HYDROCODONE BITARTRATE AND ASPIRIN
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Hydrocodone is a mu-opioid receptor agonist; aspirin irreversibly inhibits cyclooxygenase-1 (COX-1) and COX-2, reducing prostaglandin synthesis.
| Metabolism | Hydrocodone: CYP2D6, CYP3A4; Aspirin: Hydrolyzed to salicylic acid, conjugated with glycine to salicyluric acid, and glucuronidated. |
| Excretion | Hydrocodone: primarily renal (up to 60% as unchanged drug and metabolites, including norhydrocodone, hydromorphone, and conjugates); <10% biliary/fecal. Aspirin: renal excretion of salicylate and its conjugates (salicyluric acid, salicyl phenolic glucuronide, etc.); dose-dependent elimination kinetics. |
| Half-life | Hydrocodone: terminal elimination half-life of approximately 3.8-4.5 hours (range 3.3-4.4 hours in adults) in healthy individuals; prolonged in hepatic impairment and elderly. Aspirin: 15-20 minutes for parent drug; salicylate half-life is dose-dependent (2-3 hours at low doses, up to 15-30 hours at anti-inflammatory doses). |
| Protein binding | Hydrocodone: approximately 20-30% bound to plasma proteins (mainly albumin). Aspirin: 80-90% bound to albumin (dose-dependent; decreases with high concentrations). |
| Volume of Distribution | Hydrocodone: Vd ~3.5-4.7 L/kg (extensive tissue distribution). Aspirin: Vd ~0.15-0.20 L/kg (low, mainly in plasma) for parent drug; salicylate Vd ~0.17 L/kg but increases with hypoalbuminemia or acidosis. |
| Bioavailability | Hydrocodone: oral bioavailability ~50-60% (first-pass metabolism). Aspirin: oral bioavailability ~40-50% (due to presystemic hydrolysis in GI tract and liver); plasma salicylate bioavailability approaches 100% for active moiety. |
| Onset of Action | Oral: Hydrocodone analgesic effect begins within 10-20 minutes; aspirin antipyretic/analgesic effect within 15-30 minutes. Peak effects: hydrocodone at 30-60 minutes; aspirin at 1-2 hours. |
| Duration of Action | Hydrocodone: analgesic duration 4-6 hours (immediate-release). Aspirin: analgesic/antipyretic effect lasts 3-4 hours; antiplatelet effect (low dose) lasts for the lifespan of platelets (~7-10 days), but platelet function recovery depends on dose. |
One to two tablets (hydrocodone bitartrate 5-10 mg / aspirin 500 mg) orally every 4-6 hours as needed for pain; maximum daily dose: 8 tablets (hydrocodone 40 mg, aspirin 4000 mg).
| Dosage form | TABLET |
| Renal impairment | eGFR 30-60 mL/min: reduce dose by 50% or extend interval; eGFR <30 mL/min: avoid use due to accumulation of both hydrocodone and aspirin. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: start with 50% of usual dose and titrate cautiously; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for pediatric use due to risk of Reye syndrome from aspirin and respiratory depression from hydrocodone. For acute pain in adolescents ≥16 years, dose as per adult but with caution. |
| Geriatric use | Start at low end of dosing range (e.g., one tablet every 6 hours) due to increased sensitivity, reduced renal function, and higher risk of GI bleeding from aspirin. Avoid use if possible. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Breastfeeding | Hydrocodone: M/P ratio approximately 2.0 for oral solution; excreted in low amounts but may cause infant sedation. Aspirin: Not recommended; risk of Reye syndrome, platelet dysfunction in infant. Avoid use while breastfeeding. |
| Teratogenic Risk | First trimester: No adequate human studies; animal studies have not been reported. Risk cannot be ruled out. Second/third trimester: Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS) and aspirin-related risks (premature closure of ductus arteriosus, oligohydramnios, intracranial hemorrhage). Avoid chronic or high-dose aspirin in third trimester. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; interaction with alcohol; risk of life-threatening respiratory depression in elderly, cachectic, debilitated patients, or those with chronic respiratory disease; risk of opioid-induced hyperalgesia; risk of serotonin syndrome with serotonergic drugs; risk of adrenal insufficiency with prolonged use; risk of severe hypotension; risk of seizures in patients with seizure disorders; risk of severe bleeding (aspirin) especially with alcohol, anticoagulants, or pre-existing bleeding disorders; Reye's syndrome in children or teenagers with viral infections.
| Common Effects | Cough |
| Serious Effects |
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment; known or suspected gastrointestinal obstruction; hypersensitivity to hydrocodone, aspirin, or any component; children or teenagers with viral infections (risk of Reye's syndrome); severe bleeding disorders; concomitant use with MAOIs or within 14 days; pregnancy (especially third trimester); lactation.
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| Fetal Monitoring | Monitor maternal respiratory status, sedation, bowel function; fetal heart rate and growth with chronic use; signs of NOWS in neonate after delivery. Assess bleeding time if aspirin used near term. |
| Fertility Effects | Opioid use may cause menstrual irregularities and reduced fertility via hypothalamic-pituitary-gonadal axis suppression. Aspirin at high doses may interfere with ovulation; low-dose aspirin may be used for certain conditions. Effects reversible upon discontinuation. |
| Precautions |
| Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks with concomitant use of benzodiazepines or other CNS depressants; severe hypotension; gastrointestinal bleeding with aspirin; increased risk of bleeding with alcohol, anticoagulants, or NSAIDs; hypersensitivity reactions; hepatotoxicity; Reye's syndrome; use in elderly, cachectic, or debilitated patients; renal impairment; hepatic impairment; pregnancy; labor and delivery; lactation. |