Oxycodone Hydrochloride 5 mg Capsule, 30-count — NDC 40032-950-03 (Billing 40032-0950-03)

5 WARNINGS AND PRECAUTIONS Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration ( 5.7 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid ( 5.8 ) Severe Hypotension: Monitor during dosage initiation and titration. Avoid use of Oxycodone Hydrochloride Capsules in patients with circulatory shock ( 5.9 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression.

Avoid use of Oxycodone Hydrochloride Capsules in patients with impaired consciousness or coma. ( 5.10 )

5.1Addiction, Abuse, and Misuse Oxycodone Hydrochloride Capsules contain oxycodone, a Schedule II controlled substance. As an opioid, Oxycodone Hydrochloride Capsules expose users to the risks of addiction, abuse, and misuse [ see Drug Abuse and Dependence (9) ]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Oxycodone Hydrochloride Capsules.

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 Hydrochloride Capsules, and monitor all patients receiving Oxycodone Hydrochloride Capsules 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 Hydrochloride Capsules, but use in such patients necessitates intensive counseling about the risks and proper use of Oxycodone Hydrochloride Capsules along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( 2.2 ),Warnings and Precautions ( 5.3 )].

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 Hydrochloride Capsules. 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.

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.

5.2Opioid 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… [Excerpted — this section continues on DailyMed.]

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 defic… [Excerpted — this section continues on DailyMed.]

7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with Oxycodone Hydrochloride Capsules Table 1: Clinically Significant Drug Interactions with Oxycodone Hydrochloride Capsules Inhibitors of CYP3A4 and CYP2D6 Clinical Impact: The concomitant use of Oxycodone Hydrochloride Capsules and CYP3A4 inhibitors can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of Oxycodone Hydrochloride Capsules and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of Oxycodone Hydrochloride Capsules is achieved [see Warnings and Precautions ( 5.5 )].

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will decrease [see Clinical Pharmacology ( 12.3 )] , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oxycodone. Intervention: If concomitant use is necessary, consider dosage reduction of Oxycodone Hydrochloride Capsules until stable drug effects are achieved. Evaluate patients for respiratory depression and sedation at frequent intervals.

If a CYP3A4 inhibitor is discontinued, consider increasing the Oxycodone Hydrochloride Capsules dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of Oxycodone Hydrochloride Capsules and CYP3A4 inducers can decrease the plasma concentration of oxycodone [see Clinical Pharmacology ( 12.3 )] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone [see Warnings and Precautions ( 5.5 )].

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone plasma concentration will increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the Oxycodone Hydrochloride Capsule dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal.

If a CYP3A4 inducer is discontinued, consider Oxycodone Hydrochloride Capsule dosage reduction and evaluate for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5,1 , 5,3 , 5.6 )].

Examples : Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

Discontinue Oxycodone Hydrochloride Capsules if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine re… [Excerpted — this section continues on DailyMed.]

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Oxycodone Hydrochloride Capsules contains oxycodone, a Schedule II controlled substance

9.2Abuse Oxycodone Hydrochloride Capsules contains oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol. Oxycodone Hydrochloride Capsules can be abused and is subject to misuse, addiction, and criminal diversion [ see Warnings and Precautions (5.1) ] . All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. "Drug-seeking" behavior is very common in persons with substance use disorders.

Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated "loss" of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

Oxycodone Hydrochloride Capsules, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Oxycodone Hydrochloride Capsules Oxycodone Hydrochloride Capsules are for oral use only. Abuse of oxycodone poses a risk of overdose and death. The risk is increased with concurrent use of alcohol and/or other CNS depressants.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

9.3Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorp… [Excerpted — this section continues on DailyMed.]

9.1Controlled Substance Oxycodone Hydrochloride Capsules contains oxycodone, a Schedule II controlled substance