Ketalar 50: detailed information

Patient Information Leaflet

Ketalar 50, 50 mg/ml, solution for injection
Ketamine
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

Keep this leaflet as you may need to read it again.
If you have any further questions, please consult your doctor or nurse.
If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Table of contents

What Ketalar 50 is and what it is used for
Important information before using Ketalar 50
How to use Ketalar 50
Possible side effects
How to store Ketalar 50
Contents of the pack and other information

1. What Ketalar 50 is and what it is used for

Ketalar 50 is a fast-acting medicine used for general anaesthesia, administered by intravenous infusion, intravenous injection or intramuscular injection.
Ketalar 50 is used:

as a sole anaesthetic agent for short diagnostic and surgical procedures that do not require skeletal muscle relaxation;
as induction of general anaesthesia prior to administration of other anaesthetic agents;
in combination with other anaesthetic medicines.

Specific indications or types of procedures:

When intramuscular administration is preferred.
Surgical wound debridement, painful dressing changes, skin grafting in burn patients, and other surgical procedures involving body surfaces.
Certain neurological, radiodiagnostic and therapeutic procedures in children requiring immobilisation.
When airway management is difficult.

Ketamine is indicated for use in children and adults.
Note: Ketamine should be used with caution in surgical procedures involving the pharynx, larynx or trachea, as it increases salivary and tracheobronchial secretions and provides inadequate suppression of pharyngeal and laryngeal reflexes.

2. Important information before using Ketalar 50

When not to use Ketalar 50

in patients with high blood pressure;
if the patient is allergic to ketamine or any of the other ingredients of this medicine (listed in section 6);
in pregnant women with eclampsia or threatened eclampsia;
in patients with severe coronary heart disease or other heart disease;
in patients with cerebrovascular disorders (e.g. stroke);
in patients with a history of psychiatric disorders;
in patients with suspected or diagnosed schizophrenia or acute psychosis (even if well controlled pharmacologically).

Warnings and precautions
Before starting treatment with Ketalar 50, discuss this with your doctor or nurse.
Special caution is required:

in patients with increased intracranial pressure prior to anesthesia;
in patients with chronic alcohol abuse or alcohol intoxication;
in patients with liver cirrhosis or other types of liver dysfunction. Ketamine is metabolized in the liver and may therefore have a prolonged effect in patients with impaired liver function. Abnormal liver function test results associated with ketamine use have been reported, particularly with prolonged use (more than 3 days) or misuse of the medicinal product. In such cases, the doctor may consider reducing the dose;
in patients with increased intraocular pressure (e.g. glaucoma), as this pressure may significantly increase even after administration of a single dose of ketamine;
in patients with neurotic tendencies;
in patients with acute intermittent porphyria (inherited or acquired disorders of heme synthesis, a component of, among others, hemoglobin);
in patients experiencing seizures;
in patients with hyperthyroidism treated with thyroid hormones;
in patients with lung infections or upper respiratory tract infections (ketamine enhances the cough reflex, which may provoke laryngospasm);
in patients with intracranial lesions, post-head injury conditions, cerebral contusion, or hydrocephalus;
in patients with hypovolemia – reduced vascular volume due to blood loss (hemorrhage), plasma loss (burns), or extracellular fluid loss (e.g. diarrhea, vomiting), dehydration, or heart disease, particularly coronary artery disease (e.g. congestive heart failure, myocardial ischemia, myocardial infarction);
in patients with mild to moderate arterial hypertension and cardiac arrhythmia with rapid heart rate;
in children and adolescents up to 15 years of age undergoing anesthesia for diagnostic or surgical procedures, there is a relatively higher risk of critical respiratory events (e.g. laryngospasm, etc.), regardless of the type of anesthesia. The main risk factors are age, medical history, and physical condition. Children under 3 years of age, premature infants, and children or adolescents with other risk factors in their medical history should be anesthetized by an appropriately experienced anesthesiologist with adequate pediatric training. Additional notes regarding the use of Ketalar 50:
This medicine is intended exclusively for use in hospital settings by or under the supervision of experienced anesthesiologists, unless its use is necessary in emergency situations.
As with other general anesthetics, equipment for resuscitation must be available during the use of Ketalar 50.
Administration of Ketalar 50 must always be preceded by an appropriate dose of atropine, hyoscine, or another agent reducing salivary secretion.
During emergence from anesthesia, hallucinations may occur.
Since pharyngeal and laryngeal reflexes are generally preserved during anesthesia, ketamine should not be used as a sole anesthetic agent in surgical or diagnostic procedures involving the pharynx, larynx, or bronchial tree. If ketamine is used as the sole anesthetic agent, mechanical irritation of the pharynx should be avoided as much as possible. In such cases, the doctor may recommend the use of muscle relaxants, with appropriate control of respiratory function.
Vomiting may occur within several hours after anesthesia.
High plasma concentrations of the drug after intravenous administration may cause transient respiratory depression and loss of pharyngolaryngeal reflexes. To minimize these effects, the doctor may recommend slow injection of a diluted solution. Aspiration is rare in clinical practice, but this possibility should be considered.
In patients with diagnosed hypertension or cardiac dysfunction, the doctor should recommend monitoring of cardiac function.
In case of overdose of Ketalar 50, respiratory depression may occur; in such a case, the doctor may recommend respiratory support. Mechanical ventilation is preferred over the use of analeptics.
The intravenous dose should be administered slowly (over 60–120 seconds). Faster administration may cause transient respiratory depression or apnea, and increased arterial blood pressure.
In surgical procedures causing visceral pain (internal organs), Ketalar 50 should be supplemented with an agent that blocks visceral pain transmission.
If Ketalar 50 is used in outpatient settings, the patient may be discharged home only after complete recovery of consciousness. Afterwards, the patient should remain under the supervision of an adult.
Immediately after injection, blood pressure increases, reaches maximum values within a few minutes, and usually returns to pre-anesthesia levels within 15 minutes after injection.
In patients with long-term ketamine use (from 1 month to several years), cases of cystitis, including hemorrhagic cystitis, have been reported.
Ketalar 50 has been identified as a medicine with abuse potential. Ketalar 50 may cause various adverse effects, including flashback episodes (recurrence of past psychotic experiences), hallucinations, dysphoria, anxiety, insomnia, or disorientation. Cases of cystitis, including hemorrhagic cystitis, and hepatotoxicity have also been reported. With daily use over several weeks, dependence and tolerance to the drug may develop, particularly in patients with current or past substance abuse. Therefore, Ketalar 50 should be used under strict medical supervision and prescribed and administered with special caution.
Confusion may occur during recovery from anesthesia.
Some patients may experience psychiatric disturbances of varying severity, ranging from a pleasant dream-like state, through vivid imagery, hallucinations, nightmares, to delirium requiring immediate intervention. In some cases, these states are accompanied by confusion, agitation, and irrational behavior. The duration of such disturbances usually lasts up to several hours; however, in some cases, recurrences have been observed up to 24 hours after surgery.
The above reactions are less frequently observed in children and adolescents (up to 15 years of age), which is why ketamine is particularly used in pediatric anesthesia. The above reactions also occur less frequently in elderly patients (over 65 years of age). Additionally, they occur less frequently when the product is administered intramuscularly. No long-term effects of ketamine on mental function are known.

You should consult your doctor, even if the above warnings concern conditions that occurred in the past.
Long-term use
Ketalar 50 is not indicated or recommended for long-term use.
Cases of cystitis, sometimes with accompanying bleeding, and liver disease have been reported, especially during prolonged use (> 3 days) or misuse. See section 4 "Possible side effects".
Misuse and dependence
Daily use of this medicine for several weeks may lead to dependence and development of tolerance to the drug, particularly in individuals who previously abused drugs, including psychoactive substances, and were dependent on them. Other adverse effects have also been reported. See section "Long-term use".
Patients with liver dysfunction
The doctor may consider reducing the dose of the medicine in patients with liver cirrhosis or other liver function disorders.
Ketalar 50 and other medicines
Tell your doctor or nurse about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Tell your doctor if you are taking the following medicines:

barbiturates (sedatives and anticonvulsants) or narcotic agents – when used concomitantly with ketamine, they may prolong emergence from anesthesia, similarly to premedication using benzodiazepines;
diazepam – increases the half-life of ketamine and prolongs its pharmacodynamic action. Therefore, dose adjustment may be necessary;
diazepam or other benzodiazepines (sedatives and hypnotics) – increase blood concentration and reduce the clearance of ketamine (the body's drug elimination rate);
thyroid hormones – increase the risk of arterial hypertension and tachycardia (increased heart rate);
other agents causing central nervous system depression (e.g. alcohol, phenothiazines, H-receptor blockers with sedative effects (allergy medications), skeletal muscle relaxants) – may enhance central nervous system depression and (or) increase the risk of respiratory depression. Dose reduction of ketamine may be necessary when used concomitantly with other anxiolytic, sedative, or hypnotic agents;
antihypertensive agents – when administered with ketamine, increase the risk of hypotension;
sympathomimetics (directly or indirectly acting) and vasopressin – may enhance the stimulatory effect of ketamine on the sympathetic nervous system;
ergometrine – may lead to increased blood pressure;
theophylline, aminophylline – unpredictable seizures may occur;
when ketamine is administered concomitantly with drugs inhibiting CYP3A4 activity (e.g. itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, nefazodone, cyclosporine, gemfibrozil), dose reduction of ketamine may be necessary;
when ketamine is administered concomitantly with drugs inducing CYP3A4 activity (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine), dose increase of ketamine may be necessary.

Other interactions:

Barbiturates and Ketalar 50 – chemically incompatible due to precipitation and should not be administered from the same syringe.
Other general anesthetics – block the central nervous system-dependent cardiovascular stimulation caused by ketamine. Concomitant use with halothane or enflurane anesthesia has led to significant cardiovascular depression. Halothane slows the distribution and redistribution (movement of the drug between tissues) of ketamine and inhibits its hepatic metabolism.
Nitrous oxide – concomitant use with ketamine reduces the required dose of ketamine.
Gallamine – concomitant use with ketamine leads to tachycardia (increased heart rate); use of ketamine with pancuronium (a skeletal muscle relaxant)

leads to arterial hypertension. Neither of these muscle relaxants should be used concomitantly with ketamine.

Atracurium and tubocurarine (skeletal muscle relaxants leading to respiratory arrest with apnea) – ketamine may accelerate the onset of apnea.
Anesthetic agents – concomitant use with ketamine (especially at high doses or rapid administration) may increase the risk of bradycardia (slowed heart rate), decreased arterial blood pressure, or reduced cardiac output.
Thiopental – ketamine has been shown to reduce the hypnotic effect of thiopental.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or nurse before using this medicine.
Ketalar 50 crosses the placenta. Its use during pregnancy is not recommended, except for administration of Ketalar 50 during cesarean section or natural childbirth. Some newborns exposed to ketamine administered intravenously to their mothers during delivery experienced respiratory depression and scored lower on the Apgar scale.
In obstetrics, there are no data on the use of intramuscularly administered Ketalar 50 or on recommended doses for continuous intravenous infusion. Due to lack of safety data, use of Ketalar 50 is not recommended in breastfeeding women.
Driving and operating machinery
Do not drive, operate machinery, or perform hazardous activities for 24 hours or longer after anesthesia.

3. How to use Ketalar 50

Ketalar 50 is not indicated or recommended for long-term use.
Ketalar 50 should be used exclusively in hospital settings or under the supervision of an
experienced anaesthesiologist. Access to resuscitation equipment must be ensured during
administration of Ketalar 50.
Ketalar 50 may be administered as intravenous infusions, intravenous injections, or intramuscular injections.
Adults, elderly patients (over 65 years of age), and children
In elderly patients, ketamine may be used as the sole anaesthetic agent or in combination with other anaesthetic agents.
Preparation for the procedure

Ketalar 50 has been found safe when administered as the only anaesthetic agent in non-fasting patients. However, it is recommended that, for elective procedures, patients refrain from oral intake for at least 6 hours prior to anaesthesia, as ketamine may cause vomiting. The need for administration of other anaesthetic or muscle relaxant drugs cannot be excluded. Administration of Ketalar 50 may be considered in non-fasting patients if, in the physician's assessment, the benefits outweigh the potential risks.
Ketamine increases salivary secretion. The physician will decide whether to administer atropine, hyoscine, glycopyrrolate, or another agent reducing salivary secretion prior to induction of anaesthesia.
Midazolam, diazepam, lorazepam, or flunitrazepam administered during premedication or concomitantly with ketamine reduce the incidence of undesirable emergence phenomena.

Onset and duration of anaesthesia
As with other anaesthetic agents, individual response to Ketalar 50 varies depending on dose, route of administration, patient age, and concomitantly administered drugs.
The dose range may vary from 1 mg/kg body weight to 4.5 mg/kg body weight when administered intravenously and from 6.5 mg/kg body weight to 13 mg/kg body weight when administered intramuscularly. The physician will determine the appropriate dosage for each patient.
Detailed information on dosage and administration intended for healthcare professionals is provided at the end of this leaflet.
Due to the rapid onset of action following intravenous administration, the patient should be in a supported position during drug administration. Recovery of consciousness occurs gradually.
Administration of a higher than recommended dose of Ketalar 50
Overdose of Ketalar 50 may lead to respiratory depression. In such cases, symptomatic treatment should be administered.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.

Common (may occur in up to 1 in 10 people):

hallucinations
vivid dreams
nightmares
confusion
agitation
irrational behaviour
nystagmus
hypertension
tonic-clonic movements
diplopia
increased blood pressure
increased heart rate
increased respiratory rate
nausea
vomiting
flushing
acneiform rash

Uncommon (may occur in up to 1 in 100 people):

loss of appetite
anxiety
bradycardia
arrhythmia
hypotension
respiratory depression
laryngospasm
pain at injection site
rash at injection site

Rare (may occur in up to 1 in 1,000 people):

anaphylactic reactions
delirium
flashback episodes (recurrence of previous psychotic experiences)
dysphoria
insomnia
disorientation
airway obstruction
apnoea
excessive salivation
cystitis and/or dysuria, possible occurrence of haematuria
haemorrhagic cystitis

Frequency not known (cannot be estimated from the available data):

increased intraocular pressure
abnormal liver function tests
drug-induced liver injury

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder or its representative.

Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Ketalar 50

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following: EXP.
The expiry date refers to the last day of the stated month.
No special temperature storage conditions apply. Store the vials in the outer packaging. Do not freeze.
Single-use vial. After opening: considering microbiological contamination risks, if the method of opening does not exclude the risk of microbiological contamination, the medicine should be used immediately. Any unused portion of the medicine should be discarded.
Before each administration, visually inspect the solution for the presence of particulate matter and discoloration, provided that the type of solution and packaging allow such inspection.
If the medicine is not used immediately, the responsibility for storage duration and conditions lies with the user.

6. Contents of the pack and other information

What Ketalar 50 contains

The active substance is ketamine. One ml of solution contains 50 mg of ketamine in the form of ketamine hydrochloride.
The other ingredients are: benzethonium chloride, water for injections.

What Ketalar 50 looks like and contents of the pack
Ketalar 50 is a clear, colourless solution for injection.
The medicine is contained in vials made of colourless type I glass, closed with a bromobutyl rubber stopper and sealed with an aluminium cap with a polypropylene (PP) plug, packed in a cardboard carton.
Pack contents: 5 vials with 10 ml each.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Siegfried Hameln GmbH
Langes Feld 13
31789 Hameln
Germany

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Pfizer Polska Sp. z o.o.
tel. 22 335 61 00

Detailed and up-to-date information on this product can be obtained by scanning the QR code located on the outer packaging using a mobile device. The same information is also available at the following URL: https://www.pfizer.pl/ulotka-ketalar50 and on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products http://www.urpl.gov.pl.

Information intended exclusively for medical professionals

WARNING: All doses are expressed as ketamine base.
Ketalar 50 is chemically incompatible with barbiturates and diazepam due to precipitation. Therefore, these drugs must not be mixed in the same syringe or in the same infusion solution.

Dosing
The medicinal product Ketalar 50 is not indicated or recommended for prolonged use.

Adults, elderly patients (over 65 years of age), and children
Ketamine has been shown to be effective as a sole anesthetic agent or in combination with other anesthetic agents during surgical procedures in elderly patients.

Preparation for procedure

Ketalar 50 has been found safe when administered as the sole anesthetic agent in non-fasting patients. However, due to the risk of vomiting and the unpredictability of the need for additional anesthetic drugs or muscle relaxants, it is recommended that patients undergoing elective surgical procedures fast and refrain from oral intake for at least 6 hours prior to anesthesia. Ketamine may be used in non-fasting patients if, in the physician’s judgment, the benefits outweigh the potential risks.
Ketamine increases salivary secretion. Prior to administration of the anesthetic, atropine, hyoscine, glycopyrrolate, or another agent reducing salivary secretion should be administered in advance.
Midazolam, diazepam, lorazepam, or flunitrazepam used as premedication, or other agents used to support ketamine, effectively reduce the incidence of negative emergence phenomena.

Onset and duration of anesthesia
As with other general anesthetics, individual response to Ketalar 50 varies depending on dose, route of administration, patient age, and concomitant medications; therefore, dosing recommendations cannot be defined precisely. The dose should be individualized according to the patient's needs.

Due to the rapid onset after intravenous administration, the patient should be in a supported position during drug administration. An intravenous dose of 1 to 2 mg/kg body weight typically induces surgical anesthesia within 30 seconds to 1 minute after injection, with anesthetic effects lasting usually for 5 to 10 minutes. An intramuscular dose of 10 mg/kg body weight typically induces surgical anesthesia within 3 to 4 minutes after injection, with anesthetic effects lasting usually for 12 to 25 minutes. Recovery of consciousness occurs gradually.

A. Ketalar 50 used as the sole anesthetic agent

Intravenous infusion

Continuous infusion of Ketalar 50 allows more precise dosing, thereby reducing total drug consumption compared to intermittent administration. This shortens recovery time and contributes to hemodynamic stability.

For infusion, a solution containing 1 mg ketamine/mL in 5% glucose solution or 0.9% sodium chloride solution is typically used.

If fluid restriction is required, the contents of one vial of Ketalar 50 may be added to 250 mL of infusion fluid, resulting in a concentration of approximately 2 mg ketamine/mL.

Induction of anesthesia
The total induction dose administered as an infusion ranges from 0.5 to 2 mg/kg body weight.

Maintenance of anesthesia
Anesthesia may be maintained by continuous slow infusion at a rate of 10 to 40 micrograms/kg body weight/min (approximately 1 to 3 mg/min).
The infusion rate depends on the patient's response and reaction to anesthesia. The dose may be reduced when a long-acting neuromuscular blocking agent is used.

Dosing in obstetrics
In obstetrics, for vaginal delivery or cesarean section, intravenous doses of 0.2 to 1 mg/kg body weight are recommended.
However, there are no data on maintenance doses of ketamine administered by infusion in obstetrics, and recommended maintenance doses cannot be established.

Intermittent administration

Induction of anesthesia

Intravenous administration
The initial intravenous dose of ketamine may range from 1 to 4.5 mg/kg body weight.
The average dose required to achieve surgical anesthesia for procedures lasting 5 to 10 minutes is 2.0 mg/kg body weight. Intravenous administration of ketamine solution should be performed slowly (over 60 to 120 seconds). Rapid administration may cause respiratory depression and increased arterial blood pressure.

Intramuscular administration
The initial intramuscular dose of ketamine may range from 6.5 to 13 mg/kg body weight, most commonly 10 mg/kg body weight. A lower initial intramuscular dose of 4 mg/kg body weight has been used in less painful diagnostic procedures. A dose of 10 mg/kg body weight typically provides 12 to 25 minutes of surgical anesthesia.

Dosing in obstetrics
There are no data on intramuscular use of ketamine in obstetrics, and recommended doses cannot be established. Available pharmacokinetic data are provided in section 5.2 of the Summary of Product Characteristics.

Maintenance of anesthesia
A decrease in the depth of anesthesia may manifest as nystagmus, movement in response to stimuli, or vocalization. Anesthesia may be maintained by administering additional doses of ketamine intravenously or intramuscularly. However, there are no data on maintenance doses of ketamine in obstetrics, and recommended doses cannot be established.

Each supplemental maintenance dose should be ½ to a full dose of the initially recommended induction dose via the chosen route, regardless of the route used for induction.

The higher the total dose of Ketalar 50 administered, the longer the recovery of consciousness after anesthesia.

During anesthesia, unconscious and tonic-clonic limb movements may occur. These movements do not indicate inadequate depth of anesthesia and do not necessitate administration of an additional anesthetic dose.

B. Ketalar 50 as an induction agent prior to administration of other general anesthetics

Induction of anesthesia is achieved by intravenous or intramuscular administration of the full ketamine dose as specified above. If ketamine is administered intravenously and the primary anesthetic has a slow onset, a second dose of ketamine may be required 5 to 8 minutes after the initial dose. If ketamine is administered intramuscularly and the primary anesthetic has a rapid onset, administration of the primary anesthetic may be delayed until 15 minutes after ketamine injection.

C. Ketalar 50 used in combination with other anesthetic agents

Ketamine may be combined with commonly used general and local anesthetics, provided adequate respiratory exchange is maintained. The dose range of ketamine used concomitantly with other anesthetics is generally similar to that stated above; however, the second anesthetic may sometimes allow for a reduction in the ketamine dose.

Management during emergence from anesthesia

After completion of the procedure, the patient should be observed and kept in a quiet environment. This does not exclude monitoring of vital signs. If any signs of emergence delirium occur during recovery of consciousness, administration of diazepam (5 to 10 mg iv in adults) should be considered. To terminate severe emergence reactions, a hypnotic dose of a barbiturate (50 to 100 mg iv) may be administered. If either of these drugs is used, the emergence period may be prolonged.

Use in patients with hepatic impairment

Dose reduction should be considered in patients with liver cirrhosis or other hepatic dysfunction (see section 4.4 of the Summary of Product Characteristics).

Method of administration
Intravenous and intramuscular administration.