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KETALAR 100 MG/ML INJECTION

Active substance(s): KETAMINE HYDROCHLORIDE

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KETALAR®
Ketamine hydrochloride

10 mg/ml, 50 mg/ml and 100 mg/ml INJECTION

Read all of this leaflet carefully before you are given this medicine
because it contains important information for you.







If you have been given Ketalar in an emergency you will not have had a
chance to read this leaflet. Your doctor or anaesthetist will have considered
the important safety information in this leaflet, but your urgent need for
treatment may have been more important than some of the usual precautions.
If you are discharged on the same day as the operation, you should be
accompanied by another adult.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or nurse.
If you get any side effects, talk to your doctor or nurse. This includes
any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet
1. What Ketalar Injection is and what it is used for
2. What you need to know before you are given Ketalar Injection
3. How Ketalar Injection is given
4. Possible side effects
5. How to store Ketalar Injection
6. Contents of the pack and other information

1. What Ketalar Injection is and what it is used for
This medicine contains ketamine hydrochloride which belongs to a group of
medicines called anaesthetic agents, which are used to put you to sleep during
an operation. Ketalar may be used in both routine and emergency surgery.
Ketalar is used in adults, the elderly and children. Ketalar can be given
alone or in combination with other anaesthetic agents.

2. What you need to know before you are given
Ketalar Injection
v D
o not take Ketalar:
• if you are allergic to ketamine hydrochloride or any of the other
ingredients of this medicine (listed in section 6).
• if you are suffering from any condition in which an increase in blood
pressure may be harmful to you or have suffered in the past from a
medical condition which may have been caused/made worse by an
increase in blood pressure
• if you have been pregnant and during your pregnancy you have suffered
from a condition called eclampsia or pre-eclampsia which causes an
increase in your blood pressure





if you have recently suffered a stroke or serious head or brain injury
if you have severe heart disease
if you are pregnant, trying to become pregnant or breast-feeding.
However, Ketalar may safely be used in caesarean section surgery or
vaginal delivery.

v 
Warnings and precautions
Talk to your doctor or nurse if any of the following apply to you, to help them
decide if Ketalar is suitable for you. If you:
• drink large amounts of alcohol
• have a history of drug abuse or addiction
• have a history of or have current mental health problems
• have a chest infection or problems breathing
• have problems with your liver
• have increased pressure in the eye (glaucoma)
• have an inherited disease that affects the blood (porphyria)
• have ever had seizures
• are receiving treatment for your thyroid gland
• have had any injury to your head or abnormal growth in the brain

v D
riving and using machines
Caution should be taken when driving or operating machines following
treatment with Ketalar. You should not drive or operate machines in the first
24 hours after your operation.
The medicine can affect your ability to drive as it may make you sleepy or dizzy.
• Do not drive while taking this medicine until you know how it affects you.
• It is an offence to drive if this medicine affects your ability to drive.
• However, you would not be committing an offence if:
o The medicine has been prescribed to treat a medical or dental
problem and
o You have taken it according to the instructions given by the prescriber
or in the information provided with the medicine and
o It was not affecting your ability to drive safely
Talk to your doctor or pharmacist if you are not sure whether it is safe for
you to drive while taking this medicine.
v K
etalar contains sodium
Ketalar 10 mg/ml Injection: Each 1 ml contains 2.6 mg of sodium. Patients
on a sodium controlled diet should take this into consideration.



If before your operation the pressure in your spinal cord is raised, your
anaesthetist will pay special attention to this during the operation.
Other medicines and Ketalar
v 
Tell your doctor if you are taking, have recently taken or might take any other
medicines.



Ketalar is usually given together with other medicines during surgery.



When used for an operation on the chest or abdominal organs, Ketalar
is usually combined with a pain-killer.
Tell your doctor if you are taking barbiturates (e.g. thiopental) and
narcotics (morphine-like drugs) since use with Ketalar may slow your
recovery from anaesthesia. Otherwise, Ketalar may be used with all
other general and local anaesthetics.

v 
Ketalar with food and drink
It is normal not to eat or drink for at least six hours before an operation;
therefore Ketalar is usually given when your stomach is empty. If in an
emergency, this is not possible, Ketalar may still be used.
Pregnancy and breast-feeding
v 
If you are pregnant or breast-feeding, think you may be pregnant or are planning
to have a baby, ask your doctor for advice before being given this medicine.






KETALAR®
Ketamine hydrochloride

10 mg/ml, 50 mg/ml
and 100 mg/ml
INJECTION

SUMMARY OF PRODUCT CHARACTERISTICS
1. Name of medicinal product

Ketalar 10 mg/ml, 50 mg/ml, 100 mg/ml Injection

2. Qualitative and quantitative composition

Each 1 ml of solution contains:
Ketalar 10mg/ml Injection: ketamine hydrochloride equivalent to
10 mg ketamine base per ml.
Excipient(s) with known effect: Each 1 ml contains 2.6 mg of sodium
Ketalar 50mg/ml Injection: ketamine hydrochloride equivalent to
50 mg ketamine base per ml.
Ketalar 100mg/ml Injection: ketamine hydrochloride equivalent to
100 mg ketamine base per ml.
For the full list of excipients see section 6.1.

3. Pharmaceutical form

3. How Ketalar Injection is given


The following information is intended for the healthcare professional only

E xcept in an emergency, Ketalar should only be used in hospitals by
experienced anaesthetists with resuscitation equipment available.
Before your operation you will usually be given a medicine such
as atropine or hyoscine to dry up your secretions (body fluids like
saliva and tears) and another medicine called a benzodiazepine. The
benzodiazepine will help you to relax and help to prevent a side effect
known as "emergence reaction".
The dose of Ketalar depends on its use and varies from person to
person. When injected directly into a vein at a dose of 2 mg for every
kg of your bodyweight, Ketalar produces unconsciousness within
30 seconds and this lasts for 5 to 10 minutes. Because it works so
quickly, it is important to be lying down, or supported in some other way
when the drug is given. When Ketalar is injected into a muscle, at a
dose of 10 mg for every kg of bodyweight, it takes longer to work
(3 to 4 minutes) but lasts 12 to 25 minutes.
Your anaesthetist will then keep you anaesthetised with either:
§
another anaesthetic

§
more Ketalar given by injection into a muscle or vein, or in a

drip (infusion)
§
Ketalar together with another anaesthetic.

When it is injected directly into a vein, Ketalar is given over at least a
minute so that it does not slow your breathing too much. If breathing is
slowed, it can be helped mechanically.
While you are anaesthetised, your anaesthetist will watch over you
constantly, paying particular attention to your breathing, airways,
reflexes, the degree of anaesthesia and the condition of your heart.
Continued overleaf...

Solution for injection or infusion.
A clear solution for injection or infusion.

4. Clinical particulars
4.1 Therapeutic indications

Ketalar is recommended:
As an anaesthetic agent for diagnostic and surgical procedures. When used
by intravenous or intramuscular injection, Ketalar is best suited for short
procedures. With additional doses, or by intravenous infusion, Ketalar can
be used for longer procedures. If skeletal muscle relaxation is desired, a
muscle relaxant should be used and respiration should be supported.
For the induction of anaesthesia prior to the administration of other
general anaesthetic agents.
To supplement other anaesthetic 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 extractions.
Note: Eye movements may persist during ophthalmological procedures.
Anaesthesia in poor-risk patients with depression of vital functions or
where depression of vital functions must be avoided, if at all possible.
Orthopaedic 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.

Caesarean section; as an induction agent in the absence of elevated
blood pressure.
Anaesthesia in the asthmatic patient, either to minimise the risks of an
attack of bronchospasm developing, or in the presence of bronchospasm
where anaesthesia cannot be delayed.

4.2 Posology and method of administration

For intravenous infusion, intravenous injection or intramuscular injection.
NOTE: All doses are given in terms of ketamine base
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 anaesthetic agents.
Preoperative preparations
Ketalar has 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 mouth for at least six hours prior to anaesthesia.
Premedication with an anticholinergic agent (e.g. atropine, hyoscine
or glycopyrolate) or another drying agent should be given at an
appropriate interval prior to induction to reduce ketamine-induced
hypersalivation.
Midazolam, diazepam, lorazepam, or flunitrazepam used as a
premedicant or as an adjunct to ketamine, have been effective in
reducing the incidence of emergence reactions.
Onset and duration
As with other general anaesthetic agents, the individual response
to Ketalar 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 bodyweight usually produces surgical anaesthesia
within 30 seconds after injection and the anaesthetic effect usually lasts
5 to 10 minutes. An intramuscular dose of 10 mg/kg of bodyweight
usually produces surgical anaesthesia within 3 to 4 minutes following
injection and the anaesthetic effect usually lasts 12 to 25 minutes. Return
to consciousness is gradual.
A. Ketalar as the sole anaesthetic agent
Intravenous Infusion
The use of Ketalar 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.
General Anaesthesia Induction
An infusion corresponding to 0.5 – 2 mg/kg as total induction dose.
Maintenance of anaesthesia
Anaesthesia may be maintained using a microdrip infusion of
10 - 45 microgram/kg/min (approximately 1 – 3 mg/min).
The rate of infusion will depend on the patient’s reaction and response to
anaesthesia. The dosage required may be reduced when a long acting
neuromuscular blocking agent is used.

Intermittent Injection
Induction
Intravenous Route
The initial dose of Ketalar 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 anaesthesia
has been 2.0 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 and enhanced pressor
response.
Note: the 100 mg/ml concentration of ketamine should not be injected
intravenously without proper dilution. It is recommended that the drug be
diluted with an equal volume of either sterile water for injection, normal
saline, or 5% dextrose in water.
Dosage in Obstetrics
In obstetrics, for vaginal delivery or in caesarean section, intravenous
doses ranging from 0.2 to 1.0 mg/kg are recommended (see section 4.6
Fertility, pregnancy and lactation).
Intramuscular Route
The initial dose of Ketalar administered intramuscularly may range
from 6.5 mg/kg to 13 mg/kg (in terms of ketamine base). A low initial
intramuscular dose of 4 mg/kg has been used in diagnostic manoeuvres
and procedures not involving intensely painful stimuli. 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).
Dosage in Obstetrics
Data are lacking for intramuscular injection and maintenance infusion of
ketamine in the parturient population, and recommendations cannot be
made. Available data are presented in Section 5.2.
Maintenance of general anaesthesia
Lightening of anaesthesia may be indicated by nystagmus, movements in
response to stimulation, and vocalization. Anaesthesia is maintained by
the administration of additional doses of Ketalar by either the intravenous
or intramuscular route.
Each additional dose is from ½ to 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 Ketalar administered, the longer will be the
time to complete recovery.
Purposeless and tonic-clonic movements of extremities may occur
during the course of anaesthesia. These movements do not imply a
light plane and are not indicative of the need for additional doses of the
anaesthetic.
B. Ketalar as induction agent prior to the use of other general
anaesthetics
Induction is accomplished by a full intravenous or intramuscular dose of
Ketalar as defined above. If Ketalar has been administered intravenously
and the principal anaesthetic is slow-acting, a second dose of Ketalar
may be required 5 to 8 minutes following the initial dose. If Ketalar has
been administered intramuscularly and the principal anaesthetic is
rapid-acting, administration of the principal anaesthetic may be delayed
up to 15 minutes following the injection of Ketalar.

C. Ketalar as supplement to anaesthetic agents
Ketalar is clinically compatible with the commonly used general and
local anaesthetic agents when an adequate respiratory exchange
is maintained. The dose of Ketalar for use in conjunction with other
anaesthetic agents is usually in the same range as the dosage stated
above; however, the use of another anaesthetic agent may allow a
reduction in the dose of Ketalar.
D. 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 diazepam (5 to 10 mg I.V. in an
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.

4.3 Contraindications

Ketalar is contra-indicated in persons in whom an elevation of
blood pressure would constitute a serious hazard (see section 4.8).
Ketamine hydrochloride is contraindicated in patients who have shown
hypersensitivity to the drug or its components. Ketalar should not be
used in patients with eclampsia or pre-eclampsia, severe coronary or
myocardial disease, cerebrovascular accident or cerebral trauma.

4.4 Special warnings and precautions for use

To be used only in hospitals by or under the supervision of experienced
medically qualified anaesthetists except under emergency conditions.
As with any general anaesthetic agent, resuscitative equipment should be
available and ready for use.
Respiratory depression may occur with overdosage of Ketalar, 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 apnoea and enhanced pressor response.
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 Ketalar
anaesthesia under experimental conditions (Taylor, P A and Towey, R M, Brit.
Med. J. 1971, 2: 688), in clinical practice aspiration is seldom a problem.
In surgical procedures involving visceral pain pathways, Ketalar should
be supplemented with an agent which obtunds visceral pain.
When Ketalar is used on an outpatient basis, the patient should not be
released until recovery from anaesthesia is complete and then should be
accompanied by a responsible adult.
Ketalar should be used with caution in patients with the following
conditions:
Use with caution in the chronic alcoholic and the acutely alcoholintoxicated patient.
Ketamine is metabolised in the liver and hepatic clearance is required for
termination of clinical effects. 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. Abnormal liver function tests
associated with ketamine use have been reported, particularly with
extended use (>3 days) or drug abuse.

Since an increase in cerebrospinal fluid (CSF) pressure has been
reported during Ketalar anaesthesia, Ketalar should be used
with special caution in patients with preanaesthetic elevated
cerebrospinal fluid pressure.
Use with caution in patients with globe injuries and 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 in caution in patients with acute intermittent porphyria.
Use in caution in patients with seizures.
Use in caution in patients with hyperthyroidism or patients receiving
thyroid replacement (increased risk of hypertension and tachycardia)
Use in caution in patients with pulmonary or upper respiratory infection
(ketamine sensitises the gag reflex, potentially causing laryngospasm)
Use in caution in patients with intracranial mass lesions, a presence of
head injury, or hydrocephalus.
Emergence Reaction
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 behaviour which a few patients
recall as an unpleasant experience (see section 4.8).
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 minimised during the recovery period. This
does not preclude the monitoring of vital signs.
Cardiovascular
Because of the substantial increase in myocardial oxygen consumption,
ketamine should be used in caution in patients with hypovolemia,
dehydration or cardiac disease, especially coronary artery disease
(e.g. congestive heart failure, myocardial ischemia 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.
Elevation of blood pressure begins shortly after the injection of Ketalar,
reaches a maximum within a few minutes and usually returns to
preanaesthetic values within 15 minutes after injection. The median peak
rise of blood pressure in clinical studies has ranged from 20 to 25 percent
of preanaesthetic 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
Cases of cystitis including haemorrhagic cystitis have been reported
in patients being given ketamine on a long term basis. This adverse
reaction develops 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
Ketalar 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.
47266/06/16

Package leaflet: Information for the patient

4.5 Interaction with other medicinal products and other
forms of interaction

Prolonged recovery time may occur if barbiturates and/or narcotics are
used concurrently with Ketalar.
Ketalar 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 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. Co-administration 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. Co-administration 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

Pregnancy
Ketalar 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. Available data are presented in Section 5.2.
Lactation
The safe use of ketamine during lactation has not been established, and
such use is not recommended

4.7 Effects on ability to drive and use machines

Patients should be cautioned that driving a car, operating hazardous
machinery or engaging in hazardous activities should not be undertaken
for 24 hours or more after anaesthesia.
This medicine can impair cognitive function and can affect a patient’s
ability to drive safely. This class of medicine is in the list of drugs included
in regulations under 5a of the Road Traffic Act 1988. When prescribing
this medicine, patients should be told:
• The medicine is likely to affect your ability to drive
• Do not drive until you know how the medicine affects you
• It is an offence to drive while under the influence of this medicine
• However, you would not be committing an offence (called ‘statutory
defence’) if:
o
 The medicine has been prescribed to treat a medical or dental
problem and
 You have taken it according to the instructions given by the
o
prescriber and in the information provided with the medicine and
 It was not affecting your ability to drive safely
o

4.8 Undesirable effects

The following Adverse Events have been reported:
MedDRA
System Organ Class
Immune system
disorders
Metabolism and
nutrition disorders
Psychiatric disorders

Frequency†

Undesirable Effects

Rare

Anaphylactic reaction*

Uncommon

Anorexia

Common

Hallucination, Abnormal
dreams, Nightmare, Confusion,
Agitation, Abnormal behaviour
Anxiety
Delirium* Flashback*,
Dysphoria*, Insomnia,
Disorientation*
Nystagmus, Hypertonia, Tonic
clonic movements
Diplopia
Intraocular pressure increased
Blood pressure increased,
Heart rate increased
Bradycardia, Arrhythmia
Hypotension

Uncommon
Rare
Nervous system
disorders
Eye disorders

Common

Cardiac disorders

Common
Not Known
Common

Vascular disorders

Uncommon
Uncommon

MedDRA
System Organ Class
Respiratory, thoracic
and mediastinal
disorders

Frequency†
Common
Uncommon
Rare

Gastrointestinal
disorders

Common
Rare
Not known

Undesirable Effects
Respiratory rate increased
Respiratory depression,
Laryngospasm
Obstructive airway disorder*,
Apnoea*
Nausea, Vomiting
Salivary hypersecretion*
Liver function test abnormal,
Drug-induced liver injury**
Erythema, Rash morbilliform

Hepatobiliary
disorders
Common
Skin and
subcutaneous tissue
disorders
Rare
Cystitis*, Haemorrhagic cystitis*
Renal and urinary
disorders
Injection site pain, Injection
General disorders and Uncommon
site rash
administration site
conditions
† Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare
(≥1/10,000 to <1/1,000); Not known (frequency cannot be estimated
from the available data)
* AE frequency estimated from post-marketing safety database
** Extended period use (> 3 days) or drug abuse
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the Yellow Card
Scheme at www.mhra.gov.uk/yellowcard.

4.9 Overdose

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.
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.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties

ATC Code: N01AX03, Pharmacotherapeutic group: Other general
anaesthetics.
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 (reticularactivating 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.

5.2 Pharmacokinetic properties

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.

5.3 Preclinical safety data

Preclinical safety data does not add anything of further significance to the
prescriber.

6. Pharmaceutical particulars
6.1 List of excipients

Ketalar 10 mg/ml Injection: sodium chloride, benzethonium chloride,
water for injections

Ketalar 50 mg/ml Injection: benzethonium chloride, water for injections
Ketalar 100 mg/ml Injection: benzethonium chloride, water for injections

6.2 Incompatibilities

Ketalar is chemically incompatible with barbiturates and diazepam
because of precipitate formation. Therefore, these should not be mixed
in the same syringe or infusion fluid.

6.3 Shelf life

Ketalar 10 mg/ml and 50 mg/ml: 5 years
Ketalar 100 mg/ml: 3 years
For single use only. Discard any unused product at the end of each
operating session.
After dilution the solutions should be used immediately.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.
Do not freeze. Store in the original container. Discard any unused
product at the end of each operating session.

6.5 Nature and contents of container

Ketalar 10 mg/ml Injection: 20 ml white neutral glass vial with rubber
closure and aluminium flip-off cap
containing 20 ml of solution as 10 mg
ketamine base per ml.
Ketalar 50 mg/ml Injection: 10 ml vials containing 10 ml of solution as
50 mg ketamine base per ml.
Ketalar 100 mg/ml Injection:  10 ml vials containing 10 ml of solution as
100 mg ketamine base per ml.

6.6 Special precautions for disposal and other handling
For single use only. Discard any unused product at the end of each
operating session. See section 4.2.

7. marketing authorisation holder
Pfizer Limited, Sandwich, Kent CT13 9NJ, United Kingdom

8. Marketing authorisation number
PL 00057/0529, PL 00057/0530, PL 00057/0531

9. Date of first authorisation/renewal
of authorisation
1st July 2003

10. DATE OF REVISION OF THE TEXT
MM/YYYY
Ref: KE 14_0

Pfizer Limited
Sandwich, England

Package leaflet: Information for the patient
You should not be released from hospital until you have completely
recovered from the anaesthetic. If you are discharged on the same day
as the operation, you should be accompanied by another adult (see also
the section on ‘Driving and Using Machines’).
If you are given more Ketalar than you should you may experience
breathing difficulties. Your doctor or nurse may provide you with
equipment to help you breath.
If you have any further questions on the use of this medicine, ask your
doctor or nurse.

4. Possible side effects
Like all medicines, this medicine can cause side effects although not
everyone gets them.
Tell your doctor immediately if you notice pain, inflammation of the skin or
rash at the injection site.
Ketalar can sometimes cause allergic symptoms (‘anaphylaxis’) such as
breathing problems, swelling and rash. Some people have hallucinations,
vivid dreams, nightmares, feel ill at ease, confused, anxious or behave
irrationally while recovering from anaesthesia with Ketalar. These side
effects are collectively known as an ‘emergence reaction’. You will be
allowed to recover from the anaesthetic in a quiet place and this helps to
prevent the reaction (see Section 3 under ‘How Ketalar Injection is given’).
Common: may affect up to 1 in 10 people
• the following, while recovering from anaesthesia (these are
collectively known as an ‘emergence reaction’): hallucinations
(which may include flashbacks or floating sensation), vivid dreams,
nightmares, feeling ill at ease, confused, anxious and irrational
behaviour.
• unusual eye movements, increased muscle tone and muscle twitches
(which may resemble ‘fits’ or convulsions).
• double vision.
• increased blood pressure and increased pulse rate.
• breathing more quickly.
• nausea, vomiting.
• skin inflammation/rash.
Uncommon: may affect up to 1 in 100 people
• loss of appetite, feeling anxious.
• slowing of heart rate, changes in heart rhythm.
• lowering of blood pressure.
• breathing more slowly, narrowing of the voice-box leading to difficulty
in breathing.
• pain, inflammation of the skin or rash at the injection site.

Rare: may affect up to 1 in 1000 people
• allergic symptoms (‘anaphylaxis’) such as breathing problems,
swelling and rash.
• drifting in and out of consciousness (with feeling of confusion and
hallucinations), flashbacks, feeling ill at ease, sleeplessness, feeling
disorientated.
• affect on the reflexes which keep your airways clear, resulting in
temporary inability to breathe.
• increase in salivation.
• inflammation of the bladder and/or pain when urinating (‘cystitis’).
The appearance of blood in the urine may also occur.

What Ketalar looks like and contents of the pack

Not known: frequency cannot be estimated from the available data
• raised pressure in the eyes.
• abnormal results to liver function tests.
• drug-induced liver injury (when taken for more than 3 days).

Hameln Pharmaceuticals GmbH, Langes Feld 13, 31789 Hameln,
Germany.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any
possible side effects not listed in this leaflet. You can report side effects
directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By
reporting side effects you can help provide more information on the safety
of this medicine.

5. How to store Ketalar Injection




Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the
label and carton after EXP. The expiry dates refers to the last day of that
month. Your pharmacist will check this before the injection is given.
Do not freeze. This medicinal product does not require any special
storage conditions. Store in the original container in order to protect
from light.

6. Contents of the pack and other information
What Ketalar contains
• The active ingredient is ketamine hydrochloride
Each 20 ml solution contains 10 mg of ketamine base per ml
Each 10 ml solution contains 50 mg of ketamine base per ml
Each 10 ml solution contains 100 mg of ketamine base per ml
• The other ingredients are:
10 mg/ml: sodium chloride (salt), water for injections and a preservative
(benzethonium chloride).
50 mg/ml: water for injections and a preservative (benzethonium chloride).
100 mg/ml: water for injections and a preservative (benzethonium chloride).

Ketalar is a clear solution for injection or infusion available in single
glass vials and comes in three strengths. Each carton contains 1 vial.
Marketing Authorisation Holder:
Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United
Kingdom
Manufacturer:

Company contact address:
For further information on this medicine please contact Medical
Information at Pfizer Limited, Walton Oaks, Dorking Road, Tadworth,
Surrey, KT20 7NS
Telephone 01304 616161
This leaflet was last revised in 02/2016.
Ref: KE 15_0
Pfizer Limited
Sandwich, England

47266/06/16

The following information is intended for the healthcare professional only
Cases of cystitis including haemorrhagic cystitis and cases of hepatotoxicity
have also been reported. 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 Ketalar should be closely
supervised and it should be prescribed and administered with caution.

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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