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Ultiva

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Ultiva

Indications
Dosage
How Supplied

INDICATIONS

ULTIVA (remifentanil) is indicated for IV administration:

  1. As an analgesic agent for use during the induction and maintenance of general anesthesia for inpatient and outpatient procedures.
  2. For continuation as an analgesic into the immediate postoperative period in adult patients under the direct supervision of an anesthesia practitioner in a postoperative anesthesia care unit or intensive care setting.
  3. As an analgesic component of monitored anesthesia care in adult patients.

DOSAGE AND ADMINISTRATION

ULTIVA (remifentanil) is for IV use only. Continuous infusions of ULTIVA (remifentanil) should be administered only by an infusion device. The injection site should be close to the venous cannula and all IV tubing should be cleared at the time of discontinuation of infusion.

During General Anesthesia: ULTIVA (remifentanil) is not recommended as the sole agent in general anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia. ULTIVA (remifentanil) is synergistic with other anesthetics; therefore, clinicians may need to reduce doses of thiopental, propofol, isoflurane, and midazolam by up to 75% with the coadministration of ULTIVA (remifentanil) . The administration of ULTIVA (remifentanil) must be individualized based on the patient's response.

Table 10 summarizes the recommended doses in adult patients, predominately ASA physical status I, II, or III.

Table 10: Dosing Guidelines in Adults - General Anesthesia and Continuing as an Analgesic into the Postoperative Care Unit or Intensive Care Setting*

Phase Continuous IV
Infusion of ULTIVA (remifentanil)
(mcg/kg/min)
Infusion Dose
Range of ULTIVA (remifentanil)
(mcg/kg/min)
Supplemental IV
Bolus Dose of
ULTIVA (remifentanil) (mcg/kg)
Induction of Anesthesia (through intubation) 0.5 - 1*    
Maintenance of anesthesia with:
  Nitrous oxide (66%) 0.4 0.1 - 2 1
  Isoflurane (0.4 to 1.5 MAC) 0.25 0.05 - 2 1
  Propofol (100 to 200 mcg/kg/min) 0.25 0.05 - 2 1
Continuation as an analgesic into the immediate postoperativeperiod 0.1 0.025 - 0.2 not recommended
*An initial dose of 1 mcg/kg may be administered over 30 to 60 seconds.

Table 11 summarizes the recommended doses in pediatric patients, predominantly ASA physical status I, II, or III. In pediatric patients, remifentanil was administered with nitrous oxide or nitrous oxide in combination with halothane, sevoflurane, or isoflurane.

Table 11: Dosing Guidelines in Pediatric Patients - Maintenance of Anesthesia

Phase Continuous IV
Infusion of ULTIVA (remifentanil)
(mcg/kg/min)
Infusion Dose
Range of ULTIVA (remifentanil)
(mcg/kg/min)
Supplemental IV
Bolus Dose of
ULTIVA (remifentanil) (mcg/kg)
*Maintenance of anesthesia in patients aged 1 to 12 years old with:
  Halothane (0.3 to 1.5 MAC) 0.25 0.05 - 1.3 1
  Sevoflurane (0.3 to 1.5 MAC) 0.25 0.05 - 1.3 1
  Isoflurane (0.4 to 1.5 MAC) 0.25 0.05 - 1.3 1
Maintenance of anesthesia for patients from birth to 2 months of age with:
  Nitrous oxide (70%)** 0.4 0.4 - 1.0 1***
*An initial dose of 1 mcg/kg may be administered over 30 to 60 seconds.
**The initial maintenance infusion regimen of Ultiva (remifentanil) evaluated in full term pediatric patients from birth to 2 months of age undergoing pyloromyotomy was 0.4 mcg/kg/min, the approved adult regimen for use with N2O. The clearance rate observed in neonates was highly variable and on average was two times higher than in the young healthy adult population. Therefore, while a starting infusion of 0.4 mcg/kg/min may be appropriate for some neonates, an increased infusion rate may be necessary to maintain adequate surgical anesthesia, and additional bolus doses may be required. The individual dose for each patient should be carefully titrated. The use of atropine may blunt the potential for bradycardia that can occur upon administration of Ultiva. (see CLINICAL PHARMACOLOGY: Special Populations: Pediatric Patients, and DOSAGE AND ADMINISTRATION, During Maintenance of Anesthesia).
*** Boluses of 1 mcg/kg were studied in ASA 1 and 2, full-term patients weighing at least 2500 gm, undergoing pyloromyotomy who received pretreatment with atropine. Some neonates, particularly those receiving supplementation with potent inhalation agents or neuraxial anesthesia, those with significant co-morbidities or undergoing significant fluid shifts, or those who have not been pretreated with atropine, may require smaller bolus doses to avoid hypotension and/or bradycardia.

During Induction of Anesthesia: ULTIVA (remifentanil) should be administered at an infusion rate of 0.5 to 1 mcg/kg/min with a hypnotic or volatile agent for the induction of anesthesia. If endotracheal intubation is to occur less than 8 minutes after the start of the infusion of ULTIVA (remifentanil) , then an initial dose of 1 mcg/kg may be administered over 30 to 60 seconds.

During Maintenance of Anesthesia: After endotracheal intubation, the infusion rate of ULTIVA (remifentanil) should be decreased in accordance with the dosing guidelines in Tables 10 (adults) and 11 (pediatric patients). Due to the fast onset and short duration of action of ULTIVA (remifentanil) , the rate of administration during anesthesia can be titrated upward in 25% to 100% increments in adult patients or up to 50% increments in pediatric patients, or downward in 25% to 50% decrements every 2 to 5 minutes to attain the desired level of μ-opioid effect. In response to light anesthesia or transient episodes of intense surgical stress, supplem ental bolus doses of 1 mcg/kg may be administered every 2 to 5 minutes. At infusion rates > 1 mcg/kg/min, increases in the concomitant anesthetic agents should be considered to increase the depth of anesthesia. See CLINICAL PHARMACOLOGY: Special Populations: Pediatric Patients, and DOSAGE AND ADMINISTRATION, Table 11 for additional information.

Continuation as an Analgesic into the Immediate Postoperative Period Under the Direct Supervision of an Anesthesia Practitioner: Infusions of ULTIVA (remifentanil) may be continued into the immediate postoperative period for select patients for whom later transition to longer acting analgesics may be desired. The use of bolus injections of ULTIVA (remifentanil) to treat pain during the postoperative period is not recommended. When used as an IV analgesic in the immediate postoperative period, ULTIVA (remifentanil) should be initially administered by continuous infusion at a rate of 0.1 mcg/kg/min. The infusion rate may be adjusted every 5 minutes in 0.025-mcg/kg/min increments to balance the patient's Infusion rates greater than 0.2 mcg/kg/min are associated with respiratory depression (respiratory rate less than 8 breaths/min).

Guidelines for Discontinuation: Upon discontinuation of ULTIVA (remifentanil) , the IV tubing should be cleared to prevent the inadvertent administration of ULTIVA (remifentanil) at a later time.

Due to the rapid offset of action of ULTIVA (remifentanil) , no residual analgesic activity will be present within 5 to 10 minutes after discontinuation. For patients undergoing surgical procedures where postoperative pain is generally anticipated, alternative analgesics should be administered prior to discontinuation of ULTIVA (remifentanil) . The choice of analgesic should be appropriate for the patient's surgical procedure and the level of follow-up care (see Clinical Studies)

Analgesic Component of Monitored Anesthesia Care: It is strongly recommended that supplemental oxygen be supplied to the patient whenever ULTIVA (remifentanil) is administered.

Table 12 summarizes the recommended doses for monitored anesthesia care in adult patients, predominately ASA physical status I, II, or III. ULTIVA (remifentanil) has not been studied for use in children in monitored anesthesia care.

Table 12: Dosing Guidelines in Adults - Monitored Anesthesia Care

Method Timing ULTIVA Alone ULTIVA + 2 mg Midazolam
Single IV Dose Given 90 seconds before local anesthetic 1 mcg/kg over 30 to 60 seconds 0.5 mcg/kg over 30 to 60 seconds
Continuous IV Infusion Beginning 5 minutes before local anesthetic 0.1 mcg/kg/min 0.05 mcg/kg/min
After local anesthetic 0.05 mcg/kg/min (Range: 0.025 -0.2 mcg/kg/min) 0.025 mcg/kg/min (Range: 0.025 -0.2 mcg/kg/min)

Single Dose: A single IV dose of 0.5 to 1 mcg/kg over 30 to 60 seconds of ULTIVA (remifentanil) may be given 90 seconds before the placement of the local or regional anesthetic block (see PRECAUTIONS).

Continuous Infusion: When used alone as an IV analgesic component of monitored anesthesia care, ULTIVA (remifentanil) should be initially administered by continuous infusion at a rate of 0.1 mcg/kg/min beginning 5 minutes before placement of the local or regional anesthetic block. Because of the risk for hypoventilation, the infusion rate of ULTIVA (remifentanil) should be decreased to 0.05 mcg/kg/min following placement of the block. Thereafter, rate adjustments of 0.025 mcg/kg/min at 5-minute intervals may be used to balance the patient's level of analgesia and respiratory rate. Rates greater than 0.2 mcg/kg/min are generally associated with respiratory depression (respiratory rates less than 8 breaths/min). Bolus doses of ULTIVA (remifentanil) administered simultaneously with a continuous infusion of ULTIVA (remifentanil) to spontaneously breathing patients are not recommended.

Individualization of Dosage

Use in Geriatric Patients: The starting doses of ULTIVA (remifentanil) should be decreased by 50% in elderly patients ( > 65 years). ULTIVA (remifentanil) should then be cautiously titrated to effect.

Use in Pediatric Patients: See Table 11 for dosing recommendations for use of ULTIVA (remifentanil) in pediatric patients from birth to 12 years of age for maintenance of anesthesia. See CLINICAL PHARMACOLOGY: Special Populations: Pediatric Patients, and DOSAGE AND ADMINISTRATION, Table 11 and During Maintenance of Anesthesia for additional information.

ULTIVA (remifentanil) has not been studied in pediatric patients for use in the immediate postoperative period or for use as a component of monitored anesthesia care.

Use in Coronary Artery Bypass Surgery: Table 13 summarizes the recommended doses for induction, maintenance, and continuation as an analgesic into the ICU in adult patients, predominantly ASA physical status III or IV. To avoid hypotension during the induction phase, it is important to consider the concomitant medication regimens described in the Clinical Trials: Coronary Artery Bypass Surgery subsection.

Table 13: Dosing Recommendations* - Coronary Artery Bypass Surgery

Phase Continuous IV
Infusion of ULTIVA (remifentanil)
(mcg/kg/min)
Infusion Dose
Range of ULTIVA (remifentanil)
(mcg/kg/min)
Supplemental
IV Bolus Dose of
ULTIVA (remifentanil) (mcg/kg)
Induction of Anesthesia (through intubation) 1    
Maintenance of Anesthesia 1 0.125 - 4 0.5 - 1
  Continuation as an analgesic into ICU 1 0.05 - 1  
* See Clinical Trials: Coronary Artery Bypass Surgery subsection for concomitant medication regimens.

Use in Obese Patients: The starting doses of ULTIVA (remifentanil) should be based on ideal body weight (IBW) in obese patients (greater than 30% over their IBW).

Preanesthetic Medication: The need for premedication and the choice of anesthetic agents must be individualized. In clinical studies, patients who received ULTIVA (remifentanil) frequently received a benzodiazepine premedication.

Preparation for Administration: To reconstitute solution, add 1 mL of diluent per mg of remifentanil. Shake well to dissolve. When reconstituted as directed, the solution contains approximately 1 mg of remifentanil activity per 1 mL. ULTIVA (remifentanil) should be diluted to a recommended final concentration of 20, 25, 50, or 250 mcg/mL prior to administration (see Table 14). ULTIVA (remifentanil) should not be administered without dilution.

Table 14: Reconstitution and Dilution of ULTIVA (remifentanil) analgesic into ICU

Final Concentration Amount of ULTIVA in Each Vial Final Volume After Reconstitution and Dilution
20 mcg/mL 1 mg 50 mL
2 mg 100 mL
5 mg 250 mL
25 mcg/mL 1 mg 40 mL
2 mg 80 mL
5 mg 200 mL
50 mcg/mL 1 mg 20 mL
2 mg 40 mL
5 mg 100 mL
250 mcg/mL 5 mg 20 mL

Continuous IV infusions of ULTIVA (remifentanil) should be administered only by an infusion device. Infusion rates of ULTIVA (remifentanil) can be individualized for each patient using Table 15:

Table 15: IV Infusion Rates of ULTIVA (remifentanil) (mL/kg/h)

Drug Delivery Rate (mcg/kg/min) Infusion Delivery Rate (mL/kg/h)
20 mcg/mL 25 mcg/mL 50 mcg/mL 250 mcg/mL
0.0125 0.038 0.03 0.015 not recommended
0.025 0.075 0.06 0.03 not recommended
0.05 0.15 0.12 0.06 0.012
0.075 0.23 0.18 0.09 0.018
0.1 0.3 0.24 0.12 0.024
0.15 0.45 0.36 0.18 0.036
0.2 0.6 0.48 0.24 0.048
0.25 0.75 0.6 0.3 0.06
0.5 1.5 1.2 0.6 0.12
0.75 2.25 1.8 0.9 0.18
1.0 3.0 2.4 1.2 0.24
1.25 3.75 3.0 1.5 0.3
1.5 4.5 3.6 1.8 0.36
1.75 5.25 4.2 2.1 0.42
2.0 6.0 4.8 2.4 0.48

When ULTIVA (remifentanil) is used as an analgesic component of monitored analgesia care, a final concentration of 25 mcg/mL is recommended. When ULTIVA (remifentanil) is used for pediatric patients 1 year of age and older, a final concentration of 20 or 25 mcg/mL is recommended. Table 16 is a guideline for milliliter-per-hour delivery for a solution of 20 mcg/mL with an infusion device.

Table 16: IV Infusion Rates of ULTIVA (remifentanil) (mL/h) for a 20-mcg/mL Solution

Infusion Rate
(mcg/kg/min)
Patient Weight (kg)
5 10 20 30 40 50 60
0.0125 0.188 0.375 0.75 1.125 1.5 1.875 2.25
0.025 0.375 0.75 1.5 2.25 3.0 3.75 4.5
0.05 0.75 1.5 3.0 4.5 6.0 7.5 9.0
0.075 1.125 2.25 4.5 6.75 9.0 11.25 13.5
0.1 1.5 3.0 6.0 9.0 12.0 15.0 18.0
0.15 2.25 4.5 9.0 13.5 18.0 22.5 27.0
0.2 3.0 6.0 12.0 18.0 24.0 30.0 36.0
0.25 3.75 7.5 15.0 22.5 30.0 37.5 45.0
0.3 4.5 9.0 18.0 27.0 36.0 45.0 54.0
0.35 5.25 10.5 21.0 31.5 42.0 52.5 63.0
0.4 6.0 12.0 24.0 36.0 48.0 60.0 72.0

Table 17 is a guideline for milliliter-per-hour delivery for a solution of 25 mcg/mL with an infusion device.

Table 17: IV Infusion Rates of ULTIVA (remifentanil) (mL/h) for a 25-mcg/mL Solution

Infusion Rate
(mcg/kg/min)
PatientWeight (kg)
10 20 30 40 50 60 70 80 90 100
0.0125 0.3 0.6 0.9 1.2 1.5 1.8 2.1 2.4 2.7 3.0
0.025 0.6 1.2 1.8 2.4 3.0 3.6 4.2 4.8 5.4 6.0
0.05 1.2 2.4 3.6 4.8 6.0 7.2 8.4 9.6 10.8 12.0
0.075 1.8 3.6 5.4 7.2 9.0 10.8 12.6 14.4 16.2 18.0
0.1 2.4 4.8 7.2 9.6 12.0 14.4 16.8 19.2 21.6 24.0
0.15 3.6 7.2 10.8 14.4 18.0 21.6 25.2 28.8 32.4 36.0
0.2 4.8 9.6 14.4 19.2 24.0 28.8 33.6 38.4 43.2 48.0

Table 18 is a guideline for milliliter-per-hour delivery for a solution of 50 mcg/mL with an infusion device.

Table 18: IV Infusion Rates of ULTIVA (remifentanil) (mL/h) for a 50-mcg/mL Solution

Infusion Rate
(mcg/kg/min)
PatientWeight (kg)
30 40 50 60 70 80 90 100
0.025         2.1 2.4 2.7 3.0
0.05   2.4 3.0 3.6 4.2 4.8 5.4 6.0
0.075 2.7 3.6 4.5 5.4 6.3 7.2 8.1 9.0
0.1 3.6 4.8 6.0 7.2 8.4 9.6 10.8 12.0
0.15 5.4 7.2 9.0 10.8 12.6 14.4 16.2 18.0
0.2 7.2 9.6 12.0 14.4 16.8 19.2 21.6 24.0
0.25 9.0 12.0 15.0 18.0 21.0 24.0 27.0 30.0
0.5 18.0 24.0 30.0 36.0 42.0 48.0 54.0 60.0
0.75 27.0 36.0 45.0 54.0 63.0 72.0 81.0 90.0
1.0 36.0 48.0 60.0 72.0 84.0 96.0 108.0 120.0
1.25 45.0 60.0 75.0 90.0 105.0 120.0 135.0 150.0
1.5 54.0 72.0 90.0 108.0 126.0 144.0 162.0 180.0
1.75 63.0 84.0 105.0 126.0 147.0 168.0 189.0 210.0
2.0 72.0 96.0 120.0 144.0 168.0 192.0 216.0 240.0

Table 19 is a guideline for milliliter-per-hour delivery for a solution of 250 mcg/mL with an infusion device.

Table 19: IV Infusion Rates of ULTIVA (remifentanil) (mL/h) for a 250-mcg/mL Solution

Infusion Rate
(mcg/kg/min)
PatientWeight (kg)
30 40 50 60 70 80 90 100
0.1 0.72 0.96 1.20 1.44 1.68 1.92 2.16 2.40
0.15 1.08 1.44 1.80 2.16 2.52 2.88 3.24 3.60
0.2 1.44 1.92 2.40 2.88 3.36 3.84 4.32 4.80
0.25 1.80 2.40 3.00 3.60 4.20 4.80 5.40 6.00
0.5 3.60 4.80 6.00 7.20 8.40 9.60 10.80 12.00
0.75 5.40 7.20 9.00 10.80 12.60 14.40 16.20 18.00
1.0 7.20 9.60 12.00 14.40 16.80 19.20 21.60 24.00
1.25 9.00 12.00 15.00 18.00 21.00 24.00 27.00 30.00
1.5 10.80 14.40 18.00 21.60 25.20 28.80 32.40 36.00
1.75 12.60 16.80 21.00 25.20 29.40 33.60 37.80 42.00
2.0 14.40 19.20 24.00 28.80 33.60 38.40 43.20 48.00

Compatibility And Stability

Reconstitution and Dilution Prior to Administration: ULTIVA (remifentanil) is stable for 24 hours at room temperature after reconstitution and further dilution to concentrations of 20 to 250 mcg/mL with the IV fluids listed below.

Sterile Water for Injection, USP

5% Dextrose Injection, USP

5% Dextrose and 0.9% Sodium Chloride Injection, USP

0.9% Sodium Chloride Injection, USP

0.45% Sodium Chloride Injection, USP

Lactated Ringer's and 5% Dextrose Injection, USP

ULTIVA (remifentanil) is stable for 4 hours at room temperature after reconstitution and further dilution to concentrations of 20 to 250 mcg/mL with Lactated Ringer's Injection, USP.

ULTIVA (remifentanil) has been shown to be compatible with these IV fluids when coadministered into a running IV administration set.

Compatibility With Other Therapeutic Agents: ULTIVA (remifentanil) has been shown to be compatible with DIPRIVAN® (propofol) Injection when coadministered into a running IV administration set. The compatibility of ULTIVA (remifentanil) with other therapeutic agents has not been evaluated.

Incompatibilities: Nonspecific esterases in blood products may lead to the hydrolysis of remifentanil to its carboxylic acid metabolite. Therefore, administration of ULTIVA (remifentanil) into the same IV tubing with blood is not recommended.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Product should be a clear, colorless liquid after reconstitution and free of visible particulate matter.

ULTIVA (remifentanil) does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions.

HOW SUPPLIED

ULTIVA (remifentanil) should be stored at 2° to 25°C (36° to 77°F). ULTIVA (remifentanil) for IV use is supplied as follows:

List Container Concentration Quantity
4498 3 mL Vial 1 mg lyophilized powder Box of 10
4504 5 mL Vial 2 mg lyophilized powder Box of 10
4507 10 mL Vial 5 mg lyophilized powder Box of 10

ULTIVA (remifentanil) is a registered trademark of Abbott Laboratories., DIPRIVAN® is a registered trademark of Zeneca Pharmaceuticals. Revised: August, 2006, Manufactured by: Hospira, Inc., Lake Forest, IL 60045 USA. For: Abbott Laboratories, North Chicago, IL 60064 USA. FDA revision date: 3/8/2004

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

Indications
Dosage
How Supplied
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