DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Diprivan (Propofol) - Indications and Dosage

 
 



INDICATIONS AND USAGE

DIPRIVAN Injectable Emulsion is an IV sedative-hypnotic agent that can be used for both induction and/or maintenance of anesthesia as part of a balanced anesthetic technique for inpatient and outpatient surgery in adult patients and pediatric patients greater than 3 years of age. DIPRIVAN Injectable Emulsion can also be used for maintenance of anesthesia as part of a balanced anesthetic technique for inpatient and outpatient surgery in adult patients and in pediatric patients greater than 2 months of age. DIPRIVAN Injectable Emulsion is not recommended for induction of anesthesia below the age of 3 years or for maintenance of anesthesia below the age of 2 months because its safety and effectiveness have not been established in those populations.

In adult patients, DIPRIVAN Injectable Emulsion, when administered intravenously as directed, can be used to initiate and maintain monitored anesthesia care (MAC) sedation during diagnostic procedures. DIPRIVAN Injectable Emulsion may also be used for MAC sedation in conjunction with local/regional anesthesia in patients undergoing surgical procedures. (See PRECAUTIONS.)

Safety, effectiveness and dosing guidelines for DIPRIVAN Injectable Emulsion have not been established for MAC Sedation/light general anesthesia in the pediatric population undergoing diagnostic or nonsurgical procedures and therefore it is not recommended for this use. (See PRECAUTIONS, Pediatric Use).

DIPRIVAN Injectable Emulsion should only be administered to intubated, mechanically ventilated adult patients in the Intensive Care Unit (ICU) to provide continuous sedation and control of stress responses. In this setting, DIPRIVAN Injectable Emulsion should be administered only by persons skilled in the medical management of critically ill patients and trained in cardiovascular resuscitation and airway management.

DIPRIVAN Injectable Emulsion is not indicated for use in Pediatric ICU sedation since the safety of this regimen has not been established. (See PRECAUTIONS, Pediatric Use).

DIPRIVAN Injectable Emulsion is not recommended for obstetrics, including cesarean section deliveries. DIPRIVAN Injectable Emulsion crosses the placenta, and as with other general anesthetic agents, the administration of DIPRIVAN Injectable Emulsion may be associated with neonatal depression. (See PRECAUTIONS.)

DIPRIVAN Injectable Emulsion is not recommended for use in nursing mothers because DIPRIVAN Injectable Emulsion has been reported to be excreted in human milk and the effects of oral absorption of small amounts of propofol are not known. (See PRECAUTIONS.)

DOSAGE AND ADMINISTRATION

Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors, including preinduction and concomitant medications, age, ASA physical classification, and level of debilitation of the patient.

The following is abbreviated dosage and administration information which is only intended as a general guide in the use of DIPRIVAN Injectable Emulsion. Prior to administering DIPRIVAN Injectable Emulsion, it is imperative that the physician review and be completely familiar with the specific dosage and administration information detailed in the CLINICAL PHARMACOLOGY - Individualization of Dosage section.

In the elderly, debilitated, or ASA III/IV patients, rapid bolus doses should not be the method of administration. (See WARNINGS.)

Intensive Care Unit Sedation:

STRICT ASEPTIC TECHNIQUE MUST ALWAYS BE MAINTAINED DURING HANDLING. DIPRIVAN INJECTABLE EMULSION IS A SINGLE-USE PARENTERAL PRODUCT WHICH CONTAINS 0.005% DISODIUM EDETATE TO RETARD THE RATE OF GROWTH OF MICROORGANISMS IN THE EVENT OF ACCIDENTAL EXTRINSIC CONTAMINATION. HOWEVER, DIPRIVAN INJECTABLE EMULSION CAN STILL SUPPORT THE GROWTH OF MICROORGANISMS AS IT IS NOT AN ANTIMICROBIALLY PRESERVED PRODUCT UNDER USP STANDARDS. ACCORDINGLY, STRICT ASEPTIC TECHNIQUE MUST STILL BE ADHERED TO. DO NOT USE IF CONTAMINATION IS SUSPECTED. (See DOSAGE AND ADMINISTRATION, Handling Procedures.)

DIPRIVAN Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs. (See PRECAUTIONS - ICU Sedation.) For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 µg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 µg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 µg/kg/min (0.3 to 3 mg/kg/h) or higher. Dosages of DIPRIVAN Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the DIPRIVAN Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time. (See dosage guide.) EVALUATION OF LEVEL OF SEDATION AND ASSESSMENT OF CNS FUNCTION SHOULD BE CARRIED OUT DAILY THROUGHOUT MAINTENANCE TO DETERMINE THE MINIMUM DOSE OF DIPRIVAN INJECTABLE EMULSION REQUIRED FOR SEDATION (SEE CLINICAL TRIALS, ICU SEDATION). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension. (See PRECAUTIONS.).

EDTA is a strong chelator of trace metals − including zinc. Although with DIPRIVAN Injectable Emulsion there are no reports of decreased zinc levels or zinc deficiency-related adverse events, DIPRIVAN Injectable Emulsion should not be infused for longer than 5 days without providing a drug holiday to safely replace estimated or measured urine zinc losses.

At high doses (2-3 grams per day), EDTA has been reported, on rare occasions, to be toxic to the renal tubules. Studies to-date, in patients with normal or impaired renal function have not shown any alteration in renal function with DIPRIVAN Injectable Emulsion containing 0.005% disodium edetate. In patients at risk for renal impairment, urinalysis and urine sediment should be checked before initiation of sedation and then be monitored on alternate days during sedation.

SUMMARY OF DOSAGE GUIDELINES

Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.

For complete dosage information, see CLINICAL PHARMACOLOGY - Individualization of Dosage.

INDICATION

DOSAGE AND ADMINISTRATION

Induction of General Anesthesia

Healthy Adults Less Than 55 Years OF Age: 40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).

Elderly, Debilitated, or ASA III/IV Patients: 20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).

Cardiac Anesthesia: 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).

Neurosurgical Patients: 20 mg every 10 seconds until induction onset (1 to 2 mg/kg)

Pediatric Patients - healthy, from 3 years to 16 years of age: 2.5 to 3.5 mg/kg administered over 20-30 seconds.

See PRECAUTIONS − Pediatric Use: and CLINICAL PHARMACOLOGY − Pediatric patients)

Maintenance of General Anesthesia:

Infusion

Healthy Adults Less Than 55 Years of Age: 100 to 200 µg/kg/min (6 to 12 mg/kg/h).

Elderly, Debilitated, ASA III/IV Patients: 50 to 100 μg/kg/min (3 to 6 mg/kg/h).

Cardiac Anesthesia: Most patients require:

Primary DIPRIVAN Injectable Emulsion with Secondary Opioid − 100 − 150 µg/kg/min

Low-Dose DIPRIVAN Injectable Emulsion with Primary Opioid − 50 - 100 µg/kg/min

(See CLINICAL PHARMACOLOGY, Table 5)

Neurosurgical Patients: 100 to 200 µg/kg/min (6 to 12 mg/kg/h).

Pediatric Patients - healthy, from 2 months of age to 16 years of age:

125 to 300 µg/kg/min (7.5 to 18 mg/kg/h)

Following the first half hour of maintenance, if clinical signs of light anesthesia are not present, the infusion rate should be decreased. (See PRECAUTIONS − Pediatric Use: and CLINICAL PHARMACOLOGY − Pediatric patients)

Maintenance of General Anesthesia

Intermittent Bolus

Healthy Adults Less Than 55 Years Of Age: Increments of 20 to 50 mg as needed.

Initiation of MAC Sedation:

Healthy Adults Less Than 55 Years of Age: Slow infusion or slow injection techniques are recommended to avoid apnea or hypotension. Most patients require an infusion of 100 to 150  µg/kg/min (6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3 to 5 minutes followed immediately by a maintenance infusion.

Elderly, Debilitated, Neurosurgical, or ASA III/IV Patients:

Most patients require dosages similar to healthy adults. Rapid boluses are to be avoided. (See WARNINGS.)

Maintenance of MAC Sedation

Healthy Adults Less Than 55 Years of Age: A variable rate infusion technique is preferable over an intermittent bolus technique. Most patients require an infusion of 25 to 75 µg/kg/min (1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.

In Elderly, Debilitated, Neurosurgical, or ASA III/IV Patients:

Most patients require 80% of the usual adult dose. A rapid (single or repeated) bolus dose should not be used. (See WARNINGS.)

Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated

Adult Patients - Because of the residual effects of previous anesthetic or sedative agents, in most patients the initial infusion should be 5 µg/kg/min (0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10 μg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until desired clinical effect is achieved. Maintenance rates of 5 to 50 μg/kg/min (0.3 to 3 mg/kg/h) or higher may be required.

Evaluation of clinical effect and assessment of CNS function should be carried out daily throughout maintenance to determine the minimum dose of DIPRIVAN Injectable Emulsion required for sedation.

The tubing and any unused portions of DIPRIVAN Injectable Emulsion should be discarded after 12 hours because DIPRIVAN Injectable Emulsion contains no preservatives and is capable of supporting growth of microorganisms. (See WARNINGS, and DOSAGE AND ADMINISTRATION.)

Compatibility and Stability: DIPRIVAN Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.

Dilution Prior to Administration: DIPRIVAN Injectable Emulsion is provided as a ready to use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).

Administration with Other Fluids: Compatibility of DIPRIVAN Injectable Emulsion with the coadministration of blood/serum/plasma has not been established. (See WARNINGS.) When administered using a y-type infusion set, DIPRIVAN Injectable Emulsion has been shown to be compatible with the following intravenous fluids.

- 5% Dextrose Injection, USP

- Lactated Ringers Injection, USP

- Lactated Ringers and 5% Dextrose Injection

- 5% Dextrose and 0.45% Sodium Chloride Injection, USP

- 5% Dextrose and 0.2% Sodium Chloride Injection, USP

Handling Procedures

General

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

Clinical experience with the use of in-line filters and DIPRIVAN Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. DIPRIVAN Injectable Emulsion should only be administered through a filter with a pore size of 5 μm or greater unless it has been demonstrated that the filter does not restrict the flow of DIPRIVAN Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.

Do not use if there is evidence of separation of the phases of the emulsion.

Rare cases of self-administration of DIPRIVAN Injectable Emulsion by health care professionals have been reported, including some fatalities (See DRUG ABUSE AND DEPENDENCE).

STRICT ASEPTIC TECHNIQUE MUST ALWAYS BE MAINTAINED DURING HANDLING. DIPRIVAN INJECTABLE EMULSION IS A SINGLE-USE PARENTERAL PRODUCT WHICH CONTAINS 0.005% DISODIUM EDETATE TO RETARD THE RATE OF GROWTH OF MICROORGANISMS IN THE EVENT OF ACCIDENTAL EXTRINSIC CONTAMINATION. HOWEVER, DIPRIVAN INJECTABLE EMULSION CAN STILL SUPPORT THE GROWTH OF MICROORGANISMS AS IT IS NOT AN ANTIMICROBIALLY PRESERVED PRODUCT UNDER USP STANDARDS. ACCORDINGLY, STRICT ASEPTIC TECHNIQUE MUST STILL BE ADHERED TO. DO NOT USE IF CONTAMINATION IS SUSPECTED. DISCARD UNUSED PORTIONS AS DIRECTED WITHIN THE REQUIRED TIME LIMITS (SEE DOSAGE AND ADMINISTRATION, HANDLING PROCEDURES). THERE HAVE BEEN REPORTS IN WHICH FAILURE TO USE ASEPTIC TECHNIQUE WHEN HANDLING DIPRIVAN INJECTABLE EMULSION WAS ASSOCIATED WITH MICROBIAL CONTAMINATION OF THE PRODUCT AND WITH FEVER, INFECTION/SEPSIS, OTHER LIFE-THREATENING ILLNESS, AND/OR DEATH.

Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation

DIPRIVAN Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. DIPRIVAN Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing DIPRIVAN Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 6 hours after the vials have been opened.

DIPRIVAN Injectable Emulsion should be prepared for single-patient use only. Any unused portions of DIPRIVAN Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing DIPRIVAN Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 6 hours, whichever occurs sooner. The IV line should be flushed every 6 hours and at the end of the anesthetic procedure to remove residual DIPRIVAN Injectable Emulsion.

Guidelines for Aseptic Technique for ICU Sedation

DIPRIVAN Injectable Emulsion should be prepared for single-patient use only. When DIPRIVAN Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of DIPRIVAN Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of DIPRIVAN Injectable Emulsion must be discarded after 12 hours.

If DIPRIVAN Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 6 hours.

HOW SUPPLIED

DIPRIVAN Injectable Emulsion is available in ready to use 20 mL infusion vials, 50 mL infusion vials, and 100 mL infusion vials containing 10mg/mL of propofol.

20 mL infusion vials (NDC 0310-0300-22)

50 mL infusion vials (NDC 0310-0300-50)

100 mL infusion vials (NDC 0310-0300-11)

Propofol undergoes oxidative degradation, in the presence of oxygen, and is therefore packaged under nitrogen to eliminate this degradation path.

Store between 4-22°C (40-72°F). Do not freeze. Shake well before use.

All trademarks are the property of the AstraZeneca group of companies

© AstraZeneca 2001, 2004, 2005

Manufactured for:

AstraZeneca Pharmaceuticals, LP

Wilmington, DE 19850

By: AstraZeneca S.p.A.,

Caponago, Italy

Made in Italy

Rev 08/05 SIC 30193-00

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2014