The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire
population of the US, specifically the public who take a multitude of drugs and providers who
prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to
biotech and pharmaceutical companies involved in developing new drugs. The FDA has been
criticized for a lack of independence on the one hand and excessive regulatory and expanding
authority without evidence and consistency of the actions on the other hand.
The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro™, Zogenix, San
Diego, CA) on October 25, 2013, against the recommendation of the FDA’s own appointed
scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to
the approval, multiple consumer safety organizations, health care agencies, addiction treatment
providers, professional organizations, and other groups on the frontline of the opioid addiction
epidemic have expressed concern. In addition, the US Congress and various state attorneys
general raised serious concerns about the approval of Zohydro, which is highly addictive and
may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary
and essential to manage chronic pain and improve functional status with no additional risk.
Over the past 15 years, prescriptions for opioids have skyrocketed with the United States
consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone
supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction
and overdose deaths, surpassing motor vehicle injuries in the US. Recent studies assessing the
trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that
the present trend of the continued increase in the medical use of opioid analgesics appears to
contribute to increasing misuse, resulting in multiple health consequences, despite numerous
regulations enforced by multiple organizations.
The approval of Zohydro and its defense from the FDA were based on a misunderstanding of
the prevalence of chronic severe disabling pain. Based on inaccurate data from the Institute of
Medicine, in part caused by conflicts of interest, 100 million persons have been described to
suffer from severe pain -- the correct number is 22.6 million.
This manuscript analyzes 3 important principles of drug approval and utilization based on safety,
efficacy, and medical necessity. Based on the limited literature that the authors were able to
review including that which was submitted to the FDA by the manufacturers, it appears the safety,
efficacy, and medical necessity were not demonstrated. In fact, the study submitted to the FDA
showed a 50% pain improvement in only 48% of the patients in the treatment group and 21%
of the patients in the placebo group at 85 day follow-up. This is a statistically significant result
but its clinical relevance is unknown. The FDA approval decision occurring against the backdrop
of the advisory panel recommendation is concerning and may result in serious consequences in
the future.
Key words: Chronic non-cancer pain, Food and Drug Administration, opioids, Zohydro, misuse,
tolerance, addiction, dependency, medical necessity
The Impact of Saffron on Symptoms of Withdrawal Syndrome in Patients Undergoing Maintenance Treatment for Opioid Addiction in Sabzevar Parish in 2017
