کتامین
Ketamine Hydrochloride (Ketamine HCl)
کتامین

نام ژنریک

Ketamin hydrochloride

شکل دارویی

اشكال دارويي:


Injection: 50 mg/ml, 10 ml

موارد مصرف

موارد و مقدار مصرف


القا بيهوشي عمومي بويژه براي جراحي و کارهاي تشخيصي کوتاه مدت که نياز به شل کننده عضلاني نداشته باشد. به همراه بيهوش کننده‌هاي ديگر يا داروهاي با قدرت پايين مانند اکسيد نيترو.


بزرگسالان و کودکان: mg/kg 4-1 وريدي در مدت 60 ثانيه . جهت نگه داشتن بيهوشي mg/kg 13-5/6 عضلاني، با افزايش مقدار نصف دوز شروع، قابل تکرار کردن مي‌باشد.

موارد منع مصرف

موارد منع مصرف و احتياط


موارد منع مصرف: حساسيت به دارو ، بيماران قلبي ـ عروقي، آنهايي که افزايش ناگهاني فشار برايشان مضر باشد.


موارد احتياط: بيماراني که فشار CSF در آنها بالا باشد، مصرف ‌کنندگان الکل به صورت مزمن و آنهايي که مسموميت ناگهاني با الکل پيدا کرده‌اند.

موارد قابل توجه

-

تداخل دارویی

تداخل دارويي


در صورت مصرف همزمان با باربيتوراتها و اپيوئيدها مي‌تواند زمان ريکاوري را طولاني کند. بيمار به دقت مونيتور شود.


مصرف همزمان با انفلوران و هالوتان مي‌تواند دپرسيون ميوکارد، براديکاردي و افت فشارخون ايجاد کند. از استفاده توام پرهيز شود.


استفاده همزمان با شل کننده‌هاي عضلاني غير دپولاريزان، اثرات عصبي ـ عضلاني را افزايش داده و دپرسيون تنفسي را طولاني مي‌کند. بيمار به دقت مونيتور شود.


استفاده همزمان با هورمونهاي تيروئيدي، افزايش فشارخون و تاکيکاردي ايجاد مي‌کند. بيمار به دقت مونيتور شود.

مکانیزم اثر

تداخل دارويي


در صورت مصرف همزمان با باربيتوراتها و اپيوئيدها مي‌تواند زمان ريکاوري را طولاني کند. بيمار به دقت مونيتور شود.


مصرف همزمان با انفلوران و هالوتان مي‌تواند دپرسيون ميوکارد، براديکاردي و افت فشارخون ايجاد کند. از استفاده توام پرهيز شود.


استفاده همزمان با شل کننده‌هاي عضلاني غير دپولاريزان، اثرات عصبي ـ عضلاني را افزايش داده و دپرسيون تنفسي را طولاني مي‌کند. بيمار به دقت مونيتور شود.


استفاده همزمان با هورمونهاي تيروئيدي، افزايش فشارخون و تاکيکاردي ايجاد مي‌کند. بيمار به دقت مونيتور شود.

فارماكوكینتیك

فارماكوكينتيك


جذب: به سرعت و خوب جذب مي‌شود.


پخش: به سرعت وارد سيستم اعصاب مرکزي مي‌شود.


متابوليسم: در كبد به يک متابوليت فعال با يک سوم قدرت داروي تزريقي اوليه تبديل مي‌شود.


دفع: از راه ادرار دفع مي‌شود.





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روش مصرف




شروع اثر




پيک اثر




مدت اثر




وريدي




30 ثانيه




نامشخص




10-5 دقيقه




عضلاني




4-3 دقيقه




نامشخص




25- 12 دقيقه


سایر اطلاعات

طبقه‌بندي فارماكولوژيك: بيهوش کننده.


طبقه‌بندي درماني: بيهوش کننده.


طبقه‌بندي مصرف در بارداري: رده C


ملاحظات اختصاصي


1- به علت اثر کتامين بر فشارخون، اين دارو به عنوان يک ترکيب القا کننده و نگه دارنده فشارخون در بيماران هيپوولميک شناخته شده است.


2- مخلوط باربيتوراتها و کتامين در يک سرنگ ناسازگار هستند.


3- براي تزريق مستقيم، غلظت 100 ميلي‌گرم/ ميلي ليتر با حجم مساوي از آب استريل براي تزريق، محلول نرمال‌سالين، يا دکستروز 5% رقيق شود. جهت انفوزيون وريدي، يک محلول mg/ml1 با اضافه کردن 5 ميلي ليتر از ويال mg/ml 100 به 500 سي‌سي از محلول قندي 5% يا نرمال‌سالين تهيه کنيد.


4- در مدت القا بيهوشي و ريکاوري، تحريکات کلامي، بينايي و حسي را در حداقل مقدار نگه داريد.


5- اثرات جانبي جدا شدن از محيط و هالوسيناسيون منجر به سوء مصرف دارو مي‌شود.


6- در بيماران مبتلا به هيپرتانسيون يا نارسايي قلبي جبران نشده، عملکرد قلبي به صورت مرتب مونيتور شود.


7- به علت القا سريع بيهوشي، بيماران نياز به حمايت فيزيکي دارند. علائم حياتي قبل از جراحي مونيتور شود. مدت کوتاهي پس از تزريق فشارخون شروع به افزايش مي‌کند. در 10 تا 50 ? بالاي سطح قبل از بيهوشي به پيک رسيده و در مدت 15 دقيقه به سطح پايه باز مي‌گردد. علائم کلينيکي افزايش دوز شامل دپرسيون تنفسي مي‌باشد.


8- واکنشهايي مانند رويا، ديدن تصاوير، هالوسيناسيون و دليريوم در 12? بيماران و تا 24 ساعت پس از جراحي اتفاق مي‌افتد. اين واکنشها با استفاده از دوزاژ کمتر کتامين با ديازپام وريدي کمتر شده و با استفاده از باربيتوراتهاي کوتاه يا خيلي کوتاه اثر درمان مي‌شود.


9- اين واکنشها در بيماران جوانتر از 15 سال يا مسن تر از 65 سال و هنگامي که دارو عضلاني تزريق مي‌شود، کمتر اتفاق مي‌افتد.


نكات قابل توصيه به بيمار


از انجام کارهاي پر خطر تا 24 ساعت پس از بيهوشي خودداري کنيد.


مصرف در كودكان: استفاده از آن در جراحيهاي کوچک، اعمال تشخيصي و کارهاي تکراري که در آن از ترکيبات ضد درد استفاده مي‌شود مانند تعويض پانسمان سوختگي بي خطر مي‌باشد.


مصرف در سالمندان: در بيماران سالمند مشکوک به سکته مغزي، هيپرتانسيون يا بيماري قلبي با احتياط مصرف شود.


عوارض جانبي


اعصاب مرکزي: گيجي، حالات روياگونه، برانگيختگي، هالوسيناسيون، رفتارهاي غيرمنطقي، اختلالات رواني، حرکات تونيک ـ کلونيک.


قلبي ـ عروقي: زيادي شديد فشارخون، کمي فشارخون، آريتمي،
تاکيکاردي.


گوش، چشم، حلق، بيني: دوبيني، اسپاسم لارنژ، نيستاگموس.


دستگاه گوارش: ترشح زياد بزاق، بي اشتهايي خفيف، تهوع، استفراغ.


تنفسي: آپنه، دپرسيون تنفسي


پوست: راشهاي شبه سرخک، اريتم گذرا.


مسموميت و درمان


تظاهرات باليني: دپرسيون تنفسي


درمان: حمايت تنفسي، در صورت نياز از تهويه مکانيکي استفاده شود.

Ketamine Hydrochloride (Ketamine HCl)

Ketamine Hydrochloride (ketamine hcl)
Injection, USP

SPECIAL NOTE

EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS.

THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT DREAM-LIKE STATES, VIVID IMAGINARY, HALLUCINATIONS, AND EMERGENCE DELIRIUM. IN SOME CASES THESE STATES HAVE BEEN ACCOMPANIED BY CONFUSION, EXCITEMENT, AND IRRATIONAL BEHAVIOR WHICH A FEW PATIENTS RECALL AS AN UNPLEASANT EXPERIENCE.THE DURATION ORDINARILY IS NO MORE THAN A FEW HOURS; IN A FEW CASES, HOWEVER, RECURRENCES HAVE TAKEN PLACE UP TO 24 HOURS POSTOPERATIVELY. NO RESIDUAL PSYCHOLOGICAL EFFECTS ARE KNOWN TO HAVE RESULTED FROM USE OF KETAMINE.

THE INCIDENCE OF THESE EMERGENCE PHENOMENA IS LEAST IN THE YOUNG (15 YEARS OF AGE OR LESS) AND ELDERLY (OVER 65 YEARS OF AGE) PATIENT. ALSO, THEY ARE LESS FREQUENT WHEN THE DRUG IS GIVEN INTRAMUSCULARLY AND THE INCIDENCE IS REDUCED AS EXPERIENCE WITH THE DRUG IS GAINED.

THE INCIDENCE OF PSYCHOLOGICAL MANIFESTATIONS DURING EMERGENCE, PARTICULARLY DREAM-LIKE OBSERVATIONS AND EMERGENCE DELIRIUM, MAY BE REDUCED BY USING LOWER RECOMMENDED DOSAGES OF KETAMINE IN CONJUNCTION WITH INTRAVENOUS DIAZEPAM DURING INDUCTION AND MAINTENANCE OF ANESTHESIA. (See DOSAGE AND ADMINISTRATION.) 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.

IN ORDER TO TERMINATE A SEVERE EMERGENCE REACTION, THE USE OF A SMALL HYPNOTIC DOSE OF A SHORT-ACTING OR ULTRA SHORT-ACTING BARBITURATE MAY BE REQUIRED.

WHEN KETAMINE IS USED ON AN OUTPATIENT BASIS, THE PATIENT SHOULD NOT BE RELEASED UNTIL RECOVERY FROM ANESTHESIA IS COMPLETE AND THEN SHOULD BE ACCOMPANIED BY A RESPONSIBLE ADULT.

DRUG DESCRIPTION

Ketamine hydrochloride (ketamine hcl) is a nonbarbiturate anesthetic chemically designated (±)-2-(o-Chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride. It is formulated as a slightly acid (pH 3.5 to 5.5) sterile solution for intravenous or intramuscular injection in concentrations containing the equivalent of 50 mg ketamine base per milliliter and contains not more than 0.1 mg/mL benzethonium chloride added as a preservative. Ketamine hydrochloride (ketamine hcl) has the following structural formula:

Ketamine hydrochloride structural formula illustration

Molecular Formula: C13H16ClNO •HCl ...............Molecular Weight: 274.19

What are the possible side effects of ketamine (Ketalar)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have any of these serious side effects within 24 hours after you receive ketamine:

  • severe confusion;
  • hallucinations;
  • unusual thoughts; or
  • extreme fear.

Less serious side effects may include:

  • dream-like feeling;
  • double vision;
  • jerky muscle movements;
  • dizziness, drowsiness;
  • nausea, vomiting, loss of...

Read All Potential Side Effects and See Pictures of Ketamine Hydrochloride »

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Ketamine hydrochloride (ketamine hcl) injection is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketamine hydrochloride (ketamine hcl) injection is best suited for short procedures but it can be used, with additional doses, for longer procedures.

Ketamine hydrochloride (ketamine hcl) injection is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents.

Ketamine hydrochloride (ketamine hcl) injection is indicated to supplement low-potency agents, such as nitrous oxide.

Specific areas of application are described in the CLINICAL PHARMACOLOGY section.

DOSAGE AND ADMINISTRATION

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

Note: Barbiturates and ketamine, being chemically incompatible because of precipitate formation, should notbe injected from the same syringe.

If the ketamine dose is augmented with diazepam, the two drugs must be given separately. Do not mix ketamine hydrochloride (ketamine hcl) 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 administration, some airway protection may be afforded because of active laryngeal-pharyngeal reflexes. However, since aspiration may occur with ketamine and since protective reflexes may also be diminished by supplementary anesthetics and muscle relaxants, the possibility of aspiration must be considered. Ketamine is recommended for use in the patient whose stomach is not empty when, in the judgement 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 is rapid; an intravenous dose of 2 mg/kg (1 mg/lb) 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, from experience primarily in children, in a range of 9 to 13 mg/kg (4 to 6 mg/lb) usually produce surgical anesthesia within 3 to 4 minutes following injection, with the anesthetic effect usually last- ing 12 to 25 minutes.

Dosage

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

Induction

Intravenous Route: The initial dose of ketamine administered intravenously may range from 1 mg/kg to 4.5 mg/kg (0.5 to 2 mg/lb). The average amount required to produce five to ten minutes of surgical anesthesia has been 2 mg/kg (1 mg/lb).

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 lesswill 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 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 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 administered intramuscularly may range from 6.5 to 13 mg/kg (3 to 6 mg/lb). A dose of 10  mg/kg (5 mg/lb) 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 administered, the longer will be the time to complete recovery.

Adult patients induced with ketamine augmented with intravenous diazepam may be maintained on ketamine given by slow microdrip infusion technique at a dose of 0.1 to 0.5 mg/minute, augmented with diazepam 2 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 mainte- nance dosage program.

Dilution: To prepare a dilute solution containing 1 mg of ketamine per mL, aseptically transfer 10 mL (50 mg per mL vial) to 500 mL of Dextrose Injection, 5% or Sodium Chloride Injection, 0.9% 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 (ketamine hcl) injection. If fluid restriction is required, ketamine hydrochloride (ketamine hcl) injection can be added to a 250 mL infusion as described above to provide a ketamine concentration of 2 mg/mL.

Supplementary Agents

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

HOW SUPPLIED

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

NDC # 55390-475-10 Each 10 mL vial contains 50 mg/mL - supplied in a carton of 10.

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 a precipitate appears. Protect from light.

Store at controlled room temperature, 15° to 30°C (59° to 86°F).

Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146. Manufactured for: Bedford Laboratories™ Bedford, OH 44146. June 2005. FDA Rev date: 4/3/2001

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Cardiovascular

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

Eye

Diplopia and nystagmus have been noted following ketamine administration. It also may cause a slight elevation in intraocular pressure meas- urement.

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).

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).

General

Anaphylaxis. Local pain and exanthema at the injection site have infrequently been reported. Transient erythema and/or morbilliform rash have also been reported.

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, flashbacks, hallucinations, dysphoria, anxiety, insomnia, or disorientaion. Ketamine dependence and tolerance may develop in individuals with a history of drug abuse or dependence. Therefore, ketamine should be prescribed and administered with caution.

Read the Ketamine Hydrochloride (ketamine hcl) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Prolonged recovery time may occur if barbiturates and/or narcotics are used concurrently with ketamine.

Ketamine is clinically compatible with the commonly used general and local anesthetic agents when an adequate respiratory exchange is maintained.

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Cardiac function should be continually monitored during the procedure in patients found to have hypertension or cardiac decompensation.

Postoperative confusional states may occur during the recovery period. (See Special Note)

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

PRECAUTIONS

General

Ketamine should be used by or under the direction of physicians experienced in administering general anesthetics and in maintenance of an airway and in the control of respiration.

Because pharyngeal and laryngeal reflexes are usually active, ketamine should not be used alone in surgery or diagnostic procedures of the pharynx, larynx, or bronchial tree. Mechanical stimulation of the pharynx should be avoided, whenever possible, if ketamine is used alone. Muscle relaxants, with proper attention to respiration, may be required in both of these instances.

Resuscitative equipment should be ready for use.

The incidence of emergence reactions may be reduced if verbal and tactile stimulation of the patient is minimized during the recovery period.This does not preclude the monitoring of vital signs (see Special Note).

The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in respiratory depression or apnea and enhanced pressor response.

In surgical procedures involving visceral pain pathways, ketamine should be supplemented with an agent which obtunds visceral pain.

Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient.

An increase in cerebrospinal fluid pressure has been reported following administration of ketamine hydrochloride (ketamine hcl) . Use with extreme caution in patients with preanesthetic elevated cerebrospinal fluid pressure.

Usage in Pregnancy

Since the safe use in pregnancy, including obstetrics (either vaginal or abdominal delivery), has not been established, such use is not recom- mended (see Animal Pharmacology AND Toxicology, Reproduction).

Pediatric Use

See DOSAGE AND ADMINISTRATION.

Geriatric Use

Clinical studies of ketamine 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.

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

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

CONTRAINDICATIONS

Ketamine is contraindicated in those in whom a significant elevation of blood pressure would constitute a serious hazard and in those who have shown hypersensitivity to the drug.

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Ketamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression.

A patent airway is maintained partly by virtue of unimpaired pharyngeal and laryngeal reflexes. (See WARNINGS and PRECAUTIONS.)

The biotransformation of ketamine includes N-dealkylation (metabolite I), hydroxylation of the cyclohexone ring (metabolites III and IV), conjugation with glucuronic acid and dehydration of the hydroxylated metabolites to form the cyclohexene derivative (metabolite II).

Following intravenous administration, the ketamine concentration has an initial slope (alpha phase) lasting about 45 minutes with a half-life of 10 to 15 minutes. This first phase corresponds clinically to the anesthetic effect of the drug. The anesthetic action is terminated by a combination of redistribution from the CNS to slower equilibrating peripheral tissues and by hepatic biotransformation to metabolite I. This metabolite is about 1/3 as active as ketamine in reducing halothane requirements (MAC) of the rat. The later half-life of ketamine (beta phase) is 2.5 hours.

The anesthetic state produced by ketamine has been termed "dissociative anesthesia" in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centers and pathways (reticular-activating and limbic systems).

Elevation of blood pressure begins shortly after injection, reaches a maximum within a few minutes and usually returns to preanesthetic values within 15 minutes after injection. In the majority of cases, the systolic and diastolic blood pressure peaks from 10% to 50% above preanesthetic levels shortly after induction of anesthesia, but the elevation can be higher or longer in individual cases (see CONTRAINDICATIONS).

Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of ketamine (up to ten times that usually required) have been followed by prolonged but complete recovery.

Ketamine has been studied in over 12,000 operative and diagnostic procedures, involving over 10,000 patients from 105 separate studies. During the course of these studies ketamine hydrochloride (ketamine hcl) was administered as the sole agent, as induction for other general agents, or to supplement low-potency agents.

Specific areas of application have included the following:

  1. debridement, painful dressings, and skin grafting in burn patients, as well as other superficial surgical procedures.
  2. neurodiagnostic procedures such as pneumonencephalograms, ventriculograms, myelograms, and lumbar punctures. See also PRECAUTIONS concerning increased intracranial pressure.
  3. diagnostic and operative procedures of the eye, ear, nose and mouth, including dental extractions.
  4. diagnostic and operative procedures of the pharynx, larynx, or bronchial tree. NOTE: Muscle relaxants, with proper attention to respiration, may be required (see PRECAUTIONS).
  5. sigmoidoscopy and minor surgery of the anus and rectum, and circumcision.
  6. extraperitoneal procedures used in gynecology such as dilatation and curettage.
  7. orthopedic procedures such as closed reductions, manipulations, femoral pinning, amputations, and biopsies.
  8. as an anesthetic in poor-risk patients with depression of vital functions.
  9. in procedures where the intramuscular route of administration is preferred.
  10. in cardiac catheterization procedures.

In these studies, the anesthesia was rated either "excellent" or "good" by the anesthesiologist and the surgeon at 90% and 93%, respectively; rated "fair" at 6% and 4%, respectively; and rated "poor" at 4% and 3%, respectively. In a second method of evaluation, the anesthesia was rated "adequate" in at least 90% and "inadequate" in 10% or less of the procedures.

Animal Pharmacology And Toxicology

Toxicity

The acute toxicity of ketamine has been studied in several species. In mature mice and rats, the intraperitoneal LD50 values are approximately 100 times the average human intravenous dose and approximately 20 times the average human intramuscular dose. A slightly higher acute toxicity observed in neonatal rats was not sufficiently elevated to suggest an increased hazard when used in children. Daily intravenous injections in rats of five times the average human intravenous dose and intramuscular injections in dogs at four times the average human intramuscular dose demonstrated excellent tolerance for as long as 6 weeks. Similarly, twice weekly anesthetic sessions of one, three, or six hours' duration in monkeys over a four- to six-week period were well tolerated.

Interaction with Other Drugs Commonly Used for Preanesthetic Medication

Large doses (three or more times the equivalent effective human dose) of morphine, meperidine, and atropine increased the depth and prolonged the duration of anesthesia produced by a standard anesthetizing dose of ketamine in Rhesus monkeys. The prolonged duration was not of sufficient magnitude to contraindicate the use of these drugs for preanesthetic medication in human clinical trials.

Blood Pressure

Blood pressure responses to ketamine vary with the laboratory species and experimental conditions. Blood pressure is increased in normotensive and renal hypertensive rats with and without adrenalectomy and under pentobarbital anesthesia.

Intravenous ketamine produces a fall in arterial blood pressure in the Rhesus monkey and a rise in arterial blood pressure in the dog. In this respect the dog mimics the cardiovascular effect observed in man. The pressor response to ketamine injected into intact, unanesthetized dogs is accompanied by a tachycardia, rise in cardiac output and a fall in total peripheral resistance. It causes a fall in perfusion pressure following a large dose injected into an artificially perfused vascular bed (dog hindquarters), and it has little or no potentiating effect upon vasoconstriction responses of epinephrine or norepinephrine. The pressor response to ketamine is reduced or blocked by chlorpromazine (central depressant and peripheral α-adrenergic blockade), by β-adrenergic blockade, and by ganglionic blockade. The tachycardia and increase in myocardial contractile force seen in intact animals does not appear in isolated hearts (Langendorff) at a concentration of 0.1 mg of ketamine nor in Starling dog heart-lung preparations at a ketamine concentration of 50 mg/kg of HLP. These observations support the hypothesis that the hypertension produced by ketamine is due to selective activation of central cardiac stimulating mechanisms leading to an increase in cardiac output. The dog myocardium is not sensitized to epinephrine and ketamine appears to have a weak antiarrhythmic activity.

Metabolic Disposition

Ketamine is rapidly absorbed following parenteral administration. Animal experiments indicated that ketamine was rapidly distributed into body tissues, with relatively high concentrations appearing in body fat, liver, lung, and brain; lower concentrations were found in the heart, skeletal muscle, and blood plasma. Placental transfer of the drug was found to occur in pregnant dogs and monkeys. No significant degree of binding to serum albumin was found with ketamine.

Balance studies in rats, dogs, and monkeys resulted in recovery of 85% to 95% of the dose in the urine, mainly in the form of degradation products. Small amounts of drug were also excreted in the bile and feces. Balance studies with tritium-labeled ketamine in human subjects (1 mg/lb given intravenously) resulted in the mean recovery of 91% of the dose in the urine and 3% in the feces. Peak plasma levels averaged about 0.75 mcg/mL, and CSF levels were about 0.2 mcg/mL, 1 hour after dosing.

Ketamine undergoes N-demethylation and hydroxylation of the cyclohexanone ring, with the formation of water-soluble conjugates which are excreted in the urine. Further oxidation also occurs with the formation of cyclohexanone derivative. The unconjugated N-demethylated metabolite was found to be less than one-sixth as potent as ketamine. The unconjugated demethyl cyclohexanone derivative was found to be less than one-tenth as potent as ketamine. Repeated doses of ketamine administered to animals did not produce any detectable increase in microsomal enzyme activity.

Reproduction

Male and female rats, when given five times the average human intravenous dose of ketamine for three consecutive days about one week before mating, had a reproductive performance equivalent to that of salineinjected controls. When given to pregnant rats and rabbits intramuscularly at twice the average human intramuscular dose during the respective periods of organogenesis, the litter characteristics were equivalent to those of salineinjected controls. A small group of rabbits was given a single large dose (six times the average human dose) of ketamine on Day 6 of pregnancy to simulate the effect of an excessive clinical dose around the period of nidation. The outcome of pregnancy was equivalent in control and treated groups.

To determine the effect of ketamine on the perinatal and postnatal period, pregnant rats were given twice the average human intramuscular dose during Days 18 to 21 of pregnancy. Litter characteristics at birth and through the weaning period were equivalent to those of the control animals. There was a slight increase in incidence of delayed parturition by one day in treated dams of this group. Three groups each of mated beagle bitches were given 2.5 times the average human intramuscular dose twice weekly for the three weeks of the first, second, and third trimesters of pregnancy, respectively, without the development of adverse effects in the pups.

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

As appropriate, especially in cases where early discharge is possible, the duration of ketamine and other drugs employed during the conduct of anesthesia should be considered. The patients should be cautioned that driving an automobile, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of ketamine and consideration of other drugs employed) after anesthesia.

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

As appropriate, especially in cases where early discharge is possible, the duration of ketamine and other drugs employed during the conduct of anesthesia should be considered. The patients should be cautioned that driving an automobile, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of ketamine and consideration of other drugs employed) after anesthesia.

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

Ketamine Hydrochloride (ketamine hcl)
Injection, USP

SPECIAL NOTE

EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS.

THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT DREAM-LIKE STATES, VIVID IMAGINARY, HALLUCINATIONS, AND EMERGENCE DELIRIUM. IN SOME CASES THESE STATES HAVE BEEN ACCOMPANIED BY CONFUSION, EXCITEMENT, AND IRRATIONAL BEHAVIOR WHICH A FEW PATIENTS RECALL AS AN UNPLEASANT EXPERIENCE.THE DURATION ORDINARILY IS NO MORE THAN A FEW HOURS; IN A FEW CASES, HOWEVER, RECURRENCES HAVE TAKEN PLACE UP TO 24 HOURS POSTOPERATIVELY. NO RESIDUAL PSYCHOLOGICAL EFFECTS ARE KNOWN TO HAVE RESULTED FROM USE OF KETAMINE.

THE INCIDENCE OF THESE EMERGENCE PHENOMENA IS LEAST IN THE YOUNG (15 YEARS OF AGE OR LESS) AND ELDERLY (OVER 65 YEARS OF AGE) PATIENT. ALSO, THEY ARE LESS FREQUENT WHEN THE DRUG IS GIVEN INTRAMUSCULARLY AND THE INCIDENCE IS REDUCED AS EXPERIENCE WITH THE DRUG IS GAINED.

THE INCIDENCE OF PSYCHOLOGICAL MANIFESTATIONS DURING EMERGENCE, PARTICULARLY DREAM-LIKE OBSERVATIONS AND EMERGENCE DELIRIUM, MAY BE REDUCED BY USING LOWER RECOMMENDED DOSAGES OF KETAMINE IN CONJUNCTION WITH INTRAVENOUS DIAZEPAM DURING INDUCTION AND MAINTENANCE OF ANESTHESIA. (See DOSAGE AND ADMINISTRATION.) 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.

IN ORDER TO TERMINATE A SEVERE EMERGENCE REACTION, THE USE OF A SMALL HYPNOTIC DOSE OF A SHORT-ACTING OR ULTRA SHORT-ACTING BARBITURATE MAY BE REQUIRED.

WHEN KETAMINE IS USED ON AN OUTPATIENT BASIS, THE PATIENT SHOULD NOT BE RELEASED UNTIL RECOVERY FROM ANESTHESIA IS COMPLETE AND THEN SHOULD BE ACCOMPANIED BY A RESPONSIBLE ADULT.

DRUG DESCRIPTION

Ketamine hydrochloride (ketamine hcl) is a nonbarbiturate anesthetic chemically designated (±)-2-(o-Chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride. It is formulated as a slightly acid (pH 3.5 to 5.5) sterile solution for intravenous or intramuscular injection in concentrations containing the equivalent of 50 mg ketamine base per milliliter and contains not more than 0.1 mg/mL benzethonium chloride added as a preservative. Ketamine hydrochloride (ketamine hcl) has the following structural formula:

Ketamine hydrochloride structural formula illustration

Molecular Formula: C13H16ClNO •HCl ...............Molecular Weight: 274.19

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

Ketamine Hydrochloride (ketamine hcl)
Injection, USP

SPECIAL NOTE

EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS.

THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT DREAM-LIKE STATES, VIVID IMAGINARY, HALLUCINATIONS, AND EMERGENCE DELIRIUM. IN SOME CASES THESE STATES HAVE BEEN ACCOMPANIED BY CONFUSION, EXCITEMENT, AND IRRATIONAL BEHAVIOR WHICH A FEW PATIENTS RECALL AS AN UNPLEASANT EXPERIENCE.THE DURATION ORDINARILY IS NO MORE THAN A FEW HOURS; IN A FEW CASES, HOWEVER, RECURRENCES HAVE TAKEN PLACE UP TO 24 HOURS POSTOPERATIVELY. NO RESIDUAL PSYCHOLOGICAL EFFECTS ARE KNOWN TO HAVE RESULTED FROM USE OF KETAMINE.

THE INCIDENCE OF THESE EMERGENCE PHENOMENA IS LEAST IN THE YOUNG (15 YEARS OF AGE OR LESS) AND ELDERLY (OVER 65 YEARS OF AGE) PATIENT. ALSO, THEY ARE LESS FREQUENT WHEN THE DRUG IS GIVEN INTRAMUSCULARLY AND THE INCIDENCE IS REDUCED AS EXPERIENCE WITH THE DRUG IS GAINED.

THE INCIDENCE OF PSYCHOLOGICAL MANIFESTATIONS DURING EMERGENCE, PARTICULARLY DREAM-LIKE OBSERVATIONS AND EMERGENCE DELIRIUM, MAY BE REDUCED BY USING LOWER RECOMMENDED DOSAGES OF KETAMINE IN CONJUNCTION WITH INTRAVENOUS DIAZEPAM DURING INDUCTION AND MAINTENANCE OF ANESTHESIA. (See DOSAGE AND ADMINISTRATION.) 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.

IN ORDER TO TERMINATE A SEVERE EMERGENCE REACTION, THE USE OF A SMALL HYPNOTIC DOSE OF A SHORT-ACTING OR ULTRA SHORT-ACTING BARBITURATE MAY BE REQUIRED.

WHEN KETAMINE IS USED ON AN OUTPATIENT BASIS, THE PATIENT SHOULD NOT BE RELEASED UNTIL RECOVERY FROM ANESTHESIA IS COMPLETE AND THEN SHOULD BE ACCOMPANIED BY A RESPONSIBLE ADULT.

DRUG DESCRIPTION

Ketamine hydrochloride (ketamine hcl) is a nonbarbiturate anesthetic chemically designated (±)-2-(o-Chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride. It is formulated as a slightly acid (pH 3.5 to 5.5) sterile solution for intravenous or intramuscular injection in concentrations containing the equivalent of 50 mg ketamine base per milliliter and contains not more than 0.1 mg/mL benzethonium chloride added as a preservative. Ketamine hydrochloride (ketamine hcl) has the following structural formula:

Ketamine hydrochloride structural formula illustration

Molecular Formula: C13H16ClNO •HCl ...............Molecular Weight: 274.19

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

Ketamine Hydrochloride (ketamine hcl)
Injection, USP

SPECIAL NOTE

EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS.

THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT DREAM-LIKE STATES, VIVID IMAGINARY, HALLUCINATIONS, AND EMERGENCE DELIRIUM. IN SOME CASES THESE STATES HAVE BEEN ACCOMPANIED BY CONFUSION, EXCITEMENT, AND IRRATIONAL BEHAVIOR WHICH A FEW PATIENTS RECALL AS AN UNPLEASANT EXPERIENCE.THE DURATION ORDINARILY IS NO MORE THAN A FEW HOURS; IN A FEW CASES, HOWEVER, RECURRENCES HAVE TAKEN PLACE UP TO 24 HOURS POSTOPERATIVELY. NO RESIDUAL PSYCHOLOGICAL EFFECTS ARE KNOWN TO HAVE RESULTED FROM USE OF KETAMINE.

THE INCIDENCE OF THESE EMERGENCE PHENOMENA IS LEAST IN THE YOUNG (15 YEARS OF AGE OR LESS) AND ELDERLY (OVER 65 YEARS OF AGE) PATIENT. ALSO, THEY ARE LESS FREQUENT WHEN THE DRUG IS GIVEN INTRAMUSCULARLY AND THE INCIDENCE IS REDUCED AS EXPERIENCE WITH THE DRUG IS GAINED.

THE INCIDENCE OF PSYCHOLOGICAL MANIFESTATIONS DURING EMERGENCE, PARTICULARLY DREAM-LIKE OBSERVATIONS AND EMERGENCE DELIRIUM, MAY BE REDUCED BY USING LOWER RECOMMENDED DOSAGES OF KETAMINE IN CONJUNCTION WITH INTRAVENOUS DIAZEPAM DURING INDUCTION AND MAINTENANCE OF ANESTHESIA. (See DOSAGE AND ADMINISTRATION.) 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.

IN ORDER TO TERMINATE A SEVERE EMERGENCE REACTION, THE USE OF A SMALL HYPNOTIC DOSE OF A SHORT-ACTING OR ULTRA SHORT-ACTING BARBITURATE MAY BE REQUIRED.

WHEN KETAMINE IS USED ON AN OUTPATIENT BASIS, THE PATIENT SHOULD NOT BE RELEASED UNTIL RECOVERY FROM ANESTHESIA IS COMPLETE AND THEN SHOULD BE ACCOMPANIED BY A RESPONSIBLE ADULT.

DRUG DESCRIPTION

Ketamine hydrochloride (ketamine hcl) is a nonbarbiturate anesthetic chemically designated (±)-2-(o-Chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride. It is formulated as a slightly acid (pH 3.5 to 5.5) sterile solution for intravenous or intramuscular injection in concentrations containing the equivalent of 50 mg ketamine base per milliliter and contains not more than 0.1 mg/mL benzethonium chloride added as a preservative. Ketamine hydrochloride (ketamine hcl) has the following structural formula:

Ketamine hydrochloride structural formula illustration

Molecular Formula: C13H16ClNO •HCl ...............Molecular Weight: 274.19

Last reviewed on RxList: 5/23/2008
This monograph has been modified to include the generic and brand name in many instances.

Ketamine Hydrochloride Patient Information Including Side Effects

Brand Names: Ketalar

Generic Name: ketamine (Pronunciation: KET a meen)

What is ketamine (Ketamine Hydrochloride)?

Ketamine is an anesthetic medication.

Ketamine is used as a general anesthetic to prevent pain and discomfort during certain medical tests or procedures, or minor surgery.

Ketamine may also be used for purposes other than those listed in this medication guide.

What are the possible side effects of ketamine (Ketamine Hydrochloride)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have any of these serious side effects within 24 hours after you receive ketamine:

  • severe confusion;
  • hallucinations;
  • unusual thoughts; or
  • extreme fear.

Less serious side effects may include:

  • dream-like feeling;
  • double vision;
  • jerky muscle movements;
  • dizziness, drowsiness;
  • nausea, vomiting, loss of appetite; or
  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Ketamine Hydrochloride (ketamine hcl) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about ketamine (Ketamine Hydrochloride)?

Before you receive ketamine, tell your doctor if you are allergic to any drugs, or if you have a history of alcoholism.

It may take you longer to recover from anesthesia with ketamine if you have recently used a barbiturate such as phenobarbital (Luminal) or secobarbital (Seconal), or a narcotic medication such as fentanyl (Actiq, Duragesic), hydrocodone (Lortab, Vicodin), oxycodone (OxyContin), propoxyphene (Darvocet, Darvon), and others.

Ketamine may be harmful to an unborn baby. Before you receive ketamine, tell your doctor if you are pregnant.

You may feel strange or slightly confused when you first come out of anesthesia. Tell your caregivers if these feelings are severe or unpleasant.

Ketamine can cause side effects that may impair your thinking or reactions for 24 hours or longer. Be careful if you drive or do anything that requires you to be awake and alert. You will probably not be allowed to drive yourself home after your surgery or medical procedure.

Follow your doctor's instructions about any restrictions on food, beverages, or activity after you recover from anesthesia.

Side Effects Centers

Ketamine Hydrochloride Patient Information including How Should I Take

What should I discuss with my health care provider before receiving ketamine (Ketamine Hydrochloride)?

Before you receive ketamine, tell your doctor if you are allergic to any drugs, or if you have a history of alcoholism.

Ketamine may be harmful to an unborn baby. Before you receive ketamine, tell your doctor if you are pregnant.

How is ketamine given (Ketamine Hydrochloride)?

Ketamine is given as an injection through a needle placed into a vein or muscle. You will receive this injection in a clinic or hospital setting.

Your caregivers will monitor your heart function, blood pressure, and breathing while you are under the effects of ketamine.

You may feel strange or slightly confused when you first come out of anesthesia. Tell your caregivers if these feelings are severe or unpleasant.

Side Effects Centers

Ketamine Hydrochloride Patient Information including If I Miss a Dose

What happens if I miss a dose (Ketamine Hydrochloride)?

Since ketamine is usually given for anesthesia, you are not likely to be on a dosing schedule.

What happens if I overdose (Ketamine Hydrochloride)?

An overdose of ketamine is unlikely to occur since the medication is given by a doctor. Your vital signs will be closely watched while you are under anesthesia to make sure the medication is not causing any harmful effects.

What should I avoid after receiving ketamine (Ketamine Hydrochloride)?

Ketamine can cause side effects that may impair your thinking or reactions for 24 hours or longer. Be careful if you drive or do anything that requires you to be awake and alert. You will probably not be allowed to drive yourself home after your surgery or medical procedure.

Follow your doctor's instructions about any restrictions on food, beverages, or activity after you recover from anesthesia.

What other drugs will affect ketamine (Ketamine Hydrochloride)?

Before you receive ketamine, tell your doctor if you have recently used any of the following:

  • a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Luminal, Solfoton); or
  • narcotic medication such as fentanyl (Actiq, Duragesic, Ionsys), hydrocodone (Lortab, Vicodin), hydromorphone (Dilaudid, Palladone), methadone (Dolophine, Methadose), morphine (Kadian, MS Contin, Oramorph), oxycodone (OxyContin, Percocet, Roxicodone), propoxyphene (Darvocet, Darvon), and others.

If you are using any of these drugs, it may take you longer to recover from anesthesia with ketamine.

There may be other drugs that can affect ketamine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about ketamine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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