"The U.S. Food and Drug Administration today granted accelerated approval to Praxbind (idarucizumab) for use in patients who are taking the anticoagulant Pradaxa (dabigatran) during emergency situations when there is a need to reverse Pradaxa&rsqu"...
(Generic versions may still be available.)
TRACRIUM (atracurium besylate) SHOULD BE USED ONLY BY THOSE SKILLED IN AIRWAY MANAGEMENT AND RESPIRATORY SUPPORT. EQUIPMENT AND PERSONNEL MUST BE IMMEDIATELY AVAILABLE FOR ENDOTRACHEAL INTUBATION AND SUPPORT OF VENTILATION, INCLUDING ADMINISTRATION OF POSITIVE PRESSURE OXYGEN. ADEQUACY OF RESPIRATION MUST BE ASSURED THROUGH ASSISTED OR CONTROLLED VENTILATION. ANTICHOLINESTERASE REVERSAL AGENTS SHOULD BE IMMEDIATELY AVAILABLE.
DO NOT GIVE TRACRIUM (atracurium besylate) BY INTRAMUSCULAR ADMINISTRATION. TRACRIUM (atracurium besylate) has no known effect on consciousness, pain threshold, or cerebration. It should be used only with adequate anesthesia.
TRACRIUM ® (atracurium besylate) Injection, which has an acid pH, should not be mixed with alkaline solutions (e.g., barbiturate solutions) in the same syringe or administered simultaneously during intravenous infusion through the same needle. Depending on the resultant pH of such mixtures, TRACRIUM (atracurium besylate) may be inactivated and a free acid may be precipitated.
TRACRIUM (atracurium besylate) Injection 10-mL multiple-dose vials contain benzyl alcohol. In neonates, benzyl alcohol has been associated with an increased incidence of neurological and other complications which are sometimes fatal. TRACRIUM (atracurium besylate) Injection 5-mL single-use vials do not contain benzyl alcohol (see
PRECAUTIONS: Pediatric Use).
Although TRACRIUM (atracurium besylate) is a less potent histamine releaser than d-tubocurarine or metocurine, the possibility of substantial histamine release in sensitive individuals must be considered. Special caution should be exercised in administering TRACRIUM (atracurium besylate) to patients in whom substantial histamine release would be especially hazardous (e.g., patients with clinically significant cardiovascular disease) and in patients with any history (e.g., severe anaphylactoid reactions or asthma) suggesting a greater risk of histamine release.
In these patients, the recommended initial dose of TRACRIUM (atracurium besylate) is lower (0.3 to 0.4 mg/kg) than for other patients and should be administered slowly or in divided doses over 1 minute.
Since TRACRIUM (atracurium besylate) has no clinically significant effects on heart rate in the recommended dosage range, it will not counteract the bradycardia produced by many anesthetic agents or vagal stimulation. As a result, bradycardia during anesthesia may be more common with TRACRIUM (atracurium besylate) than with other muscle relaxants.
TRACRIUM (atracurium besylate) may have profound effects in patients with myasthenia gravis, Eaton-Lambert syndrome, or other neuromuscular diseases in which potentiation of nondepolarizing agents has been noted. The use of a peripheral nerve stimulator is especially important for assessing neuromuscular block in these patients. Similar precautions should be taken in patients with severe electrolyte disorders or carcinomatosis.
Multiple factors in anesthesia practice are suspected of triggering malignant hyperthermia (MH), a potentially fatal hypermetabolic state of skeletal muscle. Halogenated anesthetic agents and succinylcholine are recognized as the principal pharmacologic triggering agents in MH-susceptible patients; however, 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. Reports of MH have been rare in cases in which TRACRIUM (atracurium besylate) has been used. In studies of MH-susceptible animals (swine) and in a clinical study of MH-susceptible patients, TRACRIUM (atracurium besylate) did not trigger this syndrome.
Resistance to nondepolarizing neuromuscular blocking agents may develop in burn patients. Increased doses of nondepolarizing muscle relaxants may be required in burn patients and are dependent on the time elapsed since the burn injury and the size of the burn.
The safety of TRACRIUM (atracurium besylate) has not been established in patients with bronchial asthma.
Long-Term Use in Intensive Care Unit (ICU)
When there is a need for long-term mechanical ventilation, the benefits-to-risk ratio of neuromuscular block must be considered. The long-term (1 to 10 days) infusion of TRACRIUM (atracurium besylate) during mechanical ventilation in the ICU has been evaluated in several studies. Average infusion rates of 11 to 13 mcg/kg per minute (range: 4.5 to 29.5) were required to achieve adequate neuromuscular block. These data suggest that there is wide interpatient variability in dosage requirements. In addition, these studies have shown that dosage requirements may decrease or increase with time. Following discontinuation of infusion of TRACRIUM (atracurium besylate) in these ICU studies, spontaneous recovery of four twitches in a train-of-four occurred in an average of approximately 30 minutes (range: 15 to 75 minutes) and spontaneous recovery to a train-of-four ratio >75% (the ratio of the height of the fourth to the first twitch in a train-of-four) occurred in an average of approximately 60 minutes (range: 32 to 108 minutes).
Little information is available on the plasma levels and clinical consequences of atracurium metabolites that may accumulate during days to weeks of atracurium administration in ICU patients. Laudanosine, a major biologically active metabolite of atracurium without neuromuscular blocking activity, produces transient hypotension and in higher doses, cerebral excitatory effects (generalized muscle twitching and seizures) when administered to several species of animals. There have been rare spontaneous reports of seizures in ICU patients who have received atracurium or other agents. These patients usually had predisposing causes (such as head trauma, cerebral edema, hypoxic encephalopathy, viral encephalitis, uremia). There are insufficient data to determine whether or not laudanosine contributes to seizures in ICU patients.
WHENEVER THE USE OF TRACRIUM (atracurium besylate) OR ANY NEUROMUSCULAR BLOCKING AGENT IS CONTEMPLATED IN THE I.U. IT IS RECOMMENDED T.A. NEUROMUSCULAR TRANSMISSION BE MONITORED CONTINUOUSLY DURING ADMINISTRATION WITH THE HELP OF A NERVE STIMULATOR. ADDITIONAL DOSES OF TRACRIUM (atracurium besylate) OR ANY OTHER NEUROMUSCULAR BLOCKING AGENT SHOULD NOT BE GIVEN BEFORE THERE IS A DEFINITE RESPONSE TO T1 OR TO THE FIRST TWITCH. IF NO RESPONSE IS ELICITED, INFUSION ADMINISTRATION SHOULD BE DISCONTINUED UNTIL A RESPONSE RETURNS.
Hemofiltration has a minimal effect on plasma levels of atracurium and its metabolites, including laudanosine. The effects of hemodialysis and hemoperfusion on plasma levels of atracurium and its metabolites are unknown.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis and fertility studies have not been performed. Atracurium was evaluated in a battery of three short-term mutagenicity tests. It was nonmutagenic in both the Ames Salmonella assay at concentrations up to 1,000 mcg/plate, and in a rat bone marrow cytogenicity assay at up to paralyzing doses. A positive response was observed in the mouse lymphoma assay under conditions (80 and 100 mcg/mL, in the absence of metabolic activation) which killed over 80% of the treated cells; there was no mutagenicity at 60 mcg/mL and lower, concentrations which killed up to half of the treated cells. A far weaker response was observed in the presence of metabolic activation at concentrations (1,200 mcg/mL and higher) which also killed over 80% of the treated cells.
Mutagenicity testing is intended to simulate chronic (years to lifetime) exposure in an effort to determine potential carcinogenicity. Thus, a single positive mutagenicity response for a drug used infrequently and/or briefly is of questionable clinical relevance.
Teratogenic Effects: Pregnancy Category C. TRACRIUM (atracurium besylate) has been shown to be potentially teratogenic in rabbits when given in doses up to approximately one half the human dose. There are no adequate and well-controlled studies in pregnant women. TRACRIUM (atracurium besylate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
TRACRIUM (atracurium besylate) was administered subcutaneously on days 6 through 18 of gestation to nonventilated Dutch rabbits. Treatment groups were given either 0.15 mg/kg once daily or 0.10 mg/kg twice daily. Lethal respiratory distress occurred in two 0.15-mg/kg animals and in one 0.10-mg/kg animal, with transient respiratory distress or other evidence of neuromuscular block occurring in 10 of 19 and in 4 of 20 of the 0.15-mg/ kg and 0.10-mg/kg animals, respectively. There was an increased incidence of certain spontaneously occurring visceral and skeletal anomalies or variations in one or both treated groups when compared to nontreated controls. The percentage of male fetuses was lower (41% versus 51%) and the post-implantation losses were increased (15% versus 8%) in the group given 0.15 mg/kg once daily when compared to the controls; the mean numbers of implants (6.5 versus 4.4) and normal live fetuses (5.4 versus 3.8) were greater in this group when compared to the control group.
Labor and Delivery
It is not known whether muscle relaxants administered during vaginal delivery have immediate or delayed adverse effects on the fetus or increase the likelihood that resuscitation of the newborn will be necessary. The possibility that forceps delivery will be necessary may increase.
TRACRIUM (atracurium besylate) (0.3 mg/kg) has been administered to 26 pregnant women during delivery by cesarean section. No harmful effects were attributable to TRACRIUM (atracurium besylate) in any of the neonates, although small amounts of TRACRIUM (atracurium besylate) were shown to cross the placental barrier. The possibility of respiratory depression in the neonate should always be considered following cesarean section during which a neuromuscular blocking agent has been administered. In patients receiving magnesium sulfate, the reversal of neuromuscular block may be unsatisfactory and the dose of TRACRIUM (atracurium besylate) should be lowered as indicated.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TRACRIUM (atracurium besylate) is administered to a nursing woman.
Safety and effectiveness in pediatric patients below the age of 1 month have not been established.
Use in the Elderly
Since marketing in 1983, uncontrolled clinical experience and limited data from controlled trials have not identified differences in effectiveness, safety, or dosage requirements between healthy elderly and younger patients (see CLINICAL PHARMACOLOGY); however, as with other neuromuscular blocking agents, the use of a peripheral nerve stimulator to monitor neuromuscular function is suggested (see DOSAGE AND ADMINISTRATION).This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/8/2004
Additional Tracrium Information
- Tracrium Drug Interactions Center: atracurium iv
- Tracrium Side Effects Center
- Tracrium FDA Approved Prescribing Information including Dosage
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.