COMPOSITION :
Ketamine HCl Injection100 mg/ml, each ml contains : Ketamine HCl equivalent to Ketamine 100 mg.
Ketamine HCl Injection 50 mg/ml, each ml contains : Ketamine HCl equivalent to Ketamine 50 mg.
DESCRIPTIONS :
Ketamine HCl with Ketamine HCl (equivalent to Ketamine) as active ingredient is available in injection 100 mg/ml and 50 mg/ml.
INDICATIONS :
Ketamine is indicated as an anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketamine is best suited for short procedures but it can be used, with additional doses, for longer procedures. Ketamine is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents. Ketamine is indicated in obstetrics, for vaginal delivery or in caesarean section. Ketamine is also indicated to supplement low-potency agents, such as nitrous oxide.
Specific areas of use have included but are not limited to the following :
- Debridement, and skin grafting in burn patients.
- Neurodiagnostic procedures such as myelogram and lumbal puncture.
- Diagnostic and operative procedures of the eye, ear, nose and mouth.
- Sigmoidoscopy and minor rectal surgery.
- Cardiac cathererization procedures.
- Orthopedic procedures.
DOSAGE AND ADMINISTRATIONS :
Preoperative preparations :
While vomiting has been reported following Ketamine administration, some airway protection may be afforded because of active laryngeal-pharyngeal reflexes. Howere, since aspiration may occur with Ketamine and since protective reflexes may also be diminished by supplementary anesthetics and muscle relaxants, the possibility of aspiration must be considered. Ketamine is recommended for use in the patient whose stomach is not empty when, in the judgment of the practitioner, the benefits of the drug outweigh the possible risks.
Premedication with an anticholinergic agent (e.g., Atropine, Scopolamine or Glycopyrrolate) or another drying agent, should be given at a appropriate interval prior to induction to reduce Ketamine-induced hypersalivation.
Onset and Duration :
Because of rapid induction following the initial intravenous injection, the patient should be in a supported position during administration.
The onset of action of Ketamine is rapid; an intravenous dose of 2 mg/kgBW usually lasting five to ten minutes. If a longer effect is desired, additional increments can be administered intravenously or intramuscularly to maintain anesthesia without producing significant cumulative effects.
Intramuscular doses, from experience primarily in pediatric patients, in a range of 9 – 13 mg/kg usually produce surgical anesthesia within 3 – 4 minutes following injection, with the anesthetic effect usually lasting 12 – 25 minutes.
Dosage :
As with other general anesthetic agents, the individual response to Ketamine is somewhat varied depending on the dose, route of administration, and age of patient, so that dosage recommendation cannot be absolutely fixed. The drug should be titrated against the patient’s requirements.
Supplementary Agents :
Ketamine is compatible with the commonly used general and local anesthetic agents when an adequate respiratory exchange is maintained.
The regimen of a reduced dose of Ketamine supplemented with Diazepam can be used to produce balanced anesthesia by combination with other agents such as nitrous oxide and oxygen.
General Anesthesia Induction :
Intravenous Route :
Adults : The initial dose of Ketamine administered intravenously may range from 1 – 4.5 mg/kg. The average amount required to produce five to ten minutes of surgical anesthesia has been 2 mg/kg.
Alternatively, in adult patients an induction dose of 1.0 – 2.0 mg/kg intravenous Ketamine at a rate of 0.5 mg/kg/minutes may be used for induction of anesthesia. In addition, Diazepam in 2 – 5 mg doses, administered in a separate syringe over 60 second, may be used. In most cases, 15 mg of intravenous Diazepam or less will suffice. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by this induction dosage program.
Note : The 100 mg/ml concentration of Ketamine should not be injected intravenously without proper dilution. It is recommended the drug be diluted with an equal volume of either sterile Water For Injection, Normal saline or 5 % Dextrose in water.
Rate of Administration : It is recommended that Ketamine be administered slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.
Intramuscular Route :
Adults : The initial dose of Ketamine administered intramuscularly may range from 6.5 – 13 mg/kg. A dose of 10 mg/kg will usually produce 12 – 25 minutes of surgical anesthesia.
If the Ketamine dose is augmented with Diazepam, the two drugs must be given separately. Do not mix Ketamine and Diazepam in the same syringe or infusion flask.
Dosage in hepatic Insufficiency :
Dose reduction should be considered in patients with cirrhosis or other types of liver impairment. (see WARNINGS AND PRECAUTIONS)
Maintenance of General Anesthesia :
The maintenance dose should be adjusted according to the patient’s anesthetic needs and whether an additional anesthetic agent is employed.
Increments of one-half to the full induction dose may be repeated as needed for maintenance of anesthesia. However, it should be noted that purposeless and tonic clonic movements of extremities may occur during the course of anesthesia. These movements do not imply a light plane and are not indicative of the need for additional doses of the anesthetic. It should be recognized that the larger the total dose of Ketamine administered, the longer will be the time to complete recovery.
Adult patients induced with Ketamine augmented with intravenous Diazepam may be maintained on Ketamine given by slow micro drip infusion technique at a dose 0.1 – 0.5 mg/minute, augmented with Diazepam 2 – 5 mg administered intravenously as needed. In many cases 20 mg or less of intravenous Diazepam total for combined induction and maintenance will suffice. However, slightly more Diazepam may be required depending on the nature and duration of the operation, physical status of the patient, and other factors. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by this maintenance dosage program.
Instruction for use :
Dilution : To prepare a dilute solution containing 1 mg of Ketamine per ml, aseptically transfer 10 ml (50 mg/ml vial) or 5 ml (100 mg/ml vial) to 500 ml of 5% Dextrose injection or Sodium Chloride (0.9%) for injection and mix well. The resultant solution will contain 1 mg of Ketamine per ml. A 1 mg/ml solution of Ketamine in Dextrose 5% or Sodium Chloride 0.9% is stable for 24 hours.
The fluid requirements of the patient and duration of anesthesia must be considered when selecting the appropriate dilution of Ketamine. If fluid restriction is required, Ketamine can be added to a 250 ml infusion as described above to provide a Ketamine concentration of 2 mg/ml.
Ketamine vials in the 10 mg/ml concentration are not recommended for dilution.
OVERDOSAGE :
Respiratory depression may occur with overdosage or too rapid rate of administration of Ketamine, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.
CONTRAINDICATIONS :
Ketamine HCl is contraindicated in those in whom a significant elevation of blood pressure would constitute a serious hazard.
Ketamine HCl should not be used in patients with eclampsia or pre-eclampsia. Ketamine HCl is contraindicated in patients who have shown hypersensitivity to the drug or its components.
WARNINGS AND PRECAUTIONS :
General
Ketamine should be used by or under the derection of physicians experienced in administering general ansesthetics and in maintenance of an airway and in the control of respiration.
Resuscitative equipment should be ready for use.
The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in respiratory depression or apnea and echance pressor response.
Because pharyngeal and laryngeal reflexes are usually active, Ketamine should not be used alone in surgery or diagnostic procedures of the pharynx, larynx or bronchial tree. Mechanical stimulation of the pharynx should be avoided, whenever possible, if Ketamine is used alone. Muscle relaxants, with proper attention to respiration, may be required in both of these intsances.
In surgical procedures involving visceral pain pathways, Ketamine should be supplemented with an agent which obtunds visceral pain.
When Ketamine is used on an outpatient basis, the patient should not be released until recovery from anesthesia is complete, and then should be accompanied by a responsible adult.
Postoperative confusional states may occur during the recovery period.
Ketamine should be used with caution in patients with the following conditions :
- Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient.
- Ketamineis metabolized in the liver and hepatic clearance is required for termination of clinical effects. Abnormal liver function test associated with Ketamine use have been reported, particularly with extended use (> 3 days) or drug abuse. 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.
- An increase in cerebrospinal fluid (CSF) pressure has been reported following administration of Ketamine Use with extreme caution in patients with preanesthetic elevated cerebrospinal pressure.
- Use with caution in patients with increased intraocular pressure (e.g., glaucoma) because the pressure my 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 with caution in patients with acute intermittent porphyria.
- Use with caution in patients with seizures.
- Use with caution in patients with hyperthyroidism or patients receiving thyroid replacement (increased risk of hypertension and tachycardia).
- Use with caution in patients with pulmonary or upper respiratory infection (Ketaminesensitized the gag reflex, potentially causing laryngospasm).
- Use with caution in patients with intracranial mass lesions, a presence of head injury, globe injuries or hydrocephalus.
Emergence reaction
It should be noted that emergence reactions have occurred in approximately 12 percent of patients. 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 behavior which a few patients recall as an unpleasant experience. The duration ordinarily is no more than few hours; in few cases, however, recurrences have taken place up to 24 hours post-operatively. No residual physchological effects are known to have resulted from the use of Ketamine.
The incidence of these emergence phenomena is least in the young (15 years of age or less) and elderly (over 65 years of age) patient. Also, they are less frequent when the drug is given intramuscularly.
The incidence of psychological manifestations during emergence, particularly dreamlike observations and emergence delirium, may be reduced by using lower recommended dosages of Ketamine in conjunction with intravenous Diazepam during induction and maintenance of anesthesia. Also, the incidence of these reactions may be reduced if verbal and tactile stimulation of the patient is minimized during the recovery period.
This does not preclude the monitoring of vital signs. In order to terminate a severe emergence reaction, the use of a small hypnotic dose of a short acting or ultrashoracting barbiturate may be required.
Cardiovascular
Because of the substantial increase in myocardial oxygen consumption, Ketamine should be used with caution in patients with hypovolemia, dehydration, or cardiac disease, especially coronary artery disease (e.g., congestive heart failure, myocardial ischemia, and myocardial infraction). 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 injection, reaches a maximum within a few minutes and usually returns to preanesthetic values within 15 minutes after injection. 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 using Ketamine on a long term basis. (This adverse reaction develops in patiens receiving long term Ketamine treatment after a time ranging from 1 month to several years).
Drug Abuse and Dependence
Ketamine has been reported being used as 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, have also been reported. Ketamine dependence and tolerance may develop in individuals with a history of drug abuse or dependence.
Therefore, Ketamine should be prescribed and administered with caution.
Pregnancy and Lactation
With the exception of administration during surgery for abdominal delivery or vaginal delivery, no controlled clinical studies in pregnancy have been conducted. Ketamine readily crosses the placenta. The safe use in pregnancy has not been established, and such use is not recommended.
Ketamine is likely to be excreted in breast milk and therefore breastfeeding should be discontinued when Ketamine is in use.
Effects on Ability to Drive and Use Machines
Patients should be cautioned that driving an automobile, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of Ketamine and consideration of other drugs employed) after anesthesia. As appropriate, especially in cases where early discharge is possible, the duration of Ketamine and other drugs employed during the conduct of anesthesia should be considered.
DRUG INTERACTIONS :
- Prolonged recovery time may occur if barbiturates and/or opiate agonists are used concurrently with Ketamine.
- Benzodiazepines may prolong the half life of Ketamine; recovery from anaesthesia may be prolonged following concurrent use.
- Co-administration of drugs with a hypertensive effect (e.,Ergometrine) should be avoided.
- Sustained rises in arterial pressure have been reported in patients receiving concomitant Ketamineand thyroxine.
- Barbiturates and Ketamine HCl, being chemically incompatible because of precipitate formation, should not be injected from the same syringe.
- Ketaminemay potentiate the neuromuscular blocking effects of Atracurium and Tubocurarine, including respiratory depression with apnea.
- The use of halogenated anesthetics concomitantly with Ketaminecan lengthen the elimination half-life of Ketamine and delay recovery from anesthesia. Concurrent use of Ketamine (especially in high doses or when rapidly administered) with halogenated anesthetics can increase the risk of developing bradycardia, hypotension, or decreased cardiac output.
- The use of Ketaminewith 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.
- Ketaminehas been reported to antagonize 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 Ketamineincreases the risk of developing hypotension.
- When Ketaminea nd 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.
ADVERSE REACTIONS :
| MedDRA
System Organ Class |
Frequency | Adverse reactions |
| Immune system disorders | Rare | Anaphylactic reaction |
| Metabolism and nutrion disorders | Uncommon | Anorexia |
| Psychiatric disorders | Common | Hallucination, Abnormal dreams, Nighmare, Confusion, Agitation, Abnormal behavior |
| Uncommon | Anxiety | |
| Rare | Delirium, Flashback, Dysphoria, Insomnia, Disorientation | |
| Nervous system disorders | Common | Nystagmus, Hypertonia, Tonic clonic movements |
| Eye disorders | Common | Diplopia |
| Not known | Intraocular pressure increased | |
| Cardiac disorders | Common | Blood pressure increased, Heart rate increased |
| Uncommon | Bradycardia, Arrhythmia | |
| Vascular disorders | Uncommon | Hypotension |
| Respiratory, thoracic and mediastinal disorders | Common | Respiratory rate increased |
| Uncommon | Respiratory depression, Laryngospasm | |
| Rare | Obstructive airway disorder, Apnoea | |
| Gastrointestinal disorders | Common | Nausea, Vomiting |
| Rare | Salivary hypersecretion | |
| Hepatobilary disorders | Not known | Liver function test abnormal |
| Skin and subcutaneous tissue disorders | Common | Erythema, Rash morbiliform |
| Renal and urinary disorders | Rare | Cystitis, haemorrhagic cystitis |
| General disorders and administration site conditions | Uncommon | Injection site pain, Injection site rash |
PRESENTATION :
Ketamine HCl Injection 100 mg/ml Box, 10 vials @ 10 ml
Reg. No. : GKL2102364043A1
Ketamine HCl Injection 50 mg/ml Box, 10 vials @ 10 ml
Reg. No. : GKL2202364043B1
STORAGE :
STORE BELOW 30ºC, PROTECT FROM LIGHT
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
Date : February 15th, 2022
FOR MORE INFORMATIONS :
e-mail : info@bernofarm.com
