Pharmacy & Therapeutics - February 2009 - (Page 86)

Pharmaceutical Approval Update Mar vin M. Goldenberg, PhD, RPh, MS Fospropofol Disodium Injection (Lusedra) Manufacturer: Eisai, Woodcliff Lake, N.J. Indication: Fospropofol disodium, an intravenous (IV) sedative–hypnotic agent, is indicated for monitored anesthesia care sedation in adults undergoing diagnostic or therapeutic procedures. Drug Class: Fospropofol disodium (dihydrogen{2,6di-isopropylphenoxy}methyl phosphate) injection is a water-soluble prodrug of propofol. It is converted into propofol by alkaline phosphatase enzymes in the body after it is administered. Uniqueness of Drug: Fospropofol is metabolized into propofol by the liver. After a bolus of fospropofol is given, blood levels of propofol reach peak levels that are lower than those of an equipotent dose of propofol, and the clinical effect is more sustained. Warnings and Precautions: Monitoring. Only persons who are trained in administering general anesthesia and who are not involved in the diagnostic or therapeutic procedure should administer fospropofol. Facilities should be available to maintain a patent airway, provide artificial ventilation, administer supplemental oxygen, and begin cardiovascular resuscitation. Patients should be continuously monitored during sedation and throughout recovery for early signs of hypotension, apnea, airway obstruction, or oxygen desaturation. Respiratory depression. The product may cause a loss of spontaneous respiration. Apnea was reported in fewer than 1% of patients treated with fospropofol according to the standard or modified dosing regimen. When more than the recommended dose was given, apnea was reported in 3% of patients. Supplemental oxygen is recommended for all patients receiving fospropofol. Dosages must be tailored for each patient and titrated to effect. Lower doses are required for patients 65 years of age or older or who have severe systemic disease. The additive cardiorespiratory effects of narcotic analgesics and sedative–hypnotic agents should be considered if they are given concomitantly with fospropofol. Patients should be assessed for their ability to demonstrate purposeful responses during sedation; patients who cannot respond may lose protective reflexes. Airway assistance maneuvers may be required to manage respiratory depression. Hypoxemia. Fospropofol may cause hypoxemia that is detectable by pulse oximetry. Hypoxemia was reported in 4% of patients receiving fospropofol according to the standard or modified dosing regimens. Hypoxemia was reported among patients who continued to respond purposefully to their health care provider after receiving the drug. Therefore, retaining responsiveness did not prevent patients from becoming hypoxemic after they received an injection. When a larger-thanThe author is President of Pharmaceutical and Scientific Services at Marvin M. Goldenberg, LLC, in Westfield, N.J. His e-mail address is marvinmgoldenberg@verizon.net. recommended dose was given, hypoxemia was reported in 27% of patients. The risk of hypoxemia can be reduced by appropriate positioning of the patient and by the use of supplemental oxygen. Airway assistance maneuvers may be required to manage hypoxemia. The additive cardiorespiratory effects of narcotic analgesics and other sedative– hypnotic agents should be considered if they are given concomitantly with fospropofol. Patient unresponsiveness to stimulation. Fospropofol has not been studied for use in general anesthesia; however, it can inadvertently cause patients to become unresponsive or minimally responsive to vigorous tactile or painful stimulation. Four percent of patients who had been sedated for colonoscopy became minimally responsive or completely unresponsive to forceful tactile stimulation for 2 to 16 minutes. Among patients sedated for bronchoscopy, 16% became minimally or completely unresponsive to vigorous tactile or painful stimulation for 2 to 20 minutes. Hypotension. Hypotension has occurred after the use of fospropofol and has been reported in 4% of patients who were given the standard or modified dosing regimen. In patients receiving more than the recommended dose, hypotension was reported in 6% of patients. Patients with compromised myocardial function, reduced vascular tone, or decreased intravascular volume may be at an increased risk for hypotension. A secure IV access catheter and supplemental volume replacement fluids should be readily available. Additional pharmacological management may be necessary. Dosage and Administration. Supplemental oxygen should be used for all patients undergoing sedation with fospropofol. Patients should be continuously monitored with pulse oximetry, electrocardiograms, and frequent blood pressure measurements. Standard regimen: The initial IV bolus dose is 6.5 mg/kg, followed by supplemental doses of 1.6 mg/kg as needed. The initial dose should not exceed 16.5 mL, and any supplemental dose should not exceed 4 mL. Modified regimen: A modified regimen (75% of the standard dose) is indicated for patients 65 years of age or older with severe systemic disease, based on the American Society of Anesthesiologists (ASA) physical status classification of P3 or P4. Supplemental doses should be given only when patients can demonstrate purposeful movements in response to verbal or light tactile stimulation and no more frequently than every four minutes. For adults weighing more than 90 kg, the dose should be the same as if they weighed 90 kg. For adults weighing less than 60 kg, the dose is the same as if they weighed 60 kg. The drug is intended for single-use administration only. Standard regimen for sedation. For adults between 18 and 65 years of age who are healthy or who have mild systemic disease (ASA P1 or P2), the standard dosing regimen of fospropofol is an initial IV bolus of 6.5 mg/kg, followed by sup- 86 P&T® • February 2009 • Vol. 34 No. 2

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Pharmacy & Therapeutics - February 2009 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Pushing an Expanded Role for Pharmacists Better Asthma Management with Advanced Technology Pharmaceutical Approval Update 58th Annual Meeting, American Society of Human Genetics, 2008 American Society of Hematology, 50th Annual Meeting and Exposition 2008 San Antonio Breast Cancer Symposium Stahl’s Essential Psychopharmacology, 3rd Edition Author Guidelines

Pharmacy & Therapeutics - February 2009

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