Pharmacy & Therapeutics - September 2008 - (Page 552)

Pharmaceutical Approval Update level of repaglinide/metformin, gastrointestinal (GI) symptoms, which are common during initiation of therapy, are unlikely to be drug-related. A later occurrence of GI symptoms could be a result of lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking repaglinide/metformin do not necessarily indicate impending lactic acidosis; they may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis who shows no evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital. If the patient with lactic acidosis is taking repaglinide/metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin is dialyzable (with a clearance of up to 170 mL/ minute under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and to remove accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. Assessment of renal function. Metformin is excreted mainly by the kidneys, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Therefore, patients with renal impairment should not receive repaglinide/metformin. Before therapy with repaglinide/metformin begins and at least annually thereafter, renal function should be assessed and verified as normal. If the development of renal impairment is anticipated, renal function should be assessed more frequently and the drug should be discontinued if renal impairment is evident. Radiological studies with iodinated contrast. Intravascular contrast studies with iodinated materials can lead to acute altered renal function and have been associated with lactic acidosis in patients receiving metformin HCl. Therefore, if such a study is planned, repaglinide/metformin should be temporarily discontinued at the time of or before the procedure, and it should be withheld for 48 hours after the procedure. It should be reinstituted only after renal function has been re-evaluated and has been found to be normal. Impaired hepatic function. Hepatic impairment is associated with some cases of lactic acidosis. Therefore, repaglinide/ metformin should generally be avoided in patients with hepatic impairment. Alcohol intake. Alcohol potentiates the effect of metformin on lactate metabolism. Patients should be warned against excessive alcohol intake while receiving repaglinide plus metformin. In combination with NPH-insulin: Repaglinide is not indicated for use in combination with NPH-insulin. In seven controlled trials, there were six serious adverse events (1.4%) of myocardial ischemia with repaglinide/NPH-insulin, compared with one event (0.3%) in patients using insulin alone. Dosage and Administration: PrandiMet is available as an oral tablet containing 1 mg of repaglinide plus 500 mg of metformin HCl or 2 mg of repaglinide with 500 mg of metformin HCl. Inactive ingredients include poloxamer 188, microcrystalline cellulose, polacrillin potassium, magnesium stearate, hypromellose 3cp or 6cp, povidone, meglumine, sorbitol, talc, titanium dioxide, red or yellow iron oxide, and polyethylene glycol. Propylene glycol is present in the 2-mg/500-mg tablets. The dose should be individualized according to the patient’s current regimen and tolerability and the agent’s effectiveness. The drug can be given two or three times per day up to a maximum daily dose of repaglinide 10 mg/metformin HCl 2,500 mg. No more than 4 mg/1,000 mg should be taken per meal. Initial and maintenance doses should be individualized for each patient at the discretion of the health care provider. Blood glucose monitoring should be performed to determine the therapeutic response to this medication. Doses are usually taken within 15 minutes before a meal; however, timing can vary, and patients can take the drug either immediately before a meal or up to 30 minutes before a meal. Patients who skip a meal should be instructed to skip the drug dose for that meal. Commentar y: In diabetic patients, damage to nerves and blood vessels from hyperglycemia can lead to heart disease and stroke, kidney disease, blindness, nerve problems, gum infections, and amputation. PrandiMet is the first fixed-dose combination containing a fast-acting secretagogue (Prandin) and an insulin sensitizer (metformin). The combination safely and effectively reduces HbA1c concentrations. Prandin stimulates the release of insulin from the pancreas after a meal, thereby reducing postprandial blood glucose. Metformin decreases the amount of sugar produced by the liver, thus reducing fasting blood glucose, and helps the body respond better to the insulin it makes naturally. Source: www.prandimet.com Difluprednate Ophthalmic Emulsion 0.05% (Durezol) Manufacturer: Sirion Therapeutics, Inc., Tampa, Fla. Indication: Difluprednate ophthalmic emulsion 0.05%, a topical corticosteroid, is indicated for the treatment of inflammation and pain associated with ocular surgery. Drug Class: This sterile, aqueous anti-inflammatory corticosteroid is indicated for ophthalmic use. The chemical name is 6α,9-difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20dione 21-acetate 17-butyrate (CAS Registry No. 23674-86-4). Difluprednate has a molecular weight of 508.56. Each milliliter contains the active ingredient of difluprednate 0.5 mg (0.05%). Inactive ingredients include boric acid, castor oil, glycerin, polysorbate 80, purified water, sodium acetate, sodium EDTA, and sodium hydroxide (to adjust the pH to 5.2 to 5.8). The emulsion is essentially isotonic with a tonicity of 304 to 411 mOsm/kg, and the preservative is sorbic acid 0.1%. Uniqueness of Drug: Difluprednate inhibits the inflammatory response to various inciting agents that may delay or slow healing. Corticosteroids inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. Although the mechanism of action of ocular corticosteroids is generally unknown, corticosteroids are thought to act by inducing phospholipase A2 inhibitory proteins (lipocortins). It is postulated that these 552 P&T® • September 2008 • Vol. 33 No. 9 http://www.prandimet.com

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Pharmacy & Therapeutics - September 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Effect of Prescription Copays on Adherence and Treatment Failure with Oral Antidiabetic Medications Vaccine Declinations Present New Challenges for Public Health Universal Health Care in America Digestive Disease Week and American Diabetes Association Pharmaceutical Approval Update

Pharmacy & Therapeutics - September 2008

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