members or friends, often as first exposures. They are frequently implicated in overdoses, by themselves, or combined with alcohol, sedatives and similar medications,” he said.

“As an example, patients treated for chronic pain or dental work may only need 10 pills initially, and then reevaluation after a week,” Dr. Ranieri said. “Often, prior to the current epidemic, patients sought [and received] refills and additional supply by providers, without a face-to-face evaluation,” he said, adding that this still happens.

Another problem, said Dr. Ranieri, is that chronic noncancer pain patients can become dependent on opioid medication even if they are not fully addicted. “They may take it as prescribed initially, but then develop a tolerance, requiring more medication without getting more pain relief or a greater ability to function,” he said.

They may then request early refills, or go “provider shopping” for additional opioid medication, or they may obtain opioids from other, nonmedical sources to alleviate their pain, he said.

Nonetheless, Dr. Webster said, “Prior to rescheduling, hydrocodone was associated with less abuse per prescription than any other opioid. Since one of the goals to rescheduling was to reduce the amount of abuse and addiction, it would appear that this goal has not been met, at least not at this time.”