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How Changing Hydrocodone Scheduling Will Affect Pain Management

Since the FDA changed hydrocodone combination products from a schedule III controlled substance to a schedule II, pain practitioners and their patients need to know their options.
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The FDA has now officially rescheduled hydrocodone combination products from schedule III controlled substances to schedule II. After a decade of limited momentum, a  request came before the FDA advisory committee in 2008, with a decision to keep hydrocodone combination products as schedule III.1 On January 25, 2013, after 5 years, this came to the forefront again, with an FDA advisory committee voting 19 to 10 to reschedule hydrocodone combination products from III to II.

After a scientific review, FDA made the recommendation that DEA take this step in December 2013. "We concluded that hydrocodone combination products meet the criteria for control under Schedule II of the Controlled Substances Act, and we believe DEA’s new rule will help limit the risks of these potentially addictive but important pain-relieving products," noted Douglas C. Throckmorton, MD, Deputy Center Director for Regulatory Programs in FDA’s Center for Drug Evaluation and Research.3  Prescription opioid contributed to over 16,000 overdose deaths in the United States.4

According to the FDA, here are some of the key changes that will occur with the reclassification of hydrocodone from a Schedule III drug to a Schedule II drug:

  • If a patient needs additional medication, the prescriber must issue a new prescription. Phone–in refills for these products are no longer allowed.
  • In emergencies, small supplies can be authorized until a new prescription can be provided for the patient.
  • Patients will still have access to reasonable quantities of medication, generally up to a 30-day supply.
  • If a patient needs additional medication, the prescriber must issue a new prescription. Phone–in refills for these products are no longer allowed.
  • In emergencies, small supplies can be authorized until a new prescription can be provided for the patient.
  • Patients will still have access to reasonable quantities of medication, generally up to a 30-day supply.
- See more at: http://blogs.fda.gov/fdavoice/index.php/2014/10/re-scheduling-prescription-hydrocodone-combination-drug-products-an-important-step-toward-controlling-misuse-and-abuse/#sthash.y24tdnVy.dpuf

Products Affected

All available combination hydrocodone products will be affected by the change. A list of medications with the amount of hydrocodone and the combination medications is listed in Table 1.5-9

Alternatives to Consider

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of acute or chronic pain can provide a viable alternative to hydrocodone, but increasing usage of these agents comes with increased risks of gastrointestinal (GI) bleeds, gastroesophageal reflux disease, and fatalities (due to bleeding and renal toxicity). Given these limitations, NSAIDs may be used more appropriately to treat mild-to-moderate somatic pain and should not be considered the panacea to replace hydrocodone. As with opioids, different patients may or may not respond to the various available NSAIDs, and efficacy with one does not guarantee response or failure of another. This may lead to a lengthy period of subtherapeutic analgesia while clinicians attempt to find the NSAID that works best for the patient.

For patients who experience GI side effects from NSAIDs, treatment with antacids, H2 receptor blockers, or proton pump inhibitors (PPIs) is recommended. In certain cases, switching the NSAID to one that is more cyclo-oxygenase (COX)-2 specific, such as celecoxib (Celebrex), etodolac, or meloxicam, may be necessary.10 For chronic NSAID use, concomitant therapy with a PPI may be indicated for gastric ulcer prophylaxis. NSAIDs should be avoided in patients who have a history of gastric/duodenal ulcers, blood dyscrasias, anticoagulation therapy, cardiovascular disease, diabetes mellitus, hypertension, concomitant use of nephrotoxic medications, or renal impairment.

Tramadol is another option to consider for the treatment of acute or chronic pain. It comes in several formulations including tramadol 50 mg, tramadol/acetaminophen 37.5 mg/325 mg, and tramadol extended-release (ER) 100 mg, 200 mg, and 300 mg. The maximum recommended daily dose of tramadol is up to 400 mg per day, depending on the formulation. The medication and its metabolite desmethyltramadol work as agonists at the µ opioid receptor. In addition, they cause serotonin and norepinephrine reuptake inhibition, the latter of which contributes to the analgesic effect. It is important to note that the µ-receptor binding affinity of tramadol is 6,000 times less than that of morphine, so the opioid agonist activity only provides minimal benefit.11 It is metabolized primarily by cytochrome P450 (CYP) 2D6 (desmethyltramadol) and CYP3A4, but there are five important metabolites.12 Inhibitors or inducers of this medication may affect the analgesic and toxicity profile of this drug, the most concerning of which are serotonin syndrome and seizure. Both of these potential toxicities could be enhanced by concomitant serotonin-type antidepressants across all chemical and therapeutic classes, lithium, and several other drug classes that may affect serotonin (certain antipsychotics, triptans, etc). As with NSAIDs, tramadol has pharmacology that can result in a significant rise in blood pressure. Finally, compared to other "opioid agonists," tramadol is one of the most constipating agents.

Acetaminophen with codeine is a schedule III option for the treatment of acute pain. This medication is inferior to hydrocodone, however, because it has significant variability in action with respect to absorption and activation. Codeine requires metabolism to morphine to achieve analgesia; this is accomplished by the CYP2D6 isoenzyme, which is necessary for the conversion on first-pass metabolism through the gut. Another issue is that patients with different polymorphisms could be fast and slow metabolizers of codeine, depending on their ability to make CYP2D6. Fast metabolizers end up experiencing a lot of analgesia for the dose received and may have side effects because of this; slow metabolizers, on the other hand, may not experience any benefit from the codeine because conversion to the active form is absent or negligible. Also, certain medications commonly induce or inhibit CYP2D6 isoenzymes. The selective serotonin reuptake inhibitors, in particular, have varying potency to inhibit CYP2D6, thereby preventing the conversion of codeine to its active analgesic form of morphine.

Last updated on: May 19, 2015
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