FDA label 2b36bc08-09c9-445c-a5c4-be7fce56a2ce

BOXED WARNING WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Oxycodone and acetaminophen tablets expose 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 oxycodone and acetaminophen tablets, and monitor all patients regularly for the development of these behaviors or conditions (see WARNINGS ). Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone and acetaminophen tablets. Monitor for respiratory depression, especially during initiation of oxycodone and acetaminophen tablets or following a dose increase (see WARNINGS ). Accidental Ingestion Accidental ingestion of even one dose of oxycodone and acetaminophen tablets, especially by children, can result in a fatal overdose of oxycodone and acetaminophen tablets (see WARNINGS ). Neonatal Opioid Withdrawal Syndrome Prolonged use of oxycodone and acetaminophen tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, 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 (see WARNINGS ). Cytochrome P450 3A4 Interaction The concomitant use of oxycodone and acetaminophen tablets with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone and acetaminophen tablets plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone and acetaminophen tablets plasma concentration. Monitor patients receiving oxycodone and acetaminophen tablets and any CYP3A4 inhibitor or inducer (see CLINICAL PHARMACOLOGY , WARNINGS , PRECAUTIONS; Drug Interactions ). 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 4000 milligrams per day, and often involve more than one acetaminophen-containing product (see WARNINGS , PRECAUTIONS , ADVERSE REACTIONS , OVERDOSAGE ). WARNING: RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death (see WARNINGS , PRECAUTIONS; Drug Interactions ). Reserve concomitant prescribing of oxycodone and acetaminophen tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

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, USP immediately and seek medical care if they experience these symptoms. Do not prescribe Oxycodone and Acetaminophen Tablets, USP for patients with acetaminophen allergy.

Head Injury and Increased Intracranial Pressure The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Oxycodone produces effects on pupillary response and consciousness which may obscure neurologic signs of worsening in patients with head injuries.

Hypotensive Effect Oxycodone may cause severe hypotension particularly in individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs which compromise vasomotor tone such as phenothiazines. Oxycodone, like all opioid analgesics of the morphine-type, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. Oxycodone may produce orthostatic hypotension in ambulatory patients.

Hepatotoxicity Precaution should be taken in patients with liver disease. Hepatotoxicity and severe hepatic failure occurred in chronic alcoholics following therapeutic doses.

ADVERSE REACTIONS Postmarketing Experience Serious adverse reactions that may be associated with oxycodone and acetaminophen tablet use include adrenal insufficiency, respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, serotonin syndrome, and shock (see OVERDOSAGE ). Androgen deficiency Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as symptoms of hypogonadism, such as impotence, erectile dysfunction, or amenorrhea. The causal role of opioids in the syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation. 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 tablets 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