NORCO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORCO (NORCO).
NORCO is a combination of hydrocodone, a mu-opioid receptor agonist that inhibits ascending pain pathways and alters pain perception, and acetaminophen, which inhibits cyclooxygenase (COX) enzymes, particularly in the CNS, leading to decreased prostaglandin synthesis and antipyresis.
| Metabolism | Hydrocodone: Primarily hepatic via CYP3A4 and CYP2D6 (O-demethylation to hydromorphone, a more potent mu-opioid agonist). Acetaminophen: Hepatic metabolism via glucuronidation (UGT1A1, UGT1A6, UGT1A9), sulfation (SULT1A1, SULT1A3), and oxidation by CYP2E1 (minor), forming toxic NAPQI which is detoxified by glutathione. |
| Excretion | Hydrocodone: primarily renal (approximately 60% as unchanged drug and metabolites, including norhydrocodone, hydromorphone, and conjugated metabolites). Biliary/fecal excretion accounts for <10%. |
| Half-life | Hydrocodone: terminal elimination half-life is 3.8 to 6.0 hours (mean 4.5 hours) in adults; prolonged in hepatic or renal impairment. Acetaminophen: half-life 1.5–3 hours. |
| Protein binding | Hydrocodone: approximately 20–30% bound to plasma proteins (mainly albumin). Acetaminophen: 10–25% bound (reported up to 25%), primarily to albumin. |
| Volume of Distribution | Hydrocodone: apparent Vd is approximately 3.3–4.7 L/kg, indicating extensive tissue distribution. Acetaminophen: Vd ~0.9–1.0 L/kg. |
| Bioavailability | Oral: hydrocodone bioavailability is approximately 50–80% due to first-pass metabolism. Acetaminophen: oral bioavailability is 60–98% (mean ~88%). |
| Onset of Action | Oral: 30–60 minutes to analgesic effect, with peak effect at 1–2 hours. |
| Duration of Action | Oral: 4–6 hours; extended-release formulations (not applicable for NORCO) provide longer duration. Note: Immediate-release NORCO provides analgesia for approximately 4–6 hours. |
One tablet (5 mg hydrocodone/325 mg acetaminophen, 7.5 mg/325 mg, 10 mg/325 mg) orally every 4-6 hours as needed for pain. Maximum acetaminophen dose 4000 mg/day; maximum hydrocodone dose 60 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: Use with caution, consider reducing dose by 50% or extending interval to 6-8 hours. GFR 15-29 mL/min: Reduce dose by 50% or use every 8-12 hours. GFR <15 mL/min: Not recommended due to metabolite accumulation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce total daily dose by 50% and monitor. Child-Pugh C: Avoid use due to acetaminophen hepatotoxicity risk. |
| Pediatric use | For children ≥2 years: 0.1-0.2 mg/kg hydrocodone (based on hydrocodone component) orally every 4-6 hours as needed. Maximum single dose 10 mg hydrocodone. Maximum daily acetaminophen 75 mg/kg (up to 4000 mg). For <2 years: Not recommended. |
| Geriatric use | Start at the lowest available dose (e.g., 5 mg hydrocodone/325 mg acetaminophen) every 6 hours as needed. Due to increased sensitivity and risk of respiratory depression, max dose 40 mg hydrocodone/day. Avoid in patients with creatinine clearance <30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORCO (NORCO).
| Breastfeeding | Enters breast milk; M/P ratio not established for hydrocodone/APAP. AAP considers compatible with breastfeeding with caution due to infant sedation risk. Monitor for drowsiness, feeding difficulties. Avoid if maternal use is prolonged or high-dose. |
| Teratogenic Risk | Pregnancy Category C: First trimester – inadequate human data, animal studies show no teratogenicity at therapeutic doses; risk of neural tube defects not established. Second/third trimesters – chronic use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. Avoid in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; hepatotoxicity from acetaminophen (risk of severe liver injury at doses >4000 mg/day); CYP3A4 interactions (concomitant use with CYP3A4 inhibitors may increase hydrocodone exposure).
| Serious Effects |
["Hypersensitivity to hydrocodone, acetaminophen, or any component","Significant respiratory depression","Acute or severe bronchial asthma (without monitoring)","Known or suspected gastrointestinal obstruction (paralytic ileus)","Concomitant use with MAOIs or within 14 days of stopping MAOI"]
| Precautions | ["Addiction, abuse, and misuse","Life-threatening respiratory depression (especially in elderly, cachectic, or debilitated patients, or when used with CNS depressants)","Accidental ingestion (especially in children) can be fatal","Neonatal opioid withdrawal syndrome (prolonged use during pregnancy)","Hepatotoxicity (acetaminophen; risk increased with alcohol use or hepatic impairment)","CYP3A4 and CYP2D6 interactions (concomitant use with inhibitors or inducers may alter hydrocodone effects)","Risk of serotonin syndrome with concomitant serotonergic drugs","Adrenal insufficiency","Hypotension, risk of severe hypotension in hypovolemic patients","Seizures in patients with seizure disorders","Avoid abrupt discontinuation (taper dose)"] |
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| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, bowel function. Fetal: growth ultrasound, nonstress test in third trimester if chronic use; monitor for NOWS after delivery. Liver function tests due to acetaminophen hepatotoxicity. |
| Fertility Effects | Opioids may cause hypothalamic-pituitary-gonadal axis suppression, leading to menstrual irregularities, anovulation, and reduced fertility in women; men may experience hypogonadism and decreased sperm quality. |