Ebewe Parenta Pharmaceuticals Inc

Ebewe Parenta Pharmaceuticals Inc Drugs

• Mivacurium Chloride
  

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  Mivacurium Chloride

  

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  MIVACURIUM CHLORIDE SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY.

  The dosage information provided below is intended as a guide only. Doses of mivacurium should be individualized (see CLINICAL PHARMACOLOGY: Individualization of Dosages). Factors that may warrant dosage adjustment include but may not be limited to: the presence of significant kidney, liver, or cardiovascular disease, obesity (patients weighing ≥30% more than ideal body weight for height), asthma, reduction in plasma cholinesterase activity, and the presence of inhalational anesthetic agents.

  When using mivacurium chloride or other neuromuscular blocking agents to facilitate tracheal intubation, it is important to recognize that the most important factors affecting intubation are the depth of general anesthesia and the level of neuromuscular block. Satisfactory intubating conditions can usually be achieved before complete neuromuscular block is attained if there is adequate anesthesia.

  The use of a peripheral nerve stimulator will permit the most advantageous use of mivacurium, minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery. When using a stimulator to monitor onset of neuromuscular block, clinical studies have shown that all four twitches of the train-of-four response may be present, with little or no fade, at the times recommended for intubation. Therefore, as with other neuromuscular blocking agents, it is important to use other criteria, such as clinical evaluation of the status of relaxation of jaw muscles and vocal cords, in conjunction with peripheral muscle twitch monitoring, to guide the appropriate time of intubation.

  The onset of conditions suitable for tracheal intubation occurs earlier after a conventional intubating dose of succinylcholine than after recommended doses of mivacurium chloride.

  Adults

  Initial Doses

  Doses of 0.15 mg/kg administered over 5 to 15 seconds, 0.2 mg/kg administered over 30 seconds, or 0.25 mg/kg administered in divided doses (0.15 mg/kg followed in 30 seconds by 0.1 mg/kg) are recommended for facilitation of tracheal intubation for most patients (see Table 7).

  Table 7: Recommended Initial Dosing Regimens for Adults Dosing Paradigm* Anesthetic Induction Technique Studied Time to Generally Good-to-Excellent Intubating Conditions * Dosing instituted after induction of adequate general anesthesia. 0.15 mg/kg, I.V. (over 5 to 15 sec) Thiopental/opioid/N2O/O2 or propofol/opioid 2.5 to 3 min after completion of dose 0.2 mg/kg, I.V. (over 30 sec) Thiopental/opioid/N2O/O2 or propofol/opioid 2 to 2.5 min after completion of dose 0.25 mg/kg, I.V.( 0.15 mg/kg followed in 30 sec by 0.1 mg/kg) Propofol/opioid 1.5 to 2 min after completion of 0.15 mg/kg dose

  The purpose of slowed or divided dosing of mivacurium chloride at doses above 0.15 mg/kg is to minimize the transient decreases in blood pressure observed in some patients given these doses over 5 to 15 seconds (see CLINICAL PHARMACOLOGY, PRECAUTIONS, and ADVERSE REACTIONS). The quality of intubation conditions does not significantly differ for the times and doses of mivacurium chloride recommended in Table 7, but the onset of suitable intubation conditions may be reached earlier with higher doses. The choice of a particular dose and regimen should be based on individual circumstances and patient requirements (see CLINICAL PHARMACOLOGY: Individualization of Dosages).

  In patients with clinically significant cardiovascular disease and in patients with any history suggesting a greater sensitivity to the release of histamine or other mediators (e.g., asthma), the dose of mivacurium should be 0.15 mg/kg or less, administered over 60 seconds (see PRECAUTIONS). No data are available on the use of doses of mivacurium above 0.15 mg/kg in patients with clinically significant kidney or liver disease.

  Clinically effective neuromuscular block may be expected to last for 15 to 20 minutes (range: 9 to 38) and spontaneous recovery may be expected to be 95% complete in 25 to 30 minutes (range: 16 to 41) following 0.15 mg/kg mivacurium administered to patients receiving opioid/nitrous oxide/oxygen anesthesia. The expected duration of clinically effective block and time to 95% spontaneous recovery following 0.2 mg/kg mivacurium are approximately 20 to 30 minutes, respectively, and following 0.25 mg/kg mivacurium are approximately 25 to 35 minutes. Initiation of maintenance dosing during opioid/nitrous oxide/oxygen anesthesia is generally required approximately 15, 20 and 25 minutes following initial doses of 0.15, 0.2, and 0.25 mg/kg mivacurium, respectively (see Table 1). Maintenance doses of 0.1 mg/kg each provide approximately 15 minutes of additional clinically effective block. For shorter or longer durations of action, smaller or larger maintenance doses may be administered.

  The neuromuscular blocking action of mivacurium chloride is potentiated by isoflurane or enflurane anesthesia. Recommended initial doses of mivacurium may be used to facilitate tracheal intubation prior to the administration of these agents; however, if mivacurium chloride is first administered after establishment of stable-state isoflurane or enflurane anesthesia (administered with nitrous oxide/oxygen to achieve 1.25 MAC), the initial dose of mivacurium may be reduced by as much as 25%. Greater reductions in the dose of mivacurium may be required with higher concentrations of enflurane or isoflurane. With halothane, which has only a minimal potentiating effect on mivacurium, a smaller dosage reduction may be considered.

  Continuous Infusion

  Continuous infusion of mivacurium chloride may be used to maintain neuromuscular block. Upon early evidence of spontaneous recovery from an initial dose, an initial infusion rate of 9 to 10 mcg/kg/min is recommended. If continuous infusion is initiated simultaneously with the administration of an initial dose, a lower initial infusion rate should be used (e.g., 4 mcg/kg/min). In either case, the initial infusion rate should be adjusted according to the response to peripheral nerve stimulation and to clinical criteria. On average, an infusion rate of 5 to 7 mcg/kg/min (range: 1 to 15) may be expected to maintain neuromuscular block within the range of 89% to 99% for extended periods in adults receiving opioid/nitrous oxide/oxygen anesthesia. In some patients, particularly those with higher infusion requirements (>8 mcg/kg/min) during the first 30 minutes, the infusion rate required to maintain 89% to 99% T1 suppression may decrease gradually (by ≥30%) with time over a 4- to 6- hour period of infusion (see CLINICAL PHARMACOLOGY: Pharmacodynamics). Reduction of the infusion rate by up to 35% to 40% should be considered when mivacurium is administered during stable-state conditions of isoflurane or enflurane anesthesia (administered with nitrous oxide/oxygen to achieve 1.25 MAC). Greater reductions in the infusion rate of mivacurium may be required with greater concentrations of enflurane or isoflurane. With halothane, smaller reductions in infusion rate may be required.

  Children

  Initial Doses

  Dosage requirements for mivacurium on a mg/kg basis are higher in children than in adults. Onset and recovery of neuromuscular block occur more rapidly in children than in adults (see CLINICAL PHARMACOLOGY).

  The recommended dose of mivacurium for facilitating tracheal intubation in children 2 to 12 years of age is 0.2 mg/kg administered over 5 to 15 seconds. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.2 mg/kg of mivacurium produces maximum neuromuscular block in an average of 1.9 minutes (range: 1.3 to 3.3) and clinically effective block for 10 minutes (range: 6 to 15). Maintenance doses are generally required more frequently in children than in adults. Administration of doses of mivacurium above the recommended range (>0.2 mg/kg) is associated with transient decreases in MAP in some children (see CLINICAL PHARMACOLOGY: Hemodynamics). Mivacurium has not been studied in pediatric patients below the age of 2 years.

  Continuous Infusion

  Children require higher infusion rates of mivacurium than adults. During opioid/nitrous oxide/oxygen anesthesia, the infusion rate required to maintain 89% to 99% neuromuscular block averages 14 mcg/kg/min (range: 5 to 31). The principles for infusion of mivacurium in adults are also applicable to children (see above).

  Infusion Rate Tables

  For adults and children the amount of infusion solution required per hour depends upon the clinical requirements of the patient, the concentration of mivacurium in the infusion solution, and the patient's weight. The contribution of the infusion solution to the fluid requirements of the patient must be considered.

  Table 8 provides guidelines for delivery in mL/hr (equivalent to microdrops/min when 60 microdrops= 1 mL) of mivacurium chloride injection, equivalent to 2 mg/mL mivacurium.

  Table 8: Infusion Rates for Maintenance of Neuromuscular Block During Opioid/Nitrous Oxide/Oxygen Anesthesia Using Mivacurium Chloride Injection, equivalent to 2 mg/mL mivacurium. Patient Weight (kg) Drug Delivery Rate (mcg/kg/min) 4 5 6 7 8 10 14 16 18 20   Infusion Delivery Rate (mL/hr) 10 1.2 1.5 1.8 2.1 2.4 3.0 4.2 4.8 5.4 6.0   15 1.8 2.3 2.7 3.2 3.6 4.5 6.3 7.2 8.1 9.0   20 2.4 3.0 3.6 4.2 4.8 6.0 8.4 9.6 10.8 12.0   25 3.0 3.8 4.5 5.3 6.0 7.5 10.5 12.0 13.5 15.0   35 4.2 5.3 6.3 7.4 8.4 10.5 14.7 16.8 18.9 21.0   50 6.0 7.5 9.0 10.5 12.0 15.0 21.0 24.0 27.0 30.0   60 7.2 9.0 10.8 12.6 14.4 18.0 25.2 28.8 32.4 36.0   70 8.4 10.5 12.6 14.7 16.8 21.0 29.4 33.6 37.8 42.0   80 9.6 12.0 14.4 16.8 19.2 24.0 33.6 38.4 43.2 48.0   90 10.8 13.5 16.2 18.9 21.6 27.0 37.8 43.2 48.6 54.0   100 12.0 15.0 18.0 21.0 24.0 30.0 42.0 48.0 54.0 60.0  

  Mivacurium Chloride Injection Compatibility and Admixtures

  Y-site Administration

  Mivacurium chloride injection may not be compatible with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions).

  Studies have shown that mivacurium chloride injection is compatible with: 5% Dextrose Injection, USP 0.9% Sodium Chloride Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP Lactated Ringer's Injection, USP 5% Dextrose in Lactated Ringer's Injection Sufenta® (sufentanil citrate) Injection, diluted as directed Alfenta® (alfentanil hydrochloride) Injection, diluted as directed Sublimaze® (fentanyl citrate) Injection, diluted as directed Versed® (midazolam hydrochloride) Injection, diluted as directed Inapsine® (droperidol) Injection, diluted as directed

  Compatibility studies with other parenteral products have not been conducted.

  Dilution Stability

  Mivacurium chloride injection diluted to 0.5 mg mivacurium per mL in 5% Dextrose Injection, USP, 5% Dextrose and 0.9% Sodium Chloride Injection, USP, 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, or 5% Dextrose in Lactated Ringer's Injection is physically and chemically stable when stored in PVC (polyvinylchloride) bags at 5° to 25°C (41° to 77°F) for up to 24 hours. Aseptic techniques should be used to prepare the diluted product. Admixtures of mivacurium should be prepared for single patient use only and used within 24 hours of preparation. The unused portion of diluted mivacurium should be discarded after each case.

  NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Solutions which are not clear and colorless should not be used.

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