Oxycodone hydrochloride (oxycodone 15 mg) Dailymed

• OXYCODONE HYDROCHLORIDE should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1)
• Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of OXYCODONE HYDROCHLORIDE for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1, 5)
• Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. ( 2.1)
• Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. ( 2.1, 5.1)
• Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OXYCODONE HYDROCHLORIDE. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1, 5.2)
• Discuss availability of naloxone with the patient and caregiver and assess each patient's need for access to naloxone, both with initiating and renewing treatment with OXYCODONE HYDROCHLORIDE. Consider prescribing naloxone based on the patient's risk factors for overdose ( 2.2, 5.1, 5.2, 5.3).
• Initiate dosing with a range of 5 to 15 mg every 4 to 6 hours as needed for pain, and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose of OXYCODONE HYDROCHLORIDE. ( 2.3, 2.4)
• Do not abruptly discontinue OXYCODONE HYDROCHLORIDE in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.4, 5.14, 9.3)

2.1 Important Dosage and Administration Instructions

• OXYCODONE HYDROCHLORIDE should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.
• Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of OXYCODONE HYDROCHLORIDE for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks [see Warnings and Precautions ( 5)] .
• Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.
• There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.1)] .
• Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OXYCODONE HYDROCHLORIDE. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions ( 5.2)] .

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 [see Warnings and Precautions ( 5.2)] .

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, 5.2, 5.3)] .

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

Use of OXYCODONE HYDROCHLORIDE as the First Opioid Analgesic

Initiate treatment with OXYCODONE HYDROCHLORIDE in a dosing range of 5 to 15 mg every 4 to 6 hours as needed for pain, and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose of OXYCODONE HYDROCHLORIDE.

Although it is not possible to ul every condition that is important to the selection of the initial dose of OXYCODONE HYDROCHLORIDE, attention should be given to: 1) the daily dose, potency, and characteristics of any prior opioid 2) the reliability of any relative potency estimate used to calculate the dose of oxycodone needed, 3) the degree of opioid tolerance, 4) the general condition and medical status of the patient, and 5) the balance between pain control and adverse experiences.

Conversion from Other Opioids to OXYCODONE HYDROCHLORIDE

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. It is safer to underestimate a patient's 24-hour OXYCODONE HYDROCHLORIDE dosage than to overestimate the 24-hour OXYCODONE HYDROCHLORIDE dosage and manage an adverse reaction due to overdose. If a patient has been receiving opioid-containing medications prior to taking OXYCODONE HYDROCHLORIDE, 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, close observation and adjustment of dosage based upon the patient's response to OXYCODONE HYDROCHLORIDE is imperative. Administration of supplemental analgesia for breakthrough or incident pain and titration of the TDD of OXYCODONE HYDROCHLORIDE may be necessary, especially in patients who have disease states that are changing rapidly.

Conversion From Fixed-Ratio Opioid/Acetaminophen, Opioid/Aspirin, or Opioid/Nonsteroidal Combination Drugs

When converting patients from fixed ratio opioid/non-opioid drug regimens, a decision should be made whether or not to continue the non-opioid analgesic. If a decision is made to discontinue the use of non-opioid analgesic, it may be necessary to titrate the dose of OXYCODONE HYDROCHLORIDE in response to the level of analgesia and adverse effects afforded by the dosing regimen. If the non-opioid regimen is continued as a separate single entity agent, the starting dose of OXYCODONE HYDROCHLORIDE should be based upon the most recent dose of opioid as a baseline for further titration of oxycodone. Incremental increases should be gauged according to side effects to an acceptable level of analgesia.

Conversion from OXYCODONE HYDROCHLORIDE to Extended-Release Oxycodone

The relative bioavailability of OXYCODONE HYDROCHLORIDE compared to extended-release oxycodone products is unknown, so conversion to extended-release oxycodone may lead to increased risk of excessive sedation and respiratory depression.

Conversion from Oxycodone Immediate-Release Tablets

Oxycodone pharmacokinetics are similar for OXYCODONE HYDROCHLORIDE and oxycodone immediate-release tablets. Patients can be converted from oxycodone immediate-release to the same dose and dosing regimen of OXYCODONE HYDROCHLORIDE.

2.4 Titration and Maintenance of Therapy

Individually titrate OXYCODONE HYDROCHLORIDE to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving OXYCODONE HYDROCHLORIDE to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as reassess for the development of addiction, abuse, or misuse [see Warnings and Precautions ( 5.1, 5.14)] . 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 dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage [see Warnings and Precautions ( 5)] . 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

Do not abruptly discontinue OXYCODONE HYDROCHLORIDE 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, there are a variety of factors that should be considered, including the total daily dose of opioid (including OXYCODONE HYDROCHLORIDE) 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 reaulic. 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 comorbid pain and substance use disorders may benefit from referral to a speciaul.

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 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, evaluate 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 an extended period of time, 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 ( 5.14), Drug Abuse and Dependence ( 9.3)] .

3 Dosage Forms And Strengths

OXYCODONE HYDROCHLORIDE tablets, 5 mg, 15 mg and 30 mg with the following characteristics:

Strength	Tablet Shape	Tablet Color	Ink-Print on Tablet Side 1	Ink-Print on Tablet Side 2
5 mg	Round coated tablets	White	IDT/O 5	None
15 mg		Green	IDT/O 15	None
30 mg		Blue	IDT/O 30	None

Tablets: 5 mg, 15 mg, 30 mg ( 3)

4 Contraindications

OXYCODONE HYDROCHLORIDE is contraindicated in patients with:

• Significant respiratory depression [see Warnings and Precautions ( 5.2)]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment or hypercarbia [see Warnings and Precautions ( 5.8)]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.12)]
• Known hypersensitivity (e.g., anaphylaxis) to oxycodone [see Adverse Reactions ( 6.2)]

• 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)

5 Warnings And Precautions

• Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. ( 5.7)
• Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Regularly evaluate, particularly during initiation and titration. ( 5.8)
• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.9)
• Severe Hypotension: Regularly evaluate during dosage initiation and titration. Avoid use of OXYCODONE HYDROCHLORIDE in patients with circulatory shock. ( 5.10)
• 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 in patients with impaired consciousness or coma. ( 5.11)

5.1 Addiction, Abuse, and Misuse

OXYCODONE HYDROCHLORIDE contains oxycodone, a Schedule II controlled substance. As an opioid, OXYCODONE HYDROCHLORIDE exposes 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. Addiction can occur at recommended dosages, when taken as directed, and if the drug is misused or abused.

Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing OXYCODONE HYDROCHLORIDE, and reassess all patients receiving OXYCODONE HYDROCHLORIDE 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 but use in such patients necessitates intensive counseling about the risks and proper use of OXYCODONE HYDROCHLORIDE along with frequent reevaluation 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 ( 5.2)] .

Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing OXYCODONE HYDROCHLORIDE. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and on the proper disposal of unused drugs. 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.

5.2 Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see Overdosage ( 10)] . Carbon dioxide (CO ₂) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of OXYCODONE HYDROCHLORIDE, the risk is greatest during the initiation of therapy or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of OXYCODONE HYDROCHLORIDE are essential [see Dosage and Administration ( 2)] . Overestimating the OXYCODONE HYDROCHLORIDE dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of OXYCODONE HYDROCHLORIDE, especially by children, can result in respiratory depression and death due to an overdose of oxycodone.

Educate patients and caregivers on how to recognize respiratory depression and emphasize on the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose.

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration ( 2.4)] .

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 the treatment with OXYCODONE HYDROCHLORIDE. 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). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered.

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. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone. [see Dosage and Administration ( 2.2), Warnings and Precautions ( 5.1, 5.3), Overdosage ( 10)] .

5.3 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OXYCODONE HYDROCHLORIDE with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ( 7)] .

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including 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 ( 5.2), Overdosage ( 10)] .

Advise both patients and caregivers about the risks of respiratory depression and sedation when OXYCODONE HYDROCHLORIDE is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate dangerous machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions ( 7)] .

5.4 Neonatal Opioid Withdrawal Syndrome

Use of OXYCODONE HYDROCHLORIDE for an extended period of time during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for an extended period of time of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations ( 8.1)] .

5.5 Opioid 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 programoffered 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 their pharmacist every time an opioid analgesic is dispensed to them.
• Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.

To obtain further information on the opioid analgesic REMS and for a ul of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

5.6 Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

Concomitant use of OXYCODONE HYDROCHLORIDE with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions ( 5.2)] , particularly when an inhibitor is added after a stable dose of OXYCODONE HYDROCHLORIDE is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in OXYCODONE HYDROCHLORIDE -treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using OXYCODONE HYDROCHLORIDE with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in OXYCODONE HYDROCHLORIDE -treated patients, evaluate patients at frequent intervals and consider dosage reduction of OXYCODONE HYDROCHLORIDE until stable drugs effects are achieved [see Drug Interactions ( 7)] .

Concomitant use of OXYCODONE HYDROCHLORIDE with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using OXYCODONE HYDROCHLORIDE with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, evaluate patients at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see Drug Interactions ( 7)] .

5.7 Opioid-Induced Hyperalgesia and Allodynia

Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect [see Dependence ( 9.3)] . Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.

Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching the patient to a different opioid moiety) [ see Dosage and Administration ( 2.5), Warnings and Precautions ( 5.14) ].

5.8 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

The use of OXYCODONE HYDROCHLORIDE in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: OXYCODONE HYDROCHLORIDE -treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of OXYCODONE HYDROCHLORIDE [see Warnings and Precautions ( 5.2)] .

Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Warnings and Precautions ( 5.2)] .

Regularly evaluate patients, particularly when initiating and titrating OXYCODONE HYDROCHLORIDE and when OXYCODONE HYDROCHLORIDE is given concomitantly with other drugs that depress respiration [see Warnings and Precautions ( 5.2, 5.3)] . Alternatively, consider the use of non-opioid analgesics in these patients.

5.9 Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

5.10 Severe Hypotension

OXYCODONE HYDROCHLORIDE may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions ( 7)] . Regularly evaluate these patients for signs of hypotension after initiating or titrating the dosage of OXYCODONE HYDROCHLORIDE . In patients with circulatory shock, use of OXYCODONE HYDROCHLORIDE may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid use of OXYCODONE HYDROCHLORIDE in patients with circulatory shock.

5.11 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

In patients who may be susceptible to the intracranial effects of CO ₂retention (e.g., those with evidence of increased intracranial pressure or brain tumors), OXYCODONE HYDROCHLORIDE may reduce the respiratory drive, and the resultant CO ₂retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with OXYCODONE HYDROCHLORIDE.

Opioids may obscure the clinical course in a patient with a head injury. Avoid the use of OXYCODONE HYDROCHLORIDE in patients with impaired consciousness or coma.

5.12 Risks of Use in Patients with Gastrointestinal Conditions

OXYCODONE HYDROCHLORIDE is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus.

The oxycodone in OXYCODONE HYDROCHLORIDE may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Regularly evaluate patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

5.13 Increased Risk of Seizures in Patients with Seizure Disorders

The oxycodone in OXYCODONE HYDROCHLORIDE may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures occurring in other clinical settings associated with seizures. Regularly evaluate patients with a history of seizure disorders for worsened seizure control during OXYCODONE HYDROCHLORIDE therapy.

5.14 Withdrawal

Do not abruptly discontinue OXYCODONE HYDROCHLORIDE in a patient physically dependent on opioids. When discontinuing OXYCODONE HYDROCHLORIDE in a physically-dependent patient, gradually taper the dosage. Rapid tapering of oxycodone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration ( 2.4), Drug Abuse and Dependence ( 9.3)] .

Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including OXYCODONE HYDROCHLORIDE. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions ( 7)] .

5.15 Risks of Driving and Operating Machinery

OXYCODONE HYDROCHLORIDE may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of OXYCODONE HYDROCHLORIDE and know how they will react to the medication.