OXYCODONE AND ACETAMINOPHEN

WARNINGS Addiction, Abuse, and Misuse Oxycodone and Acetaminophen Tablets contain oxycodone, a Schedule II controlled substance. As an opioid, Oxycodone and Acetaminophen Tablets 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 and Acetaminophen Tablets. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Oxycodone and Acetaminophen Tablets, and monitor all patients receiving Oxycodone and Acetaminophen Tablets 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 and Acetaminophen Tablets, but use in such patients necessitates intensive counseling about the risks and proper use of Oxycodone and Acetaminophen Tablets along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Oxycodone and Acetaminophen Tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see PRECAUTIONS; Information for Patients/Caregivers ]. 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. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following: Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain. Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG . Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them. Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities. To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint. 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 antagonists, depending on the patient’s clinical status [see OVERDOSAGE ]. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Oxycodone and Acetaminophen Tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of Oxycodone and Acetaminophen Tablets. To reduce the risk of respiratory depression, proper dosing and titration of Oxycodone and Acetaminophen Tablets are essential [see DOSAGE AND ADMINISTRATION ]. Overestimating the Oxycodone and Acetaminophen Tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of Oxycodone and Acetaminophen Tablets, especially by children, can result in respiratory depression and death due to an overdose of Oxycodone and Acetaminophen Tablets. Neonatal Opioid Withdrawal Syndrome Prolonged use of Oxycodone and Acetaminophen Tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see PRECAUTIONS; Information for Patients/Caregivers , Pregnancy ] . Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of Oxycodone and Acetaminophen Tablets with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone hydrochloride and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see WARNINGS ], particularly when an inhibitor is added after a stable dose of Oxycodone and Acetaminophen Tablets is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Oxycodone and Acetaminophen Tablets-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using Oxycodone and Acetaminophen Tablets with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Oxycodone and Acetaminophen Tablets-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of Oxycodone and Acetaminophen Tablets until stable drug effects are achieved [see PRECAUTIONS; Drug Interactions ]. Concomitant use of Oxycodone and Acetaminophen Tablets with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease oxycodone hydrochloride plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone hydrochloride. When using Oxycodone and Acetaminophen Tablets with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see PRECAUTIONS; Drug Interactions ]. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Oxycodone and Acetaminophen Tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see PRECAUTIONS; Drug Interactions ]. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when Oxycodone and Acetaminophen Tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs. Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of Oxycodone and Acetaminophen Tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. Patients with Chronic Pulmonary Disease: Oxycodone and Acetaminophen Tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Oxycodone and Acetaminophen Tablets [see WARNINGS; Life- Threatening Respiratory Depression ]. Elderly, Cachetic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see WARNINGS; Life-Threatening Respiratory Depression ]. Monitor such patients closely, particularly when initiating and titrating Oxycodone and Acetaminophen Tablets and when Oxycodone and Acetaminophen Tablets are given concomitantly with other drugs that depress respiration [see WARNINGS; Life-Threatening Respiratory Depression ]. Alternatively, consider the use of non-opioid analgesics in these patients. Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. Severe Hypotension Oxycodone and Acetaminophen Tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see PRECAUTIONS; Drug Interactions ]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of Oxycodone and Acetaminophen Tablets. In patients with circulatory shock Oxycodone and Acetaminophen Tablets may cause vasodilatation that can further reduce cardiac output and blood pressure. Avoid the use of Oxycodone and Acetaminophen Tablets with circulatory shock. Hepatotoxicity 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 4,000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products. The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen. Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4,000 milligrams of acetaminophen per day, even if they feel well. Serious Skin Reactions Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Hypersensitivity/Anaphylaxis There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue Oxycodone and Acetaminophen Tablets immediately and seek medical care if they experience these symptoms. Do not prescribe Oxycodone and Acetaminophen Tablets for patients with acetaminophen allergy [see PRECAUTIONS; Information for Patients/Caregivers ]. Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO 2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), Oxycodone and Acetaminophen Tablets may reduce respiratory drive, and the resultant CO 2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Oxycodone and Acetaminophen Tablets. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Oxycodone and Acetaminophen Tablets in patients with impaired consciousness or coma. Risks of Use in Patients with Gastrointestinal Conditions Oxycodone and Acetaminophen Tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The administration of Oxycodone and Acetaminophen Tablets, or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions. The oxycodone in Oxycodone and Acetaminophen Tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Increased Risk of Seizures in Patients with Seizure Disorders The oxycodone in Oxycodone and Acetaminophen Tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Oxycodone and Acetaminophen Tablets therapy. Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including Oxycodone and Acetaminophen Tablets. In these patients, mixed agonist/antagonist and partial analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms. When discontinuing Oxycodone and Acetaminophen Tablets, gradually taper the dosage [see DOSAGE AND ADMINISTRATION ]. Do not abruptly discontinue Oxycodone and Acetaminophen Tablets [see DRUG ABUSE AND DEPENDENCE ]. Risks of Driving and Operating Machinery Oxycodone and Acetaminophen Tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Oxycodone and Acetaminophen Tablets and know how they will react to the medication [see PRECAUTIONS; Information for Patients/Caregivers ].