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) (children 11 yr should be tolerating a minimum opioid dose of 20 mg of oxycodone or equivalent for 5 days before initiating extended-release 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. Crosses the placenta; enters breast milk.

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 (extended-release).

Use Cautiously in:

• Head trauma
• ↑intracranial pressure
• Severe renal or hepatic disease
• Hypothyroidism
• Adrenal insufficiency
• Alcoholism
• 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 extended-release 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: 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, non-benzodiazepine 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 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 extended-release tablets every 12 hr.
• PO (Adults <50 kg): Opioid-naive patients: 0.2 mg/kg 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 extended-release tablets every 12 hr.
• PO (Children 11 yr): 0.05–0.15 mg/kg 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 extended-release tablets every 12 hr.
• Rect (Adults): 10–40 mg 3–4 times daily initially, as needed.

(Generic available)

• Immediate-release capsules: 5 mg;
• Immediate-release tablets (Roxicodone): 5 mg; 10 mg; 15 mg; 20 mg; 30 mg;
• Immediate-release tablets (abuse-deterrent) (Oxaydo): 5 mg; 7.5 mg;
• Immediate-release tablets (abuse-deterrent) (Roxybond): 5 mg; 15 mg; 30 mg;
• Oral solution: 5 mg/5 mL; 100 mg/5 mL (concentrated);
• Extended-release capsules (abuse deterrent) (Xtampza ER): 9 mg; 13.5 mg; 18 mg; 27 mg; 36 mg;
• Extended-release tablets (abuse deterrent) (Oxycontin): 10 mg; 15 mg; 20 mg; 30 mg; 40 mg; 60 mg; 80 mg;
• Rectal suppositories: 10 mg; 20 mg;
• In combination with: aspirin (Endodan, Percodan), acetaminophen (Endocet, Magnacet, Oxycet, Percocet, Xartemis XR); 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, increases of 25–50% should be administered until there is either a 50% reduction 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 extended-release 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, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Dose may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use. Monitor for respiratory depression, especially during initiation or following dose increase; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea, sleep-related hypoxemia).Geri: Pedi: Assess geriatric 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 increase 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 increased 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: Oxaydo, 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 prn 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 immediate-release to extended-release oxycodone administer total daily oral oxycodone dose once daily; dose of extended-release product can be titrated every 3–4 days (see Appendix K). To convert from another opioid to extended-release oxycodone, convert to total daily dose of oxycodone and then administer 50% of this dose as extended-release oxycodone once daily; can then titrate dose every 3–4 days. When converting from transdermal fentanyl, initiate extended-release oxycodone 18 hr after removing transdermal fentanyl patch; for each 25 mcg/hr fentanyl transdermal dose, the equianalgesic dose of extended-release hydromorphone is 12 mg once daily (should initiate at 50% of this calculated total daily dose given once daily).
  • 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 increased blood pressure, respiratory rate, or heart rate). If withdrawal symptoms occur, pause the taper for a period of time or raise 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 1 tablet at a time. Swallow extended-release tablet whole; do not crush, break, or chew. Taking broken, chewed, crushed, or dissolved extended-release tablets may lead to rapid release and absorption of a potentially fatal dose of oxycodone. Advise patients not to presoak, lick, or wet controlled-release tablets prior to placing in the mouth. Take each tablet with enough water to ensure complete swallowing immediately after placing in mouth. Dose of extended-release preparations should be based on 24-hr opioid requirement determined with short-acting opioids then converted to extended-release form.
  • Do not use Oxaydo for administration via nasogastric, gastric, or other feeding tubes as it may cause obstruction of feeding tubes.
• 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 www.fda.gov/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.

• 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 www.fda.gov/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 (by prescription, directly from a pharmacist, or as part of a community-based program).
• 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 or smoking. Caution patient to avoid driving and other activities requiring alertness until response to 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, and/or 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. Chronic use may reduce fertility in females and males.
• Emphasize the importance of aggressive prevention of constipation with the use of oxycodone.

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

Oxaydo, OxyCONTIN, Roxicodone, Roxybond, Xtampza ER

Oxy IR, OxyNEO, Supeudol

Schedule II (C-II)