ADVERSE REACTIONS
General
Adverse event information is derived from controlled clinical trials and worldwide marketing experience. In the description below, rates of the more common events represent US/Canadian clinical study results. Less frequent events are also derived from publications and marketing experience in over 8 million patients; there are insufficient data to support an accurate estimate of their incidence rates. These studies were conducted using a variety of premedicants, varying lengths of surgical/diagnostic procedures, and various other anesthetic/sedative agents. Most adverse events were mild and transient.
Anesthesia and MAC Sedation in Adults
The following estimates of adverse events for DIPRIVAN Injectable Emulsion include data from clinical trials in general anesthesia/MAC sedation (N=2889 adult patients). The adverse events listed below as probably causally related are those events in which the actual incidence rate in patients treated with DIPRIVAN Injectable Emulsion was greater than the comparator incidence rate in these trials. Therefore, incidence rates for anesthesia and MAC sedation in adults generally represent estimates of the percentage of clinical trial patients which appeared to have probable causal relationship.
The adverse experience profile from reports of 150 patients in the MAC sedation clinical trials is similar to the profile established with DIPRIVAN Injectable Emulsion during anesthesia (see below). During MAC sedation clinical trials, significant respiratory events included cough, upper airway obstruction, apnea, hypoventilation, and dyspnea.
Anesthesia in Pediatric Patients
Generally the adverse experience profile from reports of 506 DIPRIVAN Injectable Emulsion pediatric patients from 6 days through 16 years of age in the US/Canadian anesthesia clinical trials is similar to the profile established with DIPRIVAN Injectable Emulsion during anesthesia in adults (see Pediatric percentages [Peds %] below). Although not reported as an adverse event in clinical trials, apnea is frequently observed in pediatric patients.
ICU Sedation in Adults
The following estimates of adverse events include data from clinical trials in ICU sedation (N=159 adult patients). Probably related incidence rates for ICU sedation were determined by individual case report form review. Probable causality was based upon an apparent dose response relationship and/or positive responses to rechallenge. In many instances the presence of concomitant disease and concomitant therapy made the causal relationship unknown. Therefore, incidence rates for ICU sedation generally represent estimates of the percentage of clinical trial patients which appeared to have a probable causal relationship.
Incidence greater than 1% - Probably Causally Related |
Anesthesia/MAC Sedation
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ICU Sedation
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Cardiovascular:
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Bradycardia
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Bradycardia
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Arrhythmia [Peds: 1.2%]
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Tachycardia Nodal [Peds: 1.6%]
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Hypotension* [Peds 17%]
(see also CLINICAL PHARMACOLOGY
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Decreased Cardiac Output
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[Hypertension Peds:8%]
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Hypotension 26%
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Central Nervous System:
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Movement* [Peds: 17%]
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Injection Site:
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Burning/Stinging or Pain, 17.6% [Peds: 10%]
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Metabolic/Nutritional:
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Hyperlipemia*
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Respiratory
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Apnea (see also CLINICAL PHARMACOLOGY)
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Respiratory Acidosis During Weaning*
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Skin and Appendages:
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Rash [Peds: 5%]
Pruritus [Peds:2%]
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Events without an * or % had an incidence of 1%-3%
*Incidence of events 3% to 10%
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Incidence less than 1% - Probably Causally Related |
Anesthesia/MAC Sedation
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ICU Sedation
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Body as a Whole:
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Anaphylaxis/Anaphylactoid Reaction
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Perinatal Disorder
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[Tachycardia]
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[Bigeminy]
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[Bradycardia]
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[Premature Ventricular Contractions]
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[Hemorrhage]
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[ECG Abnormal]
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[Arrhythmia Atrial]
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[Fever]
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[Extremities Pain]
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[Anticholinergic Syndrome]
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Cardiovascular:
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Premature Atrial Contractions
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Syncope
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Central Nervous System:
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Hypertonia/Dystonia, Paresthesia
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Agitation
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Digestive:
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[Hypersalivation]
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[Nausea]
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Hemic/Lymphatic:
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[Leukocytosis]
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Injection Site:
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[Phlebitis]
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[Pruritus]
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Metabolic:
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[Hypomagnesemia]
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Musculoskeletal:
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Myalgia
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Nervous:
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[Dizziness]
[Agitation]
[Chills]
[Somnolence]
[Delirium]
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Respiratory:
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Wheezing
[Cough]
[Laryngospasm]
[Hypoxia]
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Decreased Lung Function
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Skin and Appendages:
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Flushing, Pruritus
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Special Senses:
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Amblyopia
[Vision Abnormal]
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Urogenital:
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Cloudy Urine
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Green Urine
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Incidence less than 1% - Causal Relationship Unknown |
Anesthesia/MAC Sedation
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ICU Sedation
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Body as a Whole:
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Asthenia, Awareness, Chest Pain,
Extremities Pain, Fever, Increased
Drug Effect, Neck Rigidity/Stiffness,
Trunk pain
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Fever, Sepsis, Trunk Pain, Whole Body Weakness
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Cardiovascular:
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Arrhythmia, Atrial Fibrillation,
Atrioventricular Heart Block,
Bigeminy, Bleeding, Bundle Branch
Block, Cardiac Arrest, ECG Abnormal, Edema, Extrasystole, Heart Block, Hypertension, Myocardial
Infarction, Myocardial Ischemia,
Premature Ventricular Contractions,
ST Segment Depression,
Supraventricular Tachycardia,
Tachycardia, Ventricular Fibrillation
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Arrhythmia, Atrial Fibrillation, Bigeminy, Cardiac
Arrest, Extrasystole, Right Heart Failure, Ventricular
Tachycardia
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Central Nervous System:
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Abnormal Dreams, Agitation,
Amorous Behavior, Anxiety,
Bucking/Jerking/Thrashing,
Chills/Shivering/Clonic/Myoclonic
Movement, Combativeness,
Confusion, Delirium, Depression,
Dizziness, Emotional Lability,
Euphoria, Fatigue, Hallucinations,
Headache, Hypotonia, Hysteria,
Insomnia, Moaning, Neuropathy,
Opisthotonos, Rigidity, Seizures,
Somnolence, Tremor, Twitching
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Chills/Shivering, Intracranial Hypertension,
Seizures, Somnolence, Thinking Abnormal
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Digestive:
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Cramping, Diarrhea, Dry Mouth,
Enlarged Parotid, Nausea, Swallowing,
Vomiting
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Ileus, Liver Function Abnormal
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Hematologic/Lymphatic:
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Coagulation Disorder, Leukocytosis
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Injection Site:
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Hives/Itching, Phlebitis,
Redness/Discoloration
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Metabolic/Nutritional:
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Hyperkalemia, Hyperlipemia
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BUN Increased, Creatinine Increased, Dehydration,
Hyperglycemia, Metabolic Acidosis, Osmolality
Increased
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Respiratory:
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Bronchospasm, Burning in Throat,
Cough, Dyspnea, Hiccough,
Hyperventilation, Hypoventilation,
Hypoxia, Laryngospasm, Pharyngitis,
Sneezing, Tachypnea, Upper Airway
Obstruction
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Hypoxia
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Skin and Appendages:
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Conjunctival Hyperemia, Diaphoresis,
Urticaria
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Rash
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Special Senses:
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Diplopia, Ear Pain, Eye Pain,
Nystagmus, Taste Perversion,
Tinnitus
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Urogenital:
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Oliguria, Urine Retention
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Kidney Failure
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