Aspirin and Oxycodone

Oxycodone and aspirin tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse, with opioids, which can occur at any dosage or duration, reserve oxycodone and aspirin tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics) • Have not been tolerated, or are not expected to be tolerated, • Have not provided adequate analgesia, or are not expected to provide adequate analgesia Oxycodone and Aspirin tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

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 of oxycodone 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. Aspirin (acetylsalicylic acid) works by inhibiting the body’s production of prostaglandins, including prostaglandins involved in inflammation.

Important Dosage and Administration Instructions Oxycodone and aspirin tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of oxycodone and aspirin tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic.

Oxycodone and aspirin tablets are contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Hypersensitivity to oxycodone or aspirin, (e.g. angioedema) • Patients with hemophilia. • Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye syndrome

Boxed warning (serious and life-threatening risks from use of oxycodone and aspirin tablets): Addiction, Abuse, and Misuse Because the use of oxycodone and aspirin tablets 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 and reassess all patients regularly for the development of these behaviors and conditions. Addiction, Abuse, and Misuse Oxycodone and aspirin tablets contain Oxycodone, a Schedule II controlled substance. As an opioid, oxycodone and aspirin tablets exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxycodone and aspirin tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.

The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse • Life-Threatening Respiratory Depression • Neonatal Opioid Withdrawal Syndrome • Opioid-Induced Hyperalgesia and Allodynia • Interactions with Benzodiazepines and Other CNS Depressants • Adrenal Insufficiency • Severe Hypotension • Gastrointestinal Adverse Reactions • Seizures • Withdrawal Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Drug -Drug Interactions Inhibitors of CYP3A4 Since the CYP3A4 isoenzyme plays a major role in the metabolism of oxycodone and aspirin tablets, drugs that inhibit CYP3A4 activity, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may cause decreased clearance of oxycodone, which could lead to an increase in oxycodone plasma concentrations. A published study showed that the co-administration of the antifungal drug, voriconazole, increased oxycodone AUC and Cmax by 3.6 and 1.7 fold, respectively. The expected clinical results would be increased or prolonged opioid effects. Inducers of CYP450 CYP450 inducers, such as rifampin, carbamazepine, and phenytoin, may induce the metabolism of oxycodone, may cause increased clearance of the drug which could lead to a decrease in oxycodone plasma concentrations.

Store at 20°- 25°C (68° - 77°F), Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Store Oxycodone and Aspirin Tablets, USP securely and dispose of properly.