oxycodone/naloxone (Rx)

Exposes users to risks of addiction, abuse and misuse, which can lead to overdose and death; assess each patient’s risk before prescribing and monitor regularly for development of these behaviors and conditions

Serious, life-threatening, or fatal respiratory depression may occur; monitor closely, especially upon initiation or following a dose increase

Instruct patients to swallow extended-release tablets whole to avoid exposure to a potentially fatal dose of oxycodone

Accidental ingestion, especially in children, can result in a fatal overdose of oxycodone

Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated; 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

Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of oxycodone

Contraindications

Significant respiratory depression

Acute or severe bronchial asthma

Known or suspected paralytic ileus and GI obstruction

Known hypersensitivity to oxycodone or naloxone

Moderate-to-severe hepatic impairment

Cautions

Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected

While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, risk is greatest during initiation of therapy or following dosage increase; monitor patients closely for respiratory depression, especially within first 24 to 72 hr of initiating therapy with and following dosage increases; accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to overdose of opioid

Deaths have occurred in nursing infants exposed to high levels of opioid in breast milk because mothers were ultra-rapid metabolizers of opioid

Profound sedation, respiratory depression, coma, and death may result from concomitant administration 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

Use in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and with 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

Monoamine oxidase inhibitors (MAOIs) may potentiate effects of opioid, opioid’s active metabolite, including respiratory depression, coma, and confusion; therapy should not be administered within 14 days of initiating or stopping MAOIs

Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of 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

Use caution when selecting dosage for an elderly patient, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function

Opioid pharmacokinetics may be altered in patients with renal failure; clearance may be decreased and metabolites may accumulate much higher plasma levels in patients with renal failure as compared to patients with normal renal function; start with a lower than normal dosage or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension

Oxycodone exposes users to the risks of addiction, abuse, and misuse; the tablet is designed to deliver oxycodone over an extended period and contains a larger amount of oxycodone

Do not ingest alcohol or OTC medications containing alcohol while taking opioid analgesics

Interactions with CNS depressants: Concomitant use may cause profound sedation, respiratory depression, and death; if coadministration is required, consider dose reduction of 1 or both drugs

Elderly, cachectic, debilitated patients, and those with chronic pulmonary disease: Monitor closely because of increased risk for life-threatening respiratory depression

May cause severe hypotension, including orthostatic hypotension and syncope; this risk is increased in patients whose ability to maintain blood pressure has been compromised by reduced blood volume or coadministration with certain CNS depressants (eg, phenothiazines, general anesthetics)

Patients with head injury or increased intracranial pressure: Monitor for sedation and respiratory depression; avoid use in patients with impaired consciousness or coma susceptible to intracranial effects of carbon dioxoide retention

Symptoms consistent with opioid withdrawal occurred in some patients in the clinical trials; monitor patients for symptoms of withdrawal during treatment

Concomitant use of CYP3A4 inhibitors may increase opioid effects

CYP3A4 inducers may increase oxycodone clearance, leading to decreased oxycodone plasma concentrations, decreased efficacy, or abstinence syndrome in physically dependent patients

May cause spasm of the sphincter of Oddi; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms (also see Contraindications)

Opioids may cause increases in the serum amylase

May aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings

May impair the mental or physical abilities needed to perform potentially hazardous activities

Avoid the use of mixed agonist/antagonist (ie, pentazocine, nalbuphine, butorphanol) or partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic; mixed agonist/antagonists may reduce the analgesic effect and/or may precipitate withdrawal symptoms

Do not abruptly discontinue; gradually taper the dose to avoid withdrawal symptoms

Prolonged use during pregnancy can result in withdrawal symptoms in the newborn

Opioid-induce hyperalgesia and allodynia

FDA-approved safety considerations for immediate-release (IR) and extended-release/long-acting (ER/LA) opioid analgesics addressing opioid crisis

Pregnancy & Lactation

Pregnancy

Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there are no available data in pregnant women to inform a drug associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects

Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

Severe fetal bradycardia reported when administered during labor; naloxone may reverse these effects; although there are no reports of fetal bradycardia earlier in pregnancy, it is possible it may occur; drug should be used in pregnancy only if clearly needed, if potential benefit outweighs risk to fetus, and if appropriate measures such as fetal monitoring are taken to detect and manage potential adverse effect on fetus

Labor or delivery

Fertility

Lactation

Drug is present in breast milk; published lactation studies report variable concentrations of drug in breast milk with administration of immediate-release formulation to nursing mothers in early postpartum period

The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped

Do not initiate oxycodone/naloxone in breastfeeding women because of the possibility of sedation or respiratory depression in an infant

Withdrawal signs can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped; naloxone may precipitate opioid withdrawal in a breast-fed infant whose mother received opioid analgesics

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.