Dissociative anaesthetic (NMDA antagonist)
Ketamine is a general anaesthetic used for diagnostic and surgical procedures that do not require skeletal muscle relaxation, for induction of anaesthesia before other anaesthetics and as a supplement to other anaesthetic agents. It acts rapidly and is used in the hospital setting, under the supervision of experienced professionals.
Also known as: Cetamina, Ketalar
Memantine + ketamine: NMDA antagonists in combination — use with caution (possible profound sedation).
The FDA memantine label documents that the combination with other NMDA antagonists (including ketamine) has not been systematically evaluated and should be approached with caution (section 7.1). Ketamine is a potent NMDA antagonist, used in anaesthesia and increasingly in low doses for resistant depression and chronic pain; the additive NMDA antagonism with memantine may potentiate dissociative effects, profound sedation and psychomotor impairment. The interaction is relevant mainly in the perioperative or therapeutic ketamine setting in patients on memantine (Alzheimer dementia). The practical guidance is to inform the anaesthetic team of current medication, monitor level of consciousness and vital signs, and adjust ketamine doses accordingly.
Memantine + ketamine: NMDA antagonists in combination — use with caution (possible profound sedation).
The FDA memantine label documents: "Use with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution" (7.1). Ketamine is a potent NMDA antagonist — combining with memantine may potentiate dissociative and sedative effects.
Monitor level of consciousness and vital signs in the perioperative setting.
Prolonged sedation, dissociation or hypertension with the combination.
Use with caution; monitor sedation, dissociation and blood pressure in the combination (anaesthetic setting).
DailyMed/FDA (NIH/NLM) — approved Memantine label (NAMENDA XR), section 7.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=617dcd31-3215-4dd8-9b6e-d888d3bf30f3 ; approved Ketamine label (KETALAR): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14e8f864-8b8a-4e7e-8439-e510d3107063
No documented food or drink interactions.
FDA label (KETALAR, 4): contraindicated in patients for whom a significant elevation of blood pressure would be a serious hazard. Ketamine raises blood pressure and heart rate (direct sympathomimetic effect).
Contraindicated in patients with uncontrolled hypertension or in whom blood pressure elevation would be a serious hazard; monitor vital signs during administration.
DailyMed/FDA (NIH/NLM) — approved Ketamine label (KETALAR), section 4 CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14e8f864-8b8a-4e7e-8439-e510d3107063
FDA label (KETALAR, 5.6): ketamine administration is associated with hepatobiliary dysfunction (most often a cholestatic pattern) with recurrent use (misuse/abuse or unapproved indications); sclerosing cholangitis reported in long-term therapy, potentially reversible on discontinuation.
Obtain baseline LFTs (including ALP and GGT) in patients receiving recurrent doses and monitor periodically; discontinue upon signs of sclerosing cholangitis.
DailyMed/FDA (NIH/NLM) — approved Ketamine label (KETALAR), section 5.6: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14e8f864-8b8a-4e7e-8439-e510d3107063
FDA label (KETALAR, 8.1): available data mostly describe use at caesarean section, with no identified risk of adverse maternal or fetal outcomes; in animal studies, developmental delays (hypoplasia of skeletal tissues) at 0.3× the human IM dose; in primates, anaesthetics blocking NMDA during peak brain development increase neuronal apoptosis when used > 3 h.
Use if benefit justifies risk; balance the benefit of adequate anaesthesia with the potential risk suggested by nonclinical data.
Literature describes the presence of ketamine and its metabolite in human milk; monitor the infant for sedation, respiratory depression and increased muscle tone/spasms; limit use to anaesthesia in lactating women (8.2).
Not specifically documented in the label (no 8.3 section with requirements).
DailyMed/FDA (NIH/NLM) — approved Ketamine label (KETALAR), section 8 Use in Specific Populations: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14e8f864-8b8a-4e7e-8439-e510d3107063
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Rapid-acting dissociative general anaesthetic: produces surgical anaesthesia within 5-10 min after IV injection (2 mg/kg within ~30 s) or within 3-4 min after IM; the anaesthetic effect typically lasts 12-25 min (IM). It raises blood pressure and heart rate (FDA label 2.2).
Non-selective, non-competitive antagonist of the NMDA receptor (ionotropic glutamate receptor); the main metabolite, norketamine, has activity at the same receptor with lower affinity (~1/3 of ketamine activity in reducing MAC in rats).
Rapid distribution after IV administration (alpha phase ~45 min); redistribution from the CNS to slower equilibrating peripheral tissues (beta phase). Hospital clinical use (IV/IM); oral absorption not relevant for anaesthetic use.
Metabolised by N-dealkylation to norketamine (active), mainly by CYP2B6 and CYP3A4; norketamine undergoes hydroxylation and glucuronic acid conjugation (12.3).
Alpha-phase half-life (anaesthetic effect): 10-15 min; redistribution half-life (beta phase): 2.5 hours.
