General Information

Targiniq is a combination product consisting of oxycodone, an opioid agonist, and naloxone, an opioid antagonist.

Targiniq ER is specifically indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. It is not indicated for use as-needed (prn) analgesic. Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve Targiniq ER for use in patients for whom alternative treatment options are inadequate.

Mechanism of Action

Targiniq is a combination product consisting of oxycodone, an opioid agonist, and naloxone, an opioid antagonist. Oxycodone hydrochloride is a full opioid agonist and is relatively selective for the mu receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Naloxone is an antagonist acting on mu, kappa and delta opioid receptors in the brain, spinal cord, and peripheral organs (e.g., intestine, heart, kidney and lungs). Naloxone antagonizes opioid effects by competing for the mu, kappa and delta opioid receptor sites with the greatest affinity for the mu receptor.

Side Effects

Adverse effects associated with the use of Targiniq ER may include, but are not limited to, the following:

· Nausea

· Vomiting

Dosing/Administration

Targiniq ER is supplied as a tablet for oral administration. For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg/5 mg tablets orally every 12 hours.

Crushing, chewing or dissolving Targiniq ER tablets will result in uncontrolled delivery of oxycodone and can lead to overdose or death.

Clinical Trial Results

FDA approval of Targiniq ER was based on one 12-week, randomized, double-blind, placebo-controlled clinical trial in opioid-experienced patients with uncontrolled moderate to severe, chronic low back pain. A total of 1,095 subjects with uncontrolled moderate to severe chronic, low back pain entered an open-label, dose-titration period for up to four weeks. Patients initiated Targiniq ER therapy at an oxycodone dose approximately equivalent to their current therapy. The dose of Targiniq ER could be up-titrated to a maximum of 40/20 mg twice daily by the investigator every one to two days as needed, based on efficacy, safety and tolerability considerations or down-titrated at any time for safety and/or tolerability reasons. During open-label titration, subjects were allowed supplemental pain medication (immediate-release oxycodone HCl 5 mg capsules) for low back pain every four hours as needed up to eight capsules per day. Fifty-five percent of patients who entered the open-label titration period achieved adequate analgesia and tolerability on TARGINIQ ER and were then randomized to their final titrated dose of Targiniq ER or matching placebo for 12 weeks of double-blind treatment. During the double-blind period, subjects were allowed one capsule of supplemental pain medication as needed, up to two capsules per day. Of the 298 patients randomized to Targiniq ER, 73 percent of the patients completed the 12-week double-blind treatment on study drug. Of the 302 patients randomized to placebo, 60 percent of the patients completed the study. Fewer patients randomized to Targiniq ER discontinued due to lack of efficacy compared to placebo, 10 percent versus 24 percent. Discontinuation due to adverse events was the same for both groups. The mean score of average pain over the last 24 hours at the end of the study (week 12/early termination) was statistically significantly lower in patients treated with Targiniq ER compared to patients treated with placebo. A higher proportion of patients treated with Targiniq ER (55 percent) had at least a 30 percent reduction in pain score from screening to week 12 compared to placebo patients (41 percent). Also, a higher proportion of patients treated with Targiniq ER (37 percent) had at least a 50 percent reduction in pain score from screening to week 12 compared to placebo patients (25 percent).