Ketamine Hydrochloride (Page 4 of 5)

Dosage

As with other general anesthetic agents, the individual response to ketamine hydrochloride injection 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.

In individuals with a history of chronic ketamine use for off-label indications, there have been case reports of genitourinary pain that may be related to the ketamine treatment, not the underlying condition (see ADVERSE REACTIONS section). Consider cessation of ketamine if genitourinary pain continues in the setting of other genitourinary symptoms.

Induction

Intravenous Route

The initial dose of ketamine hydrochloride injection administered intravenously may range from 1 mg/kg to 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 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 injection 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 hydrochloride injection 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 hydrochloride injection administered intramuscularly may range from 6.5 mg/kg to 13 mg/kg. A dose of 10 mg/kg 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 hydrochloride injection administered, the longer will be the time to complete recovery.

Adult patients induced with ketamine hydrochloride injection augmented with intravenous diazepam may be maintained on ketamine hydrochloride injection given by slow microdrip infusion technique at a dose of 0.1 mg/minute to 0.5 mg/minute, augmented with diazepam 2 mg 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 hydrochloride injection. If fluid restriction is required, ketamine hydrochloride injection can be added to a 250 mL infusion as described above to provide a ketamine hydrochloride injection concentration of 2 mg/mL.

Ketamine hydrochloride injection 10 mg/mL vials are not recommended for dilution.

Supplementary Agents

Ketamine hydrochloride injection 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 hydrochloride injection supplemented with diazepam can be used to produce balanced anesthesia by combination with other agents such as nitrous oxide and oxygen.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED

Ketamine Hydrochloride Injection, USP is supplied as the hydrochloride in concentrations equivalent to ketamine base.

NDC 67457-181-20 carton containing 10, 20 mL multi-dose vials with 10 mg/mL
NDC 67457-001-10 carton containing 10, 10 mL multi-dose vials with 50 mg/mL
NDC 67457-108-10 carton containing 10, 10 mL multi-dose vials with 100 mg/mL

Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature.]

Protect from light. Retain in carton until time of use.

ANIMAL PHARMACOLOGY AND TOXICOLOGY

Published studies in animals demonstrate that the use of anesthetic agents 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 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 an anesthetic regimen that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer increased neuronal cell loss. Data in rodents and in primates suggest that the neuronal and oligodendrocyte cell losses are associated with subtle but 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 neonates and young children who require procedures against the potential risks suggested by the nonclinical data (see WARNINGS: Pediatric Neurotoxicity, PRECAUTIONS: Pregnancy, and PRECAUTIONS: Pediatric Use).

In published studies, intraperitoneal administration of ketamine at doses greater than 40 mg/kg induced vacuolation in neuronal cells of the posterior cingulate and retrosplenial cortices in adult rats, similar to what has been reported in rodents administered other NMDA receptor antagonists. These vacuoles were demonstrated to be reversible and did not progress to degeneration or neuronal death up to doses of 80 mg/kg (1.2 times the human dose of 10 mg/kg based on body surface area). A no-effect level for neuronal vacuolation was 20 mg/kg intraperitoneal (0.3 times a human dose of 10 mg/kg on a body surface area basis). The window of vulnerability to these changes is believed to correlate with exposures in humans from the onset of puberty through adulthood. The relevance of this finding to humans is unknown.

Manufactured for:
Mylan Institutional LLC
Rockford, IL 61103 U.S.A.

Manufactured by:
Mylan Institutional
Galway, Ireland

Revised: 3/2019
MI:KETAIJ:R7

0942L102

PRINCIPAL DISPLAY PANEL — 10 mg/mL

NDC 67457-181-20

Ketamine Hydrochloride
Injection, USP CIII

200 mg/20 mL*
(10 mg/mL)

For Intramuscular or Slow Intravenous Use

Rx only 10 x 20 mL Multi-Dose Vials

Sterile

*Each mL contains:

Ketamine hydrochloride equivalent to 10 mg of ketamine with a pH range of 3.5 to 5.5. Also contains not more than 0.1 mg/mL of
benzethonium chloride added as a preservative.

Color of solution may vary from colorless to very slightly yellowish and may darken upon prolonged
exposure to light. This darkening does
not affect potency.

Do not use if precipitate appears.

Warning: Keep this and all drugs out of the reach of children.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from light. Retain in carton until time of use.

Usual Dosage: See accompanying prescribing information.

Manufactured for:
Mylan Institutional LLC
Rockford, IL 61103 U.S.A.

Manufactured by:
Mylan Institutional Galway, Ireland

MI:181:10C:R5

Mylan.com