KESSO-GESIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KESSO-GESIC (KESSO-GESIC).
KESSO-GESIC is a combination analgesic containing butalbital (barbiturate), acetaminophen, and caffeine. Butalbital depresses the CNS by enhancing GABA-A receptor activity, acetaminophen inhibits COX enzymes centrally, and caffeine is a CNS stimulant that may enhance analgesia.
| Metabolism | Butalbital: hepatic via CYP450; acetaminophen: hepatic via glucuronidation, sulfation, and CYP2E1; caffeine: hepatic via CYP1A2. |
| Excretion | Renal excretion of unchanged drug and metabolites: approximately 60% renal, 40% biliary/fecal. Major metabolites include glucuronide conjugates. |
| Half-life | Terminal elimination half-life is 2–4 hours in healthy adults. In hepatic impairment, half-life may be prolonged up to 8 hours; in renal impairment, minimal change. |
| Protein binding | Approximately 90% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.3–0.5 L/kg, indicating distribution mainly into extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 70–80% due to first-pass metabolism. Intramuscular bioavailability is near 100%. |
| Onset of Action | Oral: 30–60 minutes; intravenous: 5–10 minutes; intramuscular: 15–30 minutes. |
| Duration of Action | Analgesic effect lasts 4–6 hours after oral or parenteral administration. Duration may be shorter with rapid IV administration due to redistribution. |
Adults: 2 tablets (325 mg acetaminophen + 5 mg hydrocodone per tablet) orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
| Dosage form | CAPSULE |
| Renal impairment | CrCl 30-50 mL/min: Administer every 6 hours; CrCl <30 mL/min: Avoid use due to risk of hydrocodone accumulation; hemodialysis: Not recommended. |
| Liver impairment | Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% or extend interval; Child-Pugh Class C: Avoid use. |
| Pediatric use | Not approved for pediatric use; contraindicated in children <12 years. |
| Geriatric use | Start at lowest effective dose; consider extended intervals (every 6 hours) due to increased sensitivity and risk of adverse effects; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KESSO-GESIC (KESSO-GESIC).
| Breastfeeding | Excreted into breast milk in low concentrations (M/P ratio unknown). Compatible with breastfeeding, but caution due to potential adverse effects on infant's cardiovascular and renal systems. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Risk of major malformations (e.g., neural tube defects) associated with NSAID use. Second trimester: Possible premature closure of ductus arteriosus and oligohydramnios. Third trimester: Avoid due to risk of premature ductus arteriosus closure, oligohydramnios, and neonatal renal impairment. |
■ FDA Black Box Warning
Acetaminophen may cause severe liver injury if taken in high doses or with alcohol; risk of hepatotoxicity.
| Serious Effects |
Hypersensitivity to any component; severe hepatic disease; porphyria; concomitant use with MAOIs (potential for severe CNS depression).
| Precautions | Hepatotoxicity risk with acetaminophen; dependence and withdrawal from butalbital; CNS depression; interactions with alcohol and other CNS depressants; avoid use in patients with severe hepatic impairment. |
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| Fetal Monitoring |
| Monitor maternal renal function, blood pressure, and uterine activity. Fetal monitoring: ultrasound for ductus arteriosus patency and amniotic fluid volume. |
| Fertility Effects | May impair female fertility due to inhibition of prostaglandin synthesis, affecting implantation. Reversible upon discontinuation. No known effect on male fertility. |