Ketamine 50 mg/ml solution for injection/infusion – patient leaflet, side effects, dosage

1. What Ketamine 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. Ketamine may be used in both routine and emergency surgery. Ketamine is used in adults, the elderly and children. Ketamine can be given alone or in combination with other anaesthetic agents.

2. What you need to know before you are given Ketamine

Do not take Ketamine:

n if you are allergic to ketamine

hydrochloride or any of the other ingredients of this medicine (listed in section 6)

n 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 n 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

n if you have recently suffered a stroke or

serious head or brain injury

n if you have severe heart disease n if you are pregnant, trying to become

pregnant or breast-feeding. However, Ketamine may safely be used in caesarean section surgery or vaginal delivery.

Warnings and precautions

Talk to your doctor or nurse if any of the following apply to you, to help them decide if Ketamine is suitable for you. If you: n drink large amounts of alcohol n have a history of drug abuse or addiction n have a history of or have current mental

health problems

n have a chest infection or problems

breathing

n have problems with your liver

n have increased pressure in the eye

(glaucoma)

n have an inherited disease that affects

the blood (porphyria)

n have ever had seizures

n are receiving treatment for your thyroid

gland

n have had any injury to your head or abnormal growth in the brain

If before your operation the pressure in your spinal cord is raised, your anaesthetist will pay special attention to this during the operation.

Long-Term Use

Ketamine is not indicated and not

Bladder infection sometimes accompanied by bleeding, and liver problems have been reported particularly with long-term use (>3 days) or drug abuse (see Section 4 Possible side effects).

Drug Abuse and Addiction

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. Other adverse effects have also been reported (see “Long-Term Use”).

Other medicines and Ketamine

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Ketamine is usually given together with other medicines during surgery.

n Tell your doctor if you are taking

barbiturates (e.g. thiopental) and narcotics (morphine-like drugs) since use with Ketamine may slow your recovery from anaesthesia. Otherwise, Ketamine may be used with all other general and local anaesthetics. n Diazepam can increase the effects of

Ketamine so dose adjustments may be needed.

n Using sympathomimetics (for example adrenaline or noradrenaline) or vasopressin with Ketamine may lead to an increase in blood pressure and heart rate.

n Using Ketamine with ergometrine may lead to an increase in blood pressure. n Using Ketamine with theophylline or aminophylline may lead to an increased likelihood of seizures.

n Concomitant use of medicines used to treat high blood pressure carries the risk of developing hypotension (low blood pressure).

n When given to patients already on thyroid hormone tablets, there is an increased risk of developing a fast heart rate and high blood pressure.

Ketamine with food and drink

It is normal not to eat or drink for at least six hours before an operation; therefore Ketamine is usually given when your stomach is empty. If in an emergency, this is not possible, Ketamine may still be used.

Pregnancy and breast-feeding

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.

Driving and using machines

Caution should be taken when driving or operating machines following treatment with Ketamine. 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. n Do not drive while taking this medicine until you know how it affects you. n It is an offence to drive if this medicine affects your ability to drive.

n However, you would not be committing an offence if:

• the medicine has been prescribed to treat a medical or dental problem and
• you have taken it according to the instructions given by the prescriber or in the information provided with the medicine and
• 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.

Information about sodium content

This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium free’.

Package leaflet: Information for the user

Ketamine 50 mg/ml Solution for Injection/Infusion

ketamine hydrochloride

The following information is intended for healthcare professionals only.

For full prescribing information please refer to the SmPC.

Posology and method of administration

For intravenous infusion, intravenous injection or intramuscular injection. NOTE: All doses are given in terms of ketamine base

Ketamine is not indicated nor

recommended for long-term use (see sections 4.1 and 4.4).

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

Ketamine 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 Ketamine 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. Ketamine as the sole anaesthetic agent Intravenous Infusion

The use of Ketamine 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 Ketamine 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.

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).

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3. How Ketamine is given

n Ketamine is not indicated nor

n Except in an emergency, Ketamine

should only be used in hospitals by experienced anaesthetists with resuscitation equipment available. n 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”.

n The dose of Ketamine 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, Ketamine 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 Ketamine 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. n Your anaesthetist will then keep you

anaesthetised with either:

• another anaesthetic,

• more Ketamine given by injection

  into a muscle or vein, or in a drip (infusion),

• Ketamine together with another

  anaesthetic.

n When it is injected directly into a vein,

Ketamine 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.

n 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.

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 Ketamine than you should you may experience breathing difficulties. Your doctor or nurse may provide you with equipment to help you breathe. 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 everybody gets them.

Tell your doctor immediately if you notice pain, inflammation of the skin or rash at the injection site.

Ketamine 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 Ketamine. 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 Ketamine is given’).

Common: may affect up to 1 in 10 people

n 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,

n unusual eye movements, increased

muscle tone and muscle twitches (which may resemble ‘fits’ or convulsions), n double vision,

n increased blood pressure and increased pulse rate,

n breathing more quickly,

n nausea, vomiting,

n skin inflammation/rash.

Uncommon: may affect up to 1 in 100 people

n loss of appetite, feeling anxious, n slowing of heart rate, changes in heart rhythm,

n lowering of blood pressure,

n breathing more slowly, narrowing of the voice-box leading to difficulty in breathing,

n pain, inflammation of the skin or rash at the injection site.

Rare: may affect up to 1 in 1000 people n allergic symptoms (‘anaphylaxis’) such as breathing problems, swelling and rash,

n drifting in and out of consciousness

(with feeling of confusion and hallucinations), flashbacks, feeling ill at ease, sleeplessness, feeling disorientated,

n affect on the reflexes which keep your airways clear, resulting in temporary inability to breathe,

n increase in salivation,

n inflammation of the bladder and/or pain when urinating (‘cystitis’). The appearance of blood in the urine may also occur.

Not known: frequency cannot be estimated from the available data

n raised pressure in the eyes,

n abnormal results to liver function tests, n drug-induced liver injury (when taken for more than 3 days).

Reporting of side effects:

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Ketamine

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 bottle label and on the carton. The expiry date refers to the last day of that month.

Store in the original container in order to protect from light. This medicine requires no special temperature storage conditions.

6. Contents of the pack and other information

What Ketamine contains

n the active substance is ketamine hydrochloride. Each 10 ml vial contains 500 mg of ketamine base (50 mg/ml), n the other ingredients are water for injection, sodium hydroxide and hydrochloric acid.

What Ketamine looks like and contents of the pack

Ketamine is a clear solution for injection/ infusion available in a pack of 5 or 10 glass vials with a grey stopper covered with a blue aluminium cap.

Not all pack sizes may be marketed. Marketing Authorisation Holder

Flynn Pharma Limited

5^th Floor, 40 Mespil Road,

Dublin 4,

IRELAND, D04 C2N4

Manufacturer

Inresa Arzneimittel GmbH

Obere Hardtstr. 18

79114 Freiburg

Germany

This leaflet was last revised in July 2024

Intramuscular Route

The initial dose of Ketamine 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 Ketamine 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 Ketamine 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. Ketamine as induction agent prior to the use of other general anaesthetics

Induction is accomplished by a full intravenous or intramuscular dose of Ketamine as defined above. If Ketamine has been administered intravenously and the principal anaesthetic is slow-acting, a second dose of Ketamine may be required 5 to 8 minutes following the initial dose. If Ketamine has been administered intramuscularly and the principal anaesthetic is rapid-acting, administration of the principal anaesthetic may be delayed up to 15 minutes following the injection of Ketamine.

C. Ketamine as supplement to anaesthetic agents

Ketamine is clinically compatible with the commonly used general and local

anaesthetic agents when an adequate respiratory exchange is maintained. The dose of Ketamine 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 Ketamine.

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. Incompatibilities

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.

Shelf life

3 years

Diluted solution for infusion should be used immediately.

Chemical and physical in-use stability has been demonstrated for 48 hours at 25 °C when protected from light after dilution with Glucose 5% Intravenous Infusion or Sodium Chloride 0.9% Intravenous Infusion.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not normally be longer than 24 hours at 2-8 °C unless dilution has taken place in controlled and validated aseptic conditions. Special precautions for storage

This medicinal product does not require any special temperature storage conditions. Store in the original container. Keep the vial in the outer carton in order to protect from light.

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.

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