RATIONALE FOR INCLUSION IN PA PROGRAM Background Xartemis XR is a combination of oxycodone and acetaminophen in a dosage formulation to deliver both immediate pain relief, in less than an hour, and extended-release analgesia that lasts up to 12 hours. Xartemis XR is dosed at 2 tablets every 12 hours (1). Oxycodone is a Schedule II controlled substance and can be abused in a manner similar to other opioid agonists, legal or illicit. As an opioid, Xartemis XR exposes users to the risks of addiction, abuse, and misuse. Addiction can occur at recommended doses and if the drug is misused or abused. This should be considered when prescribing or dispensing oxycodone in a situation where misuse, abuse, or diversion are a concern. Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness. The potential for these risks should not, however, prevent the prescribing of Xartemis XR for the proper management of pain in any given patient. Patients at increased risk that are prescribed Xartemis XR necessitates intensive counseling about the risks and proper use of Xartemis XR along with intensive monitoring for signs of addiction, abuse, and misuse (1). Regulatory Status FDA-approved indication: Xartemis XR is indicated for the management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate (1). Limitations of Use: Because of the risks of addiction, abuse, misuse, overdose, and death with opioids, even at recommended doses, reserve XARTEMIS XR for use in patients for whom alternative treatment options (e.g., non-opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate (1). Xartemis XR carries several boxed warnings regarding addiction, abuse, and misuse; lifethreatening respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome; and hepatotoxicity (1).
Xartemis XR exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Each patient should be assessed for their risk prior to prescribing Xartemis XR, and all patients should be monitored regularly for the development of these behaviors or conditions (1). Serious, life-threatening, or fatal respiratory depression may occur with use of Xartemis XR. Prescribers should monitor for respiratory depression, especially during initiation of Xartemis XR or following a dose increase (1). Accidental ingestion of Xartemis XR, especially in children, can result in a fatal overdose of oxycodone. Prolonged use of Xartemis XR during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized 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 (1). Xartemis XR contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limit, and often involve more than one acetaminophen-containing product. Severe liver damage may occur if you take more than 4,000 mg of acetaminophen in 24 hours. Xartemis should not be used concomitantly with other acetaminophen-containing products (1). Xartemis XR is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma or hypercarbia, or known or suspected paralytic ileus (1). Xartemis XR is not interchangeable with other oxycodone/acetaminophen products because of differing pharmacokinetic profiles that affect the frequency of administration (1). CDC guidelines find that concurrent use of benzodiazepines and opioids might put patients at greater risk for potentially fatal overdose. Three studies of fatal overdose deaths found evidence of concurrent benzodiazepine use in 31% 61% of decedents (2)
CDC guidelines finds that given uncertain benefits and substantial risks that opioids should not be considered first-line or routine therapy for chronic pain (i.e., pain continuing or expected to continue longer than 3 months or past the time of normal tissue healing) outside of active cancer, palliative, and end-of-life care (2). FDA warns that opioids can interact with antidepressants and migraine medicines to cause a serious central nervous system reaction called serotonin syndrome, in which high levels of the chemical serotonin build up in the brain and cause toxicity (see Appendix 1 for list of drugs) (3). Safety and effectiveness of Xartemis XR in pediatric patients under the age of 18 years have not been established (1). Summary Xartemis XR is a combination of oxycodone and acetaminophen that is indicated for the management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate. Xartemis XR delivers both immediate pain relief, in less than an hour, and extended-release analgesia that lasts up to 12 hours. Xartemis XR is dosed at 2 tablets every 12 hours. Xartemis XR carries several boxed warnings regarding addiction, abuse, and misuse; life-threatening respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome; and hepatotoxicity. Safety and effectiveness of Xartemis XR in pediatric patients under the age of 18 years have not been established (1). Prior approval is required to ensure the safe, clinically appropriate and cost effective use of Xartemis XR while maintaining optimal therapeutic outcomes. References 1. Xartemis XR [package insert]. Mallinckrodt Brand Pharmaceuticals, Inc. Hazelwood, MO. March 2015. 2. Dowell D, Haegerich T, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain. CDC Guidelines 2016 3. FDA Safety Release. FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. March 22, 2016.
Appendix 1 - List of Serotonergic Medications Selective Serotonin Reuptake Inhibitors (SSRIs) paroxetine Paxil, Paxil CR, Pexeva, Brisdelle fluvoxamine Luvox, Luvox CR fluoxetine Prozac, Prozac Weekly, Sarafem, Selfemra, Symbyax sertraline Zoloft citalopram Celexa escitalopram Lexapro Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) venlafaxine Effexor XR desvenlafaxine Pristiq, Khedezla duloxetine Cymbalta milnacipran Savella Tricyclic Antidepressants (TCAs) amitriptyline No brand name currently marketed desipramine Norpramin clomipramine Anafranil imipramine Tofranil, Tofranil PM nortriptyline Pamelor, Aventyl protriptyline Vivactil doxepin Zonalon, Silenor trimipramine Surmontil Monoamine Oxidase Inhibitors (MAOIs) isocarboxazid Marplan phenelzine Nardil selegiline Emsam, Eldepryl, Zelapar tranylcypromine Parnate Other Psychiatric Medicines amoxapine No brand name currently marketed maprotiline No brand name currently marketed nefazodone No brand name currently marketed trazodone Oleptro buspirone No brand name currently marketed vilazodone Viibryd mirtazapine Remeron, Remeron Soltab
llthium Lithobid Migraine Medicines almotriptan Axert frovatriptan Frova naratriptan Amerge rizatriptan Maxalt, Maxalt-MLT sumatriptan Imitrex, Imitrex Statdose, Alsuma, Sumavel Dosepro, Zecuity, Treximet zolmitriptan Zomig, Zomig-ZMT Antiemetics ondansetron granisetron dolasetron palonosetron Zofran, Zofran ODT, Zuplenz Kytril, Sancuso Anzemet Aloxi Other Serotonergic Medicines dextromethorphan Bromfed-DM, Delsym, Mucinex DM, Nuedexta linezolid Zyvox cyclobenzaprine Amrix methylene blue St. John s wort tryptophan