Xartemis XR by Mallinckrodt Pharmaceuticals

The FDA has approved Mallinckrodt Pharmaceuticals’ Xartemis XR (oxycodone/acetaminophen) Extended-Release Tablets for the management of acute pain that is severe enough to require opioid treatment and for which alternative treatment options are inadequate. The approval carries the limitation that because of the risk for addiction, abuse, misuse, overdose, and death with opioids, even at recommended doses, Xartemis XR should be reserved for use in patients for whom alternative treatment options, such as nonopioid analgesics, are ineffective, not tolerated, or would be otherwise inadequate. Xartemis XR is a Schedule II controlled substance.¹

Pharmacology and Pharmacokinetics

Oxycodone is an opioid agonist with relative selectivity for the mu receptor. Acetaminophen is a nonopioid, nonsalicylate analgesic and antipyretic.

Xartemis XR consists of a bilayer formulation to provide both immediate and extended release.^1,2

Dosage and Administration

Each tablet of Xartemis XR consists of 7.5 mg of oxycodone and 325 mg of acetaminophen. The recommended daily dose is 2 tablets every 12 hours without regard to food. The tablets should be swallowed whole and never broken, chewed, crushed, dissolved, or split. The dose should be swallowed with enough water to ensure complete swallowing immediately after placing the tablets in the mouth.¹

Clinical Trials

The efficacy of Xartemis XR was evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-arm, multiple-dose clinical trial of 303 postsurgical patients. After 48 hours, a statistically significant improvement in pain scores was found in the Xartemis XR group compared with the placebo group.^1,2

Contraindications, Warnings, and Precautions

Xartemis XR carries the following boxed warning:

• Its use exposes users to the risk for addiction, abuse, and misuse, which may lead to overdose and death. Each patient’s risk should be assessed before prescribing and monitored throughout treatment with Xartemis XR.

• Serious, life-threatening, or fatal respiratory depression may occur.

• Accidental ingestion of Xartemis XR, especially in children, can result in a fatal overdose of oxycodone.

• Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not identified and treated.

Xartemis XR contains acetaminophen, which has been associated with acute liver failure, sometimes resulting in liver transplant and death.

Xartemis XR is contraindicated in patients with (1) a known hyper-sensitivity to oxycodone, acetaminophen, or any other components of the medication; (2) significant respiratory depression; (3) acute or severe bronchial asthma or hypercarbia; and (4) suspected or known paralytic ileus.

Xartemis XR is not interchangeable with other products that contain oxycodone and acetaminophen due to different pharmacokinetic profiles that affect the frequency of administration. If possible, avoid concomitant administration with other central nervous system depressants. Use caution in elderly, cachectic, debilitated patients or those with chronic pulmonary disease. Discontinue treatment if serious skin reactions occur. Xartemis XR may worsen increased intracranial pressure or cause hypotension. Do not use with other products that contain acetaminophen. Discontinue immediately if signs of allergic reaction occur. Use caution in patients with biliary tract disease. Concomitant use of CYP3A4 inhibitors may increase opioid effects. Mental and physical abilities may be impaired during treatment with Xartemis XR.

Concurrent use of Xartemis XR with skeletal muscle relaxants may enhance the neuromuscular blocking action and produce an increased degree of respiratory depression. Concomitant use with monoamine oxidase inhibitors may intensify the opioid effect, causing anxiety, confusion, and significant respiratory depression or coma. Mixed agonist/antagonist analgesics may precipitate withdrawal symptoms. Concurrent use with anticholinergic agents may increase the risk for urinary retention and severe constipation.

Xartemis XR is Pregnancy Category C. It should not be used during labor and delivery or in patients who are breast-feeding. Dose initiation should be conservative in patients with renal or hepatic impairment.

The most common adverse reactions are nausea, dizziness, headache, vomiting, constipation, and somnolence.¹

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

References

1. Xartemis XR [package insert]. Hazelwood, MO: Mallinckrodt Pharmaceuticals; 2014. www.xartemisxr.com/pdf/xartemisxr_prescribing_information.pdf. Accessed August 2014.

2. Mallinckrodt plc receives FDA approval for Xartemis XR (oxycodone hydrochloride and acetaminophen) extended-release tablets (CII). Mallinckrodt Pharmaceuticals website. www.mallinckrodt.com/News. Accessed August 2014.