For the management of acute and chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
There is no evidence that OXAYDO has reduced abuse liability compared with immediate-release oxycodone.
WARNING: ADDICTION, ABUSE, AND MISUSE: RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
OXAYDO exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing OXAYDO, and monitor all patients regularly for the development of these behaviors and conditions.
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 REMS for these products [see Warnings and Precautions (5.2)]. 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
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of OXAYDO. Monitor for respiratory depression, especially during initiation of OXAYDO or following a dose increase.
Accidental ingestion of even one dose of OXAYDO, especially by children, can result in a fatal overdose of oxycodone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of OXAYDO during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Cytochrome P450 3A4 Interaction
The concomitant use of OXAYDO with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving OXAYDO and any CYP3A4 inhibitor or inducer.
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
OXAYDO is indicated for the management of acute and chronic 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, reserve OXAYDO for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products):
OXAYDO is contraindicated in patients with significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; hypersensitivity to oxycodone, oxycodone salts, or any components of the product (e.g., anaphylaxis).
Addiction, Abuse, and Misuse
OXAYDO contains oxycodone, a Schedule II controlled substance. As an opioid, OXAYDO exposes users to the risks of addiction, abuse, and misuse.
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OXAYDO. 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 OXAYDO, and monitor all patients receiving OXAYDO 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 OXAYDO, but use in such patients necessitates intensive counseling about the risks and proper use of OXAYDO along with intensive monitoring for signs of addiction, abuse, and misuse.
Attempts at misuse or abuse of OXAYDO may compromise some of the extended-release properties resulting in delivery of morphine that could lead to overdose and death.
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:
To obtain further information on the opioid analgesic REMS and for a list 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.
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. Carbon dioxide (CO2) 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 OXAYDO, 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 OXAYDO are essential. Overestimating the OXAYDO dose when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of OXAYDO, especially by children, can result in respiratory depression and death due to an overdose of morphine.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of OXAYDO during pregnancy can result in withdrawal in the neonate which may be life-threatening if not recognized and treated. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly.
Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers
Concomitant use of OXAYDO 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, particularly when an inhibitor is added after a stable dose of OXAYDO is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in OXAYDO-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using OXAYDO with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in OXAYDO-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of OXAYDO until stable drug effects are achieved.
Concomitant use of OXAYDO with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid eficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone.
Monitor respectively treated patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur.
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OXAYDO with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
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.
Advise both patients and caregivers about the risks of respiratory depression and sedation when OXAYDO is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy 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.
Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients
The use of OXAYDO 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: OXAYDO-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 OXAYDO.
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.
Monitor such patients closely, particularly when initiating and titrating OXAYDO and when OXAYDO is given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients.
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 suspected, confirm adrenal insufficiency with diagnostic testing as soon as possible. Treat a confirmed case with physiologic replacement doses of corticosteroids until adrenal function recovers. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.
OXAYDO 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). Monitor these patients after initiating or titrating the dosage of OXAYDO. In patients with circulatory shock, avoid the use of OXAYDO because it may cause vasodilation that can further reduce cardiac output and blood pressure.
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 CO2 retention, OXAYDO may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with OXAYDO.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of OXAYDO in patients with impaired consciousness or coma.
Risks of Use in Patients with Gastrointestinal Conditions
OXAYDO is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The oxycodone in OXAYDO may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
Increased Risk of Seizures in Patients with Seizure Disorders
The oxycodone in OXAYDO 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. Monitor patients with a history of seizure disorders for worsened seizure control during OXAYDO therapy.
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 OXAYDO. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms.
When discontinuing OXAYDO in a physically-dependent patient, gradually taper the dosage. Do not abruptly discontinue OXAYDO in these patients.
Risks of Driving and Operating Machinery
OXAYDO 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 OXAYDO and know how they will react to the medication.
Serious adverse reactions that may be associated with OXAYDO include: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock.
The most frequent of the adverse reactions include nausea, constipation, vomiting, headache, and pruritus.
The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Monoamine Oxidase Inhibitors (MAOIs)
MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
May reduce the analgesic effect of OXAYDO and/or precipitate withdrawal symptoms.
Oxycodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. There are no available data with OXAYDO in pregnant women to inform a drug-associated risk for major birth defects and miscarriage.
Labor or Delivery
Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. OXAYDO is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including OXAYDO, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.
Oxycodone is present in breast milk. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, breastfeeding is not recommended during treatment with OXAYDO.
Females and Males of Reproductive Potential
Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.
The safety, effectiveness, and pharmacokinetics of OXAYDO in pediatric patients below the age of 18 have not been established.
Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of OXAYDO slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression.
Since oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepatic impairment. Follow a conservative approach to initiate dosing in patients with hepatic impairment. Monitor patients closely and adjust the dose based on clinical response.
Information from oxycodone HCl indicates that patients with renal impairment had higher plasma concentrations of oxycodone than subjects with normal renal function. Use a conservative approach to initiate dosing in patients with renal impairment. Monitor patients closely and adjust the dose based on clinical response.
Acute overdosage with oxycodone can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations.
Please see Full Prescribing Information, including BOXED WARNING and MEDICATION GUIDE.
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