Ketamax

Ketamax

ketamine

Manufacturer:

Rotexmedica GmbH

Distributor:

Duopharma Trade (Phils)
Full Prescribing Info
Contents
Ketamine hydrochloride.
Description
Each mL contains: Ketamine hydrochloride 50 mg, Benzethonium Chloride 0.1 mg/mL as preservative.
Ketamine Hydrochloride is the hydrochloride salt of a synthetic derivative of cyclohexanone with analgesic and anesthetic activities. Although its mechanism of action is not well understood, ketamine appears to non-competitively block N-methyl-D-aspartate (NMDA) receptors and may interact with opioid mu receptors and sigma receptors, thereby reducing pain perception, inducing sedation, and producing dissociative anesthesia.
Action
Pharmacotherapeutic group: Other general anaesthetics.
Pharmacology: Pharmacodynamics: Ketamine is a rapidly acting general anaesthetic for intravenous or intramuscular use with a distinct pharmacological action. Ketamine hydrochloride produces dissociative anaesthesia characterised by catalepsy, amnesia, and marked analgesia which may persist into the recovery period. Pharyngeal-laryngeal reflexes remain normal and skeletal muscle tone may be normal or can be enhanced to varying degrees. Mild cardiac and respiratory stimulation and occasionally respiratory depression occur.
Mechanism of Action: Ketamine induces sedation, immobility, amnesia and marked analgesia. The anaesthetic state produced by ketamine has been termed "dissociative anaesthesia" in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centres and pathways (reticular-activating and limbic systems). Numerous theories have been proposed to explain the effects of ketamine, including binding to N-methyl-D-aspartate (NMDA) receptors in the CNS, interactions with opiate receptors at central and spinal sites and interaction with norepinephrine, serotonin and muscarinic cholinergic receptors. The activity on NMDA receptors may be responsible for the analgesic as well as psychiatric (psychosis) effects of ketamine. Ketamine has sympathomimetic activity resulting in tachycardia, hypertension, increased myocardial and cerebral oxygen consumption, increased cerebral blood flow and increased intracranial and intraocular pressure. Ketamine is also a potent bronchodilator. Clinical effects observed following ketamine administration include increased blood pressure, increased muscle tone (may resemble catatonia), opening of eyes (usually accompanied by nystagmus) and increased myocardial oxygen consumption.
Pharmacokinetics: Absorption: Ketamine is rapidly absorbed following intra-muscular administration.
Distribution: Ketamine is rapidly distributed into perfused tissues including brain and placenta. Animal studies have shown ketamine to be highly concentrated in body fat, liver and lung. In humans at an intravenous bolus dose of 2.5 mg/kg, the distribution phase of ketamine lasts about 45 minutes, with a half-life of 10 to 15 minutes, which is associated with the duration of the anaesthetic effect (about 20 minutes). Plasma ketamine concentrations are about 1.8 to 2.0 μg/mL at 5 minutes after an intravenous bolus injection of 2 mg/kg dose, and about 1.7 to 2.2 μg/mL at 15 minutes after an intramuscular injection of 6 mg/kg dose in adults and children.
In parturients receiving an intramuscular dose of 250 mg (approximately 4.2 mg/kg), placental transfer rate of ketamine from maternal artery to umbilical vein was 47% at the time of delivery (1.72 versus 0.75 μg/mL). Average delivery time for these parturients was 12 minutes from the time of ketamine injection to vaginal delivery of a newborn.
Biotransformation: Biotransformation takes place in liver. Termination of anaesthetic is partly by redistribution from brain to other tissues and partly by metabolism. CYP3A4 enzyme is the primary enzyme responsible for ketamine N-demethylation to norketamine in human liver microsomes; with CYP2B6 and CYP2C9 enzymes as minor contributors.
Elimination: Elimination half-life is approximately 2-3 hours, and excretion renal, mostly as conjugated metabolites.
Indications/Uses
General parenteral anesthetic: Ketamine is recommended: As the sole anesthetic agent for diagnostic and surgical procedures. Although best suited for short procedures, Ketamine can be used, with additional doses, for longer procedures. If skeletal muscle relaxation is desired, a muscle relaxant should be used and respiration should be supported.
For the induction of anesthesia prior to the administration of other general anesthetic agent.
To supplement other anesthetic agents.
Specific areas of application or types of procedures: When the intramuscular route of administration is preferred.
Debridement, painful dressings, and skin grafting in burned patients, as well as other superficial surgical procedures.
Neurodiagnostic procedures such as pneumoencephalograms, ventriculograms, myelograms, and lumbar punctures.
Diagnostic and operative procedures of the eye, ear, nose, and mouth, including dental extraction. Note: Eye movements may persist during ophthamological procedures.
Anesthesia in poor-risk patients with depression of vital functions or where depression of vital functions must be avoided, if at all possible.
Orthopedic procedures such as closed reductions, manipulations, femoral pinning, amputations, and biopsies.
Sigmoidoscopy and minor surgery of the anus and rectum, circumcision and pilonidal sinus.
Cardiac catheterization procedures.
Cesarean section; as an induction agent in the absence of elevated blood pressure.
Anesthesia in the asthmatic patient, either to minimize the risk of an attack of bronchospasm developing, or in the presence of bronchospasm where anesthesia cannot be delayed.
Dosage/Direction for Use
Adults, elderly (over 65 years) and children: For surgery in elderly patients Ketamine has been shown to be suitable either alone or supplemented with other anesthetic agents.
Preoperative preparations: Ketamine had been safely used alone when the stomach was not empty. However, since the need for supplemental agents and muscle relaxants cannot be predicted, when preparing for elective surgery, it is advisable that nothing be given by the mouth for at least six hours prior to anesthesia.
Atropine, Scopolamine, or other drying agent should be given at an appropriate interval prior to induction.
Midazolam, Diazepam, Lorazepam, or Flunitrazepam used as a premedicant or as an adjunct to Ketamine, have been effective in reducing the incidence or emergence reactions.
Onset and duration: As with other general anesthetic agents, the individual response to Ketamine Injection is somewhat varied depending on the dose, route of administration, age of patient, and concomitant use of other agents, so that dosage recommendation cannot be absolutely fixed. The dose should be titrated against the patient's requirements.
Because of rapid induction following intravenous injection, the patient should be in a supported position during administration. An intravenous dose of 2 mg/kg of body weight usually produces surgical anesthesia within 30 seconds after injection and the anesthetic effect usually lasts 5 to 10 minutes. An intramuscular dose of 10 mg/kg body weight usually produces surgical anesthesia within 3 to 4 minutes following injection and the anesthetic effect usually lasts 12 to 25 minutes. Return to consciousness is gradual.
Ketamine Injection as the sole anesthetic agent: Intravenous Infusion: The use of Ketamine Injection by continuous infusion enables the dose to be titrated more closely, thereby reducing the amount of drug administered compared with intermittent administration. This results in a shorter recovery time and better stability of vital signs.
A solution containing 1 mg/mL of Ketamine, in dextrose 5% or sodium chloride 0.9% is suitable for administration by infusion.
Induction: An infusion corresponding to 0.5-2.0 mg Ketamine/kg as total induction dose.
Maintenance of anesthesia: Anesthesia may be maintained using a microdrip infusion of 10-45 micrograms/kg/min (1-3 mg/min). The rate of infusion will depend on the patient's reaction and response to anesthesia. The dosage required may be reduced when a long acting neuromuscular blocking agent is used.
Intermittent Injection: Induction: Intravenous route: The initial dose of Ketamine Injection administered intravenously may range from 1 mg/kg to 4.5 mg/kg (in terms of Ketamine base).
The average amount required to produce 5 to 10 minutes of surgical anesthesia has been 2 mg/kg. It is recommended that intravenous administration be accomplished slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression.
Intramuscular route: The initial dose of Ketamine hydrochloride Injection administered intramuscularly may range from 6.5 to 13 mg/kg (in terms of Ketamine base).
A low initial intramuscular dose of 4 mg/kg has been used in diagnostic maneuvers and produces not involving intensely painful stimuli. A dose of 10 mg/kg will usually produce 12 to 25 minutes of surgical anesthesia.
Maintenance of anesthesia: Lightening of anesthesia may be indicated by nystagmus, movements in response to stimulation, and vocalization.
Anesthesia is maintained by the administration of additional doses of Ketamine by either the intravenous or intramuscular route.
Each additional dose from 1/2 of the full induction dose recommended above for the route selected for maintenance, regardless of the route used for induction.
The larger the total amount of Ketamine administered, the longer will be the time to complete recovery.
Purposeless and tonic-clonic movements of extremities may occur during the course of anesthesia. These movements do not imply a light plane and are not indicative of the need for additional doses of the anesthetic.
Ketamine as induction agent prior to the use of other general anesthetics: Induction is accomplished by a full intravenous or intramuscular dose of Ketamine Injection as defined previously. If Ketamine has been administered intravenously and the principal anesthetic is slow-acting, a second dose of Ketamine may be required 5 to 8 minutes following the initial dose, If Ketamine has been administered intramuscularly and the principal anesthetic is rapid-acting, administration of the principal anesthetic may be delayed up to 15 minutes following the injection of Ketamine.
Ketamine Injection as supplement to anesthetic agents: Ketamine is clinically compatible with the commonly used general and local anesthetic agents when an adequate respiratory exchange is maintained. The dose of Ketamine for use in conjunction with other anesthetic agents is usually in the same range as the dosage stated previously; however, the use of another anesthetic agent may allow a reduction in the dose of Ketamine.
Management of patients in recovery: Following the procedure the patient should be observed but left undisturbed. This does not preclude the monitoring of vital signs. If, during the recovery, the patient shows any indication of emergence delirium, consideration may be given to the use of one of the following agents: Diazepam (5 to 10 mg i.v. in adult). A hypnotic dose of a thiobarbiturate (50 to 100 mg i.v.) may be used to terminate severe emergence reactions. If any one of these agents is employed, the patient may experience a longer recovery period.
Overdosage
Respiratory depression can result from an overdosage of ketamine hydrochloride. Supportive ventilation should be employed. Mechanical support of respiration that will maintain adequate blood oxygen saturation and carbon dioxide elimination is preferred to administration of analeptics.
Contraindications
Ketamine Injection is contraindicated in persons in whom an elevation of blood pressure would constitute a serious hazard (see Adverse Reactions). Ketamine should not be used in patients with eclampsia or pre-eclampsia.
Special Precautions
To be used only in hospitals by or under the supervision of experienced medically qualified anesthetists except under emergency conditions.
As with any general anesthetic agent, resuscitative equipment should be available and ready for use.
Barbiturates and Ketamine, being chemically incompatible because of precipitate formation, should not be injected from the same syringe.
Prolonged recovery time may occur if barbiturates and/or narcotics are used concurrently with Ketamine.
Emergence delirium phenomena may occur during the recovery period. The incidence of these reactions may be reduced if verbal and tactile stimulation of the patient is minimized during the recovery period. This does not preclude the monitoring of vital signs.
Because pharyngeal and laryngeal reflexes usually remain active, mechanical stimulation of the pharynx should be avoided unless muscle relaxants, with proper attention to respiration, are used.
Although aspiration of contrast medium has been reported during Ketamine anesthesia under experimental conditions in clinical practice aspiration is seldom a problem.
Cardiac function should be continually monitored during the procedure in patients found to have hypertension or cardiac decompensation.
Since an increase in cerebrospinal fluid pressure has been reported during Ketamine anesthesia, Ketamine should be used with special caution in patients with preanesthetic elevated cerebrospinal fluid pressure.
Respiratory depression may occur with overdosage of Ketamine, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to the administration of analeptics.
The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in transient respiratory depression or apnea.
In surgical procedures involving visceral pain pathways, Ketamine should be supplemented with an agent which obtunds visceral pain.
Use with caution in the chronic alcoholic and the actually alcohol-intoxicated patient.
When Ketamine is used in an outpatient basis, the patient should not be released until recovery from anesthesia is complete and then should be accompanied by a responsible adult.
Use In Pregnancy & Lactation
Pregnancy: Ketamax crosses the placenta. This should be borne in mind during operative obstetric procedures in pregnancy. No controlled clinical studies in pregnancy have been conducted. The use in pregnancy has not been established, and such use is not recommended, with the exception of administration during surgery for abdominal delivery or vaginal delivery.
Some neonates exposed to ketamine at maternal intravenous doses ≥1.5 mg/kg during delivery have experienced respiratory depression and low Apgar scores requiring newborn resuscitation.
Marked increases in maternal blood pressure and uterine tone have been observed at intravenous doses greater than 2 mg/kg.
Data are lacking for intramuscular injection and maintenance infusion of ketamine in the parturient population, and recommendations cannot be made.
Lactation: The safe use of ketamine during lactation has not been established, and such use is not recommended.
Adverse Reactions
Cardiovascular: Temporary elevation of blood pressure and pulse rate is frequently observed following administration of Ketamine Injection. However, hypotension and bradycardia have been reported. Arrhythmia has also occurred.
The medium peak rise of blood pressure has ranged from 20 to 25 percent of pre-anesthetic values. Depending on the condition of the patient, this elevation of blood pressure may be considered an adverse reaction or a beneficial effect.
Respiratory: Depression of respiration or apnea may occur following too rapid intravenous administration of high doses of Ketamine Injection Laryngospasm and other forms of airway obstruction have occurred during Ketamine anesthesia.
Ocular: Diplopia and nystagmus may occur following Ketamine administration. A slight elevation in intraocular pressure may also occur.
Psychological: During recovery from anesthesia the patient may experience emergence delirium, characterized by vivid dreams (pleasant and unpleasant), with or without psychomotor activity, manifested by confusion and irrational behavior. The fact that these reactions are observed less often in the young (15 years of age or less) makes Ketamine especially useful in pediatric anesthesia. These reactions are also less frequent in the elderly (over 65 years of age) patient. The incidence of emergence reactions is reduced as experience with the drug is gained. No residual psychological effects are known to have resulted from the use of Ketamine.
Neurological: In some patient, enhanced skeletal muscle tone may be manifested by tonic and clonic movements sometimes resembling seizures. These movements do not imply a light plane of anesthesia and are not indicative of a need for additional doses of the anesthetic.
Gastrointestinal: Anorexia, nausea, and vomiting have been observed, however, these are not usually severe. The great majority of patients are able to take liquids by mouth shortly after regaining consciousness.
Other: Local pain and exanthema at the injection site have infrequently been reported. Transient erythema and/or morbilliform rash have also been reported. Increased salivation leading to respiratory difficulties may occur unless an antisialogogue is used.
Symptoms and treatment of overdosage: Respiratory depression can result from an overdosage of Ketamine. Supportive ventilation should be employed. Mechanical support of respiration that will maintain adequate blood oxygen saturation and carbon dioxide elimination is preferred to administration of analeptics.
Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of Ketamine (up to 10 times that usually required) have been followed by prolonged but complete recovery.
Drug Interactions
Ketamine may potentiate the neuromuscular blocking effects of atracurium and tubocurarine including respiratory depression with apnoea.
The use of halogenated anaesthetics concomitantly with ketamine can lengthen the elimination half-life of ketamine and delay recovery from anaesthesia. Concurrent use of ketamine (especially in high doses or when rapidly administered) with halogenated anaesthetics can increase the risk of developing bradycardia, hypotension or decreased cardiac output.
The use of ketamine with other central nervous system (CNS) depressants (e.g. ethanol, phenothiazines, sedating H1-blockers or skeletal muscle relaxants) can potentiate CNS depression and/or increase risk of developing respiratory depression. Reduced doses of ketamine may be required with concurrent administration of other anxiolytics, sedatives and hypnotics.
Ketamine has been reported to antagonise the hypnotic effect of thiopental.
Patients taking thyroid hormones have an increased risk of developing hypertension and tachycardia when given ketamine.
Concomitant use of antihypertensive agents and ketamine increases the risk of developing hypotension.
When ketamine and theophylline are given concurrently, a clinically significant reduction in the seizure threshold is observed. Unpredictable extensor-type seizures have been reported with concurrent administration of these agents.
Drugs that inhibit CYP3A4 enzyme activity generally decrease hepatic clearance, resulting in increased plasma concentration of CYP3A4 substrate medications, such as ketamine. Coadministration of ketamine with drugs that inhibit CYP3A4 enzyme may require a decrease in ketamine dosage to achieve the desired clinical outcome.
Drugs that induce CYP3A4 enzyme activity generally increase hepatic clearance, resulting in decreased plasma concentration of CYP3A4 substrate medications, such as ketamine. Coadministration of ketamine with drugs that induce CYP3A4 enzyme may require an increase in ketamine dosage to achieve the desired clinical outcome.
Storage
Store at temperatures not exceeding 25°C; Protect from light.
MIMS Class
Anaesthetics - Local & General
ATC Classification
N01AX03 - ketamine ; Belongs to the class of other general anesthetics.
Presentation/Packing
Soln for inj (vial) 50 mg/mL x 10 mL x 25's.
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