Oxycodone Hydrochloride

1 INDICATIONS AND USAGE Oxycodone Hydrochloride Capsules are an opioid agonist indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. ( 1 ) Limitations of Use ( 1 ) Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Oxycodone Hydrochloride Capsules for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated, or are not expected to be tolerated, Have not provided adequate analgesia, or are not expected to provide adequate analgesia Oxycodone Hydrochloride Capsules are an opioid agonist indicated in adults 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, and misuse with opioids, even at recommended doses, [see Warnings and Precautions ( 5.1 )] , reserve Oxycodone Hydrochloride Capsules for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated, or are not expected to be tolerated, Have not provided adequate analgesia, or are not expected to provide adequate analgesia

2 DOSAGE AND ADMINISTRATION Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. ( 2.1 ) Individualize dosing based on the severity of pain, patient response, and prior analgesic experience, and risk factor for addiction, abuse, and misuse ( 2.1 ) Discuss availability of naloxone with the patient and caregiver and assess each patient's need for access to naloxone, both when initiating and renewing treatment with Oxycodone Hydrochloride Capsules. Consider prescribing naloxone based on the patient's risk factors for overdose ( 2.2 , 5.1 , 5.3 , 5.6 ). Initiate dosing with a range of 5 to 15 mg every 4 to 6 hours as needed for pain. ( 2.3 ) For control of chronic pain, administer Oxycodone Hydrochloride Capsules on a regularly scheduled basis, at the lowest dosage level to achieve adequate analgesia. ( 2.3 ) Individually titrate Oxycodone Hydrochloride Capsules to a dose that provides adequate analgesia and minimizes adverse reactions. ( 2.4 ) Do not abruptly discontinue Oxycodone Hydrochloride Capsules in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.5 ) 2.1 Important Dosage and Administration Instructions Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions (5) ]. Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [ see Warnings and Precautions (5.1) ] . Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Oxycodone Hydrochloride Capsules and adjust the dosage accordingly [ see Warnings and Precautions (5.3) ] . 2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with Oxycodone Hydrochloride Capsules [see Warnings and Precautions ( 5.3 ), Patient Counseling Information (17)]. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see Warnings and Precautions ( 5.1 , 5.3 , 5.6 )]. Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. 2.3 Initial Dosage Although it is not possible to list every condition that is important to the selection of the initial dose of Oxycodone Hydrochloride Capsules, attention must be given to: the daily dose, potency and characteristics of a full agonist or mixed agonist/antagonist the patient has been taking previously the reliability of the relative potency estimate to calculate the dose of oxycodone HCl needed the degree of opioid tolerance the general condition and medical status of the patient, including the patient's weight and age the balance between pain management and adverse reactions the type and severity of the patient's pain risk factors for abuse or addiction, including a prior history of abuse or addiction Use of Oxycodone Hydrochloride Capsules as the First Opioid Analgesic Initiate treatment with Oxycodone Hydrochloride Capsules in a dosing range of 5 to 15 mg every 4 to 6 hours as needed for pain. Titrate the dose based upon the individual patient's response to their initial dose of Oxycodone Hydrochloride Capsules . Patients with chronic pain should have their dosage given on an around-the-clock basis to prevent the reoccurrence of pain rather than treating the pain after it has occurred. This dose can then be adjusted to an acceptable level of analgesia taking into account side effects experienced by the patient. For control of severe chronic pain, Oxycodone Hydrochloride Capsules should be administered on a regularly scheduled basis, every 4 to 6 hours, at the lowest dosage level that will achieve adequate analgesia. Conversion from Other Opioids to Oxycodone Hydrochloride Capsules There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of Oxycodone Hydrochloride Capsules. It is safer to underestimate a patient's 24-hour Oxycodone Hydrochloride Capsules dosage than to overestimate the 24-hour Oxycodone Hydrochloride Capsules dosage and manage an adverse reaction due to overdose. If a patient has been receiving opioid-containing medications prior to taking Oxycodone Hydrochloride Capsules, the potency of the prior opioid relative to oxycodone should be factored into the selection of the total daily dose (TDD) of oxycodone. In converting patients from other opioids to Oxycodone Hydrochloride Capsules, close observation and adjustment of dosage based upon the patient's response to Oxycodone Hydrochloride Capsules is imperative. Administration of supplemental analgesia for breakthrough or incident pain and titration of the total daily dose of Oxycodone Hydrochloride Capsules may be necessary, especially in patients who have disease states that are changing rapidly. Conversion from Oxycodone Hydrochloride Capsules to Extended-Release Oxycodone Hydrochloride The relative bioavailability of Oxycodone Hydrochloride Capsules compared to extended-release oxycodone is unknown, so conversion to extended-release tablets must be accompanied by close observation for signs of excessive sedation and respiratory depression. 2.4 Titration and Maintenance of Therapy Individually titrate Oxycodone Hydrochloride Capsules to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Oxycodone Hydrochloride Capsules to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1 , 5.13 )]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the Oxycodone Hydrochloride Capsules dosage. If unacceptable opioid- related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid- related adverse reactions. 2.5 Safe Reduction or Discontinuation of Oxycodone Hydrochloride Capsules Do not abruptly discontinue Oxycodone Hydrochloride Capsules in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid- dependent patient taking Oxycodone Hydrochloride Capsules, there are a variety of factors that should be considered, including the total daily dose of opioid (including Oxycodone Hydrochloride Capsules) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on Oxycodone Hydrochloride Capsules who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [ see Warnings and Precautions (5.13) , Drug Abuse and Dependence (9.3) ]

4 CONTRAINDICATIONS Significant respiratory depression ( 4 ). Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) Hypersensitivity to oxycodone. ( 4 ) Oxycodone Hydrochloride capsules are contraindicated in patients with: Significant respiratory depression [ see Warnings and Precautions (5.3) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [ see Warnings and Precautions (5.7) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [ see Warnings and Precautions (5.11) ] Hypersensitivity to oxycodone (e.g., angioedema) [ see Adverse Reactions (6) ]

Not available.

6 ADVERSE REACTIONS Most common adverse reactions are nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. To report SUSPECTED ADVERSE REACTIONS, contact Novel Laboratories, Inc. at 1- 866-403-7592 or FDA at 1-800-FDA-1088 or www.fda.gov.medwatch. The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [ see Warnings and Precautions (5.1) ] Life-Threatening Respiratory Depression [ see Warnings and Precautions (5.3) ] Neonatal Opioid Withdrawal Syndrome [ see Warnings and Precautions (5.4) ] Interactions with Benzodiazepines or Other CNS Depressants [ see Warnings and Precautions (5.6) ] Adrenal Insufficiency [ see Warnings and Precautions (5.8) ] Severe Hypotension [ see Warnings and Precautions (5.9) ] Gastrointestinal Adverse Reactions [ see Warnings and Precautions (5.11) ] Seizures [ see Warnings and Precautions (5.12 )] Withdrawal [ see Warnings and Precautions (5.13) ] The following adverse reactions associated with the use of oxycodone were identified in clinical studies or postmarketing reports. Because some of these reactions were 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 associated with oxycodone use included: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock. The common adverse reactions seen on initiation of therapy with oxycodone are dose-related and are typical opioid-related adverse reactions. The most frequent adverse events include nausea, constipation, vomiting, headache, and pruritus. The frequency of these reactions depended on several factors, including clinical setting, the patient's level of opioid tolerance, and host factors specific to the individual. In all patients for whom dosing information was available (n=191) from the open-label and double-blind studies involving another formulation of 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 other less frequently observed adverse reactions from opioid analgesics, including Oxycodone Hydrochloride Capsules included: 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 thrombophlebitis, heart failure, hemorrhage, hypotension, migraine, palpitation, and tachycardia. Digestive: anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea and vomiting. Hemic and Lymphatic: anemia and leukopenia. Metabolic and Nutritional: edema, gout, hyperglycemia, iron deficiency anemia and peripheral edema. Musculoskeletal : arthralgia, arthritis, bone pain, myalgia and pathological fracture. Nervous: 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 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 ingredients contained in Oxycodone Hydrochloride Capsules. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [ see Clinical Pharmacology (12.2) ].