ADVERSE REACTIONS
6.1Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
Use of Precedex has been associated with the following serious adverse reactions:
-
Hypotension, bradycardia and sinus arrest [ see Warnings and Precautions (5.2) ]
-
Transient hypertension [ see Warnings and Precautions (5.3) ]
Most common treatment-emergent adverse reactions, occurring in greater than 2% of patients in both Intensive Care Unit and procedural sedation studies include hypotension, bradycardia and dry mouth.
Intensive Care Unit Sedation
Adverse reaction information is derived from the continuous infusion trials of Precedex for sedation in the Intensive Care Unit setting in which 1007 patients received Precedex. The mean total dose was 7.4 mcg/kg (range: 0.8 to 84.1), mean dose per hour was 0.5 mcg/kg/hr (range: 0.1 to 6.0) and the mean duration of infusion of 15.9 hours (range: 0.2 to 157.2). The population was between 17 to 88 years of age, 43% ≥ 65 years of age, 77% male and 93% Caucasian. Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 2. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [ see Warnings and Precautions (5.2) ].
Table 2: Adverse Reactions With an Incidence > 2% —Intensive Care Unit Sedation Population Body System/
Adverse Event
| All Precedex
N = 1007
| Randomized
Precedex
N = 798
| Placebo
N = 400
| Propofol
N = 188
|
n (%)
|
n (%)
|
n (%)
|
n (%)
|
Vascular Disorders
Hypotension
Hypertension
|
248 (25%)
123 (12%)
|
191 (24%)
101 (13%)
|
48 (12%)
76 (19%)
|
25 (13%)
7 (4%)
|
Gastrointestinal Disorders
Nausea
Dry mouth
Vomiting
|
90 (9%)
35 (4%)
34 (3%)
|
73 (9%)
22 (3%)
26 (3%)
|
36 (9%)
4 (1%)
21 (5%)
|
20 (11%)
1 (1%)
6 (3%)
|
Cardiac Disorders
Bradycardia
Atrial fibrillation
Tachycardia
Sinus tachycardia
Ventricular tachycardia
|
52 (5%)
44 (4%)
20 (2%)
6 (1%)
4 (0%)
|
36 (5%)
37 (5%)
15 (2%)
6 (1%)
4 (1%)
|
10 (3%)
13 (3%)
17 (4%)
2 (1%)
3 (1%)
|
0
14 (7%)
2 (1%)
4 (2%)
9 (5%)
|
General Disorders and Administration Site Conditions
Pyrexia
Hyperthermia
Chills
Edema peripheral
|
35 (4%)
19 (2%)
17 (2%)
4 (0%)
|
31 (4%)
16 (2%)
14 (2%)
2 (0%)
|
15 (4%)
12 (3%)
13 (3%)
2 (1%)
|
8 (4%)
0
4 (2%)
4 (2%)
|
Metabolism and Nutrition Disorders
Hypovolemia
Hyperglycemia
Hypocalcemia
Acidosis
|
31 (3%)
17 (2%)
7 (1%)
6 (1%)
|
22 (3%)
15 (2%)
7 (1%)
5 (1%)
|
9 (2%)
7 (2%)
0
4 (1%)
|
9 (5%)
5 (3%)
4 (2%)
4 (2%)
|
Respiratory, Thoracic and Mediastinal Disorders
Atelectasis
Pleural effusion
Hypoxia
Pulmonary edema
Wheezing
|
29 (3%)
23 (2%)
16 (2%)
9 (1%)
4 (0%)
|
23 (3%)
16 (2%)
13 (2%)
9 (1%)
4 (1%)
|
13 (3%)
4 (1%)
8 (2%)
3 (1%)
1 (0%)
|
12 (6%)
12 (6%)
5 (3%)
5 (3%)
4 (2%)
|
Psychiatric Disorders
Agitation
|
20 (2%)
|
16 (2%)
|
11 (3%)
|
1 (1%)
|
Blood and Lymphatic System Disorders
Anemia
|
19 (2%)
|
18 (2%)
|
7 (2%)
|
4 (2%)
|
Injury, Poisoning and Procedural Complications
Post-procedural hemorrhage
|
15 (2%)
|
13 (2%)
|
10 (3%)
|
7 (4%)
|
Investigations
Urine output decreased
|
6 (1%)
|
6 (1%)
|
0
|
4 (2%)
|
Procedural Sedation
Adverse reaction information is derived from the two trials for procedural sedation in which 318 patients received Precedex. The mean total dose was 1.6 mcg/kg (range: 0.5 to 6.7), mean dose per hour was 1.3 mcg/kg/hr (range: 0.3 to 6.1) and the mean duration of infusion of 1.5 hours (range: 0.1 to 6.2). The population was between 18 to 93 years of age, 30% ≥ 65 years of age, 52% male and 61% Caucasian.
Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 3. The most frequent adverse reactions were hypotension, bradycardia, and dry mouth [ see Warnings and Precautions (5.2) ]. Pre-specified criteria for the vital signs to be reported as adverse reactions are footnoted below the table. The decrease in respiratory rate and hypoxia was similar between Precedex and comparator groups in both studies.
Table 3: Adverse Reactions With an Incidence > 2% —Procedural Sedation Population Body System/
Adverse Event
| Precedex
N = 318
| Placebo
N = 113
|
n (%)
|
n (%)
|
1 Hypotension was defined in absolute and relative terms as Systolic blood pressure of <80 mmHg or ≤30% lower than pre-study drug infusion value, or diastolic blood pressure of <50 mmHg.
2 Hypertension was defined in absolute and relative terms as Systolic blood pressure >180 mmHg or ≥30% higher than pre-study drug infusion value or diastolic blood pressure of >100 mmHg.
3 Bradycardia was defined in absolute and relative terms as<40 beats per minute or ≤30% lower than pre-study drug infusion value.
4 Tachycardia was defined in absolute and relative terms as >120 beats per minute or ≥30% greater than pre-study drug infusion value.
5 Respiratory depression was defined in absolute and relative terms as respiratory rate (RR) <8 breaths per minute or > 25% decrease from baseline.
6 Hypoxia was defined in absolute and relative terms as SpO2 < 90% or 10% decrease from baseline.
|
Vascular Disorders
Hypotension1
Hypertension2
|
173 (54%)
41 (13%)
|
34 (30%)
27 (24%)
|
Respiratory, Thoracic and Mediastinal Disorders
Respiratory depression5
Hypoxia6
Bradypnea
|
117 (37%)
7 (2%)
5 (2%)
|
36 (32%)
3 (3%)
5 (4%)
|
Cardiac Disorders
Bradycardia3
Tachycardia4
|
45 (14%)
17 (5%)
|
4 (4%)
19 (17%)
|
Gastrointestinal Disorders
Nausea
Dry mouth
|
10 (3%)
8 (3%)
|
2 (2%)
1 (1%)
|
6.2Postmarketing Experience
The following adverse reactions have been identified during post approval use of Precedex. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypotension and bradycardia were the most common adverse reactions associated with the use of Precedex during post approval use of the drug.
Table 4: Adverse Reactions Experienced During Post-approval Use of Precedex Body System | Preferred Term |
Body as a Whole
|
Fever, hyperpyrexia, hypovolemia,
light anesthesia, pain, rigors
|
Cardiovascular Disorders,
General
|
Blood pressure fluctuation, heart disorder,
hypertension, hypotension, myocardial infarction
|
Central and
Peripheral Nervous
System Disorders
|
Dizziness, headache, neuralgia,
neuritis, speech disorder, convulsion
|
Gastrointestinal
System Disorders
|
Abdominal pain, diarrhea, vomiting,
nausea
|
Heart Rate and
Rhythm Disorders
|
Arrhythmia, ventricular arrhythmia,
bradycardia, hypoxia,
atrioventricular block, cardiac arrest,
extrasystoles, atrial fibrillation, heart
block, t wave inversion, tachycardia,
supraventricular tachycardia,
ventricular tachycardia
|
Liver and Biliary
System Disorders
|
Increased gamma-glutamyl transpepsidase, hepatic function abnormal,
hyperbilirubinemia, alanine transaminase,
aspartate aminotransferase
|
Metabolic and
Nutritional
Disorders
|
Acidosis, respiratory acidosis,
hyperkalemia, increased alkaline
phosphatase, thirst, hypoglycemia
|
Psychiatric
Disorders
| Agitation, confusion, delirium,
hallucination, illusion
|
Red Blood Cell
Disorders
|
Anemia
|
Renal Disorders
|
Blood urea nitrogen increased, oliguria
|
Respiratory System
Disorders
|
Apnea, bronchospasm, dyspnea,
hypercapnia, hypoventilation, hypoxia,
pulmonary congestion
|
Skin and Appendages
Disorders
|
Increased sweating
|
Vascular Disorders
|
Hemorrhage
|
Vision Disorders
|
Photopsia, abnormal vision
|
|
REPORTS OF SUSPECTED PRECEDEX SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Precedex. The information is not vetted and should not be considered as verified clinical evidence.
Possible Precedex side effects / adverse reactions in 23 year old male
Reported by a pharmacist from United States on 2012-03-02
Patient: 23 year old male weighing 131.0 kg (288.2 pounds)
Reactions: Bradyarrhythmia
Suspect drug(s):
Precedex
Possible Precedex side effects / adverse reactions in 57 year old male
Reported by a pharmacist from United States on 2012-03-15
Patient: 57 year old male weighing 143.0 kg (314.6 pounds)
Reactions: Agitation, Hypoxic-Ischaemic Encephalopathy, Pulse Absent, Bradycardia, Cardiac Arrest, Pulseless Electrical Activity
Adverse event resulted in: life threatening event
Suspect drug(s):
Precedex
Other drugs received by patient: Albutetol/ipratropium MDI; Clonidine; Famotidine; Amiodarone Hydrochloride; Valproic Acid; Diltiazem HCL; Dexmedetomodine Hydrochloride; Furosemide; Heparin
Possible Precedex side effects / adverse reactions in 5 month old female
Reported by a physician from Japan on 2012-04-18
Patient: 5 month old female
Reactions: Hepatitis Fulminant
Adverse event resulted in: life threatening event
Suspect drug(s):
Dopamine HCL
Dosage: unk
Aldactone
Dosage: unk
Administration route: Oral
Midazolam HCL
Dosage: unk
Acetaminophen
Dosage: unk
Administration route: Oral
Herbal Preparation
Dosage: unk
Administration route: Oral
Unfractionated Heparin
Aspirin
Dosage: unk
Administration route: Oral
Indication: Thrombosis Prophylaxis
Start date: 2011-12-06
End date: 2011-12-07
Lasix
Administration route: Oral
Precedex
Dosage: unk
|