Addiction doctors have petitioned the US FDA to prevent Zohydro ER, the first single-entity hydrocodone painkiller, hitting the market this month citing its potential for abuse. Its maker, Zogenix, has been tight-lipped on whether the drug’s formulation uses anti-abuse technology.
In a petition to FDA Commissioner Margaret Hamburg, 42 signatories including addiction charities and doctors, said “the highest available dosage of Zohydro will contain five to ten times more hydrocodone than Vicodin or Lortab. Someone unaccustomed to taking opioids could suffer a fatal overdose from just two capsules.”
Drugmaker Zogenix called a press conference to defend the controversial drug, saying it “should never be prescribed” on an “as-needed” basis, for short-term pain, or for moderate chronic pain.
“Zohydro should be reserved for use in patients for whom alternative treatment options such as non-opiod analgesics or immediate-release opioids are ineffective, not tolerated, or otherwise inadequate,” said Bradley Galer, Executive VP. The drug carries a black box warning, he added, meaning the package insert includes information about significant risks.
Potency vs Strength
Galer said claims Zohydro was “five to ten times more potent than other hydrocodone products” were incorrect, drawing a distinction between potency – a measure of a drug’s activity in the body, and strength – the amount of medicine delivered per pill.
“For example, although 50mg of Zohydro is stronger than of 5mg of Vicodin, the products are both equally potent since they contain hydrocodone.”
The reason Zohydro comes in a greater strength than Vicodin is because it is made to treat more severe pain, he said, and is taken less often with an extended release.
“A patient taking 10mg [of Vicodin] every four hours will have the same total daily dose of hydrocodone as a person taking Zohydro ER 30mg every 12 hours.”
Abuse deterrent formulations
Stephen Farr, Zogenix President, told journalists to minimise abuse the company was co-operating with the FDA’s Risk Evaluation and Mitigation Strategy (REMS) for Extended-Release and Long-Acting Opioids , as well as its own “voluntary initiatives” to “improve participation in educational programmes for prescribers, patients and pharmacists.”
Farr told an FDA Advisory Committee on Anesthetic and Analgesic Drug Products in December 2012 the company was “actively working on abuse- or tamper-resistant formulations” of Zohydro, but that its most promising candidates was still “in pre-clinical development now. So that would be, really, several years away from the market.”
The company refused In-Pharmatechnologist.com’s interview request and did not answer whether the version of Zohydro released this month had been specially formulated with mechanisms to deter abuse.
Abuse liability research is a growing field which finds ways to make addictive tablets harder to misuse, INC Research recently told our sister site, Outsourcing-Pharma.com .
Several extended-released opioid painkillers have been reformulated using abuse deterrent technologies.
The FDA approved abuse-deterrent labelling for reformulated OxyContin in April 2013 after the drug was made more difficult to crush or dissolve for snorting or injection. The original OxyContin was withdrawn from sale and the FDA stopped approving its generics , allowing Purdue Pharma a patent on the reformulated OxyContin.
Mallinckrodt’s Exalgo, a hydromorphone tablet, switched in 2010 to OROS (Osmotic extended-Release Oral delivery System), a technology which delivers the product steadily over 24 hours. The change avoided the overdoses associated with alcohol use associated with previous extended-release hydromorphone products.
In 2011, Endo Pharmaceutical’s incorporated INTAC Technology, created by Grünenthal, into its existing Opana (oxymorphone) pills to make them harder to cut and crush. However, a lack of formal studies meant Endo could not claim an anti-abuse formulation in its labelling.