HYDROCODONE BITARTRATE
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the central nervous system, inhibiting ascending pain pathways and altering pain perception.
| Metabolism | Primarily metabolized by CYP2D6 and CYP3A4 to hydromorphone and other metabolites; undergoes O-demethylation and N-demethylation. |
| Excretion | Renal excretion of metabolites (primarily hydromorphone and norhydrocodone) accounts for approximately 99% of elimination, with less than 1% excreted unchanged. Biliary/fecal elimination is negligible. |
| Half-life | Terminal elimination half-life is approximately 3.5-4 hours in healthy adults. In patients with hepatic impairment (Child-Pugh Class B), half-life may be prolonged to ~6 hours. In renal impairment (CrCl <30 mL/min), half-life may be extended by 30-50%. |
| Protein binding | Approximately 20-30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 3-4 L/kg, indicating extensive extravascular distribution. Higher Vd in women and elderly due to increased body fat. |
| Bioavailability | Oral bioavailability is approximately 70% (range 60-80%). Intranasal bioavailability is comparable to oral. Rectal and sublingual routes have not been well characterized. |
| Onset of Action | Immediate-release oral: 20-30 minutes. Extended-release oral: 1-2 hours. Onset after intranasal or intravenous administration is faster (5-15 minutes) but these routes are not FDA-approved. |
| Duration of Action | Immediate-release: Analgesic effect lasts 4-6 hours. Extended-release: 12 hours. Duration may be shorter in opioid-tolerant patients due to tolerance. |
| Molecular Weight | 449.49 |
Adults: 5-10 mg orally every 4-6 hours as needed for pain; maximum 60 mg/day.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | eGFR 30-50 mL/min: reduce dose by 25%; eGFR 15-29 mL/min: reduce dose by 50%; eGFR <15 mL/min: avoid use or use with extreme caution, consider alternative. |
| Liver impairment | Child-Pugh Class A: no adjustment necessary; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | Children ≥2 years: 0.1-0.2 mg/kg/dose every 4-6 hours as needed; maximum single dose 10 mg; maximum daily dose 40 mg. Not recommended for children <2 years. |
| Geriatric use | Initiate at lowest effective dose, typically 2.5-5 mg every 6 hours; monitor for respiratory depression and constipation; titrate cautiously due to increased sensitivity and potential for renal impairment. |
| 1st trimester | Limited human data; animal studies show fetal harm. Use only if benefit outweighs risk. |
| 2nd trimester | Associated with miscarriage and malformations; avoid unless no safer alternative. |
| 3rd trimester | Prolonged use may cause neonatal opioid withdrawal syndrome; avoid near term. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Yes, crosses the placenta freely; fetal exposure confirmed. |
| Breastfeeding | Enters breast milk in low levels; monitor infant for somnolence and respiratory depression. The American Academy of Pediatrics considers compatible, but caution advised with high maternal doses or prolonged use. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; respiratory depression; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants.
| Common Effects | Cough |
| Serious Effects |
Severe respiratory depressionAcute or severe bronchial asthmaParalytic ileusHypersensitivity to hydrocodone or any component
| Precautions | Respiratory depression, especially in elderly or debilitated, Risks of addiction, abuse, and misuse, Life-threatening respiratory depression, Accidental ingestion (especially in children) can be fatal, Neonatal opioid withdrawal syndrome, Interactions with CNS depressants, Adrenal insufficiency, Severe hypotension, Seizures in patients with seizure disorders, Serotonin syndrome with serotonergic drugs |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data; association with neural tube defects and other malformations in some studies but not confirmed. Second and third trimesters: Prolonged use can cause neonatal opioid withdrawal syndrome; high doses near term may lead to respiratory depression in the neonate. Avoid chronic use; use lowest effective dose for shortest duration. |
| Fetal Monitoring | Assess maternal respiratory rate, sedation level, and bowel function. Fetal monitoring for growth restriction and preterm labor with chronic use. Neonatal monitoring for signs of withdrawal (irritability, poor feeding, tremors) and respiratory depression after delivery, especially if used near term. |
| Fertility Effects | Chronic opioid use may disrupt hypothalamic-pituitary-gonadal axis, leading to decreased libido, anovulation, and irregular menses in females; in males, reduced testosterone and sperm quality. Effects are reversible upon discontinuation. Limited evidence specifically for hydrocodone. |
| Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase hydrocodone levels. High-fat meals may delay absorption of immediate-release formulations. No significant interaction with other foods. |
| Clinical Pearls | Hydrocodone bitartrate is a semisynthetic opioid agonist with antitussive properties. Use with extreme caution in patients with respiratory compromise, head injury, or COPD. Metabolism primarily via CYP3A4 and CYP2D6; coadministration with CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin) significantly alters serum levels. Consider QT prolongation risk at high doses. Naloxone should be available for overdose reversal. Avoid in patients with paralytic ileus or known hypersensitivity. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol and other central nervous system depressants (e.g., benzodiazepines) as this may cause severe sedation or respiratory depression. · Do not crush, chew, or break extended-release tablets; swallow whole. · Store securely out of reach of children and pets; dispose of unused medication via take-back programs. · May cause constipation; increase fluid and fiber intake; consider stool softeners if needed. · Report any difficulty breathing, severe drowsiness, or signs of allergic reaction (rash, swelling) immediately. · Do not suddenly stop taking this medication without medical supervision to avoid withdrawal symptoms. |