OXYCODONE HCI 40mg. Tablets.

BOXED WARNING

Like all opioid analgesics, oxycodone is associated with significant potential for overdose or poisoning; proper patient selection and counseling is recommended. The extended-release formulations are not intended for use in the management of pain following surgery, acute pain, or on an as-needed basis; extended-release tablets or capsules are intended only for patients requiring continuous, around-the-clock opioid analgesia for an extended period of time and requires an experienced clinician who is knowledgeable in the use of long-acting opioids for the management of chronic pain. In pediatric patients 11 years or older, the extended-release tablet formulation should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Further, the misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product (parenteral administration) poses a significant risk to the abuser and may result in overdose and death. Parenteral abuse of RoxyBond tablets can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Advise patients and caregivers to strictly adhere to the recommended dosing. Oxycodone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure or improper use may cause respiratory failure and a fatal overdose. Consumption with ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy. Care should be taken to avoid dosing errors due to confusion between oxycodone oral solution 20 mg/mL and other lower concentrations.

Oxycodone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from respiratory failure. Addiction may occur in patients who obtain oxycodone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. The misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product can result in overdose and death. To discourage abuse, the smallest appropriate quantity of oxycodone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

Oxycodone use is contraindicated in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) in unmonitored care settings or in the absence of resuscitative equipment. Oxycodone immediate-release tablets are specifically contraindicated in patients with hypercarbia; receipt of moderate oxycodone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for respiratory depression, low blood pressure, and death. As with other opioid agonists, oxycodone should be avoided in patients with severe pulmonary disease. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxycodone, as even usual therapeutic doses may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Oxycodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention; use of oxycodone extended-release tablets or capsules is not recommended in these patients. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a “sighing” breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring is required, particularly when CYP450 3A4 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma oxycodone concentrations and potentiate the risk of fatal respiratory depression. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxycodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. In these patients, opioid agonists should be used only under careful medical supervision at the lowest effective dose. Due to an unreasonable risk of fatal respiratory depression in patients who are not tolerant to opioids, 60 mg and 80 mg extended-release tablets are only for use in opioid tolerant patients; single extended-release tablet doses more than 40 mg and a total daily dose more than 80 mg are also only indicated in those who are opioid tolerant. Similarly, single extended-release capsule doses more than 36 mg and a total daily dose more than 72 mg are only indicated in patients who are opioid tolerant. In pediatric patients 11 years or older, the extended-release tablet should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Respiratory depression may persist for a significant period of time following the discontinuation of oxycodone controlled-release preparations, and patients require close monitoring until their respiratory rate has stabilized. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxycodone. In animal studies with rats and rabbits, no embryo-fetal toxicity was detected when oxycodone was given during organogenesis at doses 0.5- to 15-times the adult human dose of 160 mg/day. In a pre- and post-natal study in rats, oxycodone given during gestation and lactation at a dose approximately 0.4 times an adult human dose of 160 mg/day was not associated with any long-term developmental or reproductive adverse effects in pups; however, pup weight was transiently decreased during lactation and the early post-weaning period. No drug-related effects on reproductive performance in female rats were observed. Published data with rats indicate that oxycodone may result in neurobehavioral effects, including altered stress response, increased anxiety-like behavior, and altered learning and memory, in offspring when given at clinically relevant doses and below. Oxycodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because oral opioid agonists may cause respiratory depression in the newborn. Further, prolonged maternal use of opioids, such as oxycodone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.

DEA CLASS

Rx, schedule II

DESCRIPTION

Phenanthrene opioid agonist
Used for moderate to severe pain
Some products formulated to deter abuse by inhalation or injection

COMMON BRAND NAMES

Dazidox, Endocodone, ETH-Oxydose, Oxaydo, OxyContin, Oxydose, OxyFast, OxyIR, Percolone, Roxicodone, Roxybond, XTAMPZA

HOW SUPPLIED

Dazidox/Endocodone/Oxaydo/Oxycodone/Oxycodone Hydrochloride/Percolone/Roxicodone/Roxybond Oral Tab: 5mg, 7.5mg, 10mg, 15mg, 20mg, 30mg
ETH-Oxydose/Oxycodone/Oxycodone Hydrochloride/Oxydose/OxyFast/Roxicodone Oral Sol: 1mL, 5mg, 5mL, 20mg
Oxycodone/Oxycodone Hydrochloride/OxyContin Oral Tab ER: 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg
Oxycodone/Oxycodone Hydrochloride/OxyIR Oral Cap: 5mg
XTAMPZA Oral Cap ER: 9mg, 13.5mg, 18mg, 27mg, 36mg

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

Immediate-release dosage forms, extended-release tablets: There is no maximum dose of oxycodone; however, careful titration of oxycodone, especially in opiate-naive patients, is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
Extended-release capsules (Xtampza ER): 288 mg/day PO (equivalent to 320 mg/day oxycodone hydrochloride).

Immediate-release dosage forms, extended-release tablets: There is no maximum dose of oxycodone; however, careful titration of oxycodone, especially in opiate-naive patients, is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
Extended-release capsules (Xtampza ER): 288 mg/day PO (equivalent to 320 mg/day oxycodone hydrochloride).

Extended-release tablets: With appropriate dosage titration, there is no maximum dose of extended-release oxycodone in opioid-tolerant pediatric patients; however, careful titration is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
Immediate-release dosage forms and extended-release capsules (Xtampza ER): Safety and efficacy have not been established.

Extended-release tablets in Children 11 years or older: With appropriate dosage titration, there is no maximum dose of extended-release oxycodone in opioid-tolerant pediatric patients; however, careful titration is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
Extended-release tablets in Children younger than 11 years, immediate-release dosage forms, and extended-release capsules (Xtampza ER): Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Start initial therapy at one-third to one-half the normal dose and titrate dose carefully. Patients with hepatic impairment have higher plasma oxycodone and noroxycodone and lower oxymorphone concentrations than those with normal hepatic function.

Conservative initial dose and dose titration are required. Dosage should be modified depending on clinical response and degree of renal impairment. In patients with CrCl less than 60 mL/minute, the serum concentration of oxycodone is about 50% higher than in patients with normal renal function.

ADMINISTRATION

Oxycodone should be titrated from the initial recommended dosage to the dose required to relieve the patient’s pain and minimize adverse reactions.
There is no maximum dose of oxycodone; however, careful titration is required to avoid adverse reactions (i.e., drowsiness and respiratory depression).

STORAGE

Generic:
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Dazidox :
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
Endocodone :
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
ETH-Oxydose:
– Protect from light
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
Oxaydo:
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
OXECTA:
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
OxyContin:
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
Oxydose :
– Protect from light
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
OxyFast:
– Protect from light
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
OxyIR:
– Protect from light
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
Percolone:
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Roxicodone:
– Protect from light
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
Roxybond:
– Protect from moisture
– Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
XTAMPZA :
– Store at 77 degrees F; excursions permitted to 59-86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Like all opioid analgesics, oxycodone is associated with significant potential for overdose or poisoning; proper patient selection and counseling is recommended. The extended-release formulations are not intended for use in the management of pain following surgery, acute pain, or on an as-needed basis; extended-release tablets or capsules are intended only for patients requiring continuous, around-the-clock opioid analgesia for an extended period of time and requires an experienced clinician who is knowledgeable in the use of long-acting opioids for the management of chronic pain. In pediatric patients 11 years or older, the extended-release tablet formulation should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Further, the misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product (parenteral administration) poses a significant risk to the abuser and may result in overdose and death. Parenteral abuse of RoxyBond tablets can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Advise patients and caregivers to strictly adhere to the recommended dosing. Oxycodone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure or improper use may cause respiratory failure and a fatal overdose. Consumption with ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy. Care should be taken to avoid dosing errors due to confusion between oxycodone oral solution 20 mg/mL and other lower concentrations.

Oxycodone is contraindicated in patients who have or are suspected of having GI obstruction, including paralytic ileus. Due to the effects of opioid agonists on the gastrointestinal tract, oxycodone should be used cautiously in patients with GI disease such as ulcerative colitis (UC). Patients with UC or other inflammatory bowel disease may be more sensitive to constipation caused by opioid agonists. Rarely, intestinal obstruction and exacerbation of diverticulitis requiring surgical intervention to remove the tablet has been reported with OxyContin tablets. Patients at greatest risk of developing these complications include those with underlying GI disease such as gastric cancer (i.e., esophageal cancer or colon cancer with small gastrointestinal lumen); use of alternative analgesics should be considered in these patients. Use the extended-release tablets and Oxecta immediate-release tablets with caution in patients with pre-existing esophageal stricture or dysphagia, as the tablets may swell when exposed to liquids including saliva; choking, gagging, and related events have been reported with postmarket use. Choking, gagging, regurgitation, and tablets getting stuck in the throat have also occurred with OxyContin; do not pre-soak, lick, or wet the tablet prior to ingestion. Do not use Oxecta immediate-release tablets in nasogastric, gastric, or other feeding tubes as obstruction may occur; never crush, cut, chew, break, or dissolve extended-release tablets. Opioid agonists may obscure the diagnosis or clinical course in patients with an acute abdomen. Opioid agonists may exacerbate cases of diarrhea secondary to poisoning or infectious diarrhea, as a reduction in GI motility may occur with use. Antimotility agents have been used successfully in these patients. If possible, opioid agonists should not be given until the toxic substance has been eliminated.

Oxycodone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from respiratory failure. Addiction may occur in patients who obtain oxycodone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. The misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product can result in overdose and death. To discourage abuse, the smallest appropriate quantity of oxycodone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

Oxycodone use is contraindicated in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) in unmonitored care settings or in the absence of resuscitative equipment. Oxycodone immediate-release tablets are specifically contraindicated in patients with hypercarbia; receipt of moderate oxycodone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for respiratory depression, low blood pressure, and death. As with other opioid agonists, oxycodone should be avoided in patients with severe pulmonary disease. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxycodone, as even usual therapeutic doses may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Oxycodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention; use of oxycodone extended-release tablets or capsules is not recommended in these patients. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a “sighing” breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring is required, particularly when CYP450 3A4 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma oxycodone concentrations and potentiate the risk of fatal respiratory depression. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxycodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. In these patients, opioid agonists should be used only under careful medical supervision at the lowest effective dose. Due to an unreasonable risk of fatal respiratory depression in patients who are not tolerant to opioids, 60 mg and 80 mg extended-release tablets are only for use in opioid tolerant patients; single extended-release tablet doses more than 40 mg and a total daily dose more than 80 mg are also only indicated in those who are opioid tolerant. Similarly, single extended-release capsule doses more than 36 mg and a total daily dose more than 72 mg are only indicated in patients who are opioid tolerant. In pediatric patients 11 years or older, the extended-release tablet should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Respiratory depression may persist for a significant period of time following the discontinuation of oxycodone controlled-release preparations, and patients require close monitoring until their respiratory rate has stabilized. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

To reduce the risk of life-threatening adverse effects, do not use oxycodone extended-release 60 mg and 80 mg tablets in opioid-naive patients; these patients should also not receive a single dose of extended-release tablets more than 40 mg or a total daily dose more than 80 mg. Similarly, do not use a single dose of oxycodone extended-release capsules more than 36 mg or a total daily dose more than 72 mg in opioid-naive patients. Use great caution when prescribing all other formulations of oxycodone in non-tolerant patients. Adult patients who are opioid tolerant are those receiving at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, 60 mg oral hydrocodone/day, or an equianalgesic dose of another opioid for 1 week or longer. Further, oxycodone extended-release tablets are not indicated for pain in the immediate postoperative period (the first 12 to 24 hours after surgery) unless the patient is already receiving oxycodone extended-release therapy, or if the pain is expected to be moderate to severe and persist for an extended period of time. Extended-release tablets or capsules should also not be used for the treatment of mild pain or pain that is not expected to persist for an extended period of time, acute pain, or as an as-needed (prn) analgesic. Reserve use of the extended-release tablets or capsules for patients in whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Extended-release oxycodone tablets should only be used in opioid-tolerant pediatric patients 11 years or older who have received opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for 2 days immediately preceding dosing with extended-release oxycodone. The extended-release tablets must be swallowed whole and are not to be cut, broken, chewed, crushed, or dissolved. When the tablet is crushed or broken and/or if its contents are given by intravenous administration or snorted into the nostrils, the extended-release mechanism is defeated and a potentially lethal dose of oxycodone is immediately released.

As with other opioid agonists, oxycodone may cause spasm of the sphincter of Oddi. Biliary effects due to opioid agonists have resulted in increased serum amylase concentrations. Oxycodone should be used with caution in patients with biliary tract disease, including pancreatitis, or undergoing biliary tract surgery.

Abrupt discontinuation of prolonged oxycodone therapy can result in withdrawal symptoms. Gradually taper patients off prolonged oxycodone therapy to avoid a withdrawal reaction. Generally, oxycodone therapy can be decreased by 25% to 50% every 2 to 4 days with careful monitoring. Avoid use of partial agonists (e.g., buprenorphine), mixed agonist/antagonists (e.g., nalbuphine), or pure antagonists (e.g., naloxone) in patients physically dependent on opioids, as an acute withdrawal syndrome may precipitate. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and on the administered dose of the concomitant drug. If treatment of respiratory depression in an individual physically dependent on opioids is necessary, administer the opioid antagonist with extreme care; titrate the antagonist dose by using smaller than usual doses. In addition, the use of partial agonists or mixed agonist/antagonists in patients who have received or are receiving oxycodone should be avoided as these medications may reduce the analgesic effect of oxycodone.

Use oxycodone with caution in patients with CNS depression, toxic psychosis, head trauma, intracranial mass, or increased intracranial pressure. Monitor for signs of drowsiness and depressed respirations, particularly when initiating oxycodone. Opioids may aggravate such conditions and alter neurologic parameters (e.g., level of consciousness, pupillary responses). Oxycodone-induced hypoventilation can produce cerebral hypoxia, carbon dioxide retention, and raise CSF pressure. Avoid the use of oxycodone in patients with impaired consciousness.

Opioid agonists, such as oxycodone, produce cholinergic side effects (by stimulating medullary vagal nuclei) causing bradycardia and vasovagal syncope, and induce the release of histamine. In patients who are unable to maintain blood pressure due to hypovolemia or dehydration, or in those who concurrently receive other agents that compromise vasomotor tone (e.g., phenothiazines or general anesthetics), opioid agonists may induce peripheral vasodilatation and severe hypotension. These effects can cause problems in patients with cardiac disease (e.g., angina, heart failure). Oxycodone should be used with caution in patients with cardiac arrhythmias or orthostatic hypotension. Oxycodone should not be used in patients with circulatory shock.

Oxycodone and other opioid agonists can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with prostatic hypertrophy, urethral stricture, bladder obstruction, pelvic tumors, or renal disease. Drug accumulation or prolonged duration of action may occur in patients with renal failure or hepatic disease. In acute situations, patients require close monitoring to avoid excessive toxicity. In patients with renal impairment (creatinine clearance less than 60 mL/minute), the concentrations of oxycodone are approximately 50% higher than patients with normal renal function. Dose initiation in these patients should be conservative and dosage adjustments based on individual patient response. In patients with hepatic impairment, oxycodone therapy should be initiated at doses one-third to one-half the usual dose and careful dose titration is warranted.

Seizures can be precipitated by opiate agonists in patients with a preexisting seizure disorder. The incidence of these effects during oxycodone therapy is not known, but appears to be rare at normal doses. Monitor patients with a history of seizure disorders for worsened seizure control during therapy.

Use oxycodone with caution in geriatric or debilitated patients. Geriatric or debilitated patients are more susceptible to adverse reactions, especially sedation and respiratory depression, probably as a result of altered distribution of the drug and decreased elimination. Initial doses may need to be reduced, and dosages should be carefully titrated taking into account analgesic effects, adverse reactions, and concomitant drugs that may depress respiration. When using the extended-release tablets, reduce the starting dose to one-third to one-half the usual dosage in debilitated, non-opioid tolerant patients. According to the Beers Criteria, opioid agonists are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, with the exception of pain management due to recent fractures or joint replacement, since opioids can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opioid must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Individuals receiving palliative care or those in hospice settings are excluded from the Beers Criteria; the balance of benefits and harms of medication management for these patients may differ from those of the general population of older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The Guidelines caution that opioids may cause constipation, nausea, vomiting, sedation, lethargy, weakness, confusion, dysphoria, physical and psychological dependency, hallucinations, and unintended respiratory depression, especially in individuals with compromised pulmonary function. These adverse effects can lead to other consequences such as falls. In addition, the initiation of longer-acting opioids (e.g., sustained-release oxycodone) is not recommended unless shorter-acting opioids have been unsuccessful, or titration of shorter-acting doses has established a clear daily dose of opioid analgesic that can be provided by using a long-acting form.

Opioid agonists may be used in children for moderate to severe pain; however, all formulations of oxycodone should be used with caution in children. Immediate-release formulations have not been FDA-approved in neonates, infants, children, or adolescents. Oxycodone extended-release tablets are approved for pediatric use; use may be considered in opioid tolerant patients 11 years or older who have received opioids for at least 5 consecutive days and are taking a minimum of 20 mg per day of oxycodone or its equivalent for 2 days immediately preceding extended-release oxycodone initiation. These tablets cannot be crushed or broken for administration. If the calculated oxycodone dose does not coincide with an available tablet size, the dose should always be rounded down to the nearest available tablet strength. If the calculated dose is less than 20 mg/dose, there is no safe strength for conversion, and the patient should not be initiated on extended-release oxycodone. Accidental ingestion or unintended exposure by children can be fatal. Instruct patients and caregivers to keep all oxycodone dosage forms out of the reach of children and to properly discard all unneeded product. Neonates and infants younger than 6 months of age have highly variable clearance of opioid agonists. Therefore, infants younger than 6 months of age given opioid agonists must be closely monitored for apnea until 24 hours after their last dose. Clinical practice guidelines suggest close monitoring of children up to 1 year of age.

Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxycodone. In animal studies with rats and rabbits, no embryo-fetal toxicity was detected when oxycodone was given during organogenesis at doses 0.5- to 15-times the adult human dose of 160 mg/day. In a pre- and post-natal study in rats, oxycodone given during gestation and lactation at a dose approximately 0.4 times an adult human dose of 160 mg/day was not associated with any long-term developmental or reproductive adverse effects in pups; however, pup weight was transiently decreased during lactation and the early post-weaning period. No drug-related effects on reproductive performance in female rats were observed. Published data with rats indicate that oxycodone may result in neurobehavioral effects, including altered stress response, increased anxiety-like behavior, and altered learning and memory, in offspring when given at clinically relevant doses and below. Oxycodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because oral opioid agonists may cause respiratory depression in the newborn. Further, prolonged maternal use of opioids, such as oxycodone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.

Oxycodone is distributed into breast milk at varying degrees depending upon the dose. There is no information available on the effects of oxycodone on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breast-fed infant, breast-feeding is not recommended during treatment with oxycodone. Monitor infants who are exposed to oxycodone through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants if oxycodone or breast-feeding is discontinued by the mother. A retrospective study compared central nervous system (CNS) depression in breast-feeding infants of mothers receiving oxycodone (n = 139), codeine (n = 210), or acetaminophen (n = 184). Symptoms of CNS depression were determined through questionnaires completed by the mothers. CNS depression was significantly higher in breast-fed infants exposed to oxycodone compared to acetaminophen (20.1% vs. 0.5%, p less than 0.0001) and was not significantly different compared to infants exposed to codeine (16.7%, p more than 0.05). The median doses of both oxycodone and codeine in the mothers with infants that experienced symptoms were significantly higher compared to those that did not (oxycodone 0.4 mg/kg/day vs. 0.15 mg/kg/day, p = 0.0005; codeine 1.4 mg/kg/day vs. 0.9 mg/kg/day, p less than 0.001).

Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible. Monitor patients for symptoms of opioid-induced endocrinopathy. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.

Any patient receiving oxycodone should be warned about the possibility of sedation and to use caution when driving or operating machinery.

Although true opiate agonist hypersensitivity is rare, use of oxycodone is contraindicated in patients with a history of oxycodone hypersensitivity. Use this medication with caution, if at all, in patients who have demonstrated a prior hypersensitivity reaction to other opioid agonists of the phenanthrene subclass including morphine, codeine, and hydromorphone. It may be possible to treat these patients with an opioid agonist from the phenylpiperidine subclass (meperidine or fentanyl) or the diphenylheptane subclass (methadone).

Use oxycodone with caution in patients with adrenal insufficiency (i.e., Addison’s disease), hypothyroidism, or myxedema. Such patients may be at increased risk of adverse events. Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH); however, the thyroid stimulating hormone may be either stimulated or inhibited by opioids. Rarely, adrenal insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency. In addition, chronic opioid use may lead to symptoms of hypogonadism, resulting from changes in the hypothalamic-pituitary-gonadal axis. Monitor patients for symptoms of opioid-induced endocrinopathy, particularly those receiving a daily dose equivalent to 100 mg or more of morphine. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.