CO-GESIC
Clinical safety rating
cautionComprehensive clinical and safety monograph for CO-GESIC (CO-GESIC).
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.
| 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. |
| Molecular Weight | 299.4 |
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. |
| 1st trimester | Avoid; contains hydrocodone and acetaminophen; hydrocodone associated with risk of congenital malformations, acetaminophen generally considered safe but use should be limited. |
| 2nd trimester | Use only if clearly needed; risk of fetal dependence and withdrawal with prolonged use. |
| 3rd trimester | Avoid; risk of neonatal respiratory depression and withdrawal syndrome; acetaminophen overdose risk. |
Clinical note
Comprehensive clinical and safety monograph for CO-GESIC (CO-GESIC).
| Placental transfer | Both hydrocodone and acetaminophen cross the placenta; hydrocodone has high transfer, acetaminophen transfers readily. |
| Breastfeeding | Hydrocodone is excreted into breast milk; monitor infant for sedation and respiratory depression; acetaminophen is compatible in usual doses. |
| Lactation Rating | L3 (Moderately Safe) or 'Use with caution' |
| 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 | Monitor fetal heart rate and amniotic fluid index if used for extended periods. Observe infant for signs of narcotic withdrawal postnatally if maternal use was chronic. |
| Fertility Effects | No known direct effects on fertility. Chronic opioid use may cause menstrual irregularities or anovulation. |
■ 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.
| Serious Effects |
Hypersensitivity to hydrocodone, acetaminophen, or any componentSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusSuspected surgical abdomenMonoamine oxidase inhibitor (MAOI) use within 14 days
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may alter metabolism of hydrocodone. Take with food if gastrointestinal upset occurs. Avoid alcohol-containing foods or beverages. No other significant food interactions. |
| Clinical Pearls | Co-Gesic is a fixed-dose combination of hydrocodone and acetaminophen. Monitor for acetaminophen hepatotoxicity; maximum daily acetaminophen dose should not exceed 4 g. Hydrocodone is a Schedule II controlled substance with abuse potential. Use with caution in patients with respiratory compromise, COPD, or sleep apnea. Avoid concurrent use with other CNS depressants including alcohol. In opioid-tolerant patients, withdrawal may occur if discontinued abruptly. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol while taking this medication due to risk of liver damage and increased sedation. · Do not take other medications containing acetaminophen (Tylenol, many cold/flu products) to avoid exceeding the maximum daily dose (4 grams). · This medication may cause drowsiness or dizziness; do not drive or operate machinery until you know how it affects you. · Store securely out of reach of children and dispose of unused medication properly (take-back programs preferred). · Do not crush or chew extended-release formulations (if applicable). · Report signs of liver injury (yellowing skin/eyes, dark urine, abdominal pain) or respiratory depression (slow/shallow breathing) immediately. |
Loading safety data…