KETALAR - ketamine hydrochloride injection
`JHP Pharmaceuticals LLC
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`CIII
`SPECIAL NOTE
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`EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS.
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`THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT DREAM-LIKE STATES, VIVID
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`IMAGERY, HALLUCINATIONS, AND EMERGENCE DELIRIUM. IN SOME CASES THESE STATES HAVE BEEN
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`ACCOMPANIED BY CONFUSION, EXCITEMENT, AND IRRATIONAL BEHAVIOR WHICH A FEW PATIENTS RECALL AS
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`AN UNPLEASANT EXPERIENCE. THE DURATION ORDINARILY IS NO MORE THAN A FEW HOURS; IN A FEW CASES,
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`HOWEVER, RECURRENCES HAVE TAKEN PLACE UP TO 24 HOURS POSTOPERATIVELY. NO RESIDUAL
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`PSYCHOLOGICAL EFFECTS ARE KNOWN TO HAVE RESULTED FROM USE OF KETALAR.
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`THE INCIDENCE OF THESE EMERGENCE PHENOMENA IS LEAST IN THE ELDERLY (OVER 65 YEARS OF AGE)
`PATIENT. ALSO, THEY ARE LESS FREQUENT WHEN THE DRUG IS GIVEN INTRAMUSCULARLY AND THE
`INCIDENCE IS REDUCED AS EXPERIENCE WITH THE DRUG IS GAINED.
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`THE INCIDENCE OF PSYCHOLOGICAL MANIFESTATIONS DURING EMERGENCE, PARTICULARLY DREAM-LIKE
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`OBSERVATIONS AND EMERGENCE DELIRIUM, MAY BE REDUCED BY USING LOWER RECOMMENDED DOSAGES
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`OF KETALAR IN CONJUNCTION WITH INTRAVENOUS DIAZEPAM DURING INDUCTION AND MAINTENANCE OF
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`ANESTHESIA. (See DOSAGE AND ADMINISTRATION Section.) ALSO, THESE REACTIONS MAY BE REDUCED IF
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`VERBAL, TACTILE, AND VISUAL STIMULATION OF THE PATIENT IS MINIMIZED DURING THE RECOVERY PERIOD.
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`THIS DOES NOT PRECLUDE THE MONITORING OF VITAL SIGNS.
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`IN ORDER TO TERMINATE A SEVERE EMERGENCE REACTION, THE USE OF A SMALL HYPNOTIC DOSE OF A
`SHORT-ACTING OR ULTRA SHORT-ACTING BARBITURATE MAY BE REQUIRED.
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`WHEN KETALAR 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.
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`DESCRIPTION
`Ketalar is a nonbarbiturate anesthetic chemically designated dl 2-(0-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride. It
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`is formulated as a slightly acid (pH 3.5-5.5) sterile solution for intravenous or intramuscular injection in concentrations containing the
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`equivalent of either 10, 50 or 100 mg ketamine base per milliliter and contains not more than 0.1 mg/mL Phemerol® (benzethonium
`chloride) added as a preservative. The 10 mg/mL solution has been made isotonic with sodium chloride.
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`CLINICAL PHARMACOLOGY
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`Ketalar is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-
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`laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a
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`transient and minimal respiratory depression.
`A patent airway is maintained partly by virtue of unimpaired pharyngeal and laryngeal reflexes. (See WARNINGS and
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`PRECAUTIONS Sections.)
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`The biotransformation of Ketalar includes N-dealkylation (metabolite I), hydroxylation of the cyclohexone ring (metabolites III and
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`IV), conjugation with glucuronic acid and dehydration of the hydroxylated metabolites to form the cyclohexene derivative (metabolite
`II).
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`Following intravenous administration, the ketamine concentration has an initial slope (alpha phase) lasting about 45 minutes with a
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`half-life of 10 to 15 minutes. This first phase corresponds clinically to the anesthetic effect of the drug. The anesthetic action is
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`terminated by a combination of redistribution from the CNS to slower equilibrating peripheral tissues and by hepatic
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`biotransformation to metabolite I. This metabolite is about 1/3 as active as ketamine in reducing halothane requirements (MAC) of the
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`rat. The later half-life of ketamine (beta phase) is 2.5 hours.
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`The anesthetic state produced by Ketalar has been termed “dissociative anesthesia” in that it appears to selectively interrupt
`association pathways of the brain before producing somatesthetic sensory blockade. It may selectively depress the thalamoneocortical
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`system before significantly obtunding the more ancient cerebral centers and pathways (reticular-activating and limbic systems).
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`Elevation of blood pressure begins shortly after injection, reaches a maximum within a few minutes and usually returns to
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`preanesthetic values within 15 minutes after injection. In the majority of cases, the systolic and diastolic blood pressure peaks from
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`10% to 50% above preanesthetic levels shortly after induction of anesthesia, but the elevation can be higher or longer in individual
`cases (see CONTRAINDICATIONS Section).
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`Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of Ketalar (up to ten times that
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`usually required) have been followed by prolonged but complete recovery.
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`Ketalar has been studied in over 12,000 operative and diagnostic procedures, involving over 10,000 patients from 105 separate studies.
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`During the course of these studies Ketalar was administered as the sole agent, as induction for other general agents, or to supplement
`low-potency agents.
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`Reference ID: 3096050
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`Hospira, Exh. 2025, p. 1
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`Specific areas of application have included the following:
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`1. debridement, painful dressings, and skin grafting in burn patients, as well as other superficial surgical procedures.
`2. neurodiagnostic procedures such as pneumonencephalograms, ventriculograms, myelograms, and lumbar punctures. See
`also Precaution concerning increased intracranial pressure.
`3. diagnostic and operative procedures of the eye, ear, nose, and mouth, including dental extractions.
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`4. diagnostic and operative procedures of the pharynx, larynx, or bronchial tree. NOTE: Muscle relaxants, with proper attention
`to respiration, may be required (see PRECAUTIONS Section).
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`sigmoidoscopy and minor surgery of the anus and rectum, and circumcision.
`5.
`6. extraperitoneal procedures used in gynecology such as dilatation and curettage.
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`7. orthopedic procedures such as closed reductions, manipulations, femoral pinning, amputations, and biopsies.
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`8. as an anesthetic in poor-risk patients with depression of vital functions.
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`in procedures where the intramuscular route of administration is preferred.
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`10. in cardiac catheterization procedures.
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`In these studies, the anesthesia was rated either “excellent” or “good” by the anesthesiologist and the surgeon at 90% and 93%,
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`respectively; rated “fair” at 6% and 4%, respectively; and rated “poor” at 4% and 3%, respectively. In a second method of evaluation,
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`the anesthesia was rated “adequate” in at least 90%, and “inadequate” in 10% or less of the procedures.
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`INDICATIONS AND USAGE
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`Ketalar is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation.
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`Ketalar is best suited for short procedures but it can be used, with additional doses, for longer procedures.
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`Ketalar is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents.
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`Ketalar is indicated to supplement low-potency agents, such as nitrous oxide.
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`Specific areas of application are described in the CLINICAL PHARMACOLOGY Section.
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`CONTRAINDICATIONS
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`Ketamine hydrochloride 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.
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`WARNINGS
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`Cardiac function should be continually monitored during the procedure in patients found to have hypertension or cardiac
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`decompensation.
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`Postoperative confusional states may occur during the recovery period. (See Special Note.)
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`Respiratory depression may occur with overdosage or too rapid a rate of administration of Ketalar, in which case supportive
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`ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.
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`PRECAUTIONS
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`General
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`Ketalar should be used by or under the direction of physicians experienced in administering general anesthetics and in maintenance of
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`an airway and in the control of respiration.
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`Because pharyngeal and laryngeal reflexes are usually active, Ketalar should not be used alone in surgery or diagnostic procedures of
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`the pharynx, larynx, or bronchial tree. Mechanical stimulation of the pharynx should be avoided, whenever possible, if Ketalar is used
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`alone. Muscle relaxants, with proper attention to respiration, may be required in both of these instances.
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`Resuscitative equipment should be ready for use.
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`The incidence of emergence reactions may be reduced if verbal and tactile stimulation of the patient is minimized during the recovery
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`period. This does not preclude the monitoring of vital signs (see Special Note).
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`The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in respiratory
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`depression or apnea and enhanced pressor response.
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`In surgical procedures involving visceral pain pathways, Ketalar should be supplemented with an agent which obtunds visceral pain.
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`Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient.
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`An increase in cerebrospinal fluid pressure has been reported following administration of ketamine hydrochloride. Use with extreme
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`caution in patients with preanesthetic elevated cerebrospinal fluid pressure.
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`Information for Patients
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`As appropriate, especially in cases where early discharge is possible, the duration of Ketalar and other drugs employed during the
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`conduct of anesthesia should be considered. The patients should be cautioned that driving an automobile, operating hazardous
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`machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of Ketalar
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`and consideration of other drugs employed) after anesthesia.
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`Drug Interactions
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`Prolonged recovery time may occur if barbiturates and/or narcotics are used concurrently with Ketalar.
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`Ketalar is clinically compatible with the commonly used general and local anesthetic agents when an adequate respiratory exchange is
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`Reference ID: 3096050
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`Hospira, Exh. 2025, p. 2
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`maintained.
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`Usage in Pregnancy
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`Since the safe use in pregnancy, including obstetrics (either vaginal or abdominal delivery), has not been established, such use is not
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`recommended (see ANIMAL PHARMACOLOGY AND TOXICOLOGY, Reproduction).
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`Geriatric Use
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`Clinical studies of ketamine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they
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`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
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`dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other
`drug therapy.
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`Pediatric Use
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`Safety and effectiveness in pediatric patients below the age of 16 have not been established.
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`ADVERSE REACTIONS
`Cardiovascular: Blood pressure and pulse rate are frequently elevated following administration of Ketalar alone. However,
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`hypotension and bradycardia have been observed. Arrhythmia has also occurred.
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`Respiration: Although respiration is frequently stimulated, severe depression of respiration or apnea may occur following rapid
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`intravenous administration of high doses of Ketalar. Laryngospasms and other forms of airway obstruction have occurred during
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`Ketalar anesthesia.
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`Eye: Diplopia and nystagmus have been noted following Ketalar administration. It also may cause a slight elevation in intraocular
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`pressure measurement.
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`Genitourinary: Severe irritative and inflammatory urinary tract and bladder symptoms including cystitis have been reported in
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`individuals with history of chronic ketamine use or abuse.
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`Psychological: (See Special Note.)
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`Neurological: In some patients, enhanced skeletal muscle tone may be manifested by tonic and clonic movements sometimes
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`resembling seizures (see DOSAGE AND ADMINISTRATION Section).
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`Gastrointestinal: Anorexia, nausea and vomiting have been observed; however, this is not usually severe and allows the great majority
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`of patients to take liquids by mouth shortly after regaining consciousness (see DOSAGE AND ADMINISTRATION Section).
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`General: Anaphylaxis. Local pain and exanthema at the injection site have infrequently been reported. Transient erythema and/or
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`morbilliform rash have also been reported.
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`For medical advice about your adverse reactions contact your medical professional. To report SUSPECTED ADVERSE
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`REACTIONS, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1-800-332-1088) or
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`http://www.fda.gov/medwatch/.
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`DRUG ABUSE AND DEPENDENCE
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`Ketamine has been reported being used as a drug of abuse.
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`Reports suggest that ketamine produces a variety of symptoms including, but not limited to anxiety, dysphoria, disorientation,
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`insomnia, flashbacks, hallucinations, and psychotic episodes.
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`Ketamine dependence and tolerance are possible following prolonged administration. A withdrawal syndrome with psychotic features
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`has been described following discontinuation of long-term ketamine use. Therefore, ketamine should be prescribed and administered
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`with caution.
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`OVERDOSAGE
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`Respiratory depression may occur with overdosage or too rapid a rate of administration of Ketalar, in which case supportive
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`ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.
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`DOSAGE AND ADMINISTRATION
`Note: Barbiturates and Ketalar, being chemically incompatible because of precipitate formation, should not be injected from the same
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`syringe.
`If the Ketalar dose is augmented with diazepam, the two drugs must be given separately. Do not mix Ketalar 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.
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`Preoperative Preparations:
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`1. While vomiting has been reported following Ketalar administration, some airway protection may be afforded because of
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`active laryngeal-pharyngeal reflexes. However, since aspiration may occur with Ketalar and since protective reflexes may
`also be diminished by supplementary anesthetics and muscle relaxants, the possibility of aspiration must be considered.
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`Ketalar is recommended for use in the patient whose stomach is not empty when, in the judgment of the practitioner, the
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`Reference ID: 3096050
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`Hospira, Exh. 2025, p. 3
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`benefits of the drug outweigh the possible risks.
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`2. Atropine, scopolamine, or another drying agent should be given at an appropriate interval prior to induction.
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`Onset and Duration:
`Because of rapid induction following the initial intravenous injection, the patient should be in a supported position during
`administration.
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`The onset of action of Ketalar is rapid; an intravenous dose of 2 mg/kg (1 mg/lb) of body weight usually produces surgical anesthesia
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`within 30 seconds after injection, with the anesthetic effect usually lasting five to ten minutes. If a longer effect is desired, additional
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`increments can be administered intravenously or intramuscularly to maintain anesthesia without producing significant cumulative
`effects.
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`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
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`injection, with the anesthetic effect usually lasting 12 to 25 minutes.
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`Dosage:
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`As with other general anesthetic agents, the individual response to Ketalar is somewhat varied depending on the dose, route of
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`administration, and age of patient, so that dosage recommendation cannot be absolutely fixed. The drug should be titrated against the
`patient’s requirements.
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`Induction:
`Intravenous Route:
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`The initial dose of Ketalar administered intravenously may range from 1 mg/kg to 4.5 mg/kg (0.5 to 2 mg/lb). The average amount
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`required to produce five to ten minutes of surgical anesthesia has been 2 mg/kg (1 mg/lb).
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`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
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`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
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`emergence, particularly dream-like observations and emergence delirium, may be reduced by this induction dosage program.
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`Note: The 100 mg/mL concentration of Ketalar should not be injected intravenously without proper dilution. It is recommended the
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`drug be diluted with an equal volume of either Sterile Water for injection, USP, Normal Saline, or 5% Dextrose in Water.
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`Rate of Administration:
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`It is recommended that Ketalar be administered slowly (over a period of 60 seconds). More rapid administration may result in
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`respiratory depression and enhanced pressor response.
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`Intramuscular Route:
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`The initial dose of Ketalar 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)
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`will usually produce 12 to 25 minutes of surgical anesthesia.
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`Maintenance of Anesthesia:
`The maintenance dose should be adjusted according to the patient’s anesthetic needs and whether an additional anesthetic agent is
`employed.
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`Increments of one-half to the full induction dose may be repeated as needed for maintenance of anesthesia. However, it should be
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`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.
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`It should be recognized that the larger the total dose of Ketalar administered, the longer will be the time to complete recovery.
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`Adult patients induced with Ketalar augmented with intravenous diazepam may be maintained on Ketalar given by slow microdrip
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`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
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`diazepam may be required depending on the nature and duration of the operation, physical status of the patient, and other factors. The
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`incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be
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`reduced by this maintenance dosage program.
`Dilution:
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`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
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`100 mg per mL vial to 500 mL of 5% Dextrose Injection, USP or Sodium Chloride (0.9%) Injection, USP (Normal Saline) and mix
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`well. The resultant solution will contain 1 mg of ketamine per mL.
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`The fluid requirements of the patient and duration of anesthesia must be considered when selecting the appropriate dilution of Ketalar.
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`Reference ID: 3096050
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`Hospira, Exh. 2025, p. 4
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`If fluid restriction is required, Ketalar can be added to a 250 mL infusion as described above to provide a Ketalar concentration of 2
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`mg/mL.
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`Ketalar 10 mg/mL vials are not recommended for dilution.
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`Supplementary Agents:
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`Ketalar is clinically compatible with the commonly used general and local anesthetic agents when an adequate respiratory exchange is
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`maintained.
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`The regimen of a reduced dose of Ketalar supplemented with diazepam can be used to produce balanced anesthesia by combination
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`with other agents such as nitrous oxide and oxygen.
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`HOW SUPPLIED
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`Ketalar is supplied as the hydrochloride in concentrations equivalent to ketamine base.
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`NDC 42023-113-10 — Each 20-mL multi-dose vial contains 10 mg/mL. Supplied in cartons of 10.
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`NDC 42023-114-10 — Each 10-mL multi-dose vial contains 50 mg/mL. Supplied in cartons of 10.
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`NDC 42023-115-10 — Each 5-mL multi-dose vial contains 100 mg/mL. Supplied in cartons of 10.
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`Store at 20° to 25°C (68° to 77°F). (See USP controlled room temperature.)
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`Protect from light.
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`Rx only.
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`ANIMAL PHARMACOLOGY AND TOXICOLOGY
`Toxicity:
`The acute toxicity of Ketalar has been studied in several species. In mature mice and rats, the intraperitoneal LD50 values are
`approximately 100 times the average human intravenous dose and approximately 20 times the average human intramuscular dose. A
`slightly higher acute toxicity observed in neonatal rats was not sufficiently elevated to suggest an increased hazard when used in
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`pediatric patients. Daily intravenous injections in rats of five times the average human intravenous dose and intramuscular injections
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`in dogs at four times the average human intramuscular dose demonstrated excellent tolerance for as long as 6 weeks. Similarly, twice
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`weekly anesthetic sessions of one, three, or six hours’ duration in monkeys over a four- to six-week period were well tolerated.
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`Interaction with Other Drugs Commonly Used for Preanesthetic Medication:
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`Large doses (three or more times the equivalent effective human dose) of morphine, meperidine, and atropine increased the depth and
`prolonged the duration of anesthesia produced by a standard anesthetizing dose of Ketalar in Rhesus monkeys. The prolonged duration
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`was not of sufficient magnitude to contraindicate the use of these drugs for preanesthetic medication in human clinical trials.
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`Blood Pressure:
`Blood pressure responses to Ketalar vary with the laboratory species and experimental conditions. Blood pressure is increased in
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`normotensive and renal hypertensive rats with and without adrenalectomy and under pentobarbital anesthesia.
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`Intravenous Ketalar produces a fall in arterial blood pressure in the Rhesus monkey and a rise in arterial blood pressure in the dog. In
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`this respect the dog mimics the cardiovascular effect observed in man. The pressor response to Ketalar injected into intact,
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`unanesthetized dogs is accompanied by a tachycardia, rise in cardiac output and a fall in total peripheral resistance. It causes a fall in
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`perfusion pressure following a large dose injected into an artificially perfused vascular bed (dog hindquarters), and it has little or no
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`potentiating effect upon vasoconstriction responses of epinephrine or norepinephrine. The pressor response to Ketalar is reduced or
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`blocked by chlorpromazine (central depressant and peripheral α-adrenergic blockade), by β-adrenergic blockade, and by ganglionic
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`blockade. The tachycardia and increase in myocardial contractile force seen in intact animals does not appear in isolated hearts
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`(Langendorff) at a concentration of 0.1 mg of Ketalar or in Starling dog heart-lung preparations at a Ketalar concentration of 50 mg/kg
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`of HLP. These observations support the hypothesis that the hypertension produced by Ketalar is due to selective activation of central
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`cardiac stimulating mechanisms leading to an increase in cardiac output. The dog myocardium is not sensitized to epinephrine and
`Ketalar appears to have a weak antiarrhythmic activity.
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`Metabolic Disposition:
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`Ketalar is rapidly absorbed following parenteral administration. Animal experiments indicated that Ketalar was rapidly distributed into
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`body tissues, with relatively high concentrations appearing in body fat, liver, lung, and brain; lower concentrations were found in the
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`heart, skeletal muscle, and blood plasma. Placental transfer of the drug was found to occur in pregnant dogs and monkeys. No
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`significant degree of binding to serum albumin was found with Ketalar.
`Balance studies in rats, dogs, and monkeys resulted in the recovery of 85% to 95% of the dose in the urine, mainly in the form of
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`degradation products. Small amounts of drug were also excreted in the bile and feces. Balance studies with tritium-labeled Ketalar in
`human subjects (1 mg/lb given intravenously) resulted in the mean recovery of 91% of the dose in the urine and 3% in the feces. Peak
`plasma levels averaged about 0.75 µg/mL, and CSF levels were about 0.2 µg/mL, 1 hour after dosing.
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`Ketalar undergoes N-demethylation and hydroxylation of the cyclohexanone ring, with the formation of water-soluble conjugates
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`which are excreted in the urine. Further oxidation also occurs with the formation of a cyclohexanone derivative. The unconjugated N­
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`demethylated metabolite was found to be less than one-sixth as potent as Ketalar. The unconjugated demethyl cyclohexanone
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`derivative was found to be less than one-tenth as potent as Ketalar. Repeated doses of Ketalar administered to animals did not produce
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`any detectable increase in microsomal enzyme activity.
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`Reference ID: 3096050
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`Hospira, Exh. 2025, p. 5
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` Reproduction:
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` Male and female rats, when given five times the average human intravenous dose of Ketalar for three consecutive days about one
` week before mating, had a reproductive performance equivalent to that of saline-injected controls. When given to pregnant rats and
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` rabbits intramuscularly at twice the average human intramuscular dose during the respective periods of organogenesis, the litter
` characteristics were equivalent to those of saline-injected controls. A small group of rabbits was given a single large dose (six times
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` the average human dose) of Ketalar on Day 6 of pregnancy to simulate the effect of an excessive clinical dose around the period of
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` nidation. The outcome of pregnancy was equivalent in control and treated groups.
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` To determine the effect of Ketalar on the perinatal and postnatal period, pregnant rats were given twice the average human
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` intramuscular dose during Days 18 to 21 of pregnancy. Litter characteristics at birth and through the weaning period were equivalent
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` to those of the control animals. There was a slight increase in incidence of delayed parturition by one day in treated dams of this
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` group. Three groups each of mated beagle bitches were given 2.5 times the average human intramuscular dose twice weekly for the
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` three weeks of the first, second, and third trimesters of pregnancy, respectively, without the development of adverse effects in the
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`pups.
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`
`Prescribing Information as of March 2012.
`Manufactured and Distributed by:
`JHP Pharmaceuticals, LLC
`Rochester, MI 48307
`
`3000442C
`
`
`
`Reference ID: 3096050
`
`Hospira, Exh. 2025, p. 6