FDA label bf529560-a387-4f22-b83c-bfe6ba82dc1f

5 WARNINGS AND PRECAUTIONS Respiratory depression: Increased risk in elderly, debilitated patients, those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction. ( 5.1 ) Controlled substance: Oxycodone HCl is a Schedule II controlled substance with an abuse liability similar to other opioids. ( 5.2 ) CNS effects: Additive CNS depressive effects when used in conjunction with alcohol, other opioids, or illicit drugs. ( 5.3 ) Elevation of intracranial pressure: May be markedly exaggerated in the presence of head injury, or other intracranial lesions. ( 5.4 ) Hypotensive effect: Increased risk with compromised ability to maintain blood pressure. ( 5.5 ) Prolonged gastric obstruction: In patients with gastrointestinal obstruction, especially paralytic ileus. ( 5.6 ) Sphincter of Oddi spasm and diminished biliary/pancreatic secretions. Increased risk with biliary tract disease. ( 5.7 ) Special Risk Groups: Use with caution and in reduced dosages in patients with severe renal or hepatic impairment, Addison’s disease, hypothyroidism, prostatic hypertrophy, or urethral stricture, or in elderly or debilitated patients. ( 5.8 ) Impaired mental/physical abilities: Must use caution with potentially hazardous activities. ( 5.9 ) Concomitant use of CYP3A4 inhibitors may increase opioid effects. ( 5.10 ) 5.1 Respiratory Depression Respiratory depression is the primary risk of OXAYDO. Respiratory depression occurs more frequently in elderly or debilitated patients, in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, or following large initial doses of opioids given to non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration (e.g., benzodiazepines, tricyclic antidepressants, and sedative-hypnotics). OXAYDO must be used with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale, and in patients having substantially decreased respiratory reserve (e.g., severe kyphoscoliosis), hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of OXAYDO may decrease respiratory drive to the point of apnea. In these patients, alternative non-opioid analgesics should be considered, and opioids must be employed only under careful medical supervision at the lowest effective dose. 5.2 Misuse and Abuse of Opioids OXAYDO contains oxycodone HCl, an opioid agonist and a Schedule II controlled substance. Such drugs are sought by drug abusers and people with addiction disorders. OXAYDO can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing oxycodone HCl in situations where the physician or pharmacist is concerned about an increased risk of misuse or abuse. OXAYDO may be abused by crushing, chewing, snorting or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death [see Drug Abuse and Dependence ( 9 )] . Concerns about abuse and addiction should not prevent the proper management of pain. Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or misuse of this product. 5.3 Central Nervous System Depressants Patients receiving narcotic analgesics, general anesthetics, phenothiazines, benzodiazepines, other tranquilizers, sedative-hypnotics, or other central nervous system depressants concomitantly with OXAYDO may exhibit an additive central nervous system depression. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these drugs are taken in combination with the usual dosage of OXAYDO. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Patients should not consume alcoholic beverages, or any medications containing alcohol while taking OXAYDO. 5.4 Head Injury and Increased Intracranial Pressure In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the possible respiratory depressant effects of OXAYDO and its potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO 2 retention) may be markedly exaggerated. Furthermore, OXAYDO can produce effects on pupillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries. 5.5 Hypotensive Effect OXAYDO may cause severe hypotension in patients whose ability to maintain blood pressure has been compromised by a depleted intravascular volume, or after concurrent administration with drugs such as phenothiazines, general anesthetics or other agents which compromise vasomotor tone. OXAYDO may produce orthostatic hypotension in ambulatory patients. OXAYDO must be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. 5.6 Gastrointestinal Effects Do not administer OXAYDO to patients with gastrointestinal obstruction, especially paralytic ileus because oxycodone HCl diminishes propulsive peristaltic waves in the gastrointestinal tract and may prolong the obstruction. The administration of OXAYDO may obscure the diagnosis or clinical course in patients with acute abdominal condition. 5.7 Use in Pancreatic/Biliary Tract Disease Use OXAYDO with caution in patients with biliary tract disease, including acute pancreatitis, as oxycodone HCl may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions. 5.8 Special Risk Groups Use OXAYDO with caution and in reduced dosages in patients with severe renal or hepatic impairment, Addison’s disease, hypothyroidism, prostatic hypertrophy, or urethral stricture, and in elderly or debilitated patients [see Use in Specific Populations ( 8 )] . Exercise caution in the administration of OXAYDO to patients with CNS depression, toxic psychosis, acute alcoholism and delirium tremens. All opioids may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings. Keep OXAYDO out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately. 5.9 Driving and Operating Machinery OXAYDO may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating heavy machinery. The patient using OXAYDO must be cautioned accordingly [see Drug Interactions ( 7 )] . 5.10 Cytochrome P450 3A4 Inhibitors and Inducers Since the CYP3A4 isoenzyme plays a major role in the metabolism of oxycodone, drugs that alter CYP3A4 activity may cause changes in clearance of oxycodone which could lead to changes in oxycodone plasma concentrations. The expected clinical results with CYP3A4 inhibitors would be an increase in oxycodone plasma concentrations and possibly increased or prolonged opioid effects. The expected clinical results with CYP3A4 inducers would be a decrease in oxycodone plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If co-administration is necessary, caution is advised when initiating oxycodone treatment in patients currently taking, or discontinuing, CYP3A4 inhibitors or inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved [see Drug Interactions ( 7.5 ) and Clinical Pharmacology ( 12.3 )] .

6 ADVERSE REACTIONS The most common adverse reactions are nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Egalet US Inc. at 1-800-518-1084 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in 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 clinical practice. Serious adverse reactions that may be associated with OXAYDO include: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock [see Warnings and Precautions ( 5 ) and Overdosage ( 10 )] . The common adverse reactions seen on initiation of therapy with OXAYDO are dose-dependent, and their frequency depends on the clinical setting, the patient’s level of opioid tolerance, and host factors specific to the individual. They should be expected and managed as a part of opioid therapy. The most frequent of the adverse reactions include nausea, constipation, vomiting, headache, and pruritus. The frequency of adverse reactions during initiation of opioid therapy may be minimized by careful individualization of starting dosage, slow titration and the avoidance of large rapid swings in plasma concentration of the opioid. Many of these adverse reactions will abate as therapy is continued and some degree of tolerance is developed, but others may be expected to remain throughout therapy. In all patients for whom dosing information was available (n=191) from open-label and double-blind studies involving oxycodone, the following adverse reactions were recorded in oxycodone-treated patients with an incidence of ≥3%. In descending order of frequency they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. The following adverse reactions occurred in less than 3% of patients involved in clinical trials with oxycodone: Body as a Whole: abdominal pain, accidental injury, allergic reaction, back pain, chills and fever, fever, flu syndrome, infection, neck pain, pain, photosensitivity reaction, and sepsis. Cardiovascular: deep vein thrombophlebitis, heart failure, hemorrhage, hypotension, migraine, palpitation, and tachycardia. Digestive: anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea and vomiting. Hematopoietic and Lymphatic: anemia and leukopenia. Metabolism and Nutrition: edema, gout, hyperglycemia, iron deficiency anemia, and peripheral edema. Musculoskeletal: arthralgia, arthritis, bone pain, myalgia, and pathological fracture. Nervous System: agitation, anxiety, confusion, dry mouth, hypertonia, hypesthesia, nervousness, neuralgia, personality disorder, tremor, and vasodilation. Respiratory: bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder, pharyngitis, rhinitis, and sinusitis. Skin and Appendages: herpes simplex, rash, sweating, and urticaria. Special Senses: amblyopia. Urogenital: urinary tract infection.