Critics Question FDA's Decision on Zohydro Approval

The U.S. Food and Drug Administration (FDA) has recently approved Zohydro ER for long-term treatment of moderate to severe pain that is refractory to conventional management. Zohydro ER is the brand name for a drug known as hydrocodone bitartrate, which is marketed as extended release (ER) tablets. It is classified a Schedule II drug, or those that can only be dispensed with a doctor's prescription, with no refills allowed.

What is Zohydro?

Zohydro or hydrocodone is an opioid or narcotic painkiller that resembles morphine. This type of analgesic suppresses pain perception and reduces emotional responses to pain. However, in contrast to other hydrocodone products approved by the FDA (such as Norco and Vicodin), 

Opioid analgesics are often prescribed to patients with moderate to severe chronic pain that is not relieved by other analgesics like acetaminophen or other nonsteroidal anti-inflammatory drugs (NSAIDS). This type of pain usually requires long-term management using daily round-the-clock drug administration. Opioids are not given “as needed,” but must be monitored and regulated because they have the potential for abuse, addiction, and misuse, which can lead to overdose or death.

Zohydro ER, a product of Zogenix, is a pure opioid drug that packs five to ten times the narcotic effects of other hydrocodone products. In contrast, combination products contain other over-the-counter painkillers like ibuprofen (Vicoprofen) or acetaminophen (Vicodin), or an antihistamine (Hycomine) and less opioid. The extended-release tablets are designed to release its effects slowly, over about twelve hours. Like other opioid drugs, its common side effects include nausea, vomiting, constipation, somnolence, fatigue, dizziness, headache, dry mouth, and pruritus (itching).

Patients may become physically dependent on opioid pain relievers if they take these regularly. However, one should not stop taking these medications abruptly, because this can result in unpleasant withdrawal symptoms such as shaking, sweating, chills, nausea, and diarrhea. Although these are not life threatening, one can avoid these symptoms by gradually stopping opioids over time, as prescribed by the doctor.

Why Zohydro Got FDA Approval

In a 12-week trial involving more than 1,500 patients suffering from moderate and severe low back pains, it was found that patients who received Zohydro experienced significant relief from pain compared to those who took placebo. It was also observed that the drug was generally safe, well tolerated, and had side effects that were comparable to those of other opioids approved by the FDA. However, this approval was made against the recommendation of FDA’s own advisers, who expressed their concerns in a memo released in November 2012.

The advisory panel voted in December not to grant approval for the drug, citing that Zohydro has the potential to be abused more than other hydrocodone products. Advisers foresee that Zohydro will be widely abused in the US, just like extended release oxycodone products (e.g., OxyContin) in the past, before they were reformulated.

Issues Raised Against FDA Approval of Zohydro

While the FDA believes that the benefits of Zohydro outweigh its risks, critics raise issues about its effectiveness and safety. The FDA has been criticized for being too friendly with opioid manufacturers in spite of the fact that too many people have been dying from abuse and drug overdose in the past years. 

More than 130 million prescriptions for Vicodin were filled in 2010, making it the most commonly prescribed medication in the country. It is sad to note that in the same year, narcotic overdose claimed the lives of more than 16,000 people, which is about four times the number of deaths recorded a decade ago. While Vicodin tablets come in doses of five to ten milligrams combined with 300 mg acetaminophen, Zohydro ER tablets come in much higher doses (10-50 mg), without a combination drug. Critics fear that this increases the risk for more deaths due to narcotic drug abuse, especially with Zohydro’s current formulation.

Extended release medications come in coated tablets that discharge small amounts of the drug over time (12 hours for Zohydro ER). However, individuals who seek pleasure from drugs may crush, chew, or mix the tablets with alcohol to experience its full effects at once. Although another opioid product, OxyContin, was reformulated in 2010 to make it resistant to abuse, Zohydro was not required by the FDA to do the same.

While Morgan Liscinsky, FDA spokesperson, says that the agency does not require all opioid products to be abuse-deterrent, they assure consumers that Zohydro’s label will bear clear warnings about drug abuse and will advise doctors to monitor their patients for misuse or addiction. Furthermore, Zohydro manufacturer Zogenix, which is based in San Diego, issued a statement that it plans to make a formula of the drug that will deter abuse.

Is Zohydro as Effective as It Claims?

Some critics also question if Zohydro is indeed as effective as it is claimed to be, after all, the trial only took 12 weeks to complete. Experts believe that there has been little research about its effects when used for longer periods. Furthermore, patients who were involved in the study were recruited through an enriched enrollment method.

This technique allows manufacturers to include people who are more likely to respond well to their drug and weed out those who would not be able to tolerate it even before the clinical trial has began. Critics claim this is one form of cheating because the results will not accurately reflect the drug’s effectiveness in a larger group of people when it is marketed after it has been approved. Instead, the results of the current study reflected the effects of the drug in a limited experiment that showed hydrocodone reduced pain just a little better than did a placebo.

FDA justifies the enriched enrollment as that of personalized medicine that attempts to include patients for whom a drug will be most effective but experts feel that this is not realistic and could result in more deaths.