Consumer medicine information

Ketalar

Ketamine

BRAND INFORMATION

Brand name

Ketalar

Active ingredient

Ketamine

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ketalar.

What is in this leaflet

This leaflet answers some common questions about KETALAR®. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given Ketamine Injection against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What KETALAR is used for

KETALAR is used to make the body insensitive to surgical treatment. It may be used in combination with other medicines to induce anaesthesia.

This medicine belongs to a group of medicines called anaesthetics.

It works by stopping the brain from interpreting messages of pain.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is addictive.

Individuals with a history of drug abuse or dependence may develop KETALAR dependence and tolerance, however, addiction is unlikely to occur when ketamine as hydrochloride is used as prescribed for anaesthesia.

It is available only with a doctor’s prescription.

Before you are given KETALAR Injection

When you must not be given it

You must not be given KETALAR Injection if you have an allergy to:

  • any medicine containing ketamine
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

You must not be given this medicine if you have or have had any of the following medical conditions:

  • poorly controlled blood pressure
  • severe heart disease
  • heart failure
  • a recent history of stroke
  • recent heart attack
  • brain haemorrhage
  • brain trauma

You must not be given this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, it should be returned to the pharmacist for disposal.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • heart problems, including a heart attack
  • dehydration
  • high blood pressure
  • breathing problems, including chest infections and asthma
  • alcohol intoxication or history of alcohol abuse
  • drug abuse or drug dependence
  • cerebral or head problems including injury, lesions or elevated cerebrospinal fluid pressure psychiatric disorders (eg. schizophrenia, acute psychosis)
  • overactive thyroid
  • glaucoma
  • kidney or liver disease (eg. Porphyria or cirrhosis)
  • seizures (fits or convulsions)

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you are given KETALAR.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and KETALAR may interfere with each other. These include:

  • general anaesthetics (medicines used to put you to sleep during an operation) and hypnotics (eg. thiopental)
  • barbiturates (used to treat epilepsy
  • narcotic analgesics (used to relieve pain)
  • sedatives or anxiolytic drugs (medicine used to help relieve anxiety)
  • alcohol
  • benzodiazepines (medicines used as sedatives or to treat anxiety)
  • ergometrine (a medicine used sometimes after giving birth)
  • thyroxine or thyroid hormones
  • theophylline and aminophylline, medicines used for breathing problems or asthma
  • antihypertensives (medicine used to help lower high blood pressure)
  • muscle relaxants used in anaesthesia (atracurium and tubocurarine)
  • antidiuretic hormones, such as vasopressin
  • medicines affecting your heart or circulation system (medicines that increase your blood pressure should be avoided)

These medicines may be affected by ketamine or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while being treated with this medicine.

Other medicines not listed above may also interact with ketamine.

If you are not sure whether you should be given ketamine, talk to your doctor or pharmacist.

How KETALAR is given

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your age, weight and other medicines that are being given.

How it is given

KETALAR is given as an injection into a muscle, or as a slow injection into a vein. It must only be given by a nurse or doctor.

If you receive too much (overdose)

As KETALAR is given to you in a hospital under the supervision of your doctor, it is very unlikely that you will receive an overdose. You will be closely monitored in hospital during the early post-operative period so that any unwanted side effects can be treated. However, if you experience severe side effects tell your doctor immediately.

Symptoms of an overdose may include the side effects listed below in the 'Side Effects' section but are usually of a more severe nature.

Ask your doctor or pharmacist if you have any concerns.

In case of overdose, immediately contact the Poisons Information Centre 13 11 26 or go to Accident and Emergency at the nearest hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are being given KETALAR

Things you must do

Tell any doctor or nurse that are giving you this medicine if:

  • you are about to be started on any new medicine.
  • you are pregnant or are planning to become pregnant.
  • you are breastfeeding or are planning to breastfeed.

Keep all of your doctor’s appointments so that your progress can be checked.

Things to be careful of

Be careful driving or operating machinery or engage in hazardous activities for at least 24 hours after receiving KETALAR.

When KETALAR is used on an outpatient basis, you should not be released from medical care until you have completely recovered from the anaesthesia, and then you should be accompanied by a responsible adult.

Do not drink alcohol for 24 hours after you have been given this medicine.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being treated with KETALAR.

KETALAR may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • nausea, vomiting
  • increased saliva
  • pain at the injection site

The above list includes the more common side effects of your medicine.

Tell your doctor or nurse as soon as possible if you notice any of the following:

  • rash
  • double vision or abnormal eye movements
  • changes in your urine
  • yellowing of the skin (jaundice),

The above list includes serious side effects which may require medical attention.

If any of the following happen, tell your doctor or nurse immediately or go to Accident and Emergency at your nearest hospital:

  • sudden signs of allergy such as rash or hives, swelling of the face, lips or tongue, wheezing or difficulty breathing
  • confusion, excitation, irrational behaviour
  • hallucinations, vivid imagery, dream-like states, nightmares
  • movements resembling seizures
  • breathing difficulties
  • elevated blood pressure, rapid pulse rate, heart palpitations

These are very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using KETALAR

Storage

KETALAR will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light where the temperature stays below 30°C

Disposal

KETALAR is used for one dose in one patient only. Any remaining contents should be discarded.

Product description

What it looks like

KETALAR is a clear colourless solution in a glass vial.

Ingredients

KETALAR contains 200 mg/2 mL of ketamine as hydrochloride as the active ingredient.

It also contains:

  • benzethonium chloride (phemerol)
  • water for injections

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier / Sponsor

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

KETALAR 200 mg/2 mL,
5 X 2 mL vials AUST R 70073

In Australia, KETALAR® is the registered trade mark of Warner-Lambert Company LLC which has been licensed to Pfizer Australia Pty Limited.

This leaflet was updated on October 2020.

Published by MIMS December 2020

BRAND INFORMATION

Brand name

Ketalar

Active ingredient

Ketamine

Schedule

S8

 

1 Name of Medicine

Ketamine hydrochloride.

2 Qualitative and Quantitative Composition

Each mL of Ketalar contains 100 mg ketamine base (ketamine hydrochloride 115.3 mg/mL).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ketalar is a clear, colourless solution for intravenous or intramuscular injection.
It is formulated as an acid (pH 3.5 to 5.5) solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Ketalar is recommended:
1. as the sole anaesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketalar is best suited for short procedures and it can be used with additional doses, for longer procedures;
2. for the induction of anaesthesia prior to the administration of other general anaesthetic agents;
3. to supplement low-potency agents, such as nitrous oxide.

4.2 Dose and Method of Administration

Pre-operative preparation.

1. While vomiting has been reported following Ketalar administration, airway protection is usually afforded because of active laryngeal-pharyngeal reflexes. However, because these reflexes may also be diminished by supplementary anaesthetics or muscle relaxants, the possibility of aspiration must be considered. Ketalar is recommended for use in the patient whose stomach is not empty only when, in the judgment of the medical practitioner, the benefits of the drug outweigh the possible risks.
2. Atropine, hyoscine or other 'drying' agents should be given at an appropriate interval prior to induction.

Dosage.

As with other general anaesthetic agents, the individual response to Ketalar is somewhat varied depending on the dose, route of administration and age of patient, so that the dosage recommended cannot be absolutely determined in a fixed manner. The drug should be titrated against the patient's requirements.

Onset and duration.

Because of rapid induction following the initial intravenous injection, the patient should be in a supported position during administration. The onset of action of Ketalar is rapid; an intravenous dose of 2 mg/kg of body weight usually produces surgical anaesthesia within 30 seconds after injection, with the anaesthetic effect usually lasting 5 to 10 minutes. If a longer effect is desired, additional increments can be administered intravenously or intramuscularly, to maintain anaesthesia without producing significant cumulative effect.
From experience, intramuscular doses (primarily in children, in a range of 9 to 13 mg/kg) usually produce surgical anaesthesia within 3 to 4 minutes following administration, with the anaesthetic effect usually lasting 12 to 25 minutes.

Induction.

Intravenous route.

The initial dose of Ketalar administered intravenously may range from 1 mg/kg to 4.5 mg/kg. The average amount required to produce 5 to 10 minutes of surgical anaesthesia has been 2 mg/kg.

Note.

The 100 mg/mL concentration of Ketalar should not be injected intravenously without appropriate dilution. It is recommended the drug be diluted with an equal volume of either sterile water for injection, normal saline or, 5% glucose in water. To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2-8°C for not more than 24 hours.

Rate of administration.

It is recommended that Ketalar be administered slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.

Intramuscular route.

The initial dose of Ketalar administered intramuscularly ranges from 6.5 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 (see Section 4.4 Special Warnings and Precautions for Use).

Maintenance of anaesthesia.

Increments of one-half to the full induction dose may be repeated, as needed, for maintenance of anaesthesia. However, it should be noted that involuntary and tonic-clonic movements of extremities might occur during the course of anaesthesia. These movements do not imply a level of attenuated anaesthesia and are not indicative of the need for additional doses of the anaesthetic. It should be recognised that the greater the total dose of Ketalar administered, the longer will be the time to complete recovery.
This product is for one dose in one patient only. Discard any remaining contents.

4.3 Contraindications

Ketalar is contraindicated in patients with any condition in which a significant elevation of blood pressure would be hazardous, such as: severe cardiovascular disease, heart failure, severe or poorly controlled hypertension, recent myocardial infarction, history of stroke, cerebral trauma, intracerebral mass or haemorrhage. Ketamine is also contraindicated in those who have shown hypersensitivity to the drug or its components.

4.4 Special Warnings and Precautions for Use

1. Ketalar should be used by or under the direction of medical practitioners experienced in administering general anaesthetics and in maintenance of an airway and in the control of respiratory support.
2. Prolonged recovery time may occur if barbiturates and/or narcotics are used concurrently with Ketalar.
3. Post-operative confusional states may occur during the recovery period (see Section 4.4 Special Warnings and Precautions for Use, Emergence reaction).
4. Because pharyngeal and laryngeal reflexes are usually active, Ketalar 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 Ketalar is used alone. Muscle relaxants, with proper attention to respiration, may be required in both of these instances.
5. Resuscitative equipment should be ready for use.
6. The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in respiratory depression or apnoea and enhanced pressor response.
7. In surgical procedures involving visceral pain pathways, Ketalar should be supplemented with an agent which obtunds visceral pain.
8. Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient.
9. An increase in cerebrospinal fluid pressure has been reported following administration of Ketalar. Use with extreme caution in patients with pre-anaesthetic elevated cerebrospinal fluid pressure.
10. In patients with significant renal or hepatic impairment, the elimination of ketamine could potentially be delayed. Dose reductions should be considered in patients with cirrhosis or other types of liver impairment.
11. When Ketalar is used on an outpatient basis, the patient should not be released until recovery of anaesthesia is complete and should be accompanied by a responsible adult at discharge.
12. Patients should be cautioned that driving an automobile, operating machinery or engaging in other hazardous activities should not be undertaken for 24 hours or more (depending on dose and other drugs employed) after anaesthesia.
13. Use with caution in patients with increased intraocular pressure (e.g. glaucoma) because the pressure may increase significantly after a single dose of ketamine.
14. Use with caution in patients with neurotic traits or psychiatric illness (e.g. schizophrenia and acute psychosis).
15. Use with caution in patients with acute intermittent porphyria.
16. Use with caution in patients with seizures.
17. Use with caution in patients with hyperthyroidism or patients receiving thyroid replacement (increased risk of hypertension and tachycardia).
18. Use with caution in patients with pulmonary or upper respiratory infection (ketamine sensitises the gag reflex, potentially causing laryngospasm).
19. Use with caution in patients with intracranial mass lesions, a presence of head injury, globe injuries, or hydrocephalus.

Emergence reaction.

Treatment emergent adverse reactions have occurred in approximately 12% of patients. The psychological manifestations vary in severity between pleasant dream-like states, vivid imagery, hallucinations, nightmares or illusions and delirium (often consisting of dissociative or floating sensations). In some cases, these states have been accompanied by confusion, excitement and irrational behaviour, which a few patients recall as an unpleasant experience. The duration ordinarily lasts no more than a few hours; in a few cases, however, recurrences have taken place up to 24 hours post-operatively. No residual psychological effects are known to have resulted from use of Ketalar.
The incidence of these treatment emergent adverse events 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. These reactions may be reduced if verbal, tactile and visual stimulation of the patient is minimised during the recovery period.
This does not preclude the monitoring of vital signs. In addition, the use of a small hypnotic dose of a short-acting or ultrashort-acting barbiturate may be required to terminate a severe treatment-emergent adverse reaction. The incidence of emergence reactions is reduced as experience with the drug is gained.

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 ischaemia, and myocardial infarction). 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.

Long-term use.

Cases of cystitis, including haemorrhagic cystitis, acute kidney injury, hydronephrosis, and ureteral disorder (see Section 4.8 Adverse Effects (Undesirable Effects)) have been reported in patients using 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). Ketamine is not indicated nor recommended for long term use. Hepatotoxicity has also been reported in patients with extended use (> 3 days).

Drug abuse and dependence.

Ketamine has been reported being used as 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. Cases of cystitis, including haemorrhagic cystitis, acute kidney injury, hydronephrosis, ureteral disorder (see Section 4.8 Adverse Effects (Undesirable Effects)), and hepatotoxicity have also been reported. Ketamine dependence and tolerance may develop in individuals with a history of drug abuse or dependence. Therefore, ketamine should be prescribed and administered with caution.

Use in the elderly.

No data available.

Paediatric use.

Plasma half-life, clearance and volume of distribution (relative to body weight) are not significantly different between adults and children, although absorption following intramuscular injection is more rapid in the latter.

Paediatric neurotoxicity.

Some published studies in children have observed cognitive deficits after repeated or prolonged exposures to anaesthetic agents early in life. These studies have substantial limitations, and it is not clear if the observed effects are due to the anaesthetic/analgesic/sedation drug administration or other factors such as the surgery or underlying illness.
Published animal studies of some anaesthetic/analgesic/sedation drugs have reported adverse effects on brain development in early life and late pregnancy. The clinical significance of these nonclinical finding is yet to be determined.
With inhalation or infusion of such drugs, exposure is longer than the period of inhalation or infusion. Depending on the drug and patient characteristics, as well as dosage, the elimination phase may be prolonged relative to the period of administration.

Effects on laboratory tests.

There is no information available regarding the possible effects of ketamine on clinical laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Halogenated hydrocarbon inhalational anaesthetics may prolong the half-life of ketamine; recovery from anaesthesia may be prolonged following concurrent use. 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.
Diazepam is known to increase the half-life of ketamine and prolongs its pharmacodynamic effects. Dose adjustments may therefore be needed.
Sympathomimetics (directly or indirectly acting) and vasopressin may enhance the sympathomimetic effects of ketamine.
Prolonged recovery time may occur if barbiturates and/or narcotics are used concurrently with ketamine.
Benzodiazepines may prolong the half-life of ketamine; recovery from anaesthesia may be prolonged following concurrent use.
Concomitant use with ergometrine may lead to an increase in blood pressure and co-administration of drugs with a hypertensive effect should be avoided.
Sustained rises in arterial pressure have been reported in patients receiving concomitant ketamine and thyroxine.
Clinically significant reduction in seizure threshold may be observed in patients receiving concomitant ketamine and theophylline or aminophylline. Unpredictable extensor-type seizures have been reported with concurrent administration of these agents.
There is no information available on the interactions between ketamine and antihypertensive agents. However, given the marked increase in arterial pressure following administration of ketamine, cardiac function should be monitored (see Section 4.4 Special Warnings and Precautions for Use).
Barbiturates and Ketalar, being chemically incompatible because of precipitate formation, should not be injected from the same syringe.
Ketamine is clinically compatible with the commonly used general and local anaesthetic agents when an adequate respiratory exchange is maintained.
Ketamine may potentiate the neuromuscular blocking effects of atracurium and tubocurarine, including respiratory depression with apnoea.
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.
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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
With the exception of administration during surgery for abdominal delivery or vaginal delivery, no controlled clinical studies in pregnancy have been conducted. The safe use of ketamine in pregnancy has not been established, and such use is not recommended.
Limited studies in animals have not shown that ketamine causes birth defects; however, it crosses the placenta. Histological changes in the heart (degeneration and oedema of cardiac muscle), liver (diffuse haemopoietic cell infiltration, parenchymal cell degeneration) and kidneys (proximal convoluted tubule degeneration) were observed in foetuses following administration of ketamine to pregnant rats during the period of organogenesis at doses similar to the maximum human dose, on a body surface area basis; a No Observed Effect Level (NOEL) for these effects was not established. Ketamine administration to pregnant monkeys near term was associated with increased blood pCO2 and a dose-dependent respiratory depression in neonates, at a dose about one-sixteenth the maximum human dose on a body surface area basis.
Nonclinical research has shown that administration of anaesthetic and sedation drugs that block NMDA receptors, including ketamine, and/or potentiate GABA activity, can increase neuronal cell death in the brain and result in long-term deficits in cognition and behaviour of juvenile animals when administered at either high doses, or for prolonged periods, or both during the period of peak brain development. Based on comparisons across nonclinical species, the window of vulnerability of the brain to these effects is believed to correlate with human exposures in the third trimester of pregnancy through the first year of life, but may extend to approximately 3 years of age. The relevance of these nonclinical findings to human use is unknown.
See Section 4.4 Special Warnings and Precautions for Use, Paediatric neurotoxicity.
 Ketamine is likely to be excreted in breast milk and therefore breastfeeding should be discontinued when ketamine is in use.

4.7 Effects on Ability to Drive and Use Machines

This medicine can temporarily impair cognitive function, which can affect a patient's ability to drive safely. Patients should be cautioned that driving an automobile, operating machinery or engaging in other hazardous activities should not be undertaken for 24 hours or more (depending on dose and other drugs employed) after anaesthesia. The duration of the effect of ketamine and other drugs employed during the administration of anaesthesia should be considered, especially in cases where early discharge is possible.

4.8 Adverse Effects (Undesirable Effects)

Cardiovascular.

Blood pressure and pulse rate are frequently elevated following administration of Ketalar. However, hypotension and bradycardia have been observed. Arrhythmia has also occurred.

Respiration.

Although respiration is frequently stimulated, severe depression of respiration or apnoea* may occur following rapid intravenous administration of high doses of Ketalar. Laryngospasm and other forms of airway obstruction* have occurred during Ketalar anaesthesia.

Eye.

Diplopia has been noted following Ketalar administration. Ketalar may also cause a slight elevation in intraocular pressure measurement.

Psychological.

Delirium*, hallucination, confusion, abnormal behaviour, disorientation*, flashback*, dysphoria, agitation, anxiety, insomnia, nightmare, abnormal dreams have been observed. Also see Section 4.4 Special Warnings and Precautions for Use, Emergence reaction and Drug abuse and dependence.

Neurological.

In some patients, enhanced skeletal muscle tone may be manifested by tonic and clonic movements, sometimes resembling seizures (see Section 4.2 Dose and Method of Administration).
Hypertonia and nystagmus have been noted following Ketalar administration.

Gastrointestinal.

Anorexia, nausea and vomiting have been observed. However, this is not usually severe and allows the great majority of patients to take liquids by mouth shortly after regaining consciousness (see Section 4.2 Dose and Method of Administration). Hypersalivation* has also been observed.

Immune system disorders.

Anaphylaxis* has been observed.

Hepatobiliary disorders.

Drug-induced liver injury* has been reported, especially in extended period use (> 3 days) or drug abuse. Abnormal liver function test* was also identified.

Renal and urinary disorders.

Acute kidney injury*, hydronephrosis*, ureteral disorder* (including ureteral polyp, ureteritis, ureteric stenosis, and ureteric obstruction), haemorrhagic cystitis*, and cystitis* have been reported during long-term use (1 month to several years) and especially in the setting of ketamine abuse.

General.

Local pain and exanthema at the injection site have infrequently been reported. Transient erythema and/or morbilliform rash have also been reported.
*ADR identified during post-marketing use.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Respiratory depression may occur with overdosage or too rapid rate of administration of Ketalar, in which case, supportive ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.
Ketamine 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ketalar is a rapid-acting, general anaesthetic producing an anaesthetic state characterised by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally, a transient and minimal respiratory depression.
A patent airway is maintained, partly by virtue of relatively unimpaired pharyngeal and laryngeal reflexes (see Section 4.4 Special Warnings and Precautions for Use).
The anaesthetic state produced by Ketalar has been termed 'dissociative anaesthesia' in that it appears to selectively interrupt association pathways of the brain before producing somaesthetic sensory blockade. Ketalar may selectively depress the thalamo-neocortical system before significantly obtunding the more ancient cerebral centres and pathways (reticular-activating and limbic systems).
Elevation of blood pressure begins shortly after injection, reaches a maximum within a few minutes and usually returns to pre-anaesthetic values within 15 minutes after injection. The median peak rise has ranged from 20 to 25% of pre-anaesthetic values.

Clinical trials.

Ketalar ketamine (as hydrochloride) has been studied in over 12,000 operative and diagnostic procedures involving over 10,000 patients from 105 separate studies. During the course of these studies, Ketalar was administered as the sole agent, as induction for other general anaesthetic agents, or to supplement low potency agents. In these studies, the anaesthesia was rated either "excellent" or "good" by the anaesthetist and the surgeon at 90% and 93% respectively. In a second method of evaluation, the anaesthesia was rated "adequate" in at least 90% and "inadequate" in 10% or less of procedures. Specific areas of application have included the following:
1. Debridement, painful dressings and skin grafting in burn patients as well as other superficial surgical procedures.
2. Neurodiagnostic procedures such as pneumoencephalograms, ventriculograms, myelograms and lumbar punctures.
3. Diagnostic and operative procedures of the eye, ear, nose and mouth including dental extractions.
4. Diagnostic and operative procedures of the pharynx, larynx or bronchial tree.

Note.

Muscle relaxants, with proper attention to respiration, may be required (see Section 4.4 Special Warnings and Precautions for Use).
5. Sigmoidoscopy and minor surgery of the anus and rectum and circumcision.
6. Extraperitoneal procedures used in gynaecology, such as dilation and curettage.
7. Orthopaedic procedures such as closed reductions, manipulations, femoral pinning, amputations and biopsies.
8. As an anaesthetic in poor risk patients with depression of vital functions.
9. In procedures where the intramuscular route of administration is preferred.
10. In cardiac catheterisation procedures.

5.2 Pharmacokinetic Properties

Absorption.

Ketamine is rapidly absorbed following parenteral administration. Peak plasma levels averaged 0.75 microgram/mL and CSF levels were about 0.2 microgram/mL one hour after dosing. The plasma half-life is in the range of 2 to 4 hours. After IM administration (absorption half-life 2-17 minutes) it is up to 93% bioavailable.

Distribution.

Ketamine (as hydrochloride) is rapidly and extensively distributed throughout the body into highly perfused tissues including the brain. Mean volume of distribution is reported to range from approximately 1 to 3 L/kg, and the distribution half-life is approximately 7 to 11 minutes. Ketamine (as hydrochloride) is approximately 20-50% bound to plasma proteins. Ketamine is likely to be excreted in breast milk, but this is unlikely to be clinically relevant. The drug crosses the placenta in induction doses but in amounts that have no adverse effects on the neonate (see Section 4.6 Fertility, Pregnancy and Lactation).

Metabolism.

Ketamine undergoes extensive hepatic metabolism. The biotransformation includes N-dealkylation to norketamine (metabolite I), hydroxylation of the cyclohexone ring (metabolites III and IV), conjugation with glucuronic acid and dehydration of the hydroxylated metabolites to form the cyclohexene derivative (metabolite II). Norketamine (metabolite I) has about 1/6 of the potency of ketamine and is formed at concentrations in the plasma similar to those of the parent compound.

Excretion.

After intravenous bolus administration, ketamine shows a bi- or triexponential pattern of elimination. The alpha phase lasts about 45 minutes with a half-life of 10 to 15 minutes. This first phase, which represents the anaesthetic action of ketamine, is terminated by redistribution from the CNS to peripheral tissues and hepatic biotransformation to an active metabolite. The beta phase half-life is about 2.5 hours. About 90% of ketamine is excreted in the urine, mostly as metabolites, with only about 2 to 4% as the unchanged drug. Approximately 5% is recovered in the faeces. The renal clearance of ketamine hydrochloride is 15 ± 5 mL/min/kg.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Benzethonium chloride - 0.1 mg/mL benzethonium chloride added as a preservative.
Water for injections.

6.2 Incompatibilities

Barbiturates and Ketalar, being chemically incompatible because of precipitate formation, should not be injected from the same syringe.
If the ketamine dose is augmented with diazepam, the two drugs must be given separately. Do not mix ketamine and diazepam in the same syringe or infusion flask.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Protect from light.
Ketalar should not be used if the solution is coloured and/or contains particulate matter.

6.5 Nature and Contents of Container

Ketalar 200 mg (base)/2 mL, 5 x 2 mL glass vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Ketamine (as hydrochloride) is a non-barbiturate anaesthetic chemically designated (2RS)-2-(2-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride. Ketamine is a racemic mixture. The molecular weight is 274.2 and the empirical formula is C13H16ClNO.HCl.
Ketamine is freely soluble in water and methyl alcohol and is soluble in alcohol.

CAS number.

1867-66-9.

7 Medicine Schedule (Poisons Standard)

Schedule 8 - Controlled Drug.

Summary Table of Changes