NARCOTIC ANALGESICS

OxyContin (oxycodone hydrochloride) C-II

Tablets (controlled-release): 10, 20, 40, 80 mg

Manufacturer: Purdue Pharma


Indications/Dosage/Administration

Moderate to severe pain: In patients not already taking opioids, 10 mg q12h; a nonopioid analgesic or a NSAID may be continued. If the current nonopioid is discontinued, early upward dose titration may be needed. In patients taking fixed ratio opioid/nonopioid combination drugs, if patients are taking 1-5 tablets/capsules/caplets daily of a regular strength drug, 10-20 mg q12h. For patients taking 6-9 tablets/capsules/caplets daily of a regular strength drug, consider using 20-30 mg q12h. For those taking 10-12 tablets/capsules/caplets daily, consider using 30-40 mg q12h. The nonopioid may be continued as a separate drug, or a different nonopioid may be selected. If the current nonopioid is discontinued, early upward dose titration may be needed.

Drug is indicated for moderate to severe pain where use of an opioid analgesic is appropriate for more than a few days.

Administration: Swallow tablets whole; do not break, chew, or crush. Using broken, chewed, or crushed tablets could lead to rapid release and absorption of a potentially toxic dose of oxycodone. Rectal administration of tablets is not recommended.

Initiation of therapy: When starting therapy, consider patient's general condition and medical status; daily dose, potency, and type of analgesic(s) the patient has been taking; reliability of conversion estimate used to calculate oxycodone dose; patient's opioid exposure and tolerance (if any), and balance between pain control and adverse experiences.

Titration of dosage: Titrate to mild or no pain with regular use of no more than 2 doses of supplemental analgesia/24h. Have rescue medication available. Because steady-state plasma concentrations are approximated within 24-36 h, dosage may be adjusted every 1-2 days. It is appropriate to increase the q12h dose, not the dosing frequency. There is no clinical information on dosing intervals shorter than q12h. Except for increase from 10 mg to 20 mg q12h, the total daily oxycodone dose usually can be increased by 25-50% of the current dose at each increase. If signs of excessive adverse experiences are seen, the next dose may be reduced. If this adjustment leads to inadequate analgesia, a supplemental dose of immediate-release oxycodone may be given, or nonopioid analgesics may be used. Adjust dose to obtain an appropriate balance between pain relief and opioid-related adverse effects.

Use of 80-mg controlled-release tablets: This dosage strength is for use only in opioid-tolerant patients requiring daily oxycodone-equivalent dosages of 160 mg or more; use caution. Advise patients against use by others than for whom it was prescribed; such inappropriate use may have severe medical consequences.

Dosing intervals: While symmetric, around-the-clock, q12h dosing is appropriate for many patients, some patients may benefit from asymmetric dosing tailored to their pain pattern. It is usually appropriate to treat a patient with only one opioid for around-the-clock therapy.

Elderly or debilitated patients: Reduce starting dose to 33-50% of usual dose in debilitated, nontolerant patients.

Hepatic impairment: Reduce starting dose to 33-50% of usual dose and carefully titrate dose.

Renal impairment: In patients with Ccr < 60 ml/min, concentrations of oxycodone in plasma are ~ 50% higher than those with normal function. Conservatively start therapy, and adjust dosage according to clinical situation.

Gender differences: In pharmacokinetic studies, opioid-naive females demonstrated up to 25% higher average plasma concentrations and greater frequency of adverse events than males, even after adjustment for body weight; clinical relevance is low.

Patients currently on opioid therapy: If a patient has been receiving opioid-containing medications before controlled-release oxycodone therapy, determine total daily dose of other opioids. Using standard conversion ratio estimates, multiply mg/day of previous opioids by appropriate multiplication factors to obtain the equivalent total daily dose of oral oxycodone.

Multiplication Factors for Converting the Daily Dose
of Prior Opioids to the Daily Dose of Oral Oxycodone*

Mg/Day Prior Opioid ื Factor = Mg/day Oral Oxycodone

Drug Oral Prior Opioid Parenteral Prior Opioid Transdermal Prior Opioid
Oxycodone 1 — —
Codeine 0.15 — —
Fentanyl TTS — — 18 h after removal of transdermal fentanyl patch, approximately 10 mg of oxycodone q12h can be substituted for each 25 ตg/h of transdermal fentanyl to start. Follow patient closely.
Hydrocodone 0.9 — —
Hydromorphone 4 20 —
Levorphanol 7.5 15 —
Meperidine 0.1   0.4 —
Methadone 1.5   3 —
Morphine 0.5   3 —
* To be used for converting to oral oxycodone only. For patients receiving high-dose parenteral opioids, a more conservative conversion should be used. For example, for high-dose parenteral morphine, use 1.5 instead of 3 as a multiplication factor.

Divide 24-h dose in half to obtain q12h dose; round down to a dose appropriate for tablet strengths; and discontinue all other around-the-clock opioid drugs when oxycodone is initiated. In all cases, immediate-release oral oxycodone or another suitable short-acting analgesic should be made available. If pain recurs, dose can be incrementally increased to reestablish pain control.

Supplemental analgesia: Most cancer patients given around-the-clock therapy with controlled-release opioid need to have immediate-release medication available for rescue from breakthrough pain or to prevent pain that occurs predictably during certain patient activities. Immediate-release oxycodone may be use alone or with acetaminophen, aspirin, or other NSAIDs as a supplemental analgesic. Prescribe the supplemental analgesic at 25-33% of the 12-h controlled-release oxycodone dose shown below.

Table of Appropriate Supplemental Analgesia

OxyContin q12h dose (mg) prn Rescue dose of immediate-release oxycodone (mg)
10 (1ื10 mg)   5
20 (2ื10 mg)   5
30 (3ื10 mg) 10
40 (2ื20 mg) 10
60 (3ื20 mg) 15
80 (2ื40 mg) 20
120 (3ื40 mg) 30
160 (2ื80 mg) 40
240 (3ื80 mg) 60

Use rescue medication as needed for breakthrough pain and 1 h before anticipated pain. If more than 2 doses of rescue medication are needed within 24 h, titrate dose of controlled-release oxycodone upward.

Discontinuation: When patient no longer requires controlled-release oxycodone, patients receiving doses of 20-60 mg/day can usually have therapy stopped abruptly without incident; taper higher doses over several days to prevent signs and symptoms of withdrawal in physically dependent patients. Reduce daily dose by ~ 50% for the first 2 days and then by 25% every 2 days thereafter until total dose reaches 10 or 20 mg q12h. Therapy can then be discontinued. If signs of withdrawal appear, stop tapering, and slightly increase dose until signs and symptoms of opioid withdrawal disappear; begin tapering again, but with longer time periods between each dose reduction.

Conversion to parenteral opioids: To avoid overdose, follow conservative dose conversion ratios. Initiate therapy with ~ 50% of estimated equianalgesic daily dose of parenteral opioid divided into suitable individual doses based on appropriate dosing interval, and titrate based upon patient's response.


Patient Monitoring

General: Reassess need for around-the-clock opioid therapy every 6-12 mo, as appropriate. Regularly and systematically assess patient, considering patient's own reports of pain and side effects. Advise patient to report breakthrough pain and adverse experiences. Advise women of childbearing potential to consult their physician before becoming pregnant.

Blood: Plasma oxycodone measurements usually are not helpful in clinical management. Plasma concentrations of active drug may be of value in selected, unusual, or complex cases.


General Considerations

Hypersensitivity: Contraindicated in patient with known hypersensitivity to oxycodone.

Inappropriate uses: Contraindicated in any situation where opioids are contraindicated. Drug is not indicated for managing addictive disorders.

Respiratory impairment: Contraindicated in patients with significant respiratory depression in unmonitored settings or in the absence of resuscitative equipment and in those with acute or severe bronchial asthma or hypercarbia. Respiratory depression is the chief hazard of all opioid agonists and occurs most frequently in elderly or debilitated patients, usually following large initial doses in nontolerant patients, or when opioids are given with other agents that depress respiration. Use extreme caution in patients with significant COPD or cor pulmonale and in patients with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression. In such patients, even usual therapeutic doses of morphine may increase airway resistance and decrease respiratory drive to the point of apnea; consider use of alternative opioid analgesics, and use only under careful supervision at lowest effective dose.

Patient selection: Opioids given on a fixed-dosage level have a narrow therapeutic index in certain populations, especially when combined with other drugs; reserve for cases where benefits outweigh risks. Use caution in patients with acute alcoholism, adrenocortical insufficiency (eg, Addison's disease), CNS depression or coma, delirium tremens, debilitation, kyphoscoliosis associated with respiratory depression, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, severe hepatic, pulmonary, or renal dysfunction, and toxic psychosis.

Head injury, increased intracranial pressure: Respiratory depressant effects of opioids with carbon dioxide retention and secondary elevation of CSF pressure may be markedly exaggerated in the presence of head injury, intracranial lesions, or a preexisting increase in intracranial pressure. Neurologic signs of further increases in pressure in patients with head injuries may be obscured.

Postoperative use: Morphine and other opioids may decrease bowel motility. Ileus commonly occurs postoperatively, especially following intra-abdominal surgery with opioid analgesia. Cautiously monitor patient postoperatively for decreased bowel motility during opioid use. Institutte standard supportive therapy.

Hypotension: Severe hypotension may occur in patients with compromised ability to maintain blood pressure because of depleted blood volume or concurrent use of drugs such as phenothiazines or other agents that compromise vasomotor tone. Orthostatic hypotension may occur in ambulatory patients. Use caution in patients with circulatory shock.

Abdominal conditions: Administration may obscure diagnosis or clinical course in patients with acute abdominal conditions.

Paralytic ileus: Contraindicated in any patient who has or is suspected of having paralytic ileus.

Convulsive disorders: Drug may aggravate preexisting conditions in patients with convulsive disorders; all opioids may induce or aggravate seizures in some clinical settings.

Ambulatory surgery: Use of this drug is not recommended preoperatively or for management of pain in the first 12-24 h postsurgery in patients not previously taking the drug. Patients already receiving this product as part of ongoing analgesia may be safely continued if appropriate adjustments are made considering procedure, other drugs given, and temporary changes in physiology caused by the surgical intervention.

Pancreatic/biliary tract disease: Drug may cause spasm of sphincter of Oddi; use caution in patients with biliary tract disease, including acute pancreatitis. Drug may cause increased serum amylase level.

Tolerance: Significant tolerance should not occur in most patients given lowest oxycodone doses. A fraction of cancer patients develop some degree of tolerance and require progressively higher doses. Dosages can usually be increased safely to maintain an acceptable balance between pain relief and side effects. Tolerance to analgesia is usually paralleled by tolerance to side effects, except for constipation.

Physical dependence: Dependence results in withdrawal symptoms in patients who abruptly discontinue the drug or may be precipitated through use of drugs with opioid antagonist activity.

Abstinence syndrome: If drug is abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur, characterized by restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and/or mydriasis; other symptoms may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Reinstitute opioid use followed by gradual, tapered dose reduction and symptomatic support.

Opioid adverse experiences: Side effects from oxycodone are transient but may require evaluation and management; if significant adverse events occur before mild or no pain is achieved, aggressively treat events and, when events are under control, continue upward titration to an acceptable level of pain control. Adverse effects such as constipation should be anticipated and treated aggressively and prophylactically with a stimulant laxative and/or stool softener. Patients do not usually become tolerant to constipating effects of opioids. Other side effects, such as sedation and nausea, are usually self-limited and often do not persist beyond the first few days. If nausea persists and is unacceptable, consider treatment with antiemetics or other modalities. Patients receiving drug may pass an intact matrix “ghost” in the stool or via colostomy; these ghosts contain little or no residual drug and are of no clinical consequence.

Mental and/or physical impairment: Caution ambulatory patients that their ability to drive and/or perform potentially hazardous activities may be impaired.

Pregnancy: Neonates of mothers who have used oxycodone chronically may exhibit respiratory depression and/or withdrawal symptoms, either at birth and/or in the nursery. Use only if clearly needed (Pregnancy Category B).

Labor and delivery: Not recommended immediately before labor and delivery because drug may cause respiratory depression in the newborn.

Breast-feeding: Do not use in nursing mothers.

Pediatric use: Safety and effectiveness in children under 18 yr of age not established with this dosage form.


Adverse Reactions
Most frequent reactions are italicized.

Digestive: Constipation and nausea (23%), vomiting (12%), dry mouth (6%); diarrhea, anorexia, abdominal pain, dyspepsia, and gastritis (1-5%); dysphagia, eructation, flatulence, GI disorder, increased appetite, nausea and vomiting, taste perversion, and stomatitis (< 1%).

Genitourinary: Dysuria, hematuria, impotence, polyuria, urinary retention, and impaired urination (< 1%).

Neurologic: Somnolence (23%), dizziness (13%), headache (7%), asthenia (6%); nervousness, insomnia, confusion, anxiety, euphoria, twitching, abnormal dreams, and thought abnormalities (1-5%); abnormal gait, agitation, amnesia, depersonalization, depression, emotional lability, hallucination, hyperkinesia, hypesthesia, hypotonia, malaise, paresthesia, seizures, speech disorder, stupor, tinnitus, tremor, vertigo, and withdrawal syndrome with or without seizures (< 1%).

Miscellaneous: Pruritus (13%), sweating (5%); rash, dyspnea, chills, hiccups, postural hypotension, and fever (1-5%); accidental injury, chest pain, facial edema, malaise, neck pain, pain, migraine, syncope, vasodilation, ST depression, lymphadenopathy, dehydration, edema, hyponatremia, syndrome of inappropriate ADH secretion, peripheral edema, thirst, cough increased, pharyngitis, voice alteration, dry skin, exfoliative dermatitis, and abnormal vision (< 1%).


Drug Interactions

Other CNS depressants: Respiratory depression, hypotension, profound sedation, or coma. Use caution and at reduced dosage (33-50% of usual dosage) in patients concurrently receiving sedatives or hypnotics, general anesthetics, phenothiazines, other tranquilizers, and alcohol.

MAO inhibitors: Use caution.

Mixed agonist/antagonist opioid analgesics: Decreased analgesic effect and/or precipitation of withdrawal symptoms. Use caution in using pentazocine, nalbuphine, butorphanol, buprenorphine, or other agonist/antagonist analgesics concurrently.

Skeletal muscle relaxants: Increased neuromuscular blocking action. Increased respiratory depression.





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