Ketamine HCL Mylan

Ketamine HCL Mylan is indicated in children and in adults.

Ketamine HCL Mylan is recommended:

As an anaesthetic agent for diagnostic and surgical procedures. When used by intravenous or intramuscular injection, Ketamine HCL Mylan is best suited for short procedures. With additional doses, or by intravenous infusion, Ketamine HCL Mylan can be used for longer procedures. If skeletal muscle relaxation is desired, a muscle relaxant should be used and respiration should be supported.

For the induction of anaesthesia prior to the administration of other general anaesthetic agents. To supplement other anaesthetic agents.

Specific areas of application or types of procedures:

When the intramuscular route of administration is preferred.

Debridement, painful dressings, and skin grafting in burned patients, as well as other superficial surgical procedures.

Neurodiagnostic procedures such as pneumoencephalograms, ventriculograms, myelograms, and lumbar punctures.

Diagnostic and operative procedures of the eye, ear, nose, and mouth, including dental extractions.

Note: Eye movements may persist during ophthalmological procedures.

Anaesthesia in poor-risk patients with depression of vital functions or where depression of vital functions must be avoided, if at all possible.

Orthopaedic procedures such as closed reductions, manipulations, femoral pinning, amputations, and biopsies.

Sigmoidoscopy and minor surgery of the anus and rectum, circumcision and pilonidal sinus.

Cardiac catheterization procedures.

Caesarean section; as an induction agent in the absence of elevated blood pressure.

Anaesthesia in the asthmatic patient, either to minimise the risks of an attack of bronchospasm developing, or in the presence of bronchospasm where anaesthesia cannot be delayed.

Ketamine HCL Mylan injection is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketamine HCL Mylan is best suited for short procedures but it can be used, with additional doses, for longer procedures.

Ketamine HCL Mylan injection is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents.

Ketamine HCL Mylan injection is indicated to supplement low-potency agents, such as nitrous oxide.

Specific areas of application are described in the CLINICAL PHARMACOLOGY Section.

For intravenous infusion, intravenous injection or intramuscular injection.

NOTE: All doses are given in terms of Ketamine HCL Mylan base

Adults, elderly (over 65 years) and children:

For surgery in elderly patients Ketamine HCL Mylan has been shown to be suitable either alone or supplemented with other anaesthetic agents.

Preoperative preparations

Ketamine HCL Mylan 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 HCL Mylan- induced hypersalivation.

Midazolam, diazepam, lorazepam, or flunitrazepam used as a premedicant or as an adjunct to Ketamine HCL Mylan, have been effective in reducing the incidence of emergence reactions.

Onset and duration

As with other general anaesthetic agents, the individual response to Ketamine HCL Mylan 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 to10 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 HCL Mylan as the sole anaesthetic agent

Intravenous Infusion

The use of Ketamine HCL Mylan 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 HCL Mylan 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 HCL Mylan administered intravenously may range from 1 mg/kg to 4.5 mg/kg (in terms of Ketamine HCL Mylan 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

Intramuscular Route

The initial dose of Ketamine HCL Mylan administered intramuscularly may range from 6.5 mg/kg to 13 mg/kg (in terms of Ketamine HCL Mylan 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:

Dosage in Obstetrics

Data are lacking for intramuscular injection and maintenance infusion of Ketamine HCL Mylan in the parturient population, and recommendations cannot be made.

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 HCL Mylan 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 HCL Mylan 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 HCL Mylan as induction agent prior to the use of other general anaesthetics

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

C. Ketamine HCL Mylan as supplement to anaesthetic agents

Ketamine HCL Mylan is clinically compatible with the commonly used general and local anaesthetic agents when an adequate respiratory exchange is maintained. The dose of Ketamine HCL Mylan 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 HCL Mylan.

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.

Note: Barbiturates and Ketamine HCL Mylan, being chemically incompatible because of precipitate formation, should not be injected from the same syringe.

If the Ketamine HCL Mylan dose is augmented with diazepam, the two drugs must be given separately. Do not mix ketamine hydrochloride and diazepam in syringe or infusion flask. For additional information on the use of diazepam, refer to the WARNINGS and DOSAGE AND ADMINISTRATION Sections of the diazepam insert.

Preoperative Preparations

1. While vomiting has been reported following ketamine hydrochloride administration, some airway protection may be afforded because of active laryngeal-pharyngeal reflexes. However, since aspiration may occur with Ketamine HCL Mylan and since protective reflexes may also be diminished by supplementary anesthetics and muscle relaxants, the possibility of aspiration must be considered. Ketamine HCL Mylan 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.
2. Atropine, scopolamine, or another drying agent should be given at an appropriate interval prior to induction.

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 HCL Mylan is rapid; an intravenous dose of 2 mg/kg (1 mg/lb) of body weight usually produces surgical anesthesia within 30 seconds after injection, with the anesthetic effect 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, in a range of 9 to 13 mg/kg (4 to 6 mg/lb) usually produce surgical anesthesia within 3 to 4 minutes following injection, with the anesthetic effect usually lasting 12 to 25 minutes.

Dosage

As with other general anesthetic agents, the individual response to Ketamine HCL Mylan 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.

Induction

Intravenous Route

The initial dose of Ketamine HCL Mylan administered intravenously may range from 1 mg/kg to 4.5 mg/kg (0.5 to 2 mg/lb). The average amount required to produce five to ten minutes of surgical anesthesia has been 2 mg/kg (1 mg/lb).

Alternatively, in adult patients an induction dose of 1 mg to 2 mg/kg intravenous ketamine at a rate of 0.5 mg/kg/min may be used for induction of anesthesia. In addition, diazepam in 2 mg to 5 mg doses, administered in a separate syringe over 60 seconds, 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 hydrochloride 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, USP, Normal Saline, or 5% Dextrose in Water.

Rate of Administration

It is recommended that Ketamine HCL Mylan be administered slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.

Intramuscular Route

The initial dose of Ketamine HCL Mylan administered intramuscularly may range from 6.5 to 13 mg/kg (3 to 6 mg/lb). A dose of 10 mg/kg (5 mg/lb) will usually produce 12 to 25 minutes of surgical anesthesia.

Maintenance Of 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 HCL Mylan administered, the longer will be the time to complete recovery.

Adult patients induced with Ketamine HCL Mylan augmented with intravenous diazepam may be maintained on Ketamine HCL Mylan given by slow microdrip infusion technique at a dose of 0.1 to 0.5 mg/minute, augmented with diazepam 2 to 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.

Dilution

To prepare a dilute solution containing 1 mg of ketamine per mL, aseptically transfer 10 mL from a 50 mg per mL vial or 5 mL from a 100 mg per mL vial to 500 mL of 5% Dextrose Injection, USP or Sodium Chloride (0.9%) Injection, USP (Normal Saline) and mix well. The resultant solution will contain 1 mg of ketamine per mL.

The fluid requirements of the patient and duration of anesthesia must be considered when selecting the appropriate dilution of Ketamine HCL Mylan injection. If fluid restriction is required, Ketamine HCL Mylan injection can be added to a 250 mL infusion as described above to provide a Ketamine HCL Mylan concentration of 2 mg/mL. Ketamine HCL Mylan injection 10 mg/mL vials are not recommended for dilution.

Supplementary Agents

Ketamine HCL Mylan is clinically 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 HCL Mylan supplemented with diazepam can be used to produce balanced anesthesia by combination with other agents such as nitrous oxide and oxygen.

Ketamine HCL Mylan is contra-indicated in persons in whom an elevation of blood pressure would constitute a serious hazard.

Ketamine HCL Mylan should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma.

Ketamine HCL Mylan is contraindicated in those in whom a significant elevation of blood pressure would constitute a serious hazard and in those who have shown hypersensitivity to the drug.

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 Ketamine HCL Mylan, 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 Ketamine HCL Mylan 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, Ketamine HCL Mylan should be supplemented with an agent which obtunds visceral pain.

When Ketamine HCL Mylan 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.

Ketamine HCL Mylan 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 HCL Mylan 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 HCL Mylan 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 Ketamine HCL Mylan anaesthesia, Ketamine HCL Mylan 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 HCL Mylan.

- 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 HCL Mylan 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..

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 HCL Mylan 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 HCL Mylan 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 Ketamine HCL Mylan, 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 have been reported in patients being given Ketamine HCL Mylan on a long term basis. This adverse reaction develops in patients receiving long term Ketamine HCL Mylan treatment after a time ranging from 1 month to several years. Ketamine HCL Mylan 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

Ketamine HCL Mylan has been reported as being a drug of abuse. Reports suggest that Ketamine HCL Mylan 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 Ketamine HCL Mylan should be closely supervised and it should be prescribed and administered with caution.

WARNINGS

Cardiac function should be continually monitored during the procedure in patients found to have hypertension or cardiac decompensation.

Postoperative confusional states may occur during the recovery period. (See Special Note.)

Respiratory depression may occur with overdosage or too rapid a rate of administration of Ketamine HCL Mylan, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.

PRECAUTIONS

General

Ketamine HCL Mylan injection should be used by or under the direction of physicians experienced in administering general anesthetics and in maintenance of an airway and in the control of respiration.

Because pharyngeal and laryngeal reflexes are usually active, Ketamine HCL Mylan 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 HCL Mylan is used alone. Muscle relaxants, with proper attention to respiration, may be required in both of these instances.

Resuscitative equipment should be ready for use.

The incidence of emergence 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 (see Special Note).

The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in respiratory depression or apnea and enhanced pressor response.

In surgical procedures involving visceral pain pathways, Ketamine HCL Mylan should be supplemented with an agent which obtunds visceral pain.

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

An increase in cerebrospinal fluid pressure has been reported following administration of Ketamine HCL Mylan. Use with extreme caution in patients with preanesthetic elevated cerebrospinal fluid pressure.

Usage In Pregnancy

Since the safe use in pregnancy, including obstetrics (either vaginal or abdominal delivery), has not been established, such use is not recommended (see Animal Pharmacology And Toxicology, Reproduction).

Geriatric Use

Clinical studies of Ketamine HCL Mylan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 16 have not been established.

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)

* AE frequency estimated from post-marketing safety database

** Extended period use (> 3 days) or drug abuse

Reporting of suspected adverse reactions

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.

Cardiovascular: Blood pressure and pulse rate are frequently elevated following administration of Ketamine HCL Mylan alone. However, hypotension and bradycardia have been observed. Arrhythmia has also occurred.

Respiration: Although respiration is frequently stimulated, severe depression of respiration or apnea may occur following rapid intravenous administration of high doses of Ketamine HCL Mylan. Laryngospasms and other forms of airway obstruction have occurred during ketamine hydrochloride anesthesia.

Eye: Diplopia and nystagmus have been noted following Ketamine HCL Mylan administration. It also may cause a slight elevation in intraocular pressure measurement.

Genitourinary: Severe irritative and inflammatory urinary tract and bladder symptoms including cystitis have been reported in individuals with history of chronic ketamine use or abuse.

Psychological: (See Special Note.)

Neurological: In some patients, enhanced skeletal muscle tone may be manifested by tonic and clonic movements sometimes resembling seizures (see DOSAGE AND ADMINISTRATION Section).

Gastrointestinal: Anorexia, nausea and vomiting have been observed; however, this is not usually severe and allows the great majority of patients to take liquids by mouth shortly after regaining consciousness (see DOSAGE AND ADMINISTRATION Section).

General: Anaphylaxis. Local pain and exanthema at the injection site have infrequently been reported. Transient erythema and/or morbilliform rash have also been reported.

For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1- 800-332-1088) or http://www.fda.gov/medwatch/.

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 anxiety, dysphoria, disorientation, insomnia, flashbacks, hallucinations, and psychotic episodes.

Ketamine dependence and tolerance are possible following prolonged administration. A withdrawal syndrome with psychotic features has been described following discontinuation of long-term ketamine use. Therefore, ketamine should be prescribed and administered with caution.

Respiratory depression can result from an overdosage of Ketamine HCL Mylan hydrochloride. Supportive ventilation should be employed. Mechanical support of respiration that will maintain adequate blood oxygen saturation and carbon dioxide elimination is preferred to administration of analeptics.

Ketamine HCL Mylan has a wide margin of safety; several instances of unintentional administration of overdoses of Ketamine HCL Mylan (up to 10 times that usually required) have been followed by prolonged but complete recovery.

Respiratory depression may occur with overdosage or too rapid a rate of administration of Ketamine HCL Mylan, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.