KETAMINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KETAMINE HYDROCHLORIDE (KETAMINE HYDROCHLORIDE).
Noncompetitive NMDA receptor antagonist; also interacts with opioid receptors, monoaminergic receptors, and voltage-gated calcium channels.
| Metabolism | Hepatic via CYP2B6 and CYP3A4; major metabolite norketamine. |
| Excretion | Ketamine is primarily metabolized in the liver via N-demethylation to norketamine. Renal excretion accounts for approximately 90% of the dose, with 4% as unchanged drug, 16% as norketamine, and the remainder as conjugated metabolites. Fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life of ketamine is 2.5–3 hours; norketamine half-life is approximately 4 hours. Context: Prolonged elimination may occur with hepatic impairment or high-dose infusions. |
| Protein binding | Approximately 47% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 3–5 L/kg, indicating extensive tissue distribution and accumulation in lipid-rich tissues (e.g., brain, adipose). |
| Bioavailability | Oral: 17–20% (extensive first-pass metabolism); Intranasal: 45–50%; IM: 93%; Rectal: 25–50%; IV: 100%. |
| Onset of Action | IV: 30 seconds; IM: 1–5 minutes; Oral: 15–30 minutes; Intranasal: 5–15 minutes; Rectal: 10–20 minutes. |
| Duration of Action | IV: 5–15 minutes (anesthetic effect), with dissociative effects lasting 30–45 minutes; IM: 15–30 minutes (anesthetic), 30–60 minutes (dissociative); Oral: 30–60 minutes (analgesic/dissociative); Intranasal: 15–30 minutes. Context: Emergence reactions may occur up to 2 hours post-dose. |
| Action Class | General anaesthetic agents |
| Brand Substitutes | Ketolide 50mg Injection, Kmin 50mg Injection, Keta V 50mg Injection, GB-Ket 50mg Injection, Ketanik 50mg Injection |
Induction: 1-2 mg/kg IV, 0.5-1 mg/kg/min IV infusion for maintenance. Dissociative sedation: 1-1.5 mg/kg IV or 3-4 mg/kg IM. Pain management: 0.1-0.5 mg/kg IV bolus followed by 0.1-0.4 mg/kg/h IV infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose adjustment is required. Use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of active metabolite norketamine; monitor for prolonged effects. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 25-50% and titrate to effect. Child-Pugh Class C: Contraindicated or use with extreme caution; reduce dose by 50-75% and monitor closely. |
| Pediatric use | Induction: 1-2 mg/kg IV, 3-4 mg/kg IM. Maintenance: 0.5-1 mg/kg IV or IM as needed. Procedural sedation: 0.5-1 mg/kg IV, may repeat. Continuous infusion: 0.2-0.5 mg/kg/h. Maximum single dose: 2 mg/kg IV, 4 mg/kg IM. |
| Geriatric use | Reduce initial dose by 20-50% due to decreased clearance and increased sensitivity. Titrate slowly to effect. Monitor for cardiovascular and cognitive adverse effects closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KETAMINE HYDROCHLORIDE (KETAMINE HYDROCHLORIDE).
| Breastfeeding | Ketamine enters breast milk; milk-to-plasma ratio approximately 0.8-1.5. Limited data; low absolute dose (<2% maternal weight-adjusted dose). Caution with repeated high doses; monitor infant for sedation, feeding difficulties. American Academy of Pediatrics: compatible with breastfeeding after single doses. |
| Teratogenic Risk | Ketamine crosses the placenta. First trimester: Limited human data, animal studies show developmental toxicity at high doses; avoid unless essential. Second/Third trimester: Use only for indicated procedures (e.g., surgical anesthesia, procedural sedation) as maternal hypoxia may risk fetus; potential for neonatal respiratory depression if used near delivery. Neonatal effects: Possible altered neurodevelopment; consider risk-benefit. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to ketamine","Conditions where elevated blood pressure is dangerous (e.g., aneurysms, uncontrolled hypertension)","Severe coronary artery disease","Increased intracranial pressure (relative)"]
| Precautions | ["Emergence reactions (hallucinations, confusion)","Hemodynamic instability (hypertension, tachycardia)","Increased intracranial pressure","Respiratory depression","Urinary tract toxicity with chronic use"] |
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| Fetal Monitoring | Monitor maternal vital signs (blood pressure, heart rate, oxygen saturation) continuously. Fetal heart rate monitoring during and after procedure if viable. Assess for maternal emergence reactions, respiratory depression. Neonatal monitoring for respiratory depression if used near delivery. |
| Fertility Effects | Animal studies: high doses may impair spermatogenesis and reduce fertility; human data insufficient. No known long-term effect on fertility with clinical use. |