OXYCODONE AND ACETAMINOPHEN

INDICATIONS AND USAGE Oxycodone Hydrochloride and Acetaminophen Oral Solution is 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, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings ] , reserve opioid analgesics, including oxycodone hydrochloride and acetaminophen oral solution for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Ensure accuracy when prescribing, dispensing, and administering oxycodone hydrochloride and acetaminophen oral solution to avoid dosing errors due to confusion between mg and mL, and with other oxycodone hydrochloride and acetaminophen oral solutions of different concentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume. Instruct patients and caregivers on how to accurately measure and take or administer the correct dose of oxycodone hydrochloride and acetaminophen oral solution. Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication. Inform patients and caregivers that oral dosing devices may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure oxycodone hydrochloride and acetaminophen oral solution. Oxycodone hydrochloride and acetaminophen oral solution 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 [see Warnings ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of oxycodone hydrochloride and acetaminophen oral solution 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. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with oxycodone hydrochloride and acetaminophen oral solution. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings ]. Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see Warnings; Addiction, Abuse, and Misuse; Life-Threatening Respiratory Depression; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ]. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to r…

WARNINGS Risk of Accidental Overdose and Death due to Medication Errors Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with oxycodone hydrochloride and acetaminophen oral solutions of different concentrations, when prescribing, dispensing, and administering oxycodone hydrochloride and acetaminophen oral solution. Ensure that the dose is communicated clearly and dispensed accurately. Instruct patients and caregivers on how to measure and take or administer the correct dose of oxycodone hydrochloride and acetaminophen oral solution and to use extreme caution when measuring the dose. Strongly advise patients to obtain and always use a graduated device that can measure and deliver the prescribed dose accurately, and to never use household teaspoons or tablespoons to measure a dose because these are not accurate measuring devices. Addiction, Abuse, and Misuse Oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a Schedule II controlled substance. As an opioid, oxycodone hydrochloride and acetaminophen oral solution exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxycodone hydrochloride and acetaminophen oral solution. Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see A dverse Reactions ]. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing oxycodone hydrochloride and acetaminophen oral solution, and reassess all patients receiving oxycodone hydrochloride and acetaminophen oral solution for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as oxycodone hydrochloride and acetaminophen oral solution, but use in such patients necessitates intensive counseling about the risks and proper use of oxycodone hydrochloride and acetaminophen oral solution along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [see Warnings; Life-Threatening Respiratory Depression, Dosage and Administration; Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose] . Opioids are sought for nonmedical use and are subjected to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing oxycodone hydrochloride and acetaminophen oral solution. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and the proper disposal of unused drug . Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents (e.g., naloxone, …

CONTRAINDICATIONS Oxycodone hydrochloride and acetaminophen oral solution is contraindicated in patients with: Significant respiratory depression [see Warnings ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings ] Hypersensitivity to oxycodone, acetaminophen, or any other component of the product (e.g., anaphylaxis) [see Warnings, Adverse Reactions ]

ADVERSE REACTIONS The following adverse reactions have been identified during post approval use of oxycodone hydrochloride and acetaminophen oral solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serious adverse reactions that may be associated with oxycodone hydrochloride and acetaminophen oral solution use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock [see Overdosage ]. The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation, and pruritus. Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions. Hematologic reactions may include: Thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of agranulocytosis has likewise been associated with acetaminophen use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur. Other adverse reactions obtained from postmarketing experiences with oxycodone and acetaminophen are listed by organ system and in decreasing order of severity and/or frequency as follows: Body as a Whole –Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose Cardiovascular – Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias Central and Peripheral Nervous System – Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness Fluid and Electrolyte – Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis Gastrointestinal – Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastrointestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus Hepatic – Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder Hearing and Vestibular – Hearing loss, tinnitus Hematologic – Thrombocytopenia Hypersensitivity – Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction Metabolic and Nutritional – Hypoglycemia, hyperglycemia, acidosis, alkalosis Musculoskeletal – Myalgia, rhabdomyolysis Ocular – Miosis, visual disturbances, red eye Psychiatric – Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide Respiratory System – Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema Skin and Appendages – Erythema, urticaria, rash, flushing Urogenital – Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes). Postmarketing Experience Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis: Anaphylaxis has been reported with…