Ketalar

/ Pfizer

As with other general anesthetic agents, the individual response to ketamine is somewhat varied depending on the dose, route of administration, and age of patient, so that dosage recommendation cannot be absolutely fixed. The drug should be titrated against the patient’s requirements.
Supplementary Agents: Ketamine is clinically compatible with the commonly used general and local anesthetic agents
when an adequate respiratory exchange is maintained. The regimen of a reduced dose of ketamine supplemented with diazepam can be used to produce balanced anesthesia by combination with other agents such as nitrous oxide and oxygen.
General Anesthesia Induction:
Intravenous Route:
Adults: The initial dose of Ketamine administered intravenously may range from 1 mg/kg to 4.5mg/kg.The average amount required to produce 5 to 10 minutes of surgical anaesthesia has been 2.0 mg/kg. Alternatively, in adult patients an induction dose of 1.0 mg to 2.0 mg/kg intravenous ketamine at a rate of 0.5 mg/kg/min may be used for induction of anesthesia. In addition, diazepam in 2 mg to 5 mg doses, administered in a separate syringe over 60 seconds, may be used. In most cases, 15 mg of intravenous diazepam or less will suffice. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by this induction dosage program.
Rate of Administration: It is recommended that ketamine be administered slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.
Intramuscular Route
Adults: The initial dose of ketamine administered intramuscularly may range from 6.5 mg/kg to 13 mg/kg. A dose of 10 mg/kg will usually produce 12 to 25 minutes of surgical anaesthesia.
Dosage in Hepatic Insufficiency: Dose reductions should be considered in patients with cirrhosis or other types of liver impairment.

General anesthesia for diagnostic and surgical procedures, induction of anesthesia, supplement of low potency agents.

Ketamine hydrochloride is contra-indicated in those in whom a significant elevation of blood pressure would constitute a serious hazard and in those who have shown hypersensitivity to the drug or its components.

General: Ketamine should be used by or under the direction of physicians experienced in administering general anesthetics and in maintenance of an airway and in the control of respiration. Resuscitative equipment should be ready for use. The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in transient respiratory depression or apnoea and enhanced pressor response. Because pharyngeal and laryngeal reflexes are usually active, ketamine should not be used alone in surgery or diagnostic procedures of the pharynx, larynx, or bronchial tree. Mechanical stimulation of the pharynx should be avoided, whenever possible, if ketamine is used alone. Muscle relaxants, with proper attention to respiration, may be required in both of these instances.
In surgical procedures involving visceral pain pathways, ketamine should be supplemented with an agent which obtunds visceral pain.
When ketamine is used on an outpatient basis, the patient should not be released until recovery from anesthesia is complete, and then should be accompanied by a responsible adult. Postoperative confusional states may occur during the recovery period.
Ketamine should be used with caution in patients with the following conditions: Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient. Ketamine is metabolized in the liver and hepatic clearance is required for termination of clinical effects. Abnormal liver function tests associated with ketamine use have been reported, particularly with extended use (>3 days) or drug abuse. A prolonged duration of action may occur in patients with cirrhosis or other types of liver impairment. Dose reductions should be considered in these patients. Since an increase in cerebrospinal fluid (CSF) pressure has been reported during ketamine anaesthesia, Ketamine should be used with special caution in patients with preanaesthetic elevated cerebrospinal fluid pressure.
Use with caution in patients with increased intraocular pressure (e.g., glaucoma) because the pressure may increase significantly after a single dose of ketamine.
Use with caution in patients with neurotic traits or psychiatric illness (e.g., schizophrenia and acute psychosis).
Use with caution in patients with acute intermittent porphyria.
Use with caution in patients with seizures.
Use with caution in patients with hyperthyroidism or patients receiving thyroid replacement (increased risk of hypertension and tachycardia).
Use with caution in patients with pulmonary or upper respiratory infection (ketamine sensitizes the gag reflex, potentially causing laryngospasm).
Use with caution in patients with intracranial mass lesions, a presence of head injury, globe injuries, or hydrocephalus.
Emergence Reaction: It should be noted that emergence reactions have occurred in approximately 12 percent of patients. The psychological manifestations vary in severity between pleasant dream-like states, vivid imagery, hallucinations, nightmares and emergence delirium (often consisting of dissociative or floating sensations). In some cases these states have been accompanied by confusion, excitement, and irrational behavior which a few patients recall as an unpleasant experience. The duration ordinarily is no more than a few hours; in a few cases, however, recurrences have taken place up to 24 hours postoperatively. No residual psychological effects are known to have resulted from the use of ketamine. The incidence of these emergence phenomena is least in the young (15 years of age or less) and elderly (over 65 years of age) patient. Also, they are less frequent when the drug is given intramuscularly. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by using lower recommended dosages of ketamine in conjunction with intravenous diazepam during induction and maintenance of anesthesia. Also, 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. In order to terminate a severe emergence reaction, the use of a small hypnotic dose of a short-acting or ultrashort-acting
barbiturate may be required.
Cardiovascular: Because of the substantial increase in myocardial oxygen consumption, ketamine should be used with caution in patients with hypovolemia, dehydration, or cardiac disease, especially coronary artery disease (e.g., congestive heart failure, myocardial ischemia, and myocardial infraction). In addition ketamine should be used with caution in patients with mild-to-moderate hypertension and tachyarrhythmias. Cardiac function should be continually monitored during the procedure in patients found to have hypertension or cardiac decompensation. Elevation of blood pressure begins shortly after injection, reaches a maximum within a few minutes and usually returns to preanesthetic values within 15 minutes after injection. The median peak rise of blood pressure in clinical studies has ranged from 20 to 25 percent of preanesthetic values. Depending on the condition of the patient, this elevation of blood pressure may be considered a beneficial effect, or in others, an adverse reaction.
Long-Term Use: Ketamine is not indicated nor recommended for long-term use. Cases of cystitis, including haemorrhagic cystitis, acute kidney injury, hydronephrosis, and ureteral disorders have been reported in patients being given ketamine on a long term basis, especially in the setting of ketamine abuse (These adverse reactions develop in patients receiving long-term ketamine treatment after a time ranging from 1 month to several years).
Hepatotoxicity: such as mixed liver injury, cholestatic liver injury and biliary dilation has also been reported in patients with extended use (> 3 days).
Drug Abuse and Dependence: Ketamine has been reported as being a drug of abuse. Reports suggest that ketamine produces a variety of symptoms including, but not limited to, flashbacks, hallucinations, dysphoria, anxiety, insomnia, or disorientation. Other adverse effects have also been reported: see “Long-Term Use”.
If used on a daily basis for a few weeks, dependence and tolerance may develop, particularly in individuals with a history of drug abuse and dependence. Therefore, the use of Ketamine should be closely supervised and it should be prescribed and administered with caution.
See prescribing information for full details.
Side Effects: Please refer to the license holder for further details/ See prescribing information for full details.
Drug interactions:
Prolonged recovery time may occur if barbiturates and/or opiate agonists are used concurrently with Ketamine.
Ketamine is chemically incompatible with barbiturates and diazepam because of precipitate formation. Therefore, these should not be mixed in the same syringe or infusion fluid.
Diazepam is known to increase the half life of ketamine and prolongs its pharmacodynamic effects. Dose adjustments may therefore be needed.
Ketamine may potentiate the neuromuscular blocking effects of atracurium and tubocurarine, including respiratory depression with apnoea.
The use of halogenated aesthetic 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 antagonize 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 increase the risk of developing hypotension.
Sympathomimetics (directly or indirectly acting) and vasopressin may enhance the sympathomimetic effects of ketamine.
Concomitant use with ergometrine may lead to an increase in blood pressure.
When ketamine and theophylline or aminophylline are given concurrently, a clinically significant reduction in the seizures threshold may be 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.
See prescribing information for full details.

Psychiatric disorders: Common: Hallucination, Abnormal dreams, Nightmare, Confusion, Agitation, Abnormal behaviour.
Nervous system disorders: Common: Nystagmus, Hypertonia, Tonic clonic movements.
Eye disorders: Common: Diplopia.
Cardiac disorders: Common: Blood pressure increased, Heart rate increased.
See prescribing information for full details.

Prolonged recovery time may occur if barbiturates and/or opiate agonists are used concurrently with Ketamine.
Diazepam is known to increase the half‑life of ketamine and prolongs its pharmacodynamic effects. Dose adjustments may therefore be needed.
Ketamine is chemically incompatible with barbiturates and diazepam because of precipitate formation. Therefore, these should not be mixed in the same syringe or infusion fluid.
Ketamine may potentiate the neuromuscular blocking effects of atracurium and tubocurarine, including respiratory depression with apnoea.
The use of halogenated aesthetic concomitantly with ketamine can lengthen the elimination half – life of ketamine and delay recovery from anaesthesia. Concurrent use of ketamine Ketalar, (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 antagonize 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 increase the risk of developing hypotension.
Sympathomimetics (directly or indirectly acting) and vasopressin may enhance the sympathomimetic effects of ketamine.
Concomitant use with ergometrine may lead to an increase in blood pressure.
When ketamine and theophylline or aminophylline are given concurrently, a clinically significant reduction in the seizures threshold may be 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.

Pregnancy: Ketamine 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.
Lactation: The safe use of ketamine during lactation has not been established, and such use is not recommended.
Studies in animals have shown reproductive toxicity.
See prescribing information for full details.

Respiratory depression may occur with overdose or too rapid rate of administration of ketamine, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.
Ketalar® has a wide margin of safety; several instances of unintentional administration of overdoses of Ketalar® (up to 10 times that usually required) have been followed by prolonged but complete recovery.

Excipient information
Ketalar Injection 10 mg/ml contains 53 mg of sodium in each vial, equivalent to 2.65% of the WHO recommended maximum daily intake of 2 g sodium for an adult.