Praketamide

Drug overview for PRAKETAMIDE (ketamine hcl):

Generic name: ketamine HCl
Drug class: Topical Local Anesthetics
Therapeutic class: Dermatological

Ketamine hydrochloride, an N-methyl-d-aspartate (NMDA) receptor antagonist, is a nonbarbiturate general anesthetic that also has analgesic and antidepressant properties.

Ketamine hydrochloride was initially developed as an anesthetic agent; however, the drug can also produce profound analgesia and other pharmacologic effects, and is therefore used for a variety of other indications such as procedural sedation, pain management+, sedation and analgesia in the intensive care setting+, and some psychiatric indications, including treatment-resistant depression and suicidality+.

DRUG IMAGES

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The following indications for PRAKETAMIDE (ketamine hcl) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following dosing information is available for PRAKETAMIDE (ketamine hcl):

Dosing
Administration
Dosing Information
Generic

Dosage of ketamine hydrochloride is expressed in terms of ketamine.

Dosage of ketamine depends on the intended use and desired pharmacologic effect. At low doses, ketamine produces analgesia and sedation, and at higher doses, the drug produces a state of dissociative anesthesia. Ketamine has a dosing threshold at which dissociation occurs; doses at or above the threshold are referred to as ''dissociative'' or ''anesthetic,'' and doses below this threshold are referred to as ''subdissociative'' or ''subanesthetic.''

Although specific dosing ranges have not been established, dissociation generally appears at an IV dose of approximately 1-1.5 mg/kg or an IM dose of approximately 3-5 mg/kg. Once the dissociative threshold has been reached, additional administration of ketamine will not enhance or deepen sedation.

For induction of anesthesia in adults, the manufacturer recommends an initial IV ketamine dose of 1-4.5 mg/kg or an initial IM dose of 6.5-13 mg/kg.

Administer IV ketamine doses by slow IV injection over 60 seconds or as an IV infusion at a rate of 0.5 mg/kg per minute. On average, an IV dose of 2 mg/kg will produce surgical anesthesia for 5-10 minutes within 30 seconds of administration, and an IM dose of 9-13 mg/kg will produce surgical anesthesia for 12-25 minutes within 3-4 minutes following administration.

For maintenance of anesthesia in adults, additional IV doses of 0.5-4.5 mg/kg or IM doses of 3.25-13

mg/kg may be administered as needed. The manufacturer additionally states that a slow microdrip IV infusion, using a dosage of 0.1-0.5

mg/minute will maintain general anesthesia after induction with ketamine. A continuous IV infusion of 1-6 mg/kg per hour also has been recommended for maintenance of anesthesia. The maintenance dosage should be adjusted based on the patient's anesthetic requirements and concomitant use of other anesthetic agents.

The manufacturer states that the incidence of psychologic manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by using lower recommended dosages of ketamine in conjunction with an IV benzodiazepine during induction and maintenance of anesthesia.

In general, pediatric patients require higher doses of ketamine compared with adults, although there is considerable interpatient variability in dosing requirements.

Some experts recommend an initial IV ketamine dose of 1-3 mg/kg for induction of anesthesia in pediatric patients+; supplemental IV doses of 0.5-1 mg/kg may be given if clinically indicated. The recommended IM dose of ketamine for induction of anesthesia in pediatric patients is 5-10 mg/kg.

Because of possible airway complications, some experts state that ketamine is contraindicated in infants younger than 3 months of age.

For dissociative sedation in adults undergoing short painful or emotionally disturbing procedures in the emergency department, the usual IV dose of ketamine is 1 mg/kg administered by IV injection over 30-60 seconds. Dissociative sedation is usually achieved with a single IV loading dose; however, if sedation is inadequate or a prolonged period of sedation is needed for longer procedures, additional IV doses of 0.5-1 mg/kg may be administered every 5-15 minutes as needed.

Lower IV doses of ketamine (e.g., 0.2-0.75 mg/kg) also have been used to produce analgesia, particularly if a dissociative effect is not required for the procedure.

Although the IM route is not preferred in adults, some experts state that an IM dose of 4-5 mg/kg may be administered; additional doses of 2-5 mg/kg may be given after 5-10 minutes if initial sedation is inadequate or additional doses are needed for longer procedures. Lower IM doses of ketamine (e.g., 0.4-2 mg/kg) also have been used, particularly if a dissociative effect is not required for the procedure.

For dissociative sedation in pediatric patients+ 3 months of age or older undergoing short painful or emotionally disturbing procedures in the emergency department, some experts state that the usual IV dose of ketamine is 1.5-2 mg/kg administered by IV injection over 30-60 seconds. Dissociative sedation is usually achieved with a single IV loading dose; however, if initial sedation is inadequate or prolonged sedation is necessary for longer procedures, additional incremental IV doses of 0.5-1

mg/kg may be administered every 5-15 minutes as needed. These experts state that the minimum IV dose that will reliably elicit the dissociative state in children is 1.5 mg/kg; however, lower IV doses (e.g., 0.25-1 mg/kg) also have been used successfully to provide adequate procedural sedation in pediatric patients, particularly if a dissociative effect is not required for the procedure.

The recommended IM dose of ketamine for dissociative sedation in pediatric patients+ 3 months of age or older undergoing short painful or emotionally disturbing procedures in the emergency department is 4-5 mg/kg. Although dissociative sedation is usually achieved with a single IM dose, additional doses of 2-5 mg/kg may be administered after 5-10 minutes if initial sedation is inadequate or additional doses are needed for longer procedures. Although some experts state that the minimum IM dose that will reliably elicit the dissociative state in children is 4-5 mg/kg, lower IM doses (e.g., 1-2 mg/kg) also have been used successfully, particularly if a dissociative effect is not required for the procedure.

Changes in heart rate and blood pressure, respiratory depression, and apnea may occur with overdosage or by a rapid rate of administration of ketamine. Monitor patients for clinically relevant changes in heart rate and blood pressure. Assisted ventilation, including mechanical ventilation, may be required.

Several cases of accidental ketamine overdosage (with doses up to 10 or 100 times the intended dose in adults or children, respectively) resulted in prolonged sedation, but no other clinically important adverse effects or complications; ventilator support was required rarely. Death secondary to acute ketamine overdosage in the absence of multidrug intoxication is rare, although accidental deaths have been reported. A lethal dose of ketamine in humans has not been identified.

Ketamine hydrochloride usually is administered by slow (e.g., over 60 seconds) IV injection, IV infusion, or IM injection. Ketamine also has been used in IV patient-controlled analgesia (PCA), either as the sole analgesic or in combination with opioids to improve pain control and reduce opioid-related adverse effects. Ketamine also has been administered by oral+, intranasal+, rectal+, subcutaneous+, and intraosseous (IO)+ routes.

Because of extensive first-pass metabolism, the bioavailability of ketamine following oral or rectal administration is limited (approximately 20-30%). Although ketamine has been administered epidurally+ or intrathecally+, there have been concerns about potential neurotoxicity with these routes, and some experts state it may be prudent to avoid neuraxial administration of the drug. Some experts state that IV administration of ketamine is preferred to IM administration when access can be obtained readily.

IM administration is associated with a higher rate of vomiting and longer recovery times compared with IV administration. In addition, IV access can permit convenient administration of additional doses for longer procedures and allow for rapid treatment of adverse effects (e.g., IV benzodiazepines for emergence reactions). In certain patients (e.g., severely agitated or uncooperative patients, young children), IM administration may be preferred.

Store ketamine hydrochloride injection at controlled room temperature between 20-25degreesC (excursions permitted between 15-30degreesC) and protect from light. Ketamine has been reported to be compatible with several drugs when administered as additives, simultaneously in the same syringe, or when a Y-type administration set is used; specialized references should be consulted for more specific information.

No dosing information available.

No generic dosing information available.

The following adverse reaction information is available for PRAKETAMIDE (ketamine hcl):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse reactions with ketamine are emergence reactions and elevated blood pressure and pulse.

There are 22 severe adverse reactions.

More Frequent	Less Frequent
Hypertension Tachycardia	Bradycardia Hypotension

Rare/Very Rare
Abnormal hepatic function tests Acquired dilation of bile duct Acute kidney injury Anaphylaxis Apnea Cardiac arrhythmia Cholestasis Cholestatic hepatitis Cystitis Drug-induced hepatitis Hematuria Hepatic fibrosis Hepatocellular damage Hydronephrosis Increased cerebrospinal fluid pressure Laryngismus Respiratory depression Viral infection

There are 25 less severe adverse reactions.

More Frequent	Less Frequent
Acute cognitive impairment Delirium Hallucinations Tremor	Agitation Behavioral disorders Diplopia Dream disorder Drowsy Erythema Hypertonia Memory impairment Tachypnea Vomiting

Rare/Very Rare
Accidental fall Anorexia Dysuria Increased urinary frequency Injection site sequelae Muscle spasm Nausea Nystagmus Ocular hypertension Skin rash Urinary urge incontinence

The following precautions are available for PRAKETAMIDE (ketamine hcl):

Pediatric
Pregnant
Lactation
Geriatric

Although the manufacturer states that safety and efficacy of ketamine have not been established in patients younger than 16 years of age, the drug has been used widely in pediatric patients+ in a variety of clinical settings for anesthesia, procedural sedation and analgesia, postoperative analgesia, and chronic pain management. Ketamine frequently is used in children to facilitate painful procedures in the emergency department and is considered a drug of choice for this use. Ketamine may be particularly useful in pediatric patients because the drug may be administered IM.

Repeated or prolonged use of general anesthetics and sedation drugs, including ketamine, in children <3 years of age or during the third trimester of pregnancy may adversely affect neurodevelopment. In animals, use of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity leads to widespread neuronal apoptosis in the brain and long-term deficits in cognition and behavior when used for longer than 3 hours; however, the clinical relevance to humans is unknown. Ketamine may be preferred for induction of anesthesia in children with congenital heart disease with right-to-left shunt+ because of its sympathomimetic effects and hemodynamic stability.

Ketamine generally should not be used in infants younger than 3 months of age because of the potential increased risk of airway complications (e.g., airway obstruction, laryngospasm, apnea) thought to be due to age-specific differences in airway reactivity and anatomy.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

There are no adequate and well-controlled studies of ketamine in pregnant women. Although ketamine has been used for induction of anesthesia during vaginal delivery and caesarean sections, the manufacturer states that the drug is not recommended for use during pregnancy or delivery because safety has not been established. Some neonates exposed to ketamine at maternal IV doses of 1.5

mg/kg or higher during delivery have experienced respiratory depression and low Apgar scores requiring resuscitation. Marked increases in maternal blood pressure and uterine tone have been observed following administration of IV ketamine doses greater than 2 mg/kg. In animal reproduction studies using IM ketamine doses approximately 0.3-0.6

times the usual human IM dose of 10 mg/kg (based on body surface area), developmental delays, skeletal hypoplasia, and increased fetal resorptions were observed. Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs, including ketamine, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus. The clinical relevance of these animal findings to humans is not known; the potential risk of adverse neurodevelopmental effects should be considered and discussed with pregnant women undergoing procedures requiring general anesthetics and sedation drugs.

It is not known whether ketamine is distributed into milk. Because the drug should be undetectable in plasma approximately 11 hours after administration, nursing after this time period should not expose the infant to clinically relevant amounts of ketamine.

While reported clinical experience to date has not revealed age-related differences in response to ketamine when used as an anesthetic agent, clinical studies have not included sufficient numbers of patients >=65 years of age to determine whether geriatric patients respond differently than younger adults. When ketamine is used as an anesthetic agent in geriatric patients, the dosage should be selected carefully, usually starting at the low end of the dosing range, because of the greater frequency of age-related decreases in hepatic, renal, and/or cardiac function, and of concomitant disease or other drug therapy.