HYDROCODONE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the central nervous system, inhibiting ascending pain pathways and altering perception of pain.
| Metabolism | Hepatic metabolism primarily via CYP2D6 and CYP3A4 to hydromorphone (active) and norhydrocodone (inactive). |
| Excretion | Renal (67%) as conjugated morphine and normorphine, norhydrocodone, and hydromorphone; fecal (negligible). |
| Half-life | Terminal elimination half-life is approximately 3.8-4.5 hours in adults; may be prolonged in hepatic or renal impairment. |
| Protein binding | About 19-45% (primarily albumin). |
| Volume of Distribution | Approximately 3.3-4.7 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral immediate-release: 70-80%; oral extended-release: 70-80%; intranasal: approximately 50% (relative to oral); rectal: similar to oral. |
| Onset of Action | Oral immediate-release: 10-30 minutes; oral extended-release: 30-60 minutes; intranasal: 15-30 minutes; rectal: 20-30 minutes. |
| Duration of Action | Immediate-release: 4-6 hours; extended-release: 8-12 hours; analgesic effect may persist longer with repeated dosing. |
| Molecular Weight | 299.37 |
5-10 mg orally every 4-6 hours as needed for pain; maximum 60 mg/day
| Dosage form | TABLET |
| Renal impairment | eGFR 30-89 mL/min: no adjustment; eGFR <30 mL/min: reduce dose by 50% and extend interval to every 6-8 hours; avoid in ESRD |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and extend interval to every 6-8 hours; Child-Pugh C: avoid use |
| Pediatric use | Children ≥2 years: 0.1-0.2 mg/kg/dose orally every 4-6 hours as needed; maximum 10 mg/dose, 60 mg/day |
| Geriatric use | Start at lowest effective dose (2.5-5 mg every 4-6 hours); consider alternate opioid if renal impairment; monitor for confusion and constipation |
| 1st trimester | Human data suggest a potential for teratogenic effects (congenital heart defects, neural tube defects, oral clefts) with first-trimester exposure; avoid unless no safer alternative. |
| 2nd trimester | May cause fetal dependence and withdrawal if used chronically; use lowest effective dose for shortest duration. |
| 3rd trimester | Prolonged use can result in neonatal opioid withdrawal syndrome (NOWS); avoid near term. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| Placental transfer | Crosses the placenta readily; fetal concentrations can approach maternal levels. |
| Breastfeeding | Hydrocodone is excreted in breast milk. Infants exposed via breast milk may experience sedation, respiratory depression, or withdrawal. Caution is advised, especially in mothers who are ultra-rapid metabolizers of CYP2D6. Monitor infant for signs of sedation and poor feeding. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and risk of overdose with ethanol.
| Common Effects | Cough |
| Serious Effects |
Severe respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or without resuscitative equipmentKnown or suspected gastrointestinal obstruction, including paralytic ileusHypersensitivity to hydrocodone or any component of the formulation
| Precautions | Respiratory depression, decreased bowel motility, increased intracranial pressure, severe hypotension, adrenal insufficiency, opioid-induced hyperalgesia, and risk of serotonin syndrome with serotonergic drugs. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no consistent teratogenicity at therapeutic doses. Opioid use in first trimester may be associated with small increased risk of neural tube defects, but absolute risk is low. Second trimester: No specific malformations reported. Third trimester: Chronic use can cause neonatal opioid withdrawal syndrome (NOWS) in up to 60% of neonates. High doses near term may increase risk of respiratory depression at birth. |
| Fetal Monitoring | Maternal: Monitor for sedation, respiratory rate, oxygen saturation, constipation, and signs of abuse or dependence. Fetal/neonatal: Non-stress test or biophysical profile in third trimester for chronic use; neonatal monitoring for NOWS (Finnegan scoring) for at least 48-72 hours after delivery. If used near term, observe newborn for respiratory depression for 24-48 hours. |
| Fertility Effects | Opioids may cause reversible hypothalamic-pituitary-gonadal axis suppression, leading to decreased libido, erectile dysfunction, and amenorrhea or anovulation. Effects are dose-dependent and may impair fertility. Discontinuation can restore normal reproductive function. |
| Avoid grapefruit and grapefruit juice during therapy as they inhibit CYP3A4 metabolism, increasing hydrocodone exposure and risk of adverse effects. High-fat meals may increase absorption of hydrocodone; advise taking with consistent meals to maintain stable levels. Alcohol is contraindicated due to additive CNS depression and increased hepatotoxicity risk. No other significant food interactions. |
| Clinical Pearls | Hydrocodone is a prodrug metabolized by CYP2D6 to hydromorphone, a potent mu-opioid agonist. Its analgesic effect is dependent on this conversion; therefore, CYP2D6 poor metabolizers (approx. 7-10% of population) may experience reduced analgesia. Caution in renal impairment (CrCl <30 mL/min) due to accumulation of parent drug and metabolites, leading to prolonged respiratory depression. Avoid concurrent use with alcohol, benzodiazepines, or other CNS depressants due to additive respiratory depression. Monitor for serotonin syndrome when used with serotonergic drugs. Use the lowest effective dose for the shortest duration; assess for opioid-induced constipation and consider prophylactic bowel regimen. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without doctor's approval. · Do not crush, break, or chew extended-release tablets; swallow whole. · Avoid alcohol and any medications that make you drowsy (e.g., benzodiazepines, muscle relaxants) unless approved by your doctor. · This medication may cause constipation; increase fluid and fiber intake, and ask about stool softeners or laxatives. · Do not drive or operate heavy machinery until you know how this medication affects you. · Seek emergency help if you experience trouble breathing, severe drowsiness, or unresponsiveness. · Store securely out of reach of others, especially children; properly dispose of unused medication via take-back program. · Do not stop abruptly without doctor guidance to avoid withdrawal symptoms. · Report any signs of allergic reaction (rash, itching, swelling) or serotonin syndrome (agitation, hallucinations, rapid heart rate, fever, muscle stiffness) immediately. |