Pharmacy & Therapeutics - June 2008 - (Page 362)

Pharmaceutical Approval Update Mar vin M. Goldenberg, PhD, RPh, MS Azacitidine for Injection (Vidaza), Intravenous or Subcutaneous Manufacturer: Pharmion Corporation, Boulder, Colo. Drug Class: Azacitidine for injection is a pyrimidine nucleoside analogue of cytidine. The drug’s formula is 4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one. Uniqueness of Drug: Azacitidine, an antineoplastic agent, utilizes a dual mechanism of action, causing the hypomethylation of DNA and exerting direct cytotoxicity in abnormal hematopoietic cells in the bone marrow. Hypomethylation may restore normal gene function to genes controlling cellular division and differentiation (the genes presumed to be abnormal or nonfunctional in myelodysplastic syndromes). Cytotoxic effects cause the death of rapidly dividing abnormal cells. Azacitidine is not strongly active in nonproliferating cells; thus, toxicity is limited to that resulting from affected tissues. Indication: Azacitidine was approved as an injectable suspension in 2004 for the treatment of myelodysplastic syndrome subtypes, including refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions); refractory anemia with excess blasts (RAEB); refractory anemia with excess blasts in transformation (RAEB-t); and chronic myelomonocytic leukemia (CML). These syndromes result in underproduction of healthy blood cells. Medically Accepted Off-Label Uses: This category represents only those indications that have been submitted to the American Hospital Formular y Ser vice: Drug Information (AHFS DI) via a formal application process. A medically accepted off-label use of azacitidine is for acute myelogenous leukemia (AML) with multilineage dysplasia (previously RAEB-t). Dose regimen: Azacitidine 75 mg/m2 is administered as a subcutaneous (SQ) injection on days one to seven on an every28-day cycle. Strength of evidence (study endpoints): Level 3; low quality (overall). Grade of recommendation (final composite ratings): and had equity interests in Celgene; however, the consultant did not participate in or vote on the final determination. Another off-label use (as determined by AHFS DI) is for untreated AML in elderly patients (older than 60 years of age) who are not considered eligible to receive conventional induction therapy, as defined by a poor performance status or evidence of a clinically important comorbidity. Dose regimen: Azacitidine 75 mg/m2 is administered as a subcutaneous (SQ) injection on days one to seven on an every28-day cycle. Endpoints: Objective response rate (ORR) and overall survival. Grade of recommendation: B-3 for elderly patients with AML (ORR and survival) Disclosure information: AHFS DI committee members have disclosed no conflict of interest for this particular matter review. A consultant who provided expert commentary disclosed consultant activities with Pharmion and Celgene, participated in speaker’s bureau activities with MGI and Celgene, and had equity interests in Celgene; however, the consultant did not participate or vote on the final determination. Sources: www.vidaza.com; www.ashp.org/ahfs/off-labeluses/azacitidine.pdf Lubiprostone (Amitiza) Manufacturer: Sucampo Pharmaceuticals, Inc., Division of Takeda, Deerfield, Ill. Indications: Irritable bowel syndrome with constipation (new). Lubiprostone is indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) in women 18 years of age and older. IBS-C is also called constipation-predominant irritable bowel syndrome. Chronic idiopathic constipation (previously FDAapproved). Lubiprostone was approved for the treatment of B-2 for AML (previously RAEB-t) (overall survival). This was determined to be a “Reasonable Choice” (i.e., treatment option); it is reasonable to use the drug under certain conditions (e.g., patient subgroups); can be useful, effective, and beneficial and is probably recommended or indicated. Disclosure information: AHFS DI committee members have disclosed no conflict of interest for this particular matter review. A consultant who provided expert commentary disclosed consultant activities with Pharmion and Celgene, participated in speaker’s bureau activities with MGI and Celgene, The 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. chronic idiopathic constipation in adults in January 2006. Drug Class: A locally acting chloride channel activator, lubiprostone triggers type-2 chloride channels (CIC-2), a normal constituent of the luminal membrane of the human intestine that enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium serum concentrations. By increasing intestinal fluid secretion, lubiprostone increases intestinal motility, which facilitates the passage of stool and alleviates symptoms associated with IBS-C in women and with chronic idiopathic constipation in men and women. Uniqueness of Drug: Compared with current therapies on the market, lubiprostone locally activates specific chloride channels (ClC-2) in the lining of the small intestines after oral administration, thereby increasing intestinal fluids and softening bowel movements. 362 P&T® • June 2008 • Vol. 33 No. 6 http://www.vidaza.com http://www.ashp.org/ahfs/off-labeluses/azacitidine.pdf http://www.ashp.org/ahfs/off-labeluses/azacitidine.pdf

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Editorial Aliskiren Reduces Plasma Renin Activity Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Challenges in Evaluating and Standardizing Medical Devices in Health Care Facilities California e-Pedigree Rules Pose Challenges For Pharmacies Pharmaceutical Approval Update American Psychiatric Association At a Glance: Dermatology Trends in Managed Care

Pharmacy & Therapeutics - June 2008

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