|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(oks i KOE done)
Generic Available (U.S.)
Yes: Excludes controlled release tablet
Index Terms
Controlled Substance
C-II
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
OxyContin®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM208530.pdf
Oral solution: http://lvtechinc.com/pdf/oxy_solution_med_guide.pdf
REMS Components
Oral solution: Released from REMS requirement 1/25/2012
OxyContin®: Elements to Assure Safe Use; Medication Guide
Prescribing and Access Restrictions
As a requirement of the REMS program, healthcare providers who prescribe OxyContin® need to receive training on the proper use and potential risks of OxyContin®. For training, please refer to http://www.oxycontinrems.com. Prescribers will need retraining every 2 years or following any significant changes to the OxyContin® REMS program.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of moderate-to-severe pain, normally used in combination with nonopioid analgesics
OxyContin® is indicated for around-the-clock management of moderate-to-severe pain when an analgesic is needed for an extended period of time.
Use: Dental
Treatment of postoperative pain
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events were not observed in animal reproduction studies. Opioids cross the placenta; respiratory depression and withdrawal symptoms may occur in the neonate following use during pregnancy. Controlled release formulations should not be used immediately prior to or during labor.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Sedation and/or respiratory depression may occur in the infant; symptoms of opioid withdrawal may occur following the cessation of breast-feeding.
Contraindications
Hypersensitivity to oxycodone or any component of the formulation; significant respiratory depression; hypercarbia; acute or severe bronchial asthma; paralytic ileus (known or suspected)
Warnings/Precautions
Boxed warnings:
• Abuse/misuse/diversion: See “Other warnings/precautions” below.
• Controlled-release tablets: See “Dosage form specific issues” below.
• CYP3A4 inhibitors: See “Concurrent drug therapy issues” below.
• Highly-concentrated oral solutions: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).
• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).
Disease-related concerns:
• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenocortical insufficiency: Use with caution in patients with adrenocortical insufficiency, including Addison's disease.
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction; acute pancreatitis may cause constriction of sphincter of Oddi.
• CNS depression/coma: Use with caution in patients with CNS depression or coma.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with hepatic dysfunction; dose adjustment may be warranted.
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Psychosis: Use with caution in patients with toxic psychosis.
• Renal impairment: Use with caution in patients with severe renal dysfunction; dose adjustment may be warranted.
• Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.
• Seizures: Use with caution in patients with a history of seizure disorders.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
• CYP3A4 inhibitors: [U.S. Boxed Warning]: Concomitant use with CYP3A4 inhibitors may result in increased effects and potentially fatal respiratory depression.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues:
• Controlled-release tablets: [U.S. Boxed Warning]: OxyContin® is not intended for use as an “as needed” analgesic or for immediately-postoperative pain management (should be used postoperatively only if the patient has received it prior to surgery or if severe, persistent pain is anticipated). [U.S. Boxed Warning]: Do NOT crush, break, or chew controlled-release tablets; 60 mg and 80 mg strengths, a single dose >40 mg, or a total dose of >80 mg/day are for use only in opioid-tolerant patients. Tablets may be difficult to swallow and could become lodged in throat; patients with swallowing difficulties may be at increased risk. Cases of intestinal obstruction or diverticulitis exacerbation have also been reported, including cases requiring medical intervention to remove the tablet; patients with an underlying GI disease (eg, esophageal cancer, colon cancer) may be at increased risk.
Highly-concentrated oral solutions: [U.S. Boxed Warning]: Concentrated oral solutions (20 mg/mL) should only be used in opioid tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week); orders should be clearly written to include the intended dose (in mg vs mL) and the intended product concentration to be dispensed.
Other warnings/precautions:
• Abuse/misuse/diversion: [U.S. Boxed Warning]: Healthcare provider should be alert to problems of abuse, misuse, and diversion. Patients should be assessed for risk of abuse or addition prior to therapy and all patients should be monitored for signs of misuse, abuse, and addiction.
• Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
Adverse Reactions
Note: Percentages as reported with OxyContin®
>10%:
Central nervous system: Somnolence (23%), dizziness (13%)
Dermatologic: Pruritus (13%)
Gastrointestinal: Constipation (23%), nausea (23%), vomiting (12%)
1% to 10%:
Cardiovascular: Postural hypotension (1% to 5%)
Central nervous system: Headache (7%), abnormal dreams (1% to 5%), anxiety (1% to 5%), chills (1% to 5%), confusion (1% to 5%), dysphoria (1% to 5%), euphoria (1% to 5%), fever (1% to 5%), insomnia (1% to 5%), nervousness (1% to 5%), thought abnormalities (1% to 5%)
Dermatologic: Rash (1% to 5%)
Gastrointestinal: Xerostomia (6%), abdominal pain (1% to 5%), anorexia (1% to 5%), diarrhea (1% to 5%), dyspepsia (1% to 5%), gastritis (1% to 5%)
Neuromuscular & skeletal: Weakness (6%), twitching (1% to 5%)
Respiratory: Dyspnea (1% to 5%), hiccups (1% to 5%)
Miscellaneous: Diaphoresis (5%)
<1%: Agitation, amnesia, appetite increased, chest pain, cough, dehydration, depersonalization, depression, dry skin, dysphagia, dysuria, edema (including facial and peripheral), emotional lability, eructation, exfoliative dermatitis, flatulence, gait abnormalities, hallucinations, hematuria, hyperkinesia, hypoesthesia, hypotonia, impotence, lymphadenopathy, malaise, migraine, paresthesia, polyuria, speech disorder, ST segment depression, stomatitis, stupor, syncope, taste perversion, thirst, tinnitus, tremor, urinary retention, vasodilation, vertigo, vision change, voice alteration, withdrawal syndrome
Postmarketing and/or case reports: Abuse, addiction, amenorrhea, anaphylactoid reaction, anaphylaxis, cholestasis, dental caries, hepatic enzymes increased, histamine release, hypertonia, hyponatremia, ileus, intracranial pressure increased, palpitations, seizure, SIADH, tablet in stool (some controlled release dosage forms), urticaria; choking, gagging, or other swallowing difficulties due to properties of the controlled release tablets
Metabolism/Transport Effects
Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk D: Consider therapy modification
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Rifampin: May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
St Johns Wort: May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Voriconazole: May increase the serum concentration of OxyCODONE. Management: A reduced oxycodone dose may be necessary with concurrent voriconazole. Increased frequency and duration of monitoring for oxycodone-related adverse effects is recommended. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light.
Mechanism of Action
Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression
Pharmacodynamics/Kinetics
Onset of action: Pain relief: Immediate release: 10-15 minutes
Peak effect: Immediate release: 0.5-1 hour
Duration: Immediate release: 3-6 hours; Controlled release: ≤12 hours
Distribution: Vd: 2.6 L/kg; distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain
Protein binding: ~45%
Metabolism: Hepatically via CYP3A4 to noroxycodone (has weak analgesic), noroxymorphone, and alpha- and beta-noroxycodol. CYP2D6 mediated metabolism produces oxymorphone (has analgesic activity; low plasma concentrations), alpha- and beta-oxymorphol.
Bioavailability: Controlled release, immediate release: 60% to 87%
Half-life elimination: Immediate release: 2-4 hours; controlled release: ~5 hours
Time to peak, plasma: Immediate release: 1.2-1.9 hours; Controlled release: 4-5 hours
Excretion: Urine (~19% as parent; >64% as metabolites)
Dosage
Oral: Note: All doses should be titrated to appropriate effect:
Children (unlabeled use): Immediate release, initial dose: 0.1-0.2 mg/kg/dose (moderate pain) or 0.2 mg/kg/dose (severe pain) (APS 6th edition). For severe chronic pain, administer on a regularly scheduled basis, every 4-6 hours, at the lowest dose that will achieve adequate analgesia.
Adults:
Immediate release: Initial: 5-15 mg every 4-6 hours as needed; dosing range: 5-20 mg/dose (APS 6th edition). For severe chronic pain, administer on a regularly scheduled basis, every 4-6 hours, at the lowest dose that will achieve adequate analgesia.
Controlled release:
Opioid naive: 10 mg every 12 hours
Concurrent CNS depressants: Reduce usual initial oxycodone dose by 1/3 to 1/2
Conversion from transdermal fentanyl: For each 25 mcg/hour transdermal dose, substitute 10 mg controlled release oxycodone every 12 hours; should be initiated 18 hours after the removal of the transdermal fentanyl patch
Currently on opioids: Use standard conversion chart to convert daily dose to oxycodone equivalent. Divide daily dose in 2 (for twice-daily dosing, usually every 12 hours) and round down to nearest dosage form.
Dose adjustment: Doses may be adjusted by changing the total daily dose (not by changing the dosing interval). Doses may be adjusted every 1-2 days and may be increased by 25% to 50%. Dose should be gradually tapered when no longer required in order to prevent withdrawal.
Note: 60 mg and 80 mg strengths, a single dose >40 mg, or a total dose of >80 mg/day are for use only in opioid-tolerant patients.
Multiplication factors for converting the daily dose of current oral opioid to the daily dose of oral oxycodone:
Current opioid mg/day dose x factor = Oxycodone mg/day dose
Codeine mg/day oral dose x 0.15 = Oxycodone mg/day dose
Hydrocodone mg/day oral dose x 0.9 = Oxycodone mg/day dose
Hydromorphone mg/day oral dose x 4 = Oxycodone mg/day dose
Levorphanol mg/day oral dose x 7.5 = Oxycodone mg/day dose
Meperidine mg/day oral dose x 0.1 = Oxycodone mg/day dose
Methadone mg/day oral dose x 1.5 = Oxycodone mg/day dose
Morphine mg/day oral dose x 0.5 = Oxycodone mg/day dose
Note: Divide the oxycodone mg/day dose into the appropriate dosing interval for the specific form being used.
Dosing adjustment in hepatic impairment: Reduce dosage in patients with liver disease. Decrease the dose of controlled release tablets to 1/3 to 1/2 the usual starting dose; titrate carefully.
Dosing adjustment in renal impairment: Serum concentrations are increased ~50% in patients with Clcr <60 mL/minute; adjust dose based on clinical situation.
Dental Usual Dosing
Postoperative pain: Adults: Oral: 5 mg every 6 hours as needed
Administration: Oral
Controlled release: Do not moisten, crush, break, or chew controlled release tablets. Controlled release tablets are not indicated for rectal administration; increased risk of adverse events due to better rectal absorption. Controlled release tablets should be administered one at a time and each followed with water immediately after placing in the mouth.
Immediate release (Oxecta™): Must be swallowed whole with enough water to ensure complete swallowing immediately after placing in the mouth. The tablet should not be wet prior to placing in the mouth. Do not crush, chew, or dissolve the tablets. Do not administer via feeding tubes (eg, gastric, NG) due to potential for obstruction. The formulation uses technology designed to discourage common methods of tampering to prevent misuse/abuse.
Appropriate laxatives should be administered to avoid the constipating side effects associated with use. Antiemetics may be needed for persistent nausea.
Monitoring Parameters
Pain relief, respiratory and mental status, blood pressure; signs of misuse, abuse, and addiction
Reference Range
Blood level of 5 mg/L associated with fatality
Test Interactions
Some quinolones may produce a false-positive urine screening result for opiates using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opiate screens by more specific methods should be considered.
Dietary Considerations
Instruct patient to avoid high-fat meals when taking some products (food has no effect on the reformulated OxyContin®).
Patient Education
May cause physical and/or psychological dependence. Do not moisten, crush, or chew controlled release tablets. While using this medication, do not use alcohol and other prescription or OTC medications (especially sedatives, tranquilizers, antihistamines, or pain medications) without consulting prescriber. Maintain adequate hydration unless instructed to restrict fluid intake. Increase in fiber or stool softeners if okay with prescriber. May cause hypotension, dizziness, drowsiness, impaired coordination, or blurred vision; nausea, vomiting, or dry mouth; or constipation. The wax matrix from controlled release tablets may appear in stool. Report chest pain, slow or rapid heartbeat, dizziness, or persistent headache; confusion or respiratory difficulties; or severe constipation.
Geriatric Considerations
The elderly may be particularly susceptible to the CNS depressant and constipating effects of narcotics. Prophylactic use of a laxative should be considered. Serum concentrations at a given dose may also be increased relative to concentrations in younger patients.
Additional Information
Oxecta™ utilizes Acura Pharmaceutical's Aversion® technology which may help discourage misuse and abuse potential. Reduced abuse potential of Oxecta™ compared to other immediate-release oxycodone tablet formulations has not been proven; the FDA is requiring Pfizer to complete a post-approval epidemiological study to determine whether the formulation actually results in a decrease of misuse/abuse. In one clinical trial in nondependent recreational opioid users, the “drug-liking” responses and safety of crushed Oxecta™ tablets were compared to crushed immediate-release oxycodone tablets following the self-administered intranasal use. A small difference in “drug-liking” scores was observed, with lower scores reported in the crushed Oxecta™ group. In regards to safety, there was an increased incidence of nasopharyngeal and facial adverse events in the Oxecta™ group. In addition, there was decreased ability in the Oxecta™ group to completely administer the two crushed Oxecta™ tablets intranasally within a set time period. However, whether these differences translate into a significant clinical difference is unknown. Of note, pharmacokinetic studies showed that Oxecta™ is bioequivalent with oxycodone immediate-release tablets with no differences in Tmax and half-life when administered in the fasted state.
Cardiovascular Considerations
Oxycodone may cause constipation which may be problematic in patients with unstable angina, and patients after myocardial infarction. The hemodynamic responses to valsalva-like maneuvers due to straining may have adverse cardiovascular consequences in patients with critical coronary artery disease.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness and dizziness are common; may cause agitation, confusion, amnesia, depression, emotional lability, hallucinations, and malaise
Mental Health: Effects on Psychiatric Treatment
Concurrent use with psychotropics may cause additive sedation; use lower doses of both agents. Oxycodone may cause severe hypotension after concurrent administration with drugs which compromise vasomotor tone (eg, phenothiazines); monitor blood pressure.
Nursing: Physical Assessment/Monitoring
Monitor for effectiveness of pain relief. Monitor CNS and respiratory status and degree of sedation at beginning of therapy and periodically thereafter. Assess patient's physical and/or psychological dependence. For inpatients, implement safety measures to prevent falls. Discontinue slowly after prolonged use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, oral, as hydrochloride: 5 mg
Solution, oral, as hydrochloride: 5 mg/5 mL (100 mL [DSC], 500 mL [DSC])
Solution, oral, as hydrochloride [concentrate]: 20 mg/mL (30 mL)
Tablet, oral, as hydrochloride: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
Oxecta™: 5 mg, 7.5 mg
Roxicodone®: 5 mg, 15 mg, 30 mg [scored]
Tablet, controlled release, oral, as hydrochloride:
OxyCONTIN®: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 12-hour (OxyCONTIN)
10 mg (20): $50.61
20 mg (20): $85.34
40 mg (20): $153.50
60 mg (20): $211.44
80 mg (20): $287.10
Tablets (OxyCODONE HCl)
5 mg (20): $22.76
30 mg (20): $27.71
Tablets (Roxicodone)
15 mg (20): $36.54
30 mg (20): $69.86
References
Bril V, England J, Franklin GM, et al, "Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation," Neurology, 2011, 76(20):1758-65.
Kalso E and Vainio A, “Morphine and Oxycodone Hydrochloride in the Management of Cancer Pain,” Clin Pharmacol Ther, 1990, 47(5):639-46.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
“Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain,” 6th ed, Glenview, IL: American Pain Society, 2008.
Turturro MA and O'Toole KS, “Oxycodone-Induced Pulmonary Edema,” Am J Emerg Med, 1991, 9(2):201-3.
Zacher JL and Givone DM, “False-Positive Urine Opiate Screening Associated With Fluoroquinolone Use,” Ann Pharmacother, 2004, 38:1525-28.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
|
