KETAMINE HCL
Clinical safety rating
cautionComprehensive 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). |
| Molecular Weight | 237.73 |
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 | Limited human data; animal studies show potential for neurotoxicity. Use only if clearly needed. |
| 2nd trimester | Limited human data; consider risk-benefit. May cause uterine hypertonus. |
| 3rd trimester | Use near term may cause neonatal respiratory depression and neurobehavioral effects. Avoid in obstetric delivery unless for specific indications. |
Clinical note
Comprehensive clinical and safety monograph for KETAMINE HCL (KETAMINE HCL).
| Placental transfer | Rapidly crosses placenta; achieves fetal/maternal ratios of 0.5–1.0 within minutes. Peak levels in fetus correlate with maternal levels. |
| Breastfeeding | Ketamine enters breast milk in low levels. Due to potential for central nervous system effects in infants, caution is advised. The American Academy of Pediatrics considers ketamine compatible with breastfeeding if used short-term for maternal anesthesia. |
| Lactation Rating | L3 (Moderately Safe) – short-term use likely safe with monitoring. |
| 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 | 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to ketamine or excipientsSevere hypertension or risk of hypertensive crisisHistory of stroke or significant cerebrovascular diseaseElevated intracranial pressure (unless on mechanical ventilation)Severe coronary artery disease or recent myocardial infarctionEclampsia or preeclampsia with seizuresPorphyria (may induce acute attacks)
| 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. |
| Food/Dietary | No known food interactions. Avoid alcohol and grapefruit juice due to potential CYP3A4 inhibition affecting metabolism. |
| Clinical Pearls | Ketamine produces dissociative anesthesia with preserved airway reflexes and spontaneous respiration. Onset is rapid (30 seconds IV, 5 minutes IM). Emergence reactions (hallucinations, delirium) can be mitigated with benzodiazepines. Contraindicated in patients with elevated intracranial or intraocular pressure, hypertension, and severe coronary artery disease. Use with caution in psychiatric disorders. Subanesthetic doses are used for treatment-resistant depression and acute pain. |
| Patient Advice | You may experience vivid dreams or confusion as the medication wears off. · Do not drive or operate machinery for at least 24 hours after receiving ketamine. · Avoid alcohol and other sedatives for 24 hours following treatment. · Inform your doctor if you have a history of high blood pressure, glaucoma, or psychiatric illness. · This medication may cause changes in perception or feeling of detachment during administration. |
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