FDA label 69e1de5d-6df2-9602-d7f1-fa9ca0f75887

WARNINGS Anaphylaxis Severe anaphylactic reactions to neuromuscular blocking agents, including MIVACRON, have been reported. These reactions have in some cases been life-threatening and fatal. Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken. Precautions should also be taken in those individuals who have had previous anaphylactic reactions to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported in this class of drugs. Administration MIVACRON SHOULD BE ADMINISTERED IN CAREFULLY ADJUSTED DOSAGE BY OR UNDER THE SUPERVISION OF EXPERIENCED CLINICIANS WHO ARE FAMILIAR WITH THE DRUG'S ACTIONS AND THE POSSIBLE COMPLICATIONS OF ITS USE. THE DRUG SHOULD NOT BE ADMINISTERED UNLESS PERSONNEL AND FACILITIES FOR RESUSCITATION AND LIFE SUPPORT (TRACHEAL INTUBATION, ARTIFICIAL VENTILATION, OXYGEN THERAPY), AND AN ANTAGONIST OF MIVACRON ARE IMMEDIATELY AVAILABLE. IT IS RECOMMENDED THAT A PERIPHERAL NERVE STIMULATOR BE USED TO MEASURE NEUROMUSCULAR FUNCTION DURING THE ADMINISTRATION OF MIVACRON IN ORDER TO MONITOR DRUG EFFECT, DETERMINE THE NEED FOR ADDITIONAL DRUG, AND CONFIRM RECOVERY FROM NEUROMUSCULAR BLOCK. MIVACRON HAS NO KNOWN EFFECT ON CONSCIOUSNESS, PAIN THRESHOLD, OR CEREBRATION. TO AVOID DISTRESS TO THE PATIENT, NEUROMUSCULAR BLOCK SHOULD NOT BE INDUCED BEFORE UNCONSCIOUSNESS. MIVACRON IS METABOLIZED BY PLASMA CHOLINESTERASE AND SHOULD BE USED WITH GREAT CAUTION, IF AT ALL, IN PATIENTS KNOWN TO BE OR SUSPECTED OF BEING HOMOZYGOUS FOR THE ATYPICAL PLASMA CHOLINESTERASE GENE. MIVACRON Injection is acidic (pH 3.5 to 5.0) and may not be compatible with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions). Multiple-dose vials of MIVACRON contain benzyl alcohol, which is potentially toxic when administered locally to neural tissue. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources. Single-use vials do not contain benzyl alcohol (see WARNINGS and PRECAUTIONS - Pediatric Use ).

ADVERSE REACTIONS Observed in Clinical Trials MIVACRON (a mixture of three stereoisomers) was well tolerated during extensive clinical trials in inpatients and outpatients. Prolonged neuromuscular block, which is an important adverse experience associated with neuromuscular blocking agents as a class, was reported as an adverse experience in three of 2074 patients administered MIVACRON. The most commonly reported adverse experience following the administration of MIVACRON was transient, dose-dependent cutaneous flushing about the face, neck, and/or chest. Flushing was most frequently noted after the initial dose of MIVACRON and was reported in about 25% of adult patients who received 0.15 mg/kg MIVACRON over 5 to 15 seconds. When present, flushing typically began within 1 to 2 minutes after the dose of MIVACRON and lasted for 3 to 5 minutes. Of 105 patients who experienced flushing after 0.15 mg/kg MIVACRON, two patients also experienced mild hypotension that was not treated, and one patient experienced moderate wheezing that was successfully treated. Overall, hypotension was infrequently reported as an adverse experience in the clinical trials of MIVACRON. One of 332 (0.3%) healthy adults who received 0.15 mg/kg MIVACRON over 5 to 15 seconds and none of 37 cardiac surgery patients who received 0.15 mg/kg MIVACRON over 60 seconds were treated for a decrease in blood pressure in association with the administration of MIVACRON. One to two percent of healthy adults given ≥ 0.20 mg/kg MIVACRON over 5 to 15 seconds, 2% to 3% of healthy adults given 0.20 mg/kg over 30 seconds, none of 100 healthy adults given 0.25 mg/kg as a divided dose (0.15 mg/kg followed in 30 seconds by 0.10 mg/kg), and 2% to 4% of cardiac surgery patients given ≥ 0.20 mg/kg over 60 seconds were treated for a decrease in blood pressure. None of the 63 children who received the recommended dose of 0.20 mg/kg MIVACRON was treated for a decrease in blood pressure in association with the administration of MIVACRON. The following adverse experiences were reported in patients administered MIVACRON (all events judged by investigators during the clinical trials to have a possible causal relationship): Incidence Greater Than 1% Cardiovascular Flushing (16%) Incidence Less Than 1% Cardiovascular Hypotension, tachycardia, bradycardia, cardiac arrhythmia, phlebitis Respiratory Bronchospasm, wheezing, hypoxemia Dermatological Rash, urticaria, erythema, injection site reaction Nonspecific Prolonged drug effect Neurologic Dizziness Musculoskeletal Muscle spasms Observed in Clinical Practice Based on initial clinical practice experience in patients who received MIVACRON, spontaneously reported adverse events are uncommon. Some of these events occurred at recommended doses and required treatment. Anaphylaxis/Anaphylactoid Reactions : From post-marketing surveillance, MIVACRON has been associated with reports of anaphylactic/anaphylactoid reactions which in some cases have been life-threatening and fatal. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency (see WARNINGS and PRECAUTIONS ). In some of these reports, sensitivity to MIVACRON was confirmed using skin test procedures. Other adverse reaction data from clinical practice are insufficient to establish a causal relationship or to support an estimate of their incidence. These adverse events include: Musculoskeletal Diminished drug effect, prolonged drug effect Cardiovascular Hypotension (rarely severe), flushing Respiratory Bronchospasm Integumentary Rash