Dosing and uses of Percodan, Endodan (oxycodone/aspirin)
Adult dosage forms and strengths
oxycodone/aspirin
tablet: Schedule II
- 4.8355mg/325mg
Relief of Moderate to Moderately Severe Pain
Usual: 1 tablet PO q6hr PRn
Maximum: 12 tablets (4 grams aspirin) per 24 hours
Pediatric dosage forms and strengths
Safety and efficacy not established
Percodan, Endodan (oxycodone/aspirin) adverse (side) effects
Frequency not defined
Oxycodone
- Serious: Respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock
- Less serious (reported more in ambulatory patients): Lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting
- Other: Euphoria, dysphoria, constipation, and pruritus
Aspirin
- May increase risk of hemorrhage due to its effect on the gastric mucosa and platelet function
- Potential to cause anaphylaxis in hypersensitive patients as well as angioedema especially in patients with chronic urticaria
- Other adverse reactions include anorexia, reversible hepatotoxicity, leukopenia, thrombocytopenia, purpura, decreased plasma iron concentration, and shortened erythrocyte survival time
Warnings
Contraindications
Hypersensitivity
Oxycodone
- Any situation where opioids are contraindicated including significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment), acute or severe bronchial asthma or hypercarbia
- Suspected or known paralytic ileus
Aspirin
- Reye Syndrome: Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye syndrome
- Known allergy to NSAIDs
- Syndrome of asthma, rhinitis, and nasal polyps May cause severe urticaria, angioedema, or bronchospasm (asthma)
Cautions
Oxycodone
- Respiratory diseases: Anoxia, hypercapnia, respiratory depression
- Genitourinary: Prostatic hypertrophy, renal impairment, urethral stricture, urinary tract surgery
- CNS: Seizures, CNS depression, head injury, increased ICP, drug abuse/dependence, emotional lability
- Metabolic: Thyrotoxicosis, untreated myxedema, hypothyroidism, Addison's disease
- Other: Anemia, cardiac arrhythmias, vitamin K deficiency, gallbladder disease, gout, hepatic disease/impairment, hypoprothrombinemia
Aspirin
- Anemia, GI malabsorption, history of peptic ulcers, gout, hepatic disease, hypochlorhydria, hypoprothrombinemia, renal impairment, thyrotoxicosis, vitamin K deficiency, renal calculi
- Take with food or 8-12 oz water to avoid GI effects
Pregnancy and lactation
Pregnancy category: C; D if used for prolonged periods or near term
Lactation: do not take if nursing or do not nurse
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 Percodan, Endodan (oxycodone/aspirin)
Bioavailability
Oxycodone: 87%
Aspirin: 80-100%
Vd
Oxycodone: 212 L/kg
Aspirin: 0.15-0.2 L/kg
Peak Plasma Time
Oxycodone: 0.5-1 hr
Aspirin: 0.25-3 hr
Half-Life
Oxycodone: 3-4.5 hr
Aspirin: 15 min; 2-3 hr (salicylate metabolite)
Protein Bound
Oxycodone: 45%
Aspirin: 70-95% (inversely related to plasma concentration)
Metabolism
Oxycodone
- Extensively metabolized by multiple metabolic pathways to produce noroxycodone, oxymorphone and noroxymorphone
- CYP3A mediated N-demethylation to noroxycodone is the primary metabolic pathway of oxycodone with a lower contribution from CYP2D6 mediated O-demethylation to oxymorphone
Aspirin
- Biotransformation of aspirin occurs primarily in the liver by the microsomal enzyme system
- Rapidly hydrolyzed to salicylate
Excretion
Oxycodone: 8-14% (urine)
Aspirin: 80-100% (urine)
Pharmacogenomics
Oxycodone is metabolized to oxymorphone via CYP2D6; CYP2D6 poor metabolizers may not achieve adequate analgesia
Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion
Mechanism of action
Oxycodone: Opioid agonist; analgesia it the principle therapeutic action
Aspirin: Prostaglandin inhibition effect results in decreased inflammatory response; in the CNS, affects hypothalamus heat-regulating center to reduce fever; also inhibits platelet aggregation
