KETAMINE HCL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KETAMINE HCL (KETAMINE HCL).
Noncompetitive NMDA receptor antagonist; blocks glutamate binding, and modulates opioid receptors, monoaminergic receptors, and voltage-gated calcium channels.
| Metabolism | Hepatic; primarily via CYP3A4 and CYP2B6 to norketamine (active metabolite), then further metabolized by CYP2B6 and CYP2A6. |
| Excretion | Renal: 90% as metabolites (norketamine, dehydronorketamine, hydroxylated derivatives) and 4% unchanged; biliary/fecal: 3%; minor pulmonary exhalation. |
| Half-life | Terminal elimination half-life: 2–4 hours (alpha: 10–15 min, beta: 2.5–4 hr); prolonged in hepatic impairment and with repeated dosing (up to 12–24 hr for active metabolite norketamine). |
| Protein binding | 47% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 2–4 L/kg (large distribution due to high lipophilicity; deep tissue compartments). |
| Bioavailability | IM: 93%; intranasal: 45–50%; oral: 17–20% (extensive first-pass metabolism). |
| Onset of Action | IV: 30 seconds; IM: 3–5 minutes; intranasal: 5–10 minutes; oral: 15–30 minutes (first-pass metabolism reduces effect). |
| Duration of Action | IV: 5–15 min (anesthetic), 10–20 min (analgesic); IM: 10–30 min (anesthetic), 15–45 min (analgesic); intranasal: 40–60 min (dissociative effects); oral: 1–2 hours (sub-dissociative). |
Induction: 1-2 mg/kg IV; Maintenance: 0.5-1 mg/kg IV or 10-30 mcg/kg/min IV infusion; Subanesthetic: 0.1-0.5 mg/kg IV; Analgesic: IM 2-4 mg/kg; Intranasal 1-3 mg/kg. Frequency: single doses or continuous infusion per clinical need.
| Dosage form | Injectable |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR >=30 mL/min). Severe renal impairment (eGFR <30 mL/min): use with caution; no specific dosing guidelines; consider reduced doses and monitor for prolonged effects. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: consider 50% dose reduction. Child-Pugh C: avoid use or use extreme caution with significant dose reduction (e.g., 75% reduction) and monitor closely. |
| Pediatric use | Induction: 1-2 mg/kg IV; Maintenance: 0.5-1 mg/kg IV bolus or 5-20 mcg/kg/min IV infusion; IM: 2-5 mg/kg; Intranasal: 1-3 mg/kg. For procedural sedation: IV 0.5-1 mg/kg over 2-3 minutes; additional doses 0.25-0.5 mg/kg as needed. Weight-based dosing per kg. |
| Geriatric use | Elderly patients: start with lowest effective doses; typical induction dose 0.5-1 mg/kg IV; reduce maintenance infusion rates (e.g., 5-10 mcg/kg/min); monitor for increased sensitivity, cognitive impairment, and cardiovascular effects; consider dose reduction of 25-50% compared to younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KETAMINE HCL (KETAMINE HCL).
| Breastfeeding | M/P ratio unknown; ketamine enters breast milk in low amounts. Limited data; monitor infant for sedation. Weigh benefits against potential risks. |
| Teratogenic Risk | Fetal risk cannot be ruled out; animal studies show adverse effects at maternal toxic doses. Human data limited; avoid in first trimester unless benefits outweigh risks. Potential for fetal neurotoxicity in third trimester; use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to ketamine or any component","Conditions where significant blood pressure elevation is hazardous (e.g., aneurysms, uncontrolled hypertension)","Severe coronary artery disease","Increased intracranial pressure or intraocular pressure","Pregnancy (only if benefit outweighs risk)"]
| Precautions | ["Emergence reactions (delirium, hallucinations) can occur; minimize with benzodiazepines.","Hemodynamic instability: increased heart rate and blood pressure (contraindicated in hypertension/aneurysm).","Potential for abuse and dependence; schedule III controlled substance.","Laryngospasm and respiratory depression, especially at higher doses.","Increased intracranial pressure and intraocular pressure."] |
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| Monitor maternal vital signs (heart rate, blood pressure, respiratory rate), fetal heart rate, and uterine tone during administration. Observe for maternal emergence reactions or respiratory depression. |
| Fertility Effects | No significant adverse effects reported on fertility in humans; reversible effects on sperm motility and morphology at high doses in animal studies. |