MIVACRON SIDE EFFECTS

SIDE EFFECTS

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, dosedependent 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 greater than or equal to 0.2 mg/kg MIVACRON over 5 to 15 seconds, 2% to 3% of healthy adults given 0.2 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 0.1 mg/kg), and 2% to 4% of cardiac surgery patients given greater than or equal to 0.2 mg/kg over 60 seconds were treated for a decrease in blood pressure. None of the 63 children who received the recommended dose of 0.2 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. 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