Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Ketamine Hydrochloride Injection, USP is a clear, colorless to slightly yellow solution supplied as the hydrochloride salt in concentrations equivalent to ketamine base, as follows: Product Code Unit of Sale Strength (Concentration) Unit of Use PRX180605 NDC 65219-186-23 Unit of 10 500 mg/5 mL (100 mg/mL) 100 mg ketamine base (equivalent to 115.33 mg ketamine hydrochloride) NDC 65219-186-13 5 mL multiple-dose vial Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Protect from freezing. This container closure is not made with natural rubber latex.; PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Vial Label NDC 65219- 186 -13 Ketamine HCl Injection, USP CIII CONCENTRATE 500 mg/5 mL (100 mg/mL) For Slow Intravenous or Intramuscular Use MUST BE DILUTED PRIOR TO IV USE 5 mL Multiple-Dose Vial Rx Only PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Vial Label; PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Tray Label NDC 65219- 186 -23 Ketamine HCl Injection, USP CIII CONCENTRATE 500 mg/5 mL (100 mg/mL) For Slow Intravenous or Intramuscular Use MUST BE DILUTED PRIOR TO IV USE 5 mL X 10 Multiple-Dose Vials Rx Only PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Tray Label
- 16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Ketamine Hydrochloride Injection, USP is a clear, colorless to slightly yellow solution supplied as the hydrochloride salt in concentrations equivalent to ketamine base, as follows: Product Code Unit of Sale Strength (Concentration) Unit of Use PRX180605 NDC 65219-186-23 Unit of 10 500 mg/5 mL (100 mg/mL) 100 mg ketamine base (equivalent to 115.33 mg ketamine hydrochloride) NDC 65219-186-13 5 mL multiple-dose vial Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Protect from freezing. This container closure is not made with natural rubber latex.
- PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Vial Label NDC 65219- 186 -13 Ketamine HCl Injection, USP CIII CONCENTRATE 500 mg/5 mL (100 mg/mL) For Slow Intravenous or Intramuscular Use MUST BE DILUTED PRIOR TO IV USE 5 mL Multiple-Dose Vial Rx Only PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Vial Label
- PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Tray Label NDC 65219- 186 -23 Ketamine HCl Injection, USP CIII CONCENTRATE 500 mg/5 mL (100 mg/mL) For Slow Intravenous or Intramuscular Use MUST BE DILUTED PRIOR TO IV USE 5 mL X 10 Multiple-Dose Vials Rx Only PACKAGE LABEL - PRINCIPAL DISPLAY – Ketamine HCl Injection, USP 5 mL Tray Label
Overview
Ketamine Hydrochloride Injection, USP, for intravenous or intramuscular use, contains ketamine, a nonbarbiturate general anesthetic. Ketamine Hydrochloride, USP is a white crystalline powder and has a molecular formula of C 13 H 16 ClNO•HCl and a molecular weight of 274.19. The chemical name for ketamine hydrochloride is (±)-2-( o -Chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride. The chemical structure of ketamine hydrochloride is: It is formulated as a slightly acidic (pH 3.5-5.5) sterile solution for intravenous or intramuscular injection. Each milliliter (mL) of the multiple-dose vials contain 100 mg ketamine base (equivalent to 115.33 mg ketamine hydrochloride) and not more than 0.10 mg/mL benzethonium chloride added as a preservative in water for injection. Chemical Structure
Indications & Usage
Ketamine Hydrochloride Injection is indicated: as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. for the induction of anesthesia prior to the administration of other general anesthetic agents. as a supplement to other anesthetic agents. Ketamine Hydrochloride Injection is a general anesthetic indicated: as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation ( 1 ) for the induction of anesthesia prior to the administration of other general anesthetic agents ( 1 ) as a supplement to other anesthetic agents ( 1 ).
Dosage & Administration
See Full Prescribing Information for important dosage and administration instructions. ( 2 ) Induction of anesthesia: -- Intravenous route : Initially, 1 to 4.5 mg/kg administered slowly (over a period of 60 seconds). Alternatively, administer a dose of 1 to 2 mg/kg at a rate of 0.5 mg/kg/min. ( 2.2 ) -- Intramuscular route : Initially, 6.5 to 13 mg/kg. ( 2.2 ) Maintenance of anesthesia: Increments of one-half to the full induction dose may be repeated as needed ( 2.2 ). Adjust the dose according to the patient's anesthetic needs and whether an additional anesthetic agent is employed. ( 2.2 ) Supplement to other anesthetic agents : 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. ( 2.2 ) 2.1 Important Dosage and Administration Information Ketamine Hydrochloride Injection should be administered by or under the direction of physicians experienced in the administration of general anesthetics, maintenance of a patent airway, and oxygenation and ventilation. Continuously monitor vital signs in patients receiving Ketamine Hydrochloride Injection. Emergency airway equipment must be immediately available. Do not administer the 100 mg/mL concentration of Ketamine Hydrochloride Injection intravenously without proper dilution [see Dosage and Administration ( 2.3 )] . Must be used immediately after dilution. While some degree of airway protection may be afforded due to active laryngeal-pharyngeal reflexes, vomiting and aspiration may occur with Ketamine Hydrochloride Injection. Ketamine Hydrochloride Injection is not recommended for use in patients who have not followed nil per os guidelines. Due to the potential for salivation during Ketamine Hydrochloride Injection administration, administer an antisialagogue prior to induction of anesthesia. In individuals with a history of chronic Ketamine Hydrochloride Injection use for off-label indications, there have been case reports of genitourinary pain that may be related to the Ketamine Hydrochloride Injection treatment, not the underlying condition [see Adverse Reactions ( 6 )] . Consider cessation of Ketamine Hydrochloride Injection if genitourinary pain continues in the setting of other genitourinary symptoms. 2.2 Recommended Dosage and Administration The Ketamine Hydrochloride Injection dosage must be individualized and titrated to the desired clinical effect. If a longer duration of effect is desired, additional increments can be administered intravenously or intramuscularly to maintain anesthesia. However, a higher total dose will result in a longer time to complete recovery. Induction of Anesthesia 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 5 to 10 minutes of surgical anesthesia within 30 seconds following injection is 2 mg/kg. Administer Ketamine Hydrochloride Injection slowly (i.e., over a period of 60 seconds). Rapid administration may result in respiratory depression and enhanced vasopressor response. The induction dose may be administered as an intravenous infusion at a rate of 0.5 mg/kg/min. Intramuscular Route : The initial dose of Ketamine Hydrochloride Injection administered intramuscularly may range from 6.5 to 13 mg/kg. A dose of 9 to 13 mg/kg usually produces surgical anesthesia within 3 to 4 minutes following injection, with the anesthetic effect usually lasting 12 to 25 minutes. Administer a benzodiazepine, if clinically indicated, for the prevention of neuropsychological manifestations during emergence from anesthesia. Maintenance of Anesthesia Adjust the maintenance dose according to the patient's anesthetic needs and whether an additional anesthetic agent is administered. Repeat increments of one-half to the full induction dose as needed for maintenance of anesthesia. Purposeless and tonic-clonic movements of extremities may occur during the course of Ketamine Hydrochloride Injection anesthesia. These movements do not imply a light plane and are not indicative of the need for additional doses of the anesthetic. Ketamine Hydrochloride Injection given by slow microdrip infusion technique at a dose of 0.1 to 0.5 mg/minute will maintain general anesthesia in adult patients induced with Ketamine Hydrochloride Injection. Augment Ketamine Hydrochloride Injection with an intravenous benzodiazepine for the prevention of neuropsychological manifestations during emergence. Supplement to Other Anesthetic Agents Ketamine Hydrochloride Injection can be administered to supplement other general and local anesthetic agents. Continuously monitor patients for changes in respiratory and hemodynamic parameters. A reduced dose of Ketamine Hydrochloride Injection can be used to produce balanced anesthesia when used in combination with other anesthetic agents. 2.3 Preparation of Dilution Ketamine Hydrochloride Injection is a clear, colorless to slightly yellow sterile solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if product is discolored or contains particulate matter. Induction of Anesthesia : Do not intravenously inject the 100 mg/mL concentration of Ketamine Hydrochloride Injection without proper dilution. Dilute Ketamine Hydrochloride Injection with an equal volume of either Sterile Water for injection, USP, 0.9% Sodium Chloride Injection, USP (Normal Saline), or 5% Dextrose in Water. Use immediately after dilution. Maintenance of Anesthesia : To prepare a dilute solution containing 1 mg of Ketamine per mL, aseptically transfer 5 mL from a 100 mg per mL vial to 500 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (Normal Saline) and mix well. The resultant solution will contain 1 mg of ketamine per mL. Use immediately after dilution. When 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.
Warnings & Precautions
Hemodynamic Instability: Monitor vital signs and cardiac function during Ketamine Hydrochloride Injection administration. ( 5.1 ) Emergence Reactions: Postoperative confusional states may occur during the recovery period. Reduce by minimizing verbal, tactile, and visual stimulation of the patient. ( 5.2 ) Risk of Respiratory Depression: May occur with overdosage or too rapid a rate of administration. Maintain adequate oxygenation and ventilation. ( 5.3 ) Risks of Ketamine Hydrochloride Injection alone for Procedures of the Pharynx, Larynx, or Bronchial Tree : Pharyngeal and laryngeal reflexes are not suppressed with Ketamine Hydrochloride Injection when it is used alone. Avoid use as a sole anesthetic agent in surgery or diagnostic procedures of the pharynx, larynx, or bronchial tree. Muscle relaxants may be required. ( 5.4 ) Pediatric Neurotoxicity: Long-term cognitive deficits may occur when used for longer than 3 hours in children ≤3 years ( 5.5 ) 5.1 Hemodynamic Instability Transient increases in blood pressure, heart rate, and cardiac index are frequently observed following administration of Ketamine Hydrochloride Injection. Decreases in blood pressure and heart rate, arrhythmias, and cardiac decompensation have also been observed. Monitor vital signs and cardiac function during Ketamine Hydrochloride Injection administration. Ketamine Hydrochloride Injection is contraindicated in patients for whom a significant elevation of blood pressure would constitute a serious hazard [see Contraindications ( 4 )] . 5.2 Emergence Reactions Emergence delirium (postoperative confusional states or agitation) has occurred in approximately 12% of patients during the recovery period, and the duration is generally a few hours. The neuropsychological manifestations vary in severity between pleasant dream-like states, vivid imagery, hallucinations, and emergence delirium. In some cases, these states have been accompanied by confusion, excitement, and irrational behavior, which have been recalled as unpleasant experiences. No residual psychological effects are known to have resulted from use of Ketamine Hydrochloride Injection during induction and maintenance of anesthesia. Intramuscular administration results in a lower incidence of emergence reactions. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by using lower recommended dosages of Ketamine Hydrochloride Injection in conjunction with an intravenous benzodiazepine during induction and maintenance of anesthesia [see Dosage and Administration ( 2.3 )] . Also, these reactions may be reduced if verbal, tactile, and visual stimulation of the patient is minimized during the recovery period. This does not preclude the monitoring of vital signs. 5.3 Respiratory Depression Respiratory depression may occur with overdosage or a rapid rate of administration of Ketamine Hydrochloride Injection. Maintain adequate oxygenation and ventilation. 5.4 Risks of Ketamine Hydrochloride Injection Alone for Procedures of the Pharynx, Larynx, or Bronchial Tree Ketamine Hydrochloride Injection does not suppress pharyngeal and laryngeal reflexes. Avoid Ketamine Hydrochloride Injection administration as a sole anesthetic agent during procedures of the pharynx, larynx, or bronchial tree, including mechanical stimulation of the pharynx. Muscle relaxants may be required for successful completion of procedures of the pharynx, larynx, or bronchial tree. 5.5 Pediatric Neurotoxicity Published animal studies demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of these findings is not clear. However, based on the available data, 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 three years of age in humans [see Use in Specific Populations ( 8.1 , 8.4 ), Nonclinical Toxicology ( 13.2 )]. Some published studies in children suggest that similar deficits may occur after repeated or prolonged exposures to anesthetic agents early in life and may result in adverse cognitive or behavioral effects. These studies have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors such as the surgery or underlying illness. Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks. 5.6 Drug-Induced Liver Injury Ketamine administration is associated with hepatobiliary dysfunction (most often a cholestatic pattern), with recurrent use (e.g., misuse/abuse or medically supervised unapproved indications). Biliary duct dilatation with or without evidence of biliary obstruction has also been reported with recurrent use. Obtain baseline LFTs, including alkaline phosphatase and gamma glutamyl transferase, in patients receiving ketamine as part of a treatment plan that utilizes recurrent dosing. Monitor those receiving recurrent ketamine at periodic intervals during treatment. 5.7 Increase in Cerebrospinal Fluid Pressure An increase in intracranial pressure has been reported following administration of ketamine hydrochloride. Patients with elevated intracranial pressure should be in a monitored setting with frequent neurologic assessments. 5.8 Drug Interactions Theophylline or Aminophylline : Concomitant administration of Ketamine Hydrochloride Injection and theophylline or aminophylline may lower the seizure threshold [see Drug Interactions ( 7.1 )] . Consider using an alternative to Ketamine Hydrochloride Injection in patients receiving theophylline or aminophylline. Sympathomimetics and Vasopressin : Sympathomimetics and vasopressin may enhance the sympathomimetic effects of ketamine [see Drug Interactions ( 7.2 )] . Closely monitor vital signs when Ketamine Hydrochloride Injection and sympathomimetics or vasopressin are co-administered and consider dose adjustment individualized to the patient's clinical situation. Benzodiazepines, Opioid Analgesics, or Other CNS Depressants Concomitant use of ketamine with opioid analgesics, benzodiazepines, or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Drug Interactions ( 7.3 )] . Closely monitor neurological status and respiratory parameters, including respiratory rate and pulse oximetry, when Ketamine Hydrochloride Injection and opioid analgesics, benzodiazepines, or other CNS depressants are co-administered. Consider dose adjustment individualized to the patient's clinical situation.
Contraindications
Ketamine Hydrochloride Injection is contraindicated in patients for whom a significant elevation of blood pressure would constitute a serious hazard [see Warnings and Precautions ( 5.1 )] . Ketamine Hydrochloride Injection is contraindicated in patients with known hypersensitivity to ketamine or to any excipient [see Adverse Reactions ( 6 )] . In patients for whom a significant elevation of blood pressure would be a serious hazard ( 4 ). Known hypersensitivity to ketamine or to any excipient ( 4 ).
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Hemodynamic Instability [see Warnings and Precautions ( 5.1 )] Emergence Reactions [see Warnings and Precautions ( 5.2 )] Respiratory Depression [see Warnings and Precautions ( 5.3 )] Pediatric Neurotoxicity [see Warnings and Precautions ( 5.5 )] Drug-Induced Liver Injury [see Warnings and Precautions ( 5.6 )] The following adverse reactions associated with the use of Ketamine Hydrochloride Injection were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular disorders : Elevated blood pressure, heart rate, and cardiac index; decreases in blood pressure and heart rate; arrhythmias; cardiac decompensation (in patients with suspected catecholamine depletion). Eye disorders : Diplopia, nystagmus, elevation in intraocular pressure. Gastrointestinal disorders : Anorexia, nausea, vomiting, hepatobiliary dysfunction. Biliary duct dilatation with or without evidence of biliary obstruction has been reported with recurrent use (e.g., misuse/abuse or medically supervised unapproved indications). Administration site disorders : Local pain and exanthema at the injection site. Immune system disorders : Anaphylaxis. Neurologic disorders : Emergence reactions (post-operative delirium), [see Warnings and Precautions ( 5.2 )]. During administration, enhanced muscle tone and spasms (resembling a partial motor or generalized motor seizure). Psychiatric disorders : Adverse psychiatric events have occurred and/or persisted days to weeks after ketamine exposure. Renal and urinary disorders: 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 ( 2.1 )] . 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. Respiratory disorders : Respiratory depression and apnea following rapid intravenous administration of high doses of Ketamine Hydrochloride Injection; laryngospasm, and airway obstruction. Skin and subcutaneous tissue disorders : Transient erythema and/or morbilliform rash The most common adverse reactions are emergence reactions and elevated blood pressure and pulse ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Drug Interactions
Theophylline or Aminophylline : Do not co-administer with Ketamine Hydrochloride Injection as concomitant use may lower the seizure threshold ( 7.1 ). Sympathomimetics and Vasopressin : Closely monitor vital signs when co-administered with Ketamine Hydrochloride Injection. Consider dose adjustment individualized to the patient's clinical situation ( 7.2 ). Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death. Concomitant use of opioid analgesics may prolong recovery time. ( 7.3 ). 7.1 Theophylline or Aminophylline Concomitant administration of Ketamine Hydrochloride Injection and theophylline or aminophylline may lower the seizure threshold. Consider using an alternative to Ketamine Hydrochloride Injection in patients receiving theophylline or aminophylline. 7.2 Sympathomimetics and Vasopressin Sympathomimetics and vasopressin may enhance the sympathomimetic effects of ketamine. Closely monitor vital signs when Ketamine Hydrochloride Injection and sympathomimetics or vasopressin are co-administered and consider dose adjustment individualized to the patient's clinical situation. 7.3 Benzodiazepines, Opioid Analgesics, Or Other CNS Depressants Concomitant use of ketamine with opioid analgesics, benzodiazepines, or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions ( 5.8 )] . Opioid analgesics administered concomitantly with Ketamine Hydrochloride Injection may prolong time to complete recovery from anesthesia.
Storage & Handling
Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Protect from freezing. This container closure is not made with natural rubber latex.
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