1 Adverse Reaction Overview CLEVIPREX (clevidipine) was administered to 1099 hypertensive patients in peri-operative settings. No association between gender, age, race, or ethnicity and the incidence of adverse events was observed. Although infusions of lipid containing products may be associated with increases in triglycerides, no consistent changes in triglyceride levels were observed with CLEVIPREX.
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. There were many adverse events associated with the operative procedure, but relatively few that could plausibly be related to the anti-hypertensive drugs.
Thus, the ability to differentiate the adverse event profile between treatments was limited. 2% for all active comparators. The most common adverse reactions leading to study drug discontinuation in all groups were hypertension and, when combined with a beta-blocker, hypotension.
The incidence of serious adverse events and associated discontinuation rates within 1 hour of the drug infusion were similar among patients receiving CLEVIPREX and all active comparators. Placebo-controlled peri-operative studies The placebo-controlled experience with CLEVIPREX in the peri-operative setting was both small and brief (about 30 minutes).
CLEVIPREX (clevidipine) Page 10 of 25 Table 3 lists the treatment-emergent adverse events and the category “any common adverse event” in the ESCAPE-1 and ESCAPE-2 studies (see 14 CLINICAL TRIALS). CLEVIPREX (clevidipine) Page 11 of 25 Table 3 Common Adverse Events in Placebo-controlled Peri-operative Studies Adverse Event ESCAPE-1 ESCAPE-2 CLEVIPREX N=53 n (%) Placebo N=51 n (%) CLEVIPREX N=61 n (%) Placebo N=49 n (%) Any common1 adverse event 27 (51%) 21 (41%) 32 (53%) 24 (49%) Cardiac disorders Atrial fibrillation 7 (13%) 6 (12%) 13 (21%) 6 (12%) Gastrointestinal disorders Nausea 3 (6%) 5 (10%) 13 (21%) 6 (12%) General disorders and administration site conditions Pyrexia 11 (19%) 7 (14%) 3 (5%) 3 (6%) Psychiatric disorders Insomnia NR2 NR2 7 (12%) 3 (6%) Renal and urinary disorders Acute renal failure 5 (9%) 1 (2%) 4 (7%) 4 (8%) Respiratory, thoracic and mediastinal disorders Atelectasis 3 (6%) 0 (0%) NR2 NR2 1 Where the rate with CLEVIPREX exceeded the rate with placebo by at least 5% in one of the two trials.
2 Not reported. Peri-operative clinical studies using active controls Three studies called ECLIPSE compared CLEVIPREX to three active controls: nitroglycerin, sodium nitroprusside, and nicardipine (see 14 CLINICAL TRIALS). Drug exposure in these studies was longer, the pooled mean maximum dose being 10 mg/h, and the mean duration of treatment was 8 hours.
The adverse events observed within 1 hour of the end of the infusion were similar in all patients who received CLEVIPREX and those who received the comparator drugs. Rebound hypertension was assessed as the maximum increase in systolic blood pressure (SBP) from the last measurement on study drug to 1 hour after termination of the study drug.
7 to 12% of patients exhibited greater than 30% increase in SBP. 1 Clinical Trial Adverse Reactions – Pediatrics The safety and effectiveness of CLEVIPREX in children under 18 years of age have not been established. 3 Less Common Clinical Trial Adverse Reactions Adverse reactions occurring in patients treated with CLEVIPREX at a higher frequency than placebo in the ESCAPE-1 or ESCAPE-2 trials included: CLEVIPREX (clevidipine) Page 12 of 25 Blood and lymphatic system disorders: anemia, coagulopathy, leukocytosis Cardiac disorders: right bundle branch block, pericarditis, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, tachycardia, ventricular bigeminy, ventricular extrasystoles, ventricular tachycardia Gastrointestinal disorders: bowel sounds abnormal, constipation, diarrhea General disorders and administration site conditions: anasarca, application site reaction, asthenia, chest discomfort, chest pain, peripheral edema, induration, nodule, secretion discharge Infections and infestations: bacteremia, bacterial infection, bronchitis, cellulitis, oral candidiasis, pneumonia, urinary tract infection, wound infection Injury, poisoning and procedural complications: postoperative anemia, incision site complication, medical device complication, postoperative ileus, post procedural hemorrhage Investigations: abnormal blood gases, decreased cardiac output, abnormal QRS complex electrocardiogram, Gram stain positive, increased international normalised ratio, abnormal liver function test, increased troponin Metabolism and nutrition disorders: acidosis, diabetes mellitus, hyperglycemia, hyponatremia, malnutrition, metabolic acidosis Musculoskeletal and connective tissue disorders: back pain, muscle spasms Nervous system disorders: cerebrovascular accident, dizziness, headache Psychiatric disorders: abnormal behaviour, agitation, anxiety, confusional state, delirium, depression, disorientation, restlessness Renal and urinary disorders: incontinence, oliguria, nephrolithiasis, renal insufficiency Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome, cough, diaphragmatic paralysis, dyspnea, hypoxia, mediastinal hemorrhage, nasal congestion, pleural effusion, pulmonary edema, respiratory distress, respiratory failure, throat tightness, wheezing Skin and subcutaneous tissue disorders: decubitus ulcer, hyperhidrosis, subcutaneous emphysema Surgical and […]