Generic Name: oxycodone

Brand Names: Percolone, Roxicodone, Endocodone, Roxicodone Intensol, Oxyfast, Oxycodone Hydrochloride ER, OxyContin, ETH-Oxydose, Dazidox, OxyIR

Uses

Acute Pain

Relief of moderate to moderately severe pain.

Usually, temporary relief of moderate to moderately severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.

Additive analgesic effects with combinations of oxycodone and NSAIAs or acetaminophen because of differing mechanisms of action.

Consider around-the-clock dosing of analgesics in the initial stages of acute pain to avoid wide swings in pain and sedation often associated with as-needed dosing regimens.

Extended-release tablets are not intended for use on an as-needed (“prn”) basis, but when a continuous, around-the-clock analgesic is needed for an extended period of time.

Chronic Pain

For relief of malignant (cancer) pain and chronic nonmalignant pain.

In the management of chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.

Analgesic therapy must be individualized and titrated according to patient response and tolerance.

When opiate therapy is indicated, usually initiate with a mild, oral opiate like oxycodone.

Although consideration of the dependence potential of opiate agonists has often limited their effective use by many clinicians in terminally ill patients with severe, chronic pain, such consideration is irrelevant in the context of terminal illness.

Treatment of continuous or frequently recurring pain is best accomplished by the use of “around-the-clock” dosing regimens designed to prevent pain and minimize fluctuations in serum analgesic concentrations.

If pain severity increases, switching to more potent analgesics may be necessary; also consider alternative analgesic adjuncts such as tricyclic antidepressants or anticonvulsants (e.g., in the treatment of chronic nonmalignant pain such as neurogenic pain).

Dosage and Administration

General

Extended-release Tablets

• Adjust dosage according to patient tolerance and response; provide supplemental analgesia in the form of conventional preparations or another suitable short-acting analgesic for breakthrough pain or to prevent pain that occurs predictably (e.g., incident pain associated with certain activities).
• Only use the 80- and 160-mg formulations in opiate-tolerant patients whose opiate requirement is equivalent to a daily oxycodone dosage of 160 mg or more for the 80-mg tablet or 320 mg or more for the 160-mg tablet.
• Supplemental analgesia may be necessary during therapy with extended-release tablets for breakthrough pain; discontinue any other existing around-the-clock opiate regimens when extended-release oxycodone therapy is initiated.
• When therapy with oxycodone extended-release tablets is discontinued, it should be done gradually to avoid precipitation of withdrawal symptoms.

Administration

Oral Administration

Administer orally.

Extended-release Tablets

Swallow tablets whole; do not divide, crush, or chew. (See Boxed Warning.)

Food does not substantially affect the extent of oral absorption from extended-release tablets; however, patients receiving 160-mg tablets (currently not commercially available in the US) should be cautioned about administration with high-fat meals. (See Pharmacokinetics.)

Rectal Administration

Suppositories are not commercially available in the US.

When rectal administration was preferred, conventional oral tablets or solution have been administered rectally†.

If administered rectally†, insert the dosage form just inside the rectal sphincter for optimal systemic absorption of unmetabolized drug. Administration high in the rectal vault can result in rapid first-pass hepatic metabolism, with greatly diminished efficacy.

Not usually suitable for long-term administration due to rectal irritation from repeated dosing.

Although the manufacturer states that extended-release tablets should not be administered rectally, rectal administration of extended-release formulations are used widely for opiate delivery in palliative care.

Dosage

Available as oxycodone hydrochloride and oxycodone terephthalate; dosage expressed in terms of the respective salt.

Pediatric Patients

Conventional Preparations

Oral

Children <50 kg: Usually, initiate with 0.1–0.2 mg/kg every 3–4 hours as needed. Adjust according to response and tolerance.

Children ≥50 kg: Usually, initiate with 5–10 mg every 3–4 hours as needed. Adjust according to response and tolerance.

Children 6–12 Years of Age: 0.61 mg of the combined salts every 6 hours.

Children ≥12 Years of Age: 1.22 mg of the combined salts every 6 hours.

Adults

Conventional Preparations

Oral

Usually, initiate with 5–15 mg every 4–6 hours as needed. Adjust according to response and tolerance.

4.88 mg every 6 hours as the combined salts.

Extended-release Tablets

Initial Therapy with Extended-release Tablets

Oral

Initially, 10 mg every 12 hours. Patients previously receiving nonopiate analgesics may continue these drugs as dosage of the extended-release tablets is titrated to provide adequate analgesia.

Switching from Conventional Oxycodone Preparations to Extended-release Tablets

Oral

Calculate the total daily dosage of the conventional preparation and give as extended-release tablets in 2 divided doses at 12-hour intervals.

Switching from Other Opiates to Extended-release Tablets

Oral

The equivalent total daily dosage of oxycodone hydrochloride should be calculated based on standard conversion factors suggested by the manufacturer (table below) and administered as extended-release tablets in 2 divided doses at 12-hour intervals. Round down to the nearest whole tablet any calculated doses that do not correspond to an available tablet strength.

Table to be used only for conversion to oral oxycodone.

More conservative conversion for patients receiving high-dose parenteral opiates (e.g., use 0.5 instead of 3 as multiplication factor for high-dose parenteral morphine).

Patients receiving fentanyl transdermal systems may receive extended-release tablets beginning 18 hours after removal of the transdermal system. Initially, dosage of approximately 10 mg every 12 hours as extended-release tablets can be substituted for each 25-mcg/hour increment in fentanyl transdermal system dosage. Monitor patient closely as clinical experience with this dosage conversion ratio is limited.

Switching from Extended-release Tablets

Oral

When patients are switched from extended-release tablets to a parenteral opiate, conservative dose conversion ratios should be used to avoid toxicity.

Special Populations

Hepatic Impairment

Extended-release Tablets

Initially, 33–50% of the usual dosage; titrate dosage carefully.

Renal Impairment

Extended-release Tablets

Consider reduction of the initial dosage and adjust according to the clinical situation in impaired renal function (Cl_cr <60 mL/minute).

Geriatric Patients

Consider dosage reduction.

Cautions

Contraindications

• Known hypersensitivity to oxycodone or any ingredient in the formulation.
• Extended-release tablets in significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment), acute or severe bronchial asthma or hypercarbia, or with known or suspected paralytic ileus.

Warnings/Precautions

Warnings

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence following prolonged administration. Use only with careful surveillance in patients with a history of drug or alcohol dependence or abuse.

OxyContin^® has been intentionally abused by crushing extended-release tablets and “snorting” the powder or dissolving the contents in water and injecting the solution IV. The risk of toxicity is increased when used concomitantly with alcohol or other CNS depressants, including other opiates.

Abuse by chewing OxyContin^® extended-release tablets also reported.

Breaking, chewing, or crushing of extended-release tablets (e.g., OxyContin^®) results in immediate release of the opiate and the risk of a potentially fatal overdose.

Extended-release tablets (e.g., OxyContin^®) are subject to diversion and abuse.

Patients should be instructed to keep extended-release tablets (e.g., OxyContin^®) in a secure place to prevent theft.

Health-care professionals should contact the professional licensing board, or controlled substance authority in their states for information about prevention and detection of abuse or diversion.

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

Increased Intracranial Pressure or Head Trauma

Potential for increased respiratory depressant effects and elevation of CSF pressure in patients with increased intracranial pressure, head trauma, or other intracranial lesions.

Adverse effects of opiates may obscure the existence, extent, or course of intracranial pathology.

Acute Abdominal Conditions

Administration may complicate assessment of patients with acute abdominal conditions.

Respiratory Depression

Possible dose-related respiratory depression.

Use with extreme caution in patients with significant chronic obstructive respiratory disease or cor pulmonale, and in patients with substantially decreased respiratory reserve as in patients with hypoxia, hypercapnia, or preexisting respiratory depression.

Hypotension

Possible severe hypotension with extended-release tablets; especially in patients with depleted blood volume or in combination with other hypotensive agents. (See Drug Interactions.)

Ambulatory Surgery and Postoperative Use

Extended-release tablets (e.g., OxyContin^®) are not indicated for preoperative (preemptive) analgesia, or for the relief of pain in the immediate (initial 12–24 hours) postoperative period in patients not already receiving the drug or in those whose pain is mild or not expected to persist for an extended period of time.

Extended-release tablets (e.g., OxyContin^®) are indicated for postoperative use only in patients receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and to persist for an extended period of time.

Pancreatic/Biliary Tract Disease

Possible spasm of the sphincter of Oddi; use with caution in patients with biliary tract disease, including acute pancreatitis.

May increase serum amylase concentrations.

Debilitated and Special Risk Patients

Use with caution in debilitated patients and in those with hypothyroidism, Addison’s disease, and prostatic hypertrophy or urethral stricture.

Fixed-Combination Preparations

When used in fixed-combination with other drugs, consider the cautions, precautions, and contraindications applicable to each ingredient.

Specific Populations

Pregnancy

Category B or C.

Most experts state category B, with category D applying if used for prolonged periods or in high doses at term.

Lactation

Distributed into milk.

Avoid use in nursing women. If used, observe infant for GI effects, sedation, and changes in feeding patterns.

Pediatric Use

Safety and efficacy of the extended-release tablets (e.g., OxyContin^®) not established in children <18 years of age.

Safety and efficacy of other preparations not established in children; however, the drug is recommended for use in pediatric patients. (See Pediatric Dosage under Dosage and Administration.)

Geriatric Use

Possibility of reduced clearance in geriatric patients; adjust dosage. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Decreased clearance. Use with caution and consider initial dosage adjustment. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Decreased clearance. Use with caution and consider initial dosage adjustment. (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

With conventional preparations: lightheadedness, dizziness, sedation, nausea, vomiting. With extended-release tablets: constipation, nausea, somnolence, dizziness, vomiting, pruritus, headache, dry mouth, sweating, asthenia.

Interactions

Metabolized by CYP2D6.

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Following oral administration, about 60–87% of an oral dose reaches the systemic circulation.

Relative oral bioavailability of extended-release tablets to conventional oral dosage forms is the same.

Peak plasma concentrations occur within 1.4–2.6 hours for conventional oral dosage forms.

Onset

Conventional preparations: analgesia within 10–15 minutes; peak at about 1 hour.

Extended-release tablets (e.g., OxyContin^®): analgesia within 1 hour; peak effect also may occur at this time but persists.

Extended-release tablets (e.g., OxyContin^®): biphasic absorption; half-lives of 0.6 (initial release) and 6.9 (extended release) hours.

Duration

Conventional preparations: analgesia effect persists for 3–6 hours.

Food

Oral solution with a high-fat meal: extent of absorption increases 27%; rate of absorption is not affected.

Extended-release tablets (e.g., OxyContin^®) with food: peak plasma concentration increases 25%.

Distribution

Extent

Distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain.

Readily crosses the placenta.

Distributes into milk.

Plasma Protein Binding

About 45%.

Elimination

Metabolism

Extensively metabolized in the liver to noroxycodone and oxymorphone and their glucuronide conjugates.

Oxymorphone formation mediated by CYP2D6; approximately 10 times as potent as morphine parenterally and likely contributes to oxycodone’s effects.

Elimination Route

Oxycodone and its metabolites excreted principally in urine.

Half-life

Conventional preparations: 3.2–5 hours.

Extended-release tablets (e.g., OxyContin^®): apparent half-life 4.5–8 hours.

Special Populations

Renal impairment: elimination half-life increased by 1 hour compared with normal renal function. Peak plasma concentrations and AUCs for oxycodone and noroxycodone increased substantially.

Mild to moderate hepatic impairment: the elimination half-life was increased by 2.3 hours compared with normal hepatic function. Peak plasma concentrations and AUCs for oxycodone and noroxycodone increased but less substantially than with hepatic impairment.

Stability

Storage

Oral

Conventional Preparations

Tight, light-resistant containers at 15–30°C.

Extended-release Tablets

Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).

Actions

• Principal pharmacologic effects are on CNS and intestines.
• Acts at several sites within the CNS involving several systems of neurotransmitters to produce analgesia; precise mechanism of action not fully elucidated.

Advice to Patients

• Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.
• Importance of not breaking, crushing, or chewing extended-release tablets (e.g., OxyContin^®); potentially fatal overdose can occur. (See Abuse Potential under Cautions.)
• Importance of informing clinicians of breakthrough pain or adverse effects.
• Importance of taking only as prescribed; do not increase dosage or abruptly discontinue without consulting a clinician.
• Importance of protecting the drug from theft; do not give to anyone other than the individual for whom it was prescribed.
• Importance of advising patients that the matrix core of Oxycontin^® extended-release tablet does not completely dissolve and may be passed in the stool.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Oxycodone preparations are subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs. Because of concerns about the possibility of illicit use of tablets of such high strength, the manufacturer recently announced that oxycodone hydrochloride 160-mg extended-release tablets were withdrawn from the US market effective May 2001. This is a voluntary withdrawal and is not being mandated by the US Food and Drug Administration (FDA).

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions March 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.