CO-GESIC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CO-GESIC (CO-GESIC).

How it works

CO-GESIC (hydrocodone/acetaminophen) is a combination analgesic. Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes in the CNS, reducing prostaglandin synthesis and elevating pain threshold.

What the body does with it

Metabolism	Hydrocodone: primarily hepatic via CYP3A4-mediated N-demethylation to norhydrocodone (active) and O-demethylation via CYP2D6 to hydromorphone (active). Acetaminophen: hepatic via glucuronidation and sulfation; minor oxidation by CYP2E1 to NAPQI (toxic metabolite).
Excretion	Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Half-life	Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Protein binding	<20%; primarily binds to albumin.
Volume of Distribution	1.2–1.9 L/kg; suggests extensive distribution into total body water.
Bioavailability	Oral: 85–95%; rectal: 70–80%.
Onset of Action	Oral: 30–60 minutes; rectal: 60–90 minutes.
Duration of Action	4–6 hours; may be shorter with higher doses or in patients with rapid metabolism.

Classification & Brands

Dosing & administration

1-2 tablets (hydrocodone 5 mg/acetaminophen 500 mg per tablet) orally every 4-6 hours as needed for pain, maximum 8 tablets per day.

Dosage form	CAPSULE
Renal impairment	GFR 30-59 mL/min: Administer every 6 hours; GFR 10-29 mL/min: Administer every 8 hours; GFR <10 mL/min: Administer every 12 hours; avoid use in severe renal impairment.
Liver impairment	Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% and extend interval to every 8 hours; Child-Pugh Class C: Use not recommended due to hepatotoxicity risk.
Pediatric use	Children ≥2 years: Hydrocodone 0.1-0.2 mg/kg/dose (max 5 mg/dose) plus acetaminophen 10-15 mg/kg/dose (max 500 mg/dose) orally every 4-6 hours as needed; maximum 5 doses per day.
Geriatric use	Start at lower end of dosing range (e.g., 1 tablet every 6 hours) due to increased sensitivity to opioids and renal clearance decline; monitor for respiratory depression and sedation.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CO-GESIC (CO-GESIC).

Breastfeeding	No data on M/P ratio; use with caution. Low molecular weight may be excreted into breast milk; monitor infant for sedation or respiratory depression.
Teratogenic Risk	First trimester: No adequate studies; risk cannot be ruled out. Second and third trimesters: Avoid prolonged use or high doses near term due to potential premature closure of ductus arteriosus and oligohydramnios.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Risk of addiction, abuse, and misuse; serious, life-threatening or fatal respiratory depression from opioid use; accidental ingestion of acetaminophen can cause acute liver failure; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks from concomitant use with benzodiazepines or other CNS depressants.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to hydrocodone, acetaminophen, or any component; significant respiratory depression; acute or severe bronchial asthma; known or suspected GI obstruction (e.g., paralytic ileus); use of MAO inhibitors (concurrent or within 14 days).

Clinical Precautions

Precautions

Addiction, abuse, and misuse; respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risk with concomitant use of CNS depressants; severe hypotension; seizures; serotonin syndrome; adrenal insufficiency; hepatotoxicity (acetaminophen overdose); hypersensitivity reactions; constipation; urinary retention; impaired mental/physical abilities.

Clinical Tips & Counseling

Drug interactions

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CO-GESIC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CO-GESIC (CO-GESIC).

How it works

What the body does with it

Metabolism	Hydrocodone: primarily hepatic via CYP3A4-mediated N-demethylation to norhydrocodone (active) and O-demethylation via CYP2D6 to hydromorphone (active). Acetaminophen: hepatic via glucuronidation and sulfation; minor oxidation by CYP2E1 to NAPQI (toxic metabolite).
Excretion	Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Half-life	Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Protein binding	<20%; primarily binds to albumin.
Volume of Distribution	1.2–1.9 L/kg; suggests extensive distribution into total body water.
Bioavailability	Oral: 85–95%; rectal: 70–80%.
Onset of Action	Oral: 30–60 minutes; rectal: 60–90 minutes.
Duration of Action	4–6 hours; may be shorter with higher doses or in patients with rapid metabolism.

Classification & Brands

Dosing & administration

1-2 tablets (hydrocodone 5 mg/acetaminophen 500 mg per tablet) orally every 4-6 hours as needed for pain, maximum 8 tablets per day.

Dosage form	CAPSULE
Renal impairment	GFR 30-59 mL/min: Administer every 6 hours; GFR 10-29 mL/min: Administer every 8 hours; GFR <10 mL/min: Administer every 12 hours; avoid use in severe renal impairment.
Liver impairment	Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% and extend interval to every 8 hours; Child-Pugh Class C: Use not recommended due to hepatotoxicity risk.
Pediatric use	Children ≥2 years: Hydrocodone 0.1-0.2 mg/kg/dose (max 5 mg/dose) plus acetaminophen 10-15 mg/kg/dose (max 500 mg/dose) orally every 4-6 hours as needed; maximum 5 doses per day.
Geriatric use	Start at lower end of dosing range (e.g., 1 tablet every 6 hours) due to increased sensitivity to opioids and renal clearance decline; monitor for respiratory depression and sedation.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CO-GESIC (CO-GESIC).

Breastfeeding	No data on M/P ratio; use with caution. Low molecular weight may be excreted into breast milk; monitor infant for sedation or respiratory depression.
Teratogenic Risk	First trimester: No adequate studies; risk cannot be ruled out. Second and third trimesters: Avoid prolonged use or high doses near term due to potential premature closure of ductus arteriosus and oligohydramnios.
Fetal Monitoring