Special Warning : אזהרת שימוש

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 Ketamin Sintetica, 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 Ketamin Sintetica 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, Ketamin Sintetica should be supplemented with an agent which obtunds visceral pain.

When Ketamin Sintetica 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.
Ketamin Sintetica should be used with caution in patients with the following conditions:

Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient.

Ketamine is 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 Ketamin Sintetica anaesthesia, Ketamin Sintetica 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 Ketamin Sintetica, 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, acute kidney injury, hydronephrosis, and ureteral disorders have been reported in patients being given ketamine on a long term basis, especially in the setting of ketamine abuse. These adverse reactions develop in patients receiving long-term ketamine treatment after a time ranging from 1 month to several years).
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
Ketamin Sintetica 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. Adverse effects have also been reported: see “Long-Term Use”.

If used on a daily basis for a few weeks, dependence and tolerance may develop, particularly in individuals with a history of drug abuse and dependence. Therefore, the use of Ketamin Sintetica should be closely supervised and it should be prescribed and administered with caution.
Excipient information
Ketamin Sintetica 10 mg/ml contains 26mg of sodium in each vial, equivalent to 1.3% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

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. 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 o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely