KETAMINE HYDROCHLORIDE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 274.19 |
| 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 | Limited data; use only if benefit outweighs risk. Animal studies show adverse effects at high doses. Not a known teratogen in humans, but avoid routine use. |
| 2nd trimester | Use only if clearly needed. Monitor for maternal hypertension and increased uterine tone. May cause fetal heart rate changes. |
| 3rd trimester | Use near term with caution. May cause neonatal respiratory depression and neurobehavioral effects. Avoid in labor unless required for cesarean section. |
Clinical note
Comprehensive clinical and safety monograph for KETAMINE HYDROCHLORIDE (KETAMINE HYDROCHLORIDE).
| Placental transfer | Rapidly crosses placenta with fetal/maternal ratio approximately 0.7-1.0 within 2-5 minutes after IV administration. |
| Breastfeeding | Enters breast milk in low concentrations. Relative infant dose approximately 2-4% of maternal weight-adjusted dose. No adverse effects reported in breastfed infants with short-term use. Monitor for sedation and poor feeding. |
| Lactation Rating | L2 (Probably Compatible) |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
History of hypersensitivity to ketamineSevere hypertension (uncontrolled)Severe coronary artery diseaseIncreased intracranial pressure (unless on ventilator)Eclampsia or preeclampsia (relative, use extreme caution)Severe hepatic impairment (relative)
| Precautions | Emergence reactions (hallucinations, confusion), Hemodynamic instability (hypertension, tachycardia), Increased intracranial pressure, Respiratory depression, Urinary tract toxicity with chronic use |
| Food/Dietary | No significant food interactions; grapefruit juice may increase ketamine levels via CYP3A4 inhibition, but clinical relevance is unclear; avoid alcohol consumption due to additive sedative effects. |
| Clinical Pearls | Ketamine produces dissociative anesthesia with preserved airway reflexes and respiratory drive at sub-anesthetic doses; monitor for emergence reactions (hallucinations, delirium) especially in adults; co-administer a benzodiazepine to reduce psychotomimetic effects; use with caution in patients with hypertension, tachycardia, or increased intracranial pressure; can cause increased secretions, consider an anticholinergic like glycopyrrolate; analgesic doses are sub-dissociative (0.1-0.5 mg/kg IV); contraindicated in patients with severe coronary artery disease or recent cerebrovascular accident. |
| Patient Advice | You may feel detached from your body or have unusual dreams during recovery; this is normal and temporary. · Do not drive or operate machinery for 24 hours after receiving ketamine. · Avoid alcohol and other sedatives for at least 24 hours after treatment. · Report any hallucinations, confusion, or difficulty breathing to your healthcare provider immediately. · For nasal spray (esketamine), follow instructions for administration and avoid eating or drinking for 30 minutes after use. |
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