General Information

Troxyca ER is an extended release capsule formulation of oxycodone combined with naltrexone. Oxycodone is a full opioid agonist and naltrexone is an opioid antagonist.

Troxyca 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.

Troxyca ER is supplied as an extended release capsule for oral administration. The recommended dose(s) are as follows. See drug label for specific dose measure and conversions.

Use of Troxyca ER as the First Opioid Analgesic (opioid -naïve patients): Initiate treatment with Troxyca ER with 10 mg / 1.2 mg capsule orally every 12 hours.

Use of Troxyca ER in Patients who are not Opioid Tolerant (opioid -non-tolerant patients): The starting dose for patients who are not opioid -tolerant is Troxyca ER 10 mg / 1.2 mg capsule orally, every 12 hours. Use of higher starting doses in patients who are not opioid -tolerant may cause fatal respiratory depression.

Conversion from Other Oral Oxycodone HCl Formulations to Troxyca ER: Patients receiving other oral oxycodone HCl formulations may be converted to Troxyca ER by administering one half of the patient ’s total daily oral oxycodone HCl dose as Troxyca ER every 12 hours .

Conversion from Other Opioids to Troxyca ER: Discontinue all other around -the-clock opioid drugs when Troxyca ER therapy is initiated.

Clinical Results

FDA Approval

The analgesic efficacy of Troxyca ER was evaluated in one randomized, double-blind, placebo-controlled clinical trial in patients with moderate-to-severe chronic low back pain. This study utilized an enriched-enrollment, randomized-withdrawal design and was conducted in a population consisting of both opioid-experienced and opioid-naïve subjects. Subjects were titrated to effect with Troxyca ER in the open-label period, which was followed by a 12-week double-blind treatment period. Total daily doses of the oxycodone in Troxyca ER ranged from 20 mg to 160 mg administered in two equal doses approximately 12 hours apart. Subjects with controlled pain (defined as pain intensity numerical rating scale [NRS] ≤4) were randomized into the 12-week double-blind treatment period to either continue Troxyca ER or be switched to placebo. Subjects randomized to placebo were given a blinded taper of Troxyca ER according to a pre-specified schedule to prevent opioid withdrawal. Rescue medication (up to 3 grams per day of acetaminophen) was allowed throughout the study to treat episodes of breakthrough pain. Immediate-release oxycodone HCl (as a single ingredient product) was also allowed during the first 3 weeks of the open-label period to manage the initial conversion from prior therapy.

A total of 410 subjects entered the open-label titration period and 281 were successfully titrated onto Troxyca ER and randomized into the double-blind treatment period: 134 to placebo and 147 to Troxyca ER. Of these, 42.5% of subjects were previously treated with an opioid. The mean change in the weekly average pain intensity NRS scores from randomization baseline to the average of Weeks 11 and 12 was statistically significantly superior for those treated with Troxyca ER compared to placebo. A higher percentage of subjects receiving Troxyca ER, compared to placebo, had a ≥30% decrease in their weekly average NRS-pain intensity scores from Screening to Weeks 11 and 12 of the double-blind treatment period (58% versus 44% for Troxyca ER and placebo, respectively), while, 40% of subjects receiving Troxyca ER and 30% of subjects receiving placebo had a 50% decrease.

Side Effects

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

nausea

constipation

vomiting

headache

somnolence

Troxyca ER comes with a Black Box warning of the potential for Addiction, Abuse, and Misuse, Life-Threatening Respiratory Depression, Accidental ingestion, neonatal opioid withdrawal syndrome and Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in fatal overdose of oxycodone from Troxyca ER.

Mechanism of Action

Troxyca ER is an extended release capsule formulation of oxycodone combined with naltrexone. Oxycodone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with oxycodone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug. Naltrexone is an opioid antagonist that reverses the subjective and analgesic effects of mu-opioid receptor agonists by competitively binding at mu-opioid receptors.