SIDE EFFECTS
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 Children
Generally the adverse experience profile from reports
of 349 DIPRIVAN Injectable Emulsion pediatric patients
between the ages of 3 and 12 years 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) 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 |
ICU Sedation |
| Cardiovascular: |
Bradycardia
Hypotension* [Peds: 17%]
[Hypertension Peds: 8%]
(see also CLINICAL PHARMACOLOGY) |
Bradycardia,
Decreased
Cardiac Output,
Hypotension 26% |
| Central Nervous
System: |
Movement*
[Peds: 17%] |
|
| Injection
Site: |
Burning/Stinging
or Pain, 17.6% |
|
|
[Peds: 10%] |
|
| Metabolic/Nutritional: |
|
Hyperlipemia* |
| Respiratory: |
Apnea |
Respiratory
Acidosis |
|
(see also
CLINICAL PHARMACOLOGY) |
During Weaning* |
| Skin and
Appendages: |
Rash [Peds:
5%] |
|
| Events without an * or %
had an incidence of 1%-3% |
| * Incidence
of events 3% to 10% |
| Incidence
less than 1% - Probably Causally Related |
|
Anesthesia/MAC
Sedation |
ICU Sedation |
| Body as a
Whole: |
Anaphylaxis/Anaphylactoid
Reaction, Perinatal Disorder |
|
| Cardiovascular: |
Premature
Atrial Contractions,
Syncope |
|
| Central Nervous
System: |
Hypertonia/Dystonia,
Paresthesia |
Agitation |
| Digestive: |
Hypersalivation |
|
| Musculoskeletal: |
Myalgia |
|
| Respiratory: |
Wheezing |
Decreased
Lung Function |
| Skin and
Appendages: |
Flushing,
Pruritus |
|
| Special Senses: |
Amblyopia |
|
| Urogenital: |
Cloudy Urine |
Green Urine |
| Incidence
less than 1% - Causal Relationship Unknown |
|
Anesthesia/MAC
Sedation |
ICU Sedation |
| Body as a
Whole: |
Asthenia,
Awareness, Chest Pain
Extremities Pain, Fever,
Increased Drug Effect,
Neck Rigidity/Stiffness, Trunk Pain |
Fever, Sepsis,
Trunk Pain,
Whole Body Weakness |
| Cardiovascular: |
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 |
Arrhythmia,
Atrial
Fibrillation, Bigeminy,
Cardiac Arrest,
Extrasystole, Right
Heart Failure, Ventricular
Tachycardia |
| Central Nervous
System: |
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 |
Chills/Shivering,
Intracranial Hypertension,
Seizures, Somnolence,
Thinking Abnormal |
| Digestive: |
Cramping,
Diarrhea, Dry Mouth,
Enlarged Parotid, Nausea,
Swallowing, Vomiting |
Ileus, Liver
Function
Abnormal |
| Hematologic/Lymphatic: |
Coagulation
Disorder,
Leukocytosis |
. |
| Injection
Site: |
Hives/Itching,
Phlebitis,
Redness/Discoloration |
|
| Metabolic/Nutritional: |
Hyperkalemia,
Hyperlipemia
Increased |
BUN Increased,
Creatinine, Dehydration,
Hyperglycemia, Metabolic
Acidosis, Osmolality
Increased |
| Respiratory: |
Bronchospasm,
Burning in
Throat, Cough, Dyspnea,
Hiccough, Hyperventilation,
Hypoventilation, Hypoxia,
Laryngospasm, Pharyngitis,
Sneezing, Tachypnea, Upper
Airway Obstruction |
Hypoxia |
| Skin and
Appendages: |
Conjunctival
Hyperemia,
Diaphoresis, Urticaria |
Rash |
| Special Senses: |
Diplopia,
Ear Pain, Eye Pain,
Nystagmus, Taste Perversion, Tinnitus |
|
| Urogenital: |
Oliguria,
Urine Retention |
Kidney Failure |
DRUG INTERACTIONS
The induction dose requirements of DIPRIVAN Injectable
Emulsion may be reduced in patients with intramuscular
or intravenous premedication, particularly with narcotics
(eg, morphine, meperidine, and fentanyl, etc.) and combinations
of opioids and sedatives (eg, benzodiazepines, barbiturates,
chloral hydrate, droperidol, etc.). These agents may increase
the anesthetic or sedative effects of DIPRIVAN Injectable
Emulsion and may also result in more pronounced decreases
in systolic, diastolic, and mean arterial pressures and
cardiac output.
During maintenance of anesthesia or sedation, the rate
of DIPRIVAN Injectable Emulsion administration should
be adjusted according to the desired level of anesthesia
or sedation and may be reduced in the presence of supplemental
analgesic agents (eg, nitrous oxide or opioids). The concurrent
administration of potent inhalational agents (eg, isoflurane,
enflurane, and halothane) during maintenance with DIPRIVAN
Injectable Emulsion has not been extensively evaluated.
These inhalational agents can also be expected to increase
the anesthetic or sedative and cardiorespiratory effects
of DIPRIVAN Injectable Emulsion.
DIPRIVAN Injectable Emulsion does not cause a clinically
significant change in onset, intensity, or duration of
action of the commonly used neuromuscular blocking agents
(eg, succinylcholine and nondepolarizing muscle relaxants).
No significant adverse interactions with commonly used
premedications or drugs used during anesthesia or sedation
(including a range of muscle relaxants, inhalational agents,
analgesic agents, and local anesthetic agents) have been
observed.
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