"The cystic fibrosis (CF) drug Orkambi (Vertex Pharmaceuticals) has received a green light from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP).
Orkambi is a fixed-dose oral combination "...
INAPSINE (droperidol) should be administered with extreme caution in the presence of risk factors for development of prolonged QT syndrome, such as: 1) clinically significant bradycardia (less than 50 bpm), 2) any clinically significant cardiac disease, 3) treatment with Class I and Class III antiarrhythmics, 4) treatment with monoamine oxi-dase inhibitors (MAOI's), 5) concomitant treatment with other drug products known to prolong the QT interval (see PRECAUTIONS: DRUG INTERACTIONS), and 6) electrolyte imbalance, in particular hypokalemia and hypo-magnesemia, or concomitant treatment with drugs (e.g., diuretics) that may cause electrolyte imbalance.
Effects on Cardiac Conduction
A dose-dependent prolongation of the QT interval was observed within 10 minutes of droperidol administration in a study of 40 patients without known cardiac disease who underwent extracranial head and neck surgery. Significant QT prolongation was observed at all three dose levels evaluated, with 0.1, 0.175, and 0.25 mg/kg associated with prolongation of median QTc by 37, 44, and 59 msec, respectively.
Cases of QT prolongation and serious arrhythmias (e.g. torsade de pointes, ventricular arrythmias, cardiac arrest, and death) have been observed during post-marketing treatment with INAPSINE (droperidol) . Some cases have occurred in patients with no known risk factors and at doses at or below recommended doses. There has been at least one case of nonfatal torsade de pointes confirmed by rechallenge.
Based on these reports, all patients should undergo a 12-lead ECG prior to administration of INAPSINE (droperidol) to determine if a prolonged QT interval (i.e., QTc greater than 440 msec for males or 450 msec for females) is present. If there is a prolonged QT interval, INAPSINE (droperidol) should NOT be administered. For patients in whom the potential benefit of INAPSINE (droperidol) treatment is felt to outweigh the risks of potentially serious arrhythmias, ECG monitoring should be performed prior to treatment and continued for 2 to 3 hours after completing treatment to monitor for arrhythmias.
FLUIDS AND OTHER COUNTERMEASURES TO MANAGE HYPOTENSION SHOULD BE READILY AVAILABLE.
As with other CNS depressant drugs, patients who have received INAPSINE (droperidol) should have appropriate surveillance.
It is recommended that opioids, when required, initially be used in reduced doses.
As with other neuroleptic agents, very rare reports of neuroleptic malignant syndrome (altered consciousness, muscle rigidity and autonomic instability) have occurred in patients who have received INAPSINE (droperidol).
Since it may be difficult to distinguish neuroleptic malignant syndrome from malignant hyperpyrexia in the peri-operative period, prompt treatment with dantrolene should be considered if increases in temperature, heart rate or carbon dioxide production occur.
General: The initial dose of INAPSINE (droperidol) should be appropriately reduced in elderly, debilitated and other poor-risk patients. The effect of the initial dose should be considered in determining incremental doses.
Certain forms of conduction anesthesia, such as spinal anesthesia and some peridural anesthetics, can alter respiration by blocking intercostal nerves and can cause peripheral vasodilatation and hypotension because of sympathetic blockade. Through other mechanisms (see CLINICAL PHARMACOLOGY), INAPSINE (droperidol) can also alter circulation. Therefore, when INAPSINE (droperidol) is used to supplement these forms of anesthesia, the anesthetist should be familiar with the physiological alterations involved, and be prepared to manage them in the patients elected for these forms of anesthesia.
If hypotension occurs, the possibility of hypovolemia should be considered and managed with appropriate par-enteral fluid therapy. Repositioning the patient to improve venous return to the heart should be considered when operative conditions permit. It should be noted that in spinal and peridural anesthesia, tilting the patient into a head-down position may result in a higher level of anesthesia than is desirable, as well as impair venous return to the heart. Care should be exercised in moving and positioning of patients because of a possibility of orthostatic hypotension. If volume expansion with fluids plus these other countermeasures do not correct the hypotension, then the administration of pressor agents other than epinephrine should be considered. Epinephrine may paradoxically decrease the blood pressure in patients treated with INAPSINE (droperidol) due to the alpha-adrenergic blocking action of INAPSINE (droperidol) .
Since INAPSINE (droperidol) may decrease pulmonary arterial pressure, this fact should be considered by those who conduct diagnostic or surgical procedures where interpretation of pulmonary arterial pressure measurements might determine final management of the patient.
Vital signs and ECG should be monitored routinely.
Impaired Hepatic or Renal Function: INAPSINE (droperidol) should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs.
Pheochromocytoma: In patients with diagnosed/suspected pheochromocytonia, severe hypertension and tachy-cardia have been observed after the administration of INAPSINE (droperidol).
Carcinogenesis, Mutagenesis, Impairment of Fertility: No carcinogenicity studies have been carried out with INAPSINE (droperidol) . The micronucleus test in female rats revealed no mutagenic effects in single oral doses as high as 160 mg/kg. An oral study in rats (Segment I) revealed no impairment of fertility in either male or females at 0.63, 2.5 and 10 mg/kg doses (approximately 2.9 and 36 times maximum recommended human iv/im dosage).
Pregnancy: Category C: INAPSINE (droperidol) administered intravenously has been shown to cause a slight increase in mortality of the newborn rat at 4.4 times the upper human dose. At 44 times the upper human dose, mortality rate was comparable to that for control animals. Following intramuscular administration, increased mortality of the offspring at 1.8 times the upper human dose is attributed to CNS depression in the dams who neglected to remove placentae from their offspring. INAPSINE (droperidol) has not been shown to be teratogenic in animals. There are no adequate and well-controlled studies in pregnant women. INAPSINE (droperidol) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery: There are insufficient data to support the use of INAPSINE (droperidol) in labor and delivery. Therefore, such use is not recommended.
Nursing Mothers: It is not known whether INAPSINE (droperidol) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when INAPSINE (droperidol) is administered to a nursing mother. Pediatric Use: The safety of INAPSINE (droperidol) in children younger than two years of age has not been established.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/5/2008
Additional Inapsine Information
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