Pharmacy & Therapeutics - February 2009 - (Page 87)

Pharmaceutical Approval Update plemental doses of IV 1.6 mg/kg (25% of the initial dosage), as needed, to achieve the desired level of sedation. The dosage is limited by lower and upper weight bounds of 60 kg and 90 kg. Adults who weigh more than 90 kg are treated as if they weighed 90 kg. No initial dose should exceed 16.5 mL, and no supplemental dose should exceed 4 mL. Adults weighing less than 60 kg are treated as if they weighed 60 kg. Dosages lower than those specified for the lower weight limit may be used to achieve lower levels of sedation. In clinical studies, an opioid premedication (IV fentanyl citrate 50 mcg) was administered five minutes before the initial dose of fospropofol. Modified regimen for sedation in elderly patients or in those with severe systemic disease. Adults 65 years of age or older or those with ASA P3 or P4 status should receive initial and supplemental IV dosages of 75% of the standard dosing regimen. Fospropofol is administered as an IV bolus injection. In clinical studies, an opioid premedication (IV fentanyl citrate 50 mcg) was given five minutes before the first fospropofol dose. Commentar y: As an IV sedative–hypnotic agent in adults, fospropofol is a new water-soluble prodrug of propofol. The water-soluble formulation aims to bypass the disadvantages of propofol’s lipid emulsion: pain on injection, risk of infection from decreased bacterial clearance, the need for a high lipid intake during long- term administration, and dose-related cardiac and respiratory depression. Fospropofol be should be given by health care providers who are appropriately trained in administering general anesthesia. Patients should be continuously monitored during sedation and during recover y to check for early signs of hypotension, apnea, airway obstruction, or oxygen desaturation. Sources: www.eisai.com; http://vam.anest.ufl.edu; www.news-medical.net/?id=44169 Warnings and Precautions: Tumor cell mobilization in leukemia. In mobilizing HSCs, plerixafor may cause movement of leukemic cells and subsequent contamination of the apheresis product (plerixafor). (The collection process is sometimes called leukapheresis or apheresis, the removal of white blood cells.) Therefore, plerixafor is not intended for HSC mobilization or harvest in patients with leukemia. Hematological effects: Leukocytosis. Administration of plerixafor with G-CSF increases circulating leukocytes as well as HSCs. White blood cell counts should be monitored in patients receiving plerixafor. Clinical judgment should be used if peripheral blood neutrophil counts exceed 50,000/mcL. Thrombocytopenia. Thrombocytopenia has been observed in patients receiving plerixafor. Platelet counts should be monitored in all patients who receive plerixafor and who then undergo apheresis. Potential for tumor cell mobilization. When plerixafor is used with G-CSF for HSC mobilization‚ tumor cells may be released from the marrow and may collect in the leukapheresis product. The effect of potential re-infusion of tumor cells has not been thoroughly studied. Splenic enlargement and potential for rupture. Higher absolute and relative spleen weights associated with extramedullary hematopoiesis were observed following prolonged daily plerixafor subcutaneous (SQ) administration (two to four weeks) in rats at doses approximately four-fold higher than the recommended human dose based on body surface area. The effect of plerixafor on spleen size has not been evaluated. Patients who receive plerixafor with G-CSF and who report left upper-abdominal pain or scapular or shoulder pain should be assessed for splenic integrity. Pregnancy category D. Plerixafor may cause fetal harm when administered to pregnant women. It was teratogenic in animals. There are no adequate controlled studies of the drug during pregnancy. Women of childbearing age should be advised to avoid becoming pregnant while they are receiving plerixafor. If the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. Dosage and Administration. Plerixafor treatment is initiated after the patient has received G-CSF once daily for four days. The plerixafor dose is repeated for up to four consecutive days. The dose is based on 0.24 mg/kg of the patient’s actual body weight and is given by SQ injection approximately 11 hours before apheresis begins. In patients with renal impairment (a creatinine clearance of 50 mL/minute or less), the dose should be decreased by one-third to 0.16 mg/kg. Each singleuse vial is filled to deliver 1.2 mL of a 20-mg/mL solution containing 24 mg of plerixafor. Commentar y: Plerixafor, in combination with G-CSF, was designed to mobilize HSCs from the bone marrow into the bloodstream, where they could be collected, making it more likely for patients with certain types of cancers (NHL and MM) to undergo to autologous transplantation. Currently, before transplantation takes place, patients usually receive a prescribed dose of chemotherapy, growth factors (G-CSF), or both, to help mobilize HSCs into the bloodstream. Plerixafor (Mozobil) Manufacturer: Genzyme Corporation, Cambridge, Mass. Indication: Plerixafor, in combination with granulocyte–colony stimulating factor (G-CSF), is indicated for mobilizing hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). Dr ug Class: The agent’s chemical name is l,1´-[1,4phenylenebis(methylene)]-bis-1,4,8,11-tetra-azacyclotetradecane. The molecular formula is C28H54N8, and the molecular weight is 502.79 g/mol. Uniqueness of Product: Plerixafor, an inhibitor of the CXCR4 chemokine receptor, blocks binding of its cognate ligand, stromal cell–derived factor-1 (SDF-1). SDF-1 and CXCR4 play a role in the trafficking and homing of human HSCs to the marrow. After the stem cells are in the marrow, stem cell CXCR4 anchors these cells to the marrow matrix, either directly via SDF-1 or through the induction of other adhesion molecules. Plerixafor has resulted in leukocytosis and elevation of circulating hematopoietic progenitor cells in mice, dogs, and humans. CD34+ cells mobilized by plerixafor were capable of engraftment with long-term repopulating capacity up to one year in canine transplantation. Vol. 34 No. 2 • February 2009 • P&T® 87 http://www.eisai.com http://vam.anest.ufl.edu http://www.news-medical.net/?id=44169

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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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