Ketamine Hydrochloride (Page 3 of 5)

Effect of Anesthetic and Sedation Drugs on Early Brain Development

Studies conducted in young animals and children suggest repeated or prolonged use of general anesthetic or sedation drugs in children younger than 3 years may have negative effects on their developing brains. Discuss with parents and caregivers the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs (see WARNINGS: Pediatric Neurotoxicity).

Drug Interactions

Prolonged recovery time may occur if barbiturates and/or narcotics are used concurrently with ketamine hydrochloride injection. Ketamine hydrochloride injection is clinically compatible with the commonly used general and local anesthetic agents when an adequate respiratory exchange is maintained.

Geriatric Use

Clinical studies of ketamine hydrochloride 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.

Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as ketamine hydrochloride injection, that either block NMDA receptors or potentiate the activity of GABA during the period of rapid brain growth or synaptogenesis, results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately 3 years of age in humans.

In primates, exposure to 3 hours of ketamine that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer of isoflurane increased neuronal cell loss. Data from isoflurane-treated rodents and ketamine-treated primates suggest that the neuronal and oligodendrocyte cell losses are associated with prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates, and young children who require procedures with the potential risks suggested by the nonclinical data (see WARNINGS: Pediatric Neurotoxicity and PRECAUTIONS: Pregnancy).

ADVERSE REACTIONS

Cardiovascular

Blood pressure and pulse rate are frequently elevated following administration of ketamine hydrochloride injection 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 hydrochloride injection. Laryngospasms and other forms of airway obstruction have occurred during ketamine hydrochloride injection anesthesia.

Eye

Diplopia and nystagmus have been noted following ketamine hydrochloride injection administration. It also may cause a slight elevation in intraocular pressure measurement.

Genitourinary

In individuals with history of chronic ketamine use or abuse, lower urinary tract and bladder symptoms including dysuria, increased urinary frequency, urgency, urge incontinence, and hematuria have been reported (see DOSAGE AND ADMINISTRATION section). In addition, diagnostic studies performed to assess the cause of these symptoms have reported cystitis (including cystitis non-infective, cystitis interstitial, cystitis ulcerative, cystitis erosive and cystitis hemorrhagic) as well as hydronephrosis and reduced bladder capacity.

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 Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or 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.

OVERDOSAGE

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

DOSAGE AND ADMINISTRATION

Note: Barbiturates and ketamine hydrochloride injection, being chemically incompatible because of precipitate formation, should not be injected from the same syringe.

If the ketamine hydrochloride injection dose is augmented with diazepam, the two drugs must be given separately. Do not mix ketamine hydrochloride injection 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 injection administration, some airway protection may be afforded because of active laryngeal-pharyngeal reflexes. However, since aspiration may occur with ketamine hydrochloride injection and since protective reflexes may also be diminished by supplementary anesthetics and muscle relaxants, the possibility of aspiration must be considered. Ketamine hydrochloride injection 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 hydrochloride injection is rapid; an intravenous dose of 2 mg/kg 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 mg/kg to 13 mg/kg usually produce surgical anesthesia within 3 to 4 minutes following injection, with the anesthetic effect usually lasting 12 to 25 minutes.