FDA label bc7ce430-9a37-4654-b256-3a7ef0643e9b

Warnings Use of DIPRIVAN Injectable Emulsion has been associated with both fatal and life-threatening anaphylactic and anaphylactoid reactions. For general anesthesia or monitored anesthesia care (MAC) sedation, DIPRIVAN Injectable Emulsion should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure. Sedated patients should be continuously monitored, and facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Patients should be continuously monitored for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation. These cardiorespiratory effects are more likely to occur following rapid bolus administration, especially in the elderly, debilitated, or ASA-PS III or IV patients. For sedation of intubated, mechanically ventilated patients in the Intensive Care Unit (ICU), DIPRIVAN Injectable Emulsion should be administered only by persons skilled in the management of critically ill patients and trained in cardiovascular resuscitation and airway management. Use of DIPRIVAN Injectable Emulsion infusions for both adult and pediatric ICU sedation has been associated with a constellation of metabolic derangements and organ system failures, referred to as Propofol Infusion Syndrome, that have resulted in death. The syndrome is characterized by severe metabolic acidosis, hyperkalemia, lipemia, rhabdomyolysis, hepatomegaly, cardiac and renal failure. The following appear to be major risk factors for the development of these events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents: vasoconstrictors, steroids, inotropes and/or prolonged, high-dose infusions of propofol (greater than 5 mg/kg/h for more than 48h). The syndrome has also been reported following large-dose, short-term infusions during surgical anesthesia. In the setting of prolonged need for sedation, increasing propofol dose requirements to maintain a constant level of sedation, or onset of metabolic acidosis during administration of a propofol infusion, consideration should be given to using alternative means of sedation. Abrupt discontinuation of DIPRIVAN Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of DIPRIVAN Injectable Emulsion should be adjusted to maintain a light level of sedation through the weaning process or evaluation of sedation level (see PRECAUTIONS) . DIPRIVAN Injectable Emulsion should not be coadministered through the same IV catheter with blood or plasma because compatibility has not been established. In vitro tests have shown that aggregates of the globular component of the emulsion vehicle have occurred with blood/plasma/serum from humans and animals. The clinical significance of these findings is not known. There have been reports in which failure to use aseptic technique when handling DIPRIVAN Injectable Emulsion was associated with microbial contamination of the product and with fever, infection, sepsis, other life-threatening illness, and death. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures.).

Adverse Reactions 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 ICU Sedations Cardiovascular Bradycardia Arrhythmia (Peds: 1.2%) Tachycardia Nodal (Peds: 1.6%) Hypotension* (Peds: 17%) (see also CLINICAL PHARMACOLOGY Hypertension (Peds: 8%) Bradycardia Central Nervous System Movement* (Peds:17%) Injection Site Burning/Stinging or Pain, 17.6% (Peds: 10%) Metabolic/Nutritional Hyperlipemia* Respiratory Apnea (see also CLINICAL PHARMACOLOGY Respiratory Acidosis During Weaning* Skin and Appendages Rash (Peds: 5%) Pruritus (Peds: 2%) Events without an * or % had an icidence of 1% to 3% *Incidence of events 3% to 10% Incidence less than 1% - Probably Causally Related A nesthesia/Mac Sedation ICU Sedation Body as a Whole Anaphylaxis/Anaphylactoid Reaction Perinatal Disorder (Tachycardia) (Bigeminy) (Bradycardia) (Premature Ventricular Contractions) (Hemorrhage) (ECG Abnormal) (Arrhythmia Atrial) (Fever) (Extremities Pain) (Anticholinergic Syndrome) Cardiovascular Premature Atrial Contractions Syncope Central Nervous System Hypertonia/Dystonia, Pareshesia Agitation Digestive (Hypersalivation) (Nausea) Hemic/Lymphatic (Leukocytosis) Injection Site (Plebitis) (Pruritus) Metabolic (Hypomagnesemia) Musculoskeletal Myalgia Nervous (Dizziness) (Agitation) (Chills) (Somnolence) (Delirium) Respiratory Wheezing (Cough) (Laryngospasm) (Hypoxia) Decreased Lung Function Skin and Appendages Flushing, Pruritus Special Senses Amblyopia (Vision Abnormal) 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 Arrythmia, 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 Parotic, Nausea, Swallowing, Vomiting Ileus, Liver Function Abnormal Hematologic/Lymphatic Coagulation Disorder, Leukocytosis Injection Site Hives/Itching, Phlebitis, Redness/Discoloration Metabolic/Nutritional Hyperkalemia, Hyperlipemia BUN Increased, Creatinine Increased, 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

<table ID="i2944226e-94fb-4eca-81cd-7f0d0b48d67f" width="916" border="1"> <tbody> <tr> <td/> <td>Anesthesia/MAC Sedation</td> <td>ICU Sedations</td> </tr> <tr> <td>Cardiovascular </td> <td>Bradycardia Arrhythmia (Peds: 1.2%) Tachycardia Nodal (Peds: 1.6%) Hypotension* (Peds: 17%) (see also CLINICAL PHARMACOLOGY Hypertension (Peds: 8%)</td> <td>Bradycardia </td> </tr> <tr> <td>Central Nervous System </td> <td>Movement* (Peds:17%) </td> <td/> </tr> <tr> <td>Injection Site </td> <td>Burning/Stinging or Pain, 17.6% (Peds: 10%) </td> <td/> </tr> <tr> <td>Metabolic/Nutritional </td> <td/> <td>Hyperlipemia* </td> </tr> <tr> <td>Respiratory </td> <td>Apnea (see also CLINICAL PHARMACOLOGY </td> <td>Respiratory Acidosis During Weaning* </td> </tr> <tr> <td>Skin and Appendages </td> <td>Rash (Peds: 5%) Pruritus (Peds: 2%) </td> <td/> </tr> </tbody> </table>

<table ID="if00fbbc5-ca9d-4034-8bae-85c5a440b56e" width="921" border="1"> <tbody> <tr> <td/> <td>A<content styleCode="bold">nesthesia/Mac Sedation</content> </td> <td> <content styleCode="bold">ICU Sedation</content> </td> </tr> <tr> <td>Body as a Whole </td> <td>Anaphylaxis/Anaphylactoid Reaction Perinatal Disorder (Tachycardia) (Bigeminy) (Bradycardia) (Premature Ventricular Contractions) (Hemorrhage) (ECG Abnormal) (Arrhythmia Atrial) (Fever) (Extremities Pain) (Anticholinergic Syndrome)</td> <td/> </tr> <tr> <td>Cardiovascular </td> <td>Premature Atrial Contractions Syncope</td> <td/> </tr> <tr> <td>Central Nervous System </td> <td>Hypertonia/Dystonia, Pareshesia </td> <td>Agitation </td> </tr> <tr> <td>Digestive </td> <td>(Hypersalivation) (Nausea)</td> <td/> </tr> <tr> <td>Hemic/Lymphatic </td> <td>(Leukocytosis) </td> <td/> </tr> <tr> <td>Injection Site </td> <td>(Plebitis) (Pruritus)</td> <td/> </tr> <tr> <td>Metabolic </td> <td>(Hypomagnesemia) </td> <td/> </tr> <tr> <td>Musculoskeletal </td> <td>Myalgia </td> <td/> </tr> <tr> <td>Nervous </td> <td>(Dizziness) (Agitation) (Chills) (Somnolence) (Delirium)</td> <td/> </tr> <tr> <td>Respiratory </td> <td>Wheezing (Cough) (Laryngospasm) (Hypoxia)</td> <td>Decreased Lung Function </td> </tr> <tr> <td>Skin and Appendages </td> <td>Flushing, Pruritus </td> <td/> </tr> <tr> <td>Special Senses </td> <td>Amblyopia (Vision Abnormal)</td> <td/> </tr> <tr> <td>Urogenital </td> <td>Cloudy Urine </td> <td>Green Urine </td> </tr> </tbody> </table>

<table ID="ia8e62316-8cc1-4132-82b4-c9b877da821b" width="920" border="1"> <tbody> <tr> <td/> <td>Anesthesia/MAC Sedation</td> <td>ICU Sedation</td> </tr> <tr> <td>Body as a Whole</td> <td>Asthenia, Awareness, Chest Pain, Extremities Pain, Fever, Increased Drug Effect, Neck Rigidity/Stiffness, Trunk Pain</td> <td>Fever, Sepsis, Trunk Pain, Whole Body Weakness</td> </tr> <tr> <td>Cardiovascular</td> <td>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</td> <td>Arrythmia, Atrial Fibrillation, Bigeminy, Cardiac Arrest, Extrasystole, Right Heart Failure, Ventricular Tachycardia</td> </tr> <tr> <td>Central Nervous System</td> <td>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</td> <td>Chills/Shivering, Intracranial Hypertension, Seizures, Somnolence, Thinking Abnormal</td> </tr> <tr> <td>Digestive</td> <td>Cramping, Diarrhea, Dry Mouth, Enlarged Parotic, Nausea, Swallowing, Vomiting</td> <td>Ileus, Liver Function Abnormal</td> </tr> <tr> <td>Hematologic/Lymphatic </td> <td>Coagulation Disorder, Leukocytosis </td> <td/> </tr> <tr> <td>Injection Site</td> <td>Hives/Itching, Phlebitis, Redness/Discoloration</td> <td/> </tr> <tr> <td>Metabolic/Nutritional</td> <td>Hyperkalemia, Hyperlipemia</td> <td>BUN Increased, Creatinine Increased, Dehydration, Hyperglycemia, Metabolic Acidosis, Osmolality Increased</td> </tr> <tr> <td>Respiratory</td> <td>Bronchospasm, Burning in Throat, Cough, Dyspnea, Hiccough, Hyperventilation, Hypoventilation, Hypoxia, Laryngospasm, Pharyngitis, Sneezing, Tachypnea, Upper Airway Obstruction</td> <td>Hypoxia</td> </tr> <tr> <td>Skin and Appendages</td> <td>Conjunctival Hyperemia, Diaphoresis, Urticaria</td> <td>Rash</td> </tr> <tr> <td>Special Senses</td> <td>Diplopia, Ear Pain, Eye Pain, Nystagmus, Taste Perversion, Tinnitus</td> <td/> </tr> <tr> <td>Urogenital </td> <td>Oliguria, Urine Retention </td> <td>Kidney Failure </td> </tr> </tbody> </table>