Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Pfizer Limited, Sandwich, Kent CT13 9NJ, United Kingdom
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Ketalar is contra-indicated in persons in whom an elevation of blood pressure would constitute a serious hazard (see section 4.8).
Ketalar should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma.
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 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 Ketalar anaesthesia, Ketalar should be used with special caution in patients with pre-anaesthetic 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.
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.
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 pre-anaesthetic values within 15 minutes after injection. The median peak rise of blood pressure in clinical studies has ranged from 20 to 25 percent of pre-anaesthetic 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.
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).
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. 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.
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.
Diazepam is known to increase the half-life of ketamine and prolongs its pharmacodynamic effects. Dose adjustments may therefore be needed.
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.
Sympathomimetics (directly or indirectly acting) and vasopressin may enhance the sympathomimetic effects of ketamine.
Concomitant use with ergometrine may lead to an increase in blood pressure.
When ketamine and theophylline or aminophylline are given concurrently, a clinically significant reduction in the seizure threshold may be 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. Coadministration of ketamine with drugs that inhibit CYP3A4 enzyme may require a decrease in ketamine dosage to achieve the desired clinical outcome.
Drugs that induce CYP3A4 enzyme activity generally increase hepatic clearance, resulting in decreased plasma concentration of CYP3A4 substrate medications, such as ketamine. Coadministration of ketamine with drugs that induce CYP3A4 enzyme may require an increase in ketamine dosage to achieve the desired clinical outcome.
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.
The safe use of ketamine during lactation has not been established, and such use is not recommended.
Studies in animals have shown reproductive toxicity (see section 5.3).
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 following Adverse Events have been reported: 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)
Rare: Anaphylactic reaction*
Uncommon: Anorexia
Common: Hallucination, Abnormal dreams, Nightmare, Confusion, Agitation, Abnormal behaviour
Uncommon: Anxiety
Rare: Delirium* Flashback*, Dysphoria*, Insomnia, Disorientation*
Common: Nystagmus, Hypertonia, Tonic clonic movements
Common: Diplopia
Not Known: Intraocular pressure increased
Common: Blood pressure increased, Heart rate increased
Uncommon: Bradycardia, Arrhythmia
Uncommon: Hypotension
Common: Respiratory rate increased
Uncommon: Respiratory depression, Laryngospasm
Rare: Obstructive airway disorder*, Apnoea*
Common: Nausea, Vomiting
Rare: Salivary hypersecretion*
Not known: Liver function test abnormal, Drug-induced liver injury**
Common: Erythema, Rash morbilliform
Rare: Cystitis*, Haemorrhagic cystitis*
Uncommon: Injection site pain, Injection site rash
* AE frequency estimated from post-marketing safety database
** Extended period use (>3 days) or drug abuse
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.
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.
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