TARGINIQ ER (oxycodone hydrochloride and naloxone hydrochloride extended-release tablets) is a combination product containing an opioidagonist, oxycodone, and an opioid antagonist, naloxone. TARGINIQ ER is supplied as 10 mg/5 mg, 20 mg/10 mg, and 40 mg/20 mg tablets for oral administration. The tablet strengths, a 2:1 ratio in each, describe the amount of oxycodone and naloxone per tablet as the hydrochloride salts, respectively. The structural formula for oxycodone hydrochloride is as follows:
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C18H21NO4 •HCl MW 351.83The chemical name is 4, 5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride.
Oxycodone is a white, odorless crystalline powder derived from the opium alkaloid, thebaine. Oxycodone hydrochloride dissolves in water (1 g in 6 to 7 mL). It is slightly soluble in alcohol (octanol water partition coefficient 0.7).
The structural formula for naloxone hydrochloride is as follows:
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C19H21NO4 •HCl MW 363.84The chemical name is (-)-17-Allyl-4,5α -epoxy-3,14-dihydroxy-morphinan-6-one hydrochloride.
Naloxone hydrochloride occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform.
While Targiniq has only been approved for patients who have chronic pain that has not responded to other medications, the FDA acknowledged the medication can still be abused simply by taking too many pills. Currently, that is the most common way oxycodone is misused.
The 10 mg/5 mg, 20 mg/10 mg and 40 mg/20 mg extended-release tablets contain the following inactive ingredients: lactose monohydrate, stearyl alcohol, ethyl cellulose, povidone, talc, magnesium stearate, polyvinyl alcohol partially hydrolyzed, titanium dioxide, and Macrogol. The 20 mg/10 mg extended-release tablets also contain: Iron oxide red. The 40 mg/20 mg extended-release tablets also contain: Iron oxide yellow.
The film-coated extended-release tablets are color coded to distinguish different strengths as follows:
The 10 mg/5 mg extended-release tablets are white.
The 20 mg/10 mg extended-release tablets are pink.
The 40 mg/20 mg extended-release tablets are yellow.
Experts made the same point.
“When the pills are swallowed they are as addictive and dangerous as pure oxycodone,” Andrew Kolodny, chief medical officer of the Phoenix House, an alcohol and drug abuse treatment provider, told CNN.
“In a sense it’s playing a game of ‘whack a mole,’ because if people are addicted to opiates, they will find an opiate,” Caleb Banta-Green, senior research scientist at the Alcohol and Drug Abuse Institute at the University of Washington, told the news service.
The FDA has come under intense pressure in recent years to restrict the use of narcotic painkillers following reports of escalating painkiller abuse in the United States.
In 2012 alone, 259 million prescriptions were written for powerful painkillers. That’s enough for every adult to have their own bottle of pills, U.S. Centers for Disease Control and Prevention officials have said.
And deaths linked to overdoses of narcotic painkillers have quadrupled since 1990, reaching more than 17,000 deaths in 2011, according to the latest CDC estimates.
FDA officials noted Wednesday that approvals of painkillers that are formulated to deter potential abuse are part of a larger effort to curb abuse while still providing some avenue of relief for patients who suffer intense daily pain that does not respond to other medications. In 2010, Purdue Pharma introduced a hard-to-crush version of Oxycontin, and research has shown that abuse of Oxycontin has since decreased, according to CNN.
“The FDA is committed to combating the misuse and abuse of all opioids, and the development of opioids that are harder to abuse is needed in order to help address the public health crisis of prescription drug abuse in the U.S.,” Dr. Sharon Hertz, deputy director of the division of anesthesia, analgesia and addiction products in the FDA’s Center for Drug Evaluation and Research, said in an agency news release.
Targiniq’s approval was based on the results of a study that involved more than 600 patients struggling with lower back pain, the agency said. The medication proved to be both safe and effective, with the most common side effect being nausea and vomiting.
Still, the FDA will require Purdue Pharma to conduct further studies to monitor any abuse of the drug.
WARNING
ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and CYTOCHROME P450 3A4 INTERACTION
Addiction, Abuse, and Misuse
TARGINIQ™ ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing TARGINIQ ER and monitor all patients regularly for the development of these behaviors or conditions.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of TARGINIQ ER. Monitor for respiratory depression, especially during initiation of TARGINIQ ER or following a dose increase. Instruct patients to swallow TARGINIQ ER tablets whole; crushing, chewing, or dissolving TARGINIQ ER tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone
Accidental Ingestion
Accidental ingestion of even one dose of TARGINIQ ER, especially by children, can result in a fatal overdose of oxycodone
Neonatal Opioid Withdrawal Syndrome
Prolonged use of TARGINIQ ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see WARNINGS AND PRECAUTIONS].
Cytochrome P450 3A4 Interaction
The concomitant use of TARGINIQ ER with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving TARGINIQ ER and any CYP3A4 inhibitor or inducer