Ketamine Hydrochloride (Page 2 of 5)
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.
6 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
7 DRUG INTERACTIONS
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.
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