FDA label f2bbcfcb-b0de-413e-aca1-cc786d10b7c1

WARNING: RISK OF MEDICATION ERRORS Oxycodone Hydrochloride Oral Solution USP is available as a 100 mg per 5 mL (20 mg/mL) concentration and is indicated for use in opioid-tolerant patients only. Take care when prescribing and administering Oxycodone Hydrochloride Oral Solution USP to avoid dosing errors due to confusion between mg and mL, and other oxycodone solutions with different concentrations, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. Keep Oxycodone Hydrochloride Oral Solution USP out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately. WARNING: RISK OF MEDICATION ERRORS See full prescribing information for complete boxed warning Oxycodone Hydrochloride Oral Solution USP, 100 mg per 5 mL (20 mg/mL) is available in one concentration, as 20 mg oxycodone hydrochloride per mL of solution. The 100 mg per 5 mL (20 mg/mL) concentration is indicated for use in opioid-tolerant patients only. Take care to avoid dosing errors due to confusion between mg and mL, and other oxycodone solutions with different concentrations, which could result in accidental overdose and death. (5.1) Keep Oxycodone Hydrochloride Oral Solution USP out of the reach of children.

IMPORTANT: Keep oxycodone hydrochloride oral solution in a safe place away from children. Accidental use by a child is a medical emergency and can cause death. If a child accidentally takes oxycodone hydrochloride oral solution, get emergency help right away.

5 WARNINGS AND PRECAUTIONS Risk of Medication Errors: Use caution when prescribing, dispensing, and administering to avoid dosing errors due to confusion between different concentrations and between mg and mL, which could result in accidental overdose and death. (5.1) • Respiratory depression: Increased risk in elderly, debilitated patients, those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction. (5.2) • Misuse, Abuse and Diversion: Oxycodone hydrochloride is a Schedule II controlled substance with an abuse liability similar to other opioids. (5.3) • CNS effects: Additive CNS depressive effects when used in conjunction with alcohol, other opioids, or illicit drugs. (5.4) • Elevation of intracranial pressure: May be markedly exaggerated in the presence of head injury, other intracranial lesions. (5.5) • Hypotensive effect: Increased risk with compromised ability to maintain blood pressure. (5.6) • Prolonged gastric obstruction: In patients with gastrointestinal obstruction, especially paralytic ileus. (5.7) • Sphincter of Oddi spasm and diminished biliary/pancreatic secretions. Increased risk with biliary tract disease. (5.8) • 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, elderly, CNS depression, toxic psychosis, acute alcoholism and delirium tremens, may aggravate or induce seizures. (5.9) • Impaired mental/physical abilities: Caution must be used with potentially hazardous activities. (5.10) • Concomitant use of CYP3A4 inhibitors may increase opioid effects (5.11) • 5.1 Risk of Medication Errors Oxycodone hydrochloride oral solution is available in 100 mg per 5 mL (20 mg/mL) concentration. Use caution when prescribing, dispensing, and administering oxycodone hydrochloride oral solution to avoid dosing errors due to confusion between mg and mL, and other oxycodone solutions with different concentrations, which could result in accidental overdose and death. Use caution to ensure the dose is communicated clearly and dispensed accurately. Always use the enclosed calibrated syringe when administering oxycodone hydrochloride oral solution 100 mg per 5 mL (20 mg/mL) to ensure the dose is measured and administered accurately. 5.2 Respiratory Depression Respiratory depression is the primary risk of oxycodone hydrochloride. Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation. Use oxycodone hydrochloride with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale and in patients having a substantially decreased respiratory reserve (e.g., severe kyphoscoliosis), hypoxia, hypercapnia, or preexisting respiratory depression. In such patients, even usual therapeutic doses of oxycodone hydrochloride may increase airway resistance and decrease respiratory drive to the point of apnea. Consider alternative non-opioid analgesics, and use oxycodone hydrochloride only under careful medical supervision at the lowest effective dose in such patients. Oxycodone hydrochloride 100 mg per 5 mL (20 mg/mL) oral solution is for use in . Administration of this formulation may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids. opioid-tolerant patients only 5.3 Misuse, Abuse and Diversion of Opioids Oxycodone hydrochloride is an opioid agonist and a Schedule II controlled substance. Such drugs are sought by drug abusers and people with addiction disorders. Diversion of Schedule II products is an act subject to criminal penalty. Oxycodone hydrochloride can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing oxycodone hydrochloride in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Oxycodone hydrochloride 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, addiction, and diversion 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 diversion of this product. 5.4 Interactions with Alcohol and Drugs of Abuse Oxycodone hydrochloride may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, profound sedation, coma or death may result. 5.5 Use In 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 oxycodone hydrochloride and its potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO retention) may be markedly exaggerated. Furthermore, oxycodone hydrochloride can produce effects on pupillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries. 2 5.6 Hypotensive Effect Oxycodone hydrochloride may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume or concurrent administration of drugs such as phenothiazines or general anesthetics. Oxycodone hydrochloride may produce orthostatic hypotension and syncope in ambulatory patients. Administer oxycodone hydrochloride with caution to patients in circulatory shock, as vasodilation produced by the drug may further reduce cardiac output and blood pressure. 5.7 Gastrointestinal Effects Do not administer oxycodone hydrochloride to patients with gastrointestinal obstruction, especially paralytic ileus because oxycodone hydrochloride diminishes propulsive peristaltic waves in the gastrointestinal tract and may prolong the obstruction. The administration of oxycodone hydrochloride may obscure the diagnosis or clinical course in patients with acute abdominal condition. 5.8 Use In Pancreatic/Biliary Tract Disease Use oxycodone hydrochloride with caution in patients with biliary tract disease, including acute pancreatitis, as oxycodone hydrochloride may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions. 5.9 Special Risk Groups Use oxycodone hydrochloride 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 (8.5)] Exercise caution in the administration of oxycodone hydrochloride 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 oxycodone hydrochloride oral solution out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately. 5.10 Driving and Operating Machinery Caution patients that oxycodone hydrochloride could impair the mental and/or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Caution patients about the potential combined effects of oxycodone hydrochloride with other CNS depressants, including other opioids, phenothiazines, sedative/hypnotics and alcohol. [See Drug Interactions (7)] 5.11 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. [Drug Interactions (7.4) and Clinical Pharmacology (12.3)]

6 ADVERSE REACTIONS Serious adverse reactions that may be associated with oxycodone therapy in clinical use are those observed with other opioid analgesics and include: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock. The common adverse events seen on initiation of therapy with oxycodone are also typical opioid side effects. These events 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 adverse events include nausea, constipation, vomiting, headache, and pruritus. The frequency of adverse events 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 common adverse events may 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 the open-label and double-blind studies involving immediate-release oxycodone, the following adverse events were recorded in oxycodone treated patients with an incidence ≥3%. In descending order of frequency they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. The following adverse experiences occurred in less than 3% of patients involved in clinical trials with oxycodone: abdominal pain, accidental injury, allergic reaction, back pain, chills and fever, fever, flu syndrome, infection, neck pain, pain, photosensitivity reaction, and sepsis. Body as a Whole: : deep thrombophlebitis, heart failure, hemorrhage, hypotension, migraine, palpitation, and tachycardia. Cardiovascular : anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea and vomiting. Digestive : anemia and leukopenia. Hemic and Lymphatic : edema, gout, hyperglycemia, iron deficiency anemia and peripheral edema. Metabolic and Nutritional : arthralgia, arthritis, bone pain, myalgia and pathological fracture. Musculoskeletal agitation, anxiety, confusion, dry mouth, hypertonia, hypesthesia, nervousness, neuralgia, personality disorder, tremor, and vasodilation. Nervous: : bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder, pharyngitis, rhinitis, and sinusitis. Respiratory : herpes simplex, rash, sweating, and urticaria. Skin and Appendages : amblyopia. Special Senses : urinary tract infection Urogenital Most common adverse reactions are nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. (6) To report SUSPECTED ADVERSE REACTIONS, contact Roxane Laboratories, Inc at 800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch