HYDROCODONE

Clinical safety rating: avoid

Positive evidence of fetus risks but benefits may outweigh risks in some cases

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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

Use during pregnancy

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.

Breastfeeding

Hydrocodone is excreted into breast milk (M/P ratio approximately 2.0-2.5). Relative infant dose is estimated at 2-3% of maternal weight-adjusted dose. Breastfeeding is generally considered acceptable with caution; monitor infant for sedation, poor feeding, and respiratory depression. Avoid in mothers with ultra-rapid CYP2D6 metabolizers due to increased risk of morphine accumulation.

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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	Cough
Serious Effects

Absolute Contraindications

Significant respiratory depression, acute or severe bronchial asthma, known or suspected gastrointestinal obstruction (e.g., paralytic ileus), and hypersensitivity to hydrocodone.

Clinical Precautions

Precautions

Respiratory depression, decreased bowel motility, increased intracranial pressure, severe hypotension, adrenal insufficiency, opioid-induced hyperalgesia, and risk of serotonin syndrome with serotonergic drugs.

Clinical Tips & Counseling

Drug interactions

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