Use with caution in patients with head injury and increased intracranial pressure (respiratory depressant effects increased and may also elevate CSF pressure). May mask diagnosis or clinical course in patients with acute abdominal conditions.

Enhanced analgesia has been seen in elderly patients on therapeutic doses of narcotics; duration of action may be increased in the elderly; the elderly may be particularly susceptible to the CNS depressant and constipating effects of narcotics

Oxycodone: Substrate of CYP2D6 (major)

Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C8/9, 2D6, 2E1, 3A4

Anesthetics, general: May have additive CNS depression; consider lowering dose of one or both agents

Anticholinergics: Concomitant use may lead to paralytic ileus

CNS depressants: May have additive CNS depression; consider lowering dose of one or both agents

CYP2D6 inhibitors: May decrease the effects of oxycodone. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Phenothiazines: May have additive CNS depression with phenothiazine and other tranquilizers; consider lowering dose of one or both agents

Sedative hypnotics: May have additive CNS depression; consider lowering dose of one or both agents

Oxycodone, as with other narcotic (opiate) analgesics, blocks pain perception in the cerebral cortex by binding to specific receptor molecules (opiate receptors) within the neuronal membranes of synapses. This binding results in a decreased synaptic chemical transmission throughout the CNS thus inhibiting the flow of pain sensations into the higher centers. Mu and kappa are the two subtypes of the opiate receptor which oxycodone binds to to cause analgesia.

Acetaminophen inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center

Children: Maximum acetaminophen dose: Children <45 kg: 90 mg/kg/day; children >45 kg: 4 g/day

Mild to moderate pain: Initial dose, based on oxycodone content: 0.05-0.1 mg/kg/dose

Severe pain: Initial dose, based on oxycodone content: 0.3 mg/kg/dose

Adults:

Mild to moderate pain: Initial dose, based on oxycodone content: 5 mg

Severe pain: Initial dose, based on oxycodone content: 15-30 mg. Do not exceed acetaminophen 4 g/day.

Elderly: Doses should be titrated to appropriate analgesic effects: Initial dose, based on oxycodone content: 2.5-5 mg every 6 hours. Do not exceed acetaminophen 4 g/day.

Dosage adjustment in hepatic impairment: Dose should be reduced in patients with severe liver disease.

Acetaminophen: A study by Hylek, et al, suggested that the combination of acetaminophen with warfarin (Coumadin®) may cause enhanced anticoagulation. The following recommendations have been made by Hylek, et al, and supported by an editorial in JAMA by Bell.

Dose and duration of acetaminophen should be as low as possible, individualized and monitored

For patients who reported taking the equivalent of at least 4 regular strength (325 mg) tablets for longer than a week, the odds of having an INR >6.0 were increased 10-fold above those not taking acetaminophen. Risk decreased with lower intakes of acetaminophen reaching a background level of risk at a dose of 6 or fewer 325 mg tablets per week.

Caplet (Roxicet™ 5/500): Oxycodone hydrochloride 5 mg and acetaminophen 500 mg

Capsule: Oxycodone hydrochloride 5 mg and acetaminophen 500 mg

Tylox®: Oxycodone hydrochloride 5 mg and acetaminophen 500 mg [contains sodium benzoate and sodium metabisulfite]

Solution, oral (Roxicet™): Oxycodone hydrochloride 5 mg and acetaminophen 325 mg per 5 mL (5 mL, 500 mL) [contains alcohol <0.5%]

Tablet: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg; oxycodone hydrochloride 7.5 mg and acetaminophen 325 mg; oxycodone hydrochloride 7.5 mg and acetaminophen 500 mg; oxycodone hydrochloride 10 mg and acetaminophen 325 mg; oxycodone hydrochloride 10 mg and acetaminophen 650 mg

Endocet® 5/325 [scored]: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg

Endocet® 7.5/325: Oxycodone hydrochloride 7.5 mg and acetaminophen 325 mg

Endocet® 7.5/500: Oxycodone hydrochloride 7.5 mg and acetaminophen 500 mg

Endocet® 10/325: Oxycodone hydrochloride 10 mg and acetaminophen 325 mg

Endocet® 10/650: Oxycodone hydrochloride 10 mg and acetaminophen 650 mg

Percocet® 2.5/325: Oxycodone hydrochloride 2.5 mg and acetaminophen 325 mg

Percocet® 5/325 [scored]: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg

Percocet® 7.5/325: Oxycodone hydrochloride 7.5 mg and acetaminophen 325 mg

Percocet® 7.5/500: Oxycodone hydrochloride 7.5 mg and acetaminophen 500 mg

Percocet® 10/325: Oxycodone hydrochloride 10 mg and acetaminophen 325 mg

Percocet® 10/650: Oxycodone hydrochloride 10 mg and acetaminophen 650 mg

Roxicet™ [scored]: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg

American Pain Society, "Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain," 4th ed, Skokie, IL: American Pain Society, 1999.

Cooper SA, Precheur H, Rauch D, et al, "Evaluation of Oxycodone and Acetaminophen in Treatment of Postoperative Pain,"Oral Surg Oral Med Oral Pathol, 1980, 50(6):496-501.

Dionne RA, "New Approaches to Preventing and Treating Postoperative Pain,"J Am Dent Assoc, 1992, 123(6):26-34.

Gobetti JP, "Controlling Dental Pain,"J Am Dent Assoc, 1992, 123(6):47-52.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.

Olkkola KT, Hamunen K, and Maunuksela EL, "Clinical Pharmacokinetics and Pharmacodynamics of Opioid Analgesics in Infants and Children,"Clin Pharmacokinet, 1995, 28(5):385-404.

Sinatra RS and Harrison DM, "Oxymorphone in Patient-Controlled Analgesia,"Clin Pharm, 1989, 8(8):541, 544.

"The Management of Chronic Pain in Older Persons. AGS Panel on Chronic Pain in Older Persons, American Geriatric Society,"Geriatrics, 1998, 53(Suppl 3):8-24.