Nondepolarizing Skeletal Neuromuscular Blocking Agent
Action And Clinical Pharmacology: Doxacurium is a long-acting, nondepolarizing, skeletal neuromuscular blocking agent for i.v. administration. Nondepolarizing agents antagonize the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plates. This antagonism is inhibited, and neuromuscular block reversed, by acetylcholinesterase inhibitors such as neostigmine.
Pharmacodynamics: Doxacurium is approximately 2.5 to 3 times more potent than pancuronium and 10 to 12 times more potent than metocurine. Doxacurium in doses of 1.5 to 2´ED95 has a clinical duration of action (range and variability) similar to that of equipotent doses of pancuronium and metocurine (historic data and limited comparison).
The average ED95 (dose required to produce 95% suppression of the adductor pollicis muscle twitch response to ulnar nerve stimulation) of doxacurium is 0.025 mg/kg (range: 0.020 to 0.033 mg/kg) in adults receiving balanced anesthesia.
An initial doxacurium dose of 0.025 mg/kg (ED95) administered after 10 to 100% recovery from an intubating dose of 1 mg/kg succinylcholine is followed by maximum block in about 9 to 10 minutes (range: 5 to 16 minutes). The duration of clinically effective neuromuscular block (i.e., time from injection to 25% recovery) is approximately 55 minutes (range: 9 to 145 minutes) during balanced anesthesia.
An initial dose of 0.05 mg/kg (2Â´ED95) in patients receiving balanced anesthesia, generally produces sufficient block for intubation within 4 to 5 minutes. Neuromuscular block reaches a maximum in 5 to 6 minutes (range: 2.5 to 13 minutes), and has a clinically effective duration of approximately 100 minutes (range: 39 to 232 minutes) (see Table IV under Dosage).
Intubation is generally possible 3 to 4 minutes after administration of a 0.08 mg/kg (3Â´ED95) dose. The time to onset of the maximum neuromuscular blocking effect averages 3.5 minutes (range: 2.4 to 5 minutes). Clinically effective block lasts for approximately 160 minutes (range: 110 to 338 minutes).
As with other long-acting agents, the duration of neuromuscular block associated with doxacurium shows considerable interpatient variability. An analysis of 390 cases in U.S. clinical trials utilizing a variety of premedications, varying lengths of surgery and various anesthetic agents, indicates that approximately two-thirds of the patients had clinical durations within 30 minutes of the duration predicted by dose (based on mg/kg actual body weight). Patients Â³60 years old were approximately twice as likely to experience prolonged clinical duration (30 minutes longer than predicted).
Most patients receiving doxacurium in clinical trials required pharmacologic reversal prior to full spontaneous recovery from neuromuscular block; therefore, relatively few data are available on the time from injection to 95% recovery of the twitch response. As a class, long-acting neuromuscular blocking agents may be associated with prolonged times to full spontaneous recovery. Some patients may require as long as 3 to 4 hours to exhibit full spontaneous recovery following initial doses of 0.025 to 0.05 mg/kg doxacurium and even longer following an initial dose of 0.08 mg/kg.
Cumulative neuromuscular blocking effects are not associated with the repeated administration of maintenance doses of doxacurium at 25% twitch recovery. Therefore, in a particular patient, maintenance doses can be administered at relatively regular intervals with predictable results. As with initial doses, however, the duration of action following maintenance doses of doxacurium may vary considerably between patients.
To achieve comparable levels of block, children require higher doxacurium doses on a mg/kg basis than do adults. The doxacurium ED95 for children 2 to 12 years of age receiving halothane anesthesia is approximately 0.03 mg/kg. The onset time and duration of block are shorter in children than in adults. During halothane anesthesia, doses of 0.03 mg/kg and 0.05 mg/kg doxacurium produce maximal block in approximately 7 and 4 minutes, respectively. The duration of clinically effective block is approximately 30 minutes after an initial dose of 0.03 mg/kg and approximately 45 minutes after 0.05 mg/kg. Doxacurium has not been studied in children under 2 years of age.
The neuromuscular block produced by doxacurium may be antagonized by anticholinesterase agents. As with other nondepolarizing neuromuscular blocking agents, the deeper the level of neuromuscular block at reversal, the longer is the time required for recovery of neuromuscular function.
Hemodynamics: Administration of doxacurium doses up to and including 0.08 mg/kg (approximately 3´ED95) over 5 to 15 seconds revealed no dose-related effects on mean arterial blood pressure (MAP) or heart rate (HR) in healthy adult patients during steady state balanced anesthesia or in patients with serious cardiovascular disease undergoing coronary artery bypass grafting, cardiac valvular repair or vascular repair. In 2 to 12 year old children receiving halothane anesthesia, no dose-related changes in MAP or HR were observed following the administration of up to 0.05 mg/kg doxacurium over 5 to 15 seconds.
Doxacurium doses of 0.03 to 0.08 mg/kg (1.2 to 3´ED95) were not associated with dose-dependent changes in mean plasma histamine concentration. Clinical experience with more than 1 000 patients indicates that adverse reactions typically associated with histamine release (e.g., bronchospasm, hypotension, tachycardia, cutaneous flushing, urticaria, etc.) are infrequent following the administration of doxacurium (see Adverse Effects).
Pharmacokinetics: Pharmacokinetic and pharmacodynamic results from a study of 24 healthy young adult patients and 8 healthy elderly patients. The pharmacokinetics are linear over the dosage range tested (i.e., plasma concentrations are approximately proportional to dose). The pharmacokinetics of doxacurium are similar in healthy young adult and elderly patients. Some healthy elderly patients tend to be more sensitive to the neuromuscular blocking effects than healthy young adult patients receiving the same dose. The time to maximum block is longer in elderly patients than in young adult patients (11.2 minutes vs 7.7 minutes at 0.025 mg/kg doxacurium). In addition, the clinically effective durations of block are more variable and tend to be longer in some healthy elderly patients than in healthy young adult patients receiving the same dose.
The pharmacokinetics of doxacurium are not significantly altered in liver transplant patients. Sensitivity to the neuromuscular blocking effects of Nuromax was highly variable in patients undergoing liver transplantation. Three of 7 patients developed 50% block, suggesting that these patients may have a reduced sensitivity to this drug. In those patients who developed >50% neuromuscular block, the time to maximum block and the clinically effective duration of action tended to be longer than in healthy young adult patients (see Dosage, Individualization of Dosages). No data are available from patients with liver disease not requiring transplantation.
Consecutively administered maintenance doses of 0.005 mg/kg doxacurium, each given at a 25% T1 recovery following the preceding dose, do not result in a progressive increase in the plasma concentration of doxacurium or a progressive increase in the depth or duration of block produced by each dose.
Doxacurium is not metabolized in vitro in fresh human plasma. Plasma protein binding of doxacurium is approximately 30% in human plasma.
In vivo data from humans suggest that doxacurium is not metabolized and that the major elimination pathway is excretion of the unchanged drug in urine and bile. In studies of healthy adult patients, 24 to 38% of an administered dose was recovered as parent drug in the urine over 6 to 12 hours after dosing. High bile concentrations of doxacurium (relative to plasma) have been found 35 to 90 minutes after administration in patients undergoing cholecystectomy. The overall extent of biliary excretion is unknown. The data derived from analysis of human urine and bile are consistent with data from in vivo studies in the rat, cat and dog, which indicate that all of an administered dose of doxacurium is recovered as parent drug in the urine and bile of these species.
Indications And Clinical Uses: As an adjunct to general anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. Doxacurium may also be used for non-emergency tracheal intubation.
Contra-Indications: Patients who have a known hypersensitivity to it.
Nuromax contains benzyl alcohol and is not indicated for use in newborns (children less than 1 month of age). In newborn infants, benzyl alcohol has been associated with an increased incidence of neurological and other complications which are sometimes fatal.
Manufacturers’ Warnings In Clinical States: Doxacurium should be used only by those trained in airway management and respiratory support. Equipment and personnel must be immediately available for tracheal intubation and support of ventilation, including administration of positive pressure oxygen. Adequacy of respiration must be assured through assisted or controlled ventilation. Reversal agents should be immediately available.
Clinicians administering long-acting neuromuscular blocking agents such as doxacurium should employ a peripheral nerve stimulator to monitor drug response, need for additional relaxant and adequacy of spontaneous recovery or anticholinesterase antagonism.
Doxacurium has no known effect on consciousness, pain threshold or cerebration. To avoid distress to the patient, neuromuscular block should not be induced before unconsciousness.
Doxacurium injection is acidic (pH 4.0 to 5) and should not be mixed with alkaline solutions of pH >8.5 (e.g., barbiturate solutions).
Neuromuscular blocking agents may have a profound effect in patients with neuromuscular diseases (e.g., myasthenia gravis, myasthenic [Eaton-Lambert] syndrome). In these and other conditions in which prolonged neuromuscular block is a possibility (e.g., carcinomatosis), the use of a peripheral nerve stimulator and a small test dose of doxacurium may be of value in assessing the level of neuromuscular block and monitoring dosage requirements. Muscle relaxants with a shorter duration of action than doxacurium may be more suitable for these patients.
Precautions: General: Doxacurium has no clinically significant effects on heart rate; therefore, doxacurium will not counteract the bradycardia produced by many anesthetic agents or by vagal stimulation.
No data are available to support the use of doxacurium by i.m. injection.
Burns: Resistance to nondepolarizing neuromuscular blocking agents may develop in patients with burns depending upon the time elapsed since the injury and the size of the burn. Doxacurium has not been studied in patients with burns.
Electrolyte Abnormalities: Acid/base and/or serum electrolyte abnormalities may antagonize or potentiate the action of neuromuscular blocking agents. For example, hyperkalemia has been reported to antagonize nondepolarizing neuromuscular blockers, while hypokalemia has been associated with an enhancement of their activity.
Asthma: As doxacurium has not been studied in patients with asthma or a history of severe anaphylactoid reactions, it should be administered with caution to these patient groups.
Renal and Hepatic Disease: The effects of renal and hepatic dysfunction on the action of doxacurium have been studied in patients with end-stage kidney (n=8) or liver (n=7) disease undergoing kidney and liver transplantation (see Pharmacology). The possibility of prolonged neuromuscular block in patients undergoing renal transplantation, and the possibility of a variable onset and duration of action in patients undergoing liver transplantation, must be considered when doxacurium is used in such patients.
Obesity: In obese patients, administration of doxacurium on the basis of actual body weight is associated with prolonged neuromuscular blockade. Ideal body weight should be considered in dosage calculations for obese patients, and appropriate attention paid to the attendant risk of underdosing. Severe obesity may pose airway or ventilatory problems requiring special care before, during or after the use of nondepolarizing neuromuscular blockers such as doxacurium.
Malignant Hyperthermia (MH): Doxacurium has not been studied in MH-susceptible patients. In a study of MH-susceptible Pietrain pigs (n=8) doxacurium did not trigger MH. Since MH can develop in the absence of established triggering agents, the clinician should be prepared to recognize and treat MH in any patient scheduled for general anesthesia.
Hypothermia: Hypothermia (25 to 28°C) has been associated with a decreased requirement for nondepolarizing neuromuscular blocking agents.
Long-Term Use in the Intensive Care Unit (ICU): The long-term use of doxacurium in patients undergoing mechanical ventilation in the intensive care unit has not been studied. When there is a need for long-term mechanical ventilation, the relative benefits and risks of inducing neuromuscular block with doxacurium must be considered.
Drug Interactions: Doxacurium has been administered following succinylcholine-facilitated tracheal intubation. Prior administration of succinylcholine has no clinically important effect on the neuromuscular blocking action of doxacurium. The depth, onset and duration of neuromuscular block produced by an ED95 dose of doxacurium given in the absence of prior administration of succinylcholine was not consistently altered when the same dose was given after complete (95%) or partial (10%) recovery from an intubating dose of succinylcholine. The administration of doxacurium before succinylcholine to attenuate succinylcholine-induced side effects (e.g., muscle fasciculations, postoperative myalgia) has not been studied.
There are no clinical data on the concomitant use of doxacurium and other nondepolarizing neuromuscular blocking agents.
Isoflurane, enflurane and halothane reduce the ED50 of doxacurium by 30 to 45%.
Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as doxacurium include certain antibiotics (e.g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin and sodium colistimethate), magnesium salts, lithium, local anesthetics, procainamide and quinidine.
Concomitant phenytoin and carbamazepine treatment may be associated with an increase in the onset time of doxacurium and a decrease in its duration of block. Similar interactions have been reported for other nondepolarizing neuromuscular relaxants.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis and fertility studies have not been performed. Doxacurium was evaluated in a battery of 4 short-term mutagenicity tests. It was non-mutagenic in the Ames Salmonella assay, in the mouse lymphoma assay and in the human lymphocyte assay. In the in vivo rat bone marrow cytogenetic assay, statistically significant increases in the incidence of structural abnormalities, relative to vehicle controls, were observed in male rats dosed with 0.1 mg/kg (0.625 mg/m doxacurium and sacrificed at 6 hours, but not at 24 or 48 hours, and in female rats dosed with 0.2 mg/kg (1.25 mg/m doxacurium and sacrificed at 24 hours, but not at 6 or 48 hours. There was no increase in structural abnormalities in either male or female rats given 0.3 mg/kg (1.875 mg/m doxacurium and sacrificed at 6, 24 or 48 hours. Thus, the incidence of abnormalities in the in vivo rat bone marrow cytogenetic assay was not dose-dependent and, therefore, the likelihood that the observed abnormalities were treatment-related or clinically significant is low.
Pregnancy: Doxacurium was not shown to be teratogenic when given to nonventilated pregnant rats and mice by the s.c. route at sub-paralyzing doses. Studies at paralyzing doses have not been performed. There are no studies in pregnant women. Because animal reproduction studies have not been performed under conditions that would approximate those of clinical use, doxacurium should not be used during pregnancy unless, in the opinion of the physician, the potential benefits outweigh the unknown hazards. The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of toxemia of pregnancy.
Labor and Delivery: As the duration of action of doxacurium exceeds that of operative obstetrics, this drug is not recommended for use in patients undergoing cesarean section. The use of doxacurium during labor or during vaginal delivery or cesarean section has not been studied. It is not known whether doxacurium administered to the mother has immediate or delayed effects on the fetus.
Lactation: It is not known whether doxacurium is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when doxacurium is administered to a nursing woman.
Children: For children 2 to 12 years of age, see Pharmacology and Dosage. The safety and efficacy of doxacurium in children less than 2 years of age have not been studied.
Geriatrics: Doxacurium has been used in elderly patients, including patients with significant cardiovascular disease. In elderly patients, the onset of maximum block is slower and the duration of neuromuscular block produced by doxacurium is more variable, and in some cases longer, than in young adult patients (see Pharmacology and Dosage). As with other long-acting neuromuscular blocking agents, the possibility of prolonged block must be considered when doxacurium is administered to elderly patients, especially those known to have reduced liver or kidney function.
Increased Volume of Distribution: The onset of action of neuromuscular blocking agents may be delayed in patients who have increased volumes of distribution as a result of old age, edematous states or cardiovascular disease. In these patients, more time should be permitted for the drug to achieve its maximum effect. Increased doses should be avoided, owing to the possibility of a markedly prolonged duration of action.
Adverse Reactions: The most frequent adverse reaction to nondepolarizing blocking agents as a class consists of an extension of the pharmacological action beyond the time needed for surgery and anesthesia. This effect may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or apnea which require manual or mechanical ventilation until recovery is judged to be clinically adequate (see Overdose: Symptoms and Treatment). Inadequate reversal of neuromuscular block is possible with doxacurium, as with all nondepolarizing agents. Prolonged neuromuscular block and inadequate reversal may lead to postoperative complications.
Observed in Clinical Trials: Adverse experiences were uncommon among the 1 034 surgical patients and volunteers who received doxacurium and other drugs in U.S. clinical studies in the course of a wide variety of procedures conducted during balanced or inhalational anesthesia. The following adverse experiences were reported in patients administered doxacurium (all events judged by investigators during the clinical trials to have a possible causal relationship): Incidence greater than 1%: none.
Incidence less than 1%: Cardiovascula*: hypotension, flushing, ventricular fibrillation, myocardial infarction.
Respiratory: bronchospasm, wheezing.
Dermatological: urticaria, injection site reaction.
Special Senses: diplopia.
Nonspecific: difficult neuromuscular block reversal, prolonged drug effect, fever.
Reports of ventricular fibrillation (n=1) and myocardial infarction (n=1) were limited to ASA Class 3-4 patients undergoing cardiac surgery (n=142).
0.3% incidence. All other reactions unmarked were 0.1%.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: The possibility of iatrogenic overdose can be minimized by carefully monitoring muscle twitch response to peripheral nerve stimulation. Because a long duration of neuromuscular block may result from overdose, a peripheral nerve stimulator should be used to monitor recovery. Residual neuromuscular block beyond the time needed for surgery and anesthesia may occur with doxacurium as with other neuromuscular blocking agents. This may be manifested by skeletal muscle weakness, low tidal volume or apnea. A nerve stimulator may be used to differentiate residual neuromuscular block from other causes of apnea or decreased tidal volume, such as narcotics, barbiturates or other CNS depressants. The primary treatment of overdose with nondepolarizing neuromuscular blocking agents is maintenance of a patent airway and manual or mechanical ventilation until recovery of normal respiration is assured. Recovery may be facilitated by administration of an anticholinesterase agent such as neostigmine in conjunction with an appropriate anticholinergic agent. In general, as with other nondepolarizing neuromuscular blocking agents, reversal should not be attempted until evidence of spontaneous recovery from neuromuscular block is present (see Dosage, Reversal).
Dosage And Administration: Doxacurium should be administered only i.v.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Like other long-acting neuromuscular blocking agents, doxacurium displays variability in the duration of its effect and has the potential for prolonged clinical duration. The dosage information provided below is intended as a guide only. Doses should be individualized (see Individualization of Dosage). Factors that may warrant dosage adjustment include: advanced age, concomitant drug treatment, type of surgical procedure or general anesthetic, the presence of kidney or liver disease or obesity (patients weighing ³30% more than ideal body weight for height). The use of a peripheral nerve stimulator will permit the most advantageous use of doxacurium and minimize the possibility of overdosage or underdosage and assist in the evaluation of recovery.
Adults: The recommended dosage range in adults receiving balanced anesthesia is 0.025 to 0.08 mg/kg (1 to 3 times the ED95 value). The potency of doxacurium is enhanced by halogenated anesthetics. If doxacurium is administered during steady-state isoflurane, enflurane or halothane anesthesia, initial and maintenance doses should be reduced by approximately one-third.
In North American clinical trials performed in ASA 1 and 2 adults, the ED95 values in Table III were obtained for doxacurium in the presence of different anesthetic agents.
Initial Doses: An initial 0.025 mg/kg (ED95) dose of doxacurium administered during balanced anesthesia should be preceded by pre-intubation with succinylcholine. Doxacurium may be given as soon as recovery from the effects of succinylcholine becomes evident. An initial dose of 0.025 mg/kg doxacurium provides approximately 60 minutes of clinically effective neuromuscular block for surgery.
When administered as a component of a thiopental/narcotic induction-intubation paradigm with the intention to produce a long duration of neuromuscular block during surgery, an initial 0.05 mg/kg (2´ED95) dose of doxacurium generally produces good-to-excellent conditions for tracheal intubation in approximately 4 to 5 minutes. Clinically effective neuromuscular block following a dose of 0.05 mg/kg doxacurium may be expected to last approximately 100 minutes in patients receiving balanced anesthesia.
An initial dose of 0.08 mg/kg (3´ED95) doxacurium should be reserved for instances in which a need for very prolonged neuromuscular block is anticipated. Good-to-excellent intubation conditions may generally be expected approximately 3 to 4 minutes after administration of this dose. Clinically effective block may be expected to persist for 160 minutes or more.
Maintenance Doses: The need for maintenance dosing should be based on use of a peripheral nerve stimulator and/or clinical criteria. Maintenance doses will generally be required about 60 minutes after an initial dose of 0.025 mg/kg doxacurium or 100 minutes after an initial dose of 0.05 mg/kg doxacurium during balanced anesthesia. Repeated maintenance doses administered at 25% twitch recovery may be expected to be required at relatively regular intervals in individual patients. The interval may vary considerably between patients. Maintenance doses of 0.005 and 0.01 mg/kg doxacurium provide an average 30 minutes (range: 9 to 57 minutes) and 45 minutes (range: 14 to 108 minutes) respectively, of additional clinically effective neuromuscular block. For shorter and longer desired durations, smaller or larger maintenance doses may be administered.
If doxacurium is administered during steady-state isoflurane, enflurane or halothane anesthesia, maintenance doses should be reduced by approximately 30 to 40%.
Children: Dose-response studies in children 2 to 12 years of age indicate that the dose requirements for doxacurium on a mg/kg basis are higher in children than in adults and that recovery from neuromuscular block induced by doxacurium occurs more rapidly. In children anesthetized with halothane, an initial doxacurium dose of 0.03 mg/kg (ED95) produces maximal block in about 7 minutes (range: 5 to 11 minutes), and clinically effective block persists for approximately 30 minutes (range: 12 to 54 minutes). An initial dose of 0.05 mg/kg produces maximal block in about 4 minutes (range: 2 to 10 minutes) and clinically effective block persists for approximately 45 minutes (range: 30 to 80 minutes). Maintenance doses of doxacurium may be required with slightly greater frequency in children than in adults. Because of the potentiating effect of halothane, a higher dose of doxacurium may be required in children receiving balanced anesthesia than in children receiving halothane anesthesia to achieve a comparable onset and duration of neuromuscular block. Doxacurium has not been studied in children under 2 years of age.
Reversal: Once spontaneous recovery is evident, reversal of the neuromuscular block produced by doxacurium can be achieved with various anticholinesterase agents such as neostigmine in conjunction with an appropriate anticholinergic agent. As with other nondepolarizing neuromuscular blocking agents, the time required for anticholinesterase-mediated recovery may be lengthened if reversal is attempted at a deep level of block or if inadequate doses of reversal agent are employed.
In clinical trials, a dose of 1 mg/kg edrophonium was not as effective as a dose of 0.06 mg/kg neostigmine in antagonizing moderate to deep levels of neuromuscular block (i.e.,
Patients should be evaluated for adequate clinical evidence of antagonism, e.g., 5-second head lift and grip strength. Ventilation must be supported until no longer required. As with other neuromuscular blocking agents, physicians should be alert to the possibility that the action of the drugs used to antagonize neuromuscular block may wear off before the effects of doxacurium on the neuromuscular junction have declined sufficiently.
Antagonism may be delayed in the presence of debilitation or carcinomatosis, and during the concomitant use of certain broad spectrum antibiotics, or anesthetic agents and other drugs which enhance neuromuscular block or cause respiratory depression (see Precautions, Drug Interactions). Under such circumstances the management is the same as that of prolonged neuromuscular block.
Individualization of Dosages: Recommended doses of doxacurium are more likely to be associated with a prolonged duration of clinically effective block in the elderly or in patients with obesity or renal impairment than in healthy young adult patients of normal body weight (see Pharmacology). In elderly patients or patients who have kidney disease, the potential for a prolongation of block may be reduced by decreasing the initial doxacurium dose and by titrating the dose to achieve the desired depth of block. For obese patients (i.e., patients weighing ³30% more than ideal body weight for height), ideal body weight should be used when determining the dose.
Dosage requirements for patients with serious liver disease are variable; some patients may require a higher than normal initial doxacurium dose to achieve clinically effective block. Once adequate block is established, the clinical duration of block may be prolonged relative to patients with normal liver function.
As is the case with pancuronium, metocurine and vecuronium, resistance to doxacurium, manifested by a reduced intensity and/or shortened duration of block, must be considered when doxacurium is selected for use in patients receiving phenytoin or carbamazepine (see Precautions, Drug Interactions). Similarly, a reduction in dosage of doxacurium must be considered in cachectic or debilitated patients, in patients with neuromuscular diseases, severe electrolyte abnormalities, or carcinomatosis, and in other patients in whom potentiation of neuromuscular block or difficulty with reversal is anticipated. Increased doses of doxacurium may be required in burn patients (see Precautions).
Stability and Storage: The injection should be stored at room temperature between 15 and 25°C. Do not freeze.
Parenteral Products: Doxacurium injection may not be compatible with alkaline solutions with a pH greater than 8.5 (e.g., barbiturate solutions).
When administered through a y-site during i.v. infusion, doxacurium is physically and chemically compatible with the following diluents: 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 and Lactated Ringer’s Injection.
Doxacurium diluted up to 1:10 in 5% Dextrose Injection USP or 0.9% Sodium Chloride Injection, USP is physically and chemically stable stored in polypropylene syringes at room temperature, 15 to 25°C for up to 24 hours. Since dilution diminishes the preservative effectiveness of benzyl alcohol, aseptic techniques should be used to prepare the diluted product. Immediate use of the diluted product is preferred; any unused portion of diluted doxacurium should be discarded after 8 hours.
Availability And Storage: Each mL of injection contains: doxacurium chloride 1 mg. Multiple-dose vials of 5 mL containing 0.9% w/v benzyl alcohol as a preservative. May also contain hydrochloric acid as a pH adjuster and water for injection. Store at room temperature between 15 and 25°C. Does not require refrigeration. Do not freeze.
NUROMAX Glaxo Wellcome Doxacurium Chloride Nondepolarizing Skeletal Neuromuscular Blocking Agent
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