oxycodone/acetaminophen (Percocet, Tylox, Primlev, Roxicet, Endocet, Xartemis XR)
Classes: Analgesics, Opioid Combos
Dosing and uses of Percocet, Tylox (oxycodone/acetaminophen)
Adult dosage forms and strengths
oxycodone/acetaminophen
tablet: Schedule II
- 2.5mg/325mg
- 5mg/300mg; 5mg/325mg
- 7.5mg/300mg; 7.5mg/325mg
- 10mg/300mg; 10mg/325mg
oral solution: Schedule II
- (5mg/325mg)/5mL
tablet, extended release: Schedule II
- 7.5mg/325mg (Xartemis XR)
Acute Pain
Indicated for management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate
Extended-release tablet (Xartemis XR): 2 tab PO q12hr without regard to food
The second dose of 2 tablets may be administered as early as 8 hr after the initial dose if analgesia required at that time; subsequent doses are to be administered 2 tablets q12hr
Not to exceed total 4 g/day of acetaminophen (total daily dose from any source)
Moderate-to-Severe Pain
2.5 mg/325 mg: 1-2 tablets PO q6hr
5 mg/325 mg, 7.5 mg/500 mg, 10 mg/650 mg: 1 tablet PO q6hr
Not to exceed total 4 g/day of acetaminophen (total daily dose from any source)
Chronic pain: Administer as scheduled dosing around the clock
Intermittent or breakthrough pain: Administer as needed
Dosing Modifications
Hepatic impairment: Reduce dose in cases of severe impairment
Renal impairment: Elimination half-life prolonged with end-stage renal impairment; dose reduction may be required
Dosing Considerations
Adjust dose according to severity of pain and patient response
Extended-release (Xartemis XR) is a bilayer formulation of oxycodone and acetaminophen (contains immediate- and extended-release layers) which is not interchangeable with other oxycodone/acetaminophen products because of differing pharmacokinetic profiles
Administration
Extended-release tablet: Swallow whole with enough water to ensure complete swallowing after placing in mouth; do not break, chew, cut, crush, dissolve or split the tablets
Discontinuation: Opioid tolerance may occur; gradually taper dose when discontinuing if patient treated for more than a few weeks
Pediatric dosage forms and strengths
tablet: Schedule II
- 2.5mg/325mg
- 5mg/300mg; 5mg/325mg
- 7.5mg/300mg; 7.5mg/325mg
- 10mg/300mg; 10mg/325mg
oral solution: Schedule II
- (5mg/325mg)/5mL
Pain (Off-Label)
Initial dose
- Initial dose based on oxycodone component
- Moderate pain: 0.05-0.1 mg/kg/dose PO q4-6hr PRN
- Severe pain: 0.3 mg/kg/dose PO q6hr
Maximum dose
- Maximum dose based on acetaminophen component
- <45 kg: Not to exceed acetaminophen 90 mg/kg/day PO
- >45 kg: Not to exceed acetaminophen 4 g/day PO
Dosing Considerations
Adjust dose according to pain severity and patient response
In cases of severe pain or if tolerant to the analgesic effects, a higher dose may be required
For chronic pain, administer scheduled doses around-the-clock; otherwise may take as needed for intermittent pain
Discontinuation: Opioid tolerance may occur; gradually taper dose when discontinuing if treated for more than a few weeks
Dosing Modifications
Hepatic impairment: Reduce dose in cases of severe impairment
Renal impairment: Elimination half-life prolonged with end-stage renal impairment; dose reduction may be required
Percocet, Tylox (oxycodone/acetaminophen) adverse (side) effects
Frequency not defined
Lightheadedness
Dizziness
Drowsiness or sedation
Nausea and vomiting
Euphoria
Dysphoria
Constipation
Pruritus
Skin and urticarial eruptions
Fatal hepatic necrosis (rare; associated with high/chronic acetaminophen use)
Renal tubular necrosis
Warnings
Black box warnings
Oxycodone
- Risk of addiction, abuse, and misuse, which can lead to overdose and death; assess patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions
- Serious, life-threatening, or fatal respiratory depression may occur
- Accidental consumption, especially in children, can result in fatal overdose
- Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated
Acetaminophen
- Hepatotoxicity may occur with acetaminophen doses that exceed 4 g/day; take into account all acetaminophen-containing products the patient is taking, including PRN doses and OTC products
- Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplantation or death
- New dosage limit allows no more than 325 mg/dosage unit for prescription medications that contain acetaminophen
- Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times a day (12 dosage units) and still not exceed the maximum daily dose of acetaminophen of 4 g/day
Contraindications
Hypersensitivity
Suspected or known paralytic ileus
Acute or severe bronchial asthma or hypercarbia
Significant respiratory depression (bronchial asthma, hypercarbia, COPD)
Cautions
Extended release formulation is not interchangeable with other oxycodone/acetaminophen products due to differing pharmacokinetic parameters
Use caution in head injury and increased intracranial pressure, severe hepatic/renal impairment, hypothyroidism, and Addison's disease
Individuals with history of addiction; tolerance and physical dependence may occur
May cause hypotension, particularly if the patient has depleted blood volume or if the medication is used concurrently with drugs that compromise vasomotor tone (eg, phenothiazines)
Caution with other CNS depressants (eg, alcohol, sedatives, antiemetics, general anesthetics); consider dose reduction of 1 or both drugs
Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplantation or death; risk increases in individuals with underlying liver disease, alcohol ingestion, and/or use of more than 1 acetaminophen-containing product (see Black box warnings)
Acetaminophen: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash
FDA is asking manufacturers to limit acetaminophen in prescription products to 325 mg/dosage unit; manufacturers have until January 14, 2014, to comply
Pregnancy and lactation
Pregnancy category: C
Lactation: Oxycodone and acetaminophen are excreted into breast milk in low concentration; use caution; possibility of sedation or respiratory depression in the infant
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Percocet, Tylox (oxycodone/acetaminophen)
Mechanism of action
Oxycodone: Opioid agonist that is relatively selective for mu and kappa opioid receptors; inhibits ascending pain pathways, which causes alteration in response to pain; produces analgesia, respiratory depression, and sedation
Acetaminophen: Nonopioid, nonsalicylate analgesic; may work peripherally to block pain impulse generation; acts on hypothalamus to produce antipyresis
Absorption
Bioavailability: Oxycodone (87%); acetaminophen (100%)
Onset: Oxycodone (10-15 min)
Duration: Oxycodone (3-6 hr)
Peak plasma time: Oxycodone (0.5-1 hr)
Distribution
Protein bound: Acetaminophen (20-50%); oxycodone (45%)
Vd: 2.6 L/kg (oxycodone)
Metabolism
Oxycodone
- Metabolized via hepatic P450 enzyme CYP2D6 and CYP3A4
- Active prodrug metabolized to oxymorphone (active metabolite) via CYP2D6
- CYP2D6 poor metabolizers may not achieve adequate analgesia because of decreased conversion to active metabolite
- Ultrarapid metabolizers (up to 7% of whites and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion
Acetaminophen
- Metabolized in liver by microsomal enzyme systems
- 80-85% conjugated, principally with glucuronic acid and to a lesser extent with sulfuric acid and cysteine
- 4% metabolized by CYP450 to toxic metabolite (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone [NAPQI]), which is detoxified by conjugation with glutathione; high doses may deplete fixed amount of glutathione in body, causing NAPQI accumulation
Elimination
Oxycodone
- Half-life: 3.5 hr
- Excretion: Primarily in urine (8-14% as free oxycodone)
Acetaminophen
- Half-life: 2-4 hr
- Excretion: 90-100% in urine (principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)
