ox-i-KOE-done

Therapeutic Classification: opioid analgesics

Pharmacologic Classification: opioid agonists, opioid agonists nonopioid analgesic combinations

• Moderate to severe pain.
• Pain severe enough to require daily, around-the-clock long-term opioid treatment and for which alternative treatment options are inadequate (extended release [ER]) (children 11 yr should be tolerating a minimum opioid dose of 20 mg of oxycodone or equivalent for 5 days before initiating ER oxycodone therapy).

• Binds to opiate receptors in the CNS.
• Alters the perception of and response to painful stimuli, while producing generalized CNS depression.

• Decreased pain.

Absorption: Well absorbed from the GI tract.

Distribution: Widely distributed to tissues.

Protein Binding: 38–45%.

Metabolism/Excretion: Mostly metabolized by the liver by the CYP3A4 isoenzyme and to a lesser extent by the CYP2D6 isoenzyme.

Half-life: 2–3 hr.

(analgesic effects)

†Extended release.

Contraindicated in:

• Hypersensitivity
• Some products contain alcohol or bisulfites and should be avoided in patients with known intolerance or hypersensitivity
• Significant respiratory depression
• Paralytic ileus
• Acute or severe bronchial asthma
• Acute, mild, intermittent, or postoperative pain (ER).

Use Cautiously in:

• Personal or family history of substance use disorder or mental illness
• Head trauma
• ↑intracranial pressure
• Severe renal impairment
• Severe hepatic impairment
• Hypothyroidism
• Adrenal insufficiency
• Seizure disorders
• Undiagnosed abdominal pain
• Prostatic hyperplasia
• Difficulty swallowing or GI disorders that may predispose patient to obstruction (↑ risk for GI obstruction)
• OB: Avoid chronic use; prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Children <11 yr (safety and effectiveness of ER products not established)
• Geri: ↑risk of respiratory depression in older adults; initial dose ↓ recommended.

CV: orthostatic hypotension.

Derm: flushing, sweating.

EENT: blurred vision, diplopia, miosis.

Endo: adrenal insufficiency.

GI: constipation, choking, dry mouth, GI obstruction, nausea, vomiting.

GU: urinary retention.

Neuro: confusion, sedation, dizziness, dysphoria, euphoria, floating feeling, hallucinations, headache, unusual dreams.

Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA).
Misc: allodynia, opioid-induced hyperalgesia, physical dependence, psychological dependence, tolerance.

Drug-Drug:

• Use with caution in patients receiving MAO inhibitors (may result in unpredictable reactions; ↓ initial dose of oxycodone to 25% of usual dose).
• Additive CNS depression with alcohol, antihistamines, and sedative/hypnotics.
• Mixed agonist/antagonist analgesics, including nalbuphine or butorphanol, and partial agonist analgesics, including buprenorphine, may ↓ oxycodone's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
• Concurrent use of CYP3A4 inhibitors, including ritonavir, ketoconazole, itraconazole, fluconazole, clarithromycin, erythromycin, nefazodone, diltiazem, verapamil, nelfinavir, and fosamprenavir, ↑ levels and risk of opioid toxicity; careful monitoring during initiation, dose changes, or discontinuation of the inhibitor is recommended.
• Concurrent use with CYP3A4 inducers, including barbiturates, carbamazepine, efavirenz, corticosteroids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, or rifampin, may ↓ fentanyl levels and analgesia; if inducers are discontinued or dosage ↓, patients should be monitored for signs of opioid toxicity, and necessary dose adjustments should be made.
• CYP2D6 inhibitors may ↑ levels.
• Use with benzodiazepines or other CNS depressants, including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
• Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5-HT₃ receptor antagonists, linezolid, methylene blue, and triptans, ↑ risk of serotonin syndrome.

• PO (Adults 50 kg): Opioid-naive patients: 5–10 mg (immediate release [IR]) every 3–4 hr initially, as needed. Once optimal analgesia is obtained, patients with chronic pain may be converted to an equivalent 24-hr dose given in 2 divided doses as ER tablets every 12 hr.
• PO (Adults <50 kg): Opioid-naive patients: 0.2 mg/kg (IR) every 3–4 hr initially, as needed. Once optimal analgesia is obtained, patients with chronic pain may be converted to an equivalent 24-hr dose given in 2 divided doses as ER tablets every 12 hr.
• PO (Children 11 yr): 0.05–0.15 mg/kg (IR) every 4–6 hr as needed, as immediate-release product. Once optimal analgesia is obtained, patients with chronic pain may be converted to an equivalent 24-hr dose given in 2 divided doses as ER tablets every 12 hr.
• Rect (Adults): 10–40 mg 3–4 times daily initially, as needed.

(Generic available)

• Immediate-release tablets (Roxicodone): 5 mg; 10 mg; 15 mg; 20 mg; 30 mg;
• Immediate-release tablets (abuse deterrent) (Roxybond): 5 mg; 15 mg; 30 mg;
• Immediate-release capsules: 5 mg;
• Oral solution: 5 mg/5 mL; 100 mg/5 mL (concentrated);
• Extended-release tablets (abuse deterrent) (Oxycontin): 10 mg; 15 mg; 20 mg; 30 mg; 40 mg; 60 mg; 80 mg;
• Extended-release capsules (abuse deterrent) (Xtampza ER): 9 mg; 13.5 mg; 18 mg; 27 mg; 36 mg;
• Rectal suppositories: 10 mg; 20 mg;
• In combination with: aspirin (generic only), acetaminophen (Endocet, Nalocet, Percocet, Prolate); see Appendix [not included in this PDA edition].

• Assess type, location, and intensity of pain prior to and 1 hr (peak) after administration. When titrating opioid doses, ↑ of 25–50% should be administered until there is either a 50% in the patient's pain rating on a numerical or visual analog scale or the patient reports satisfactory pain relief. A repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal.
• Patients taking ER tablets may also be given supplemental short-acting opioid doses for breakthrough pain.
• An equianalgesic chart (see Appendix K) should be used when changing routes or when changing from one opioid to another.
• Assess BP, HR, and respiratory rate before and periodically during administration. If respiratory rate <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Dose may need to be ↓ by 25–50%. Initial drowsiness will ↓ with continued use. Monitor for respiratory depression, especially during initiation or following dose ↑; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea, sleep-related hypoxemia).Geri: Pedi: Assess older adults and pediatric patients frequently; more sensitive to the effects of opioid analgesics and may experience side effects and respiratory complications more frequently.
• Prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Patients who receive oxycodone for pain rarely develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy; may ↑ risk of overdose. Prolonged use of opioids should be reserved for patients whose pain remains severe enough to require them and alternative treatment options continue to be inadequate. Many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine.
• Assess bowel function routinely. Prevention of constipation should be instituted with ↑ intake of fluids and bulk and laxatives to minimize constipating effects. Stimulant laxatives should be administered routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid induced constipation.
• Assess risk for opioid addiction, abuse, or misuse prior to administration. Abuse or misuse of extended-release preparations by crushing, chewing, snorting, or injecting dissolved product will result in uncontrolled delivery of oxycodone and can result in overdose and death. Abuse deterrent: Xtampza ER and Oxycontin are abuse deterrent formulations that are difficult to crush and if crushed result in a gel.

• May ↑ plasma amylase and lipase levels.

• If an opioid antagonist is required to reverse respiratory depression or coma, naloxone is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by IV push every 2 min. For children and patients weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain.

• High Alert:Accidental overdose of opioid analgesics has resulted in fatalities. Before administering, clarify all ambiguous orders. Pedi: Medication errors with opioid analgesics are common in pediatric patients; calculate doses carefully. Use appropriate measuring devices
• Do not confuse short-acting oxycodone with long-acting Oxycontin. Do not confuse oxycodone with hydrocodone, oxybutynin, or oxymorphone. Do not confuse Oxycontin with MS Contin, oxybutynin, oxymorphone, or oxytocin.
• Explain therapeutic value of medication prior to administration to enhance the analgesic effect.
  • Regularly administered doses may be more effective than as needed administration. Analgesic is more effective if given before pain becomes severe.
  • Coadministration with nonopioid analgesics may have additive analgesic effects and may permit lower doses.
  • When converting from IR to ER oxycodone, administer total daily oral oxycodone dose once daily; dose of ER product can be titrated every 3–4 days (see Appendix K). To convert from another opioid to ER oxycodone, convert to total daily dose of oxycodone and then administer 50% of this dose as ER oxycodone once daily; can then titrate dose every 3–4 days.
  • Oxycodone should be discontinued gradually after long-term use to prevent withdrawal symptoms. For patients on long-acting agents who are physically opioid-dependent, initiate the taper by a small enough increment (no greater than 10–25% of total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2–4 wk. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. Monitor frequently to manage pain and withdrawal symptoms (restlessness; lacrimation; rhinorrhea; yawning; perspiration; chills; myalgia; mydriasis; irritability; anxiety; backache; joint pain; weakness; abdominal cramps; insomnia; nausea; anorexia; vomiting; diarrhea; or ↑ BP, respiratory rate, or HR). If withdrawal symptoms occur, pause the taper for a period of time or ↑ the dose of opioid analgesic to the previous dose, and then proceed with a slower taper. Also, monitor patients for changes in mood, emergence of suicidal thoughts, or use of other substances. 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.
• PO: May be administered with food or milk to minimize GI irritation.
  • Administer solution with properly calibrated measuring device.
• Extended Release: DNC: Take one tablet at a time. Swallow ER tablet whole; do not crush, break, or chew. Taking broken, chewed, crushed, or dissolved ER tablets may lead to rapid release and absorption of a potentially fatal dose of oxycodone. Advise patients not to presoak, lick, or wet ER tablets prior to placing in the mouth. Take each tablet with enough water to ensure complete swallowing immediately after placing in mouth. Dose of ER preparations should be based on 24-hr opioid requirement determined with short-acting opioids then converted to extended-release form.
  • ER oxycodone capsules (Xtampza ER) are not equivalent to ER oxycodone tablets (Oxycontin).
• REMS: FDA strongly encourages health care professionals to complete a REMS-compliant 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, available at OpioidAnalgesicREMSBlueprint. Information on programs can be found at 1-800-503-0784 or .
• Discuss availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing therapy, especially if patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. 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. However, the presence of risk factors for overdose should not prevent the proper management of pain in any patient.

• Explain purpose and side effects of oxycodone to patient. Instruct them to take medication as directed and when to ask for pain medication. Do not share medication with others, even if they have similar symptoms; may be harmful. Keep out of children's reach. Advise patient to read Patient Informationbefore starting and with each Rx refill in case of changes.
• REMS: Instruct patient on how and when to ask for and take pain medication. Do not stop taking without discussing with health care professional; may cause withdrawal symptoms if discontinued abruptly after prolonged use. Do not increase doses without discussing with health care professional; may lead to overdose. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide is available at OpioidAnalgesicREMSPCG.
• Advise patient that oxycodone is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
• Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (Rx, direct from pharmacist, or state programs). OTC naloxone nasal spray is available at pharmacies nationwide for overdose or accidental ingestion.
• Advise patient to notify health care professional if pain control is not adequate or if severe or persistent side effects occur.
• Medication may cause drowsiness or dizziness. Advise patient to call for assistance when ambulating and to avoid driving or other activities that require alertness until response to the medication is known.
• Advise patients taking Oxycontin tablets that empty matrix tablets may appear in stool.
• Advise patient to make position changes slowly to minimize orthostatic hypotension.
• Emphasize the importance of aggressive prevention of constipation with the use of oxycodone.
• Advise patient to avoid concurrent use of alcohol or other CNS depressants with this medication; may cause overdose.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
• Advise patient that good oral hygiene, frequent mouth rinses, and sugarless gum or candy may decrease dry mouth.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, failure to gain weight); usually occur the first days after birth. Monitor infants exposed to oxycodone through breast milk for excess sedation and respiratory depression. Doses of less than 60 mg/day of the IR formulation are unlikely to result in clinically relevant exposure in breastfed infants. Chronic use may ↓ fertility in females and males.

• Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.

OxyCONTIN, Roxicodone, Roxybond, Xtampza ER

Oxy IR, OxyNEO, Supeudol

Schedule II (C-II)