Latest Key Approvals and Alerts in Diabetes & Endocrinology: June 2-October 24, 2011
On October 19, 2011, the US Food and Drug Administration (FDA) granted expanded approval for the injectable glucagon-like peptide-1 receptor agonist exenatide (Byetta®, Amylin Pharmaceuticals, Inc., San Diego, CA, and Eli Lilly and Company, Indianapolis, IN). Exenatide is now approved as an adjunct to insulin glargine, with or without metformin and/or thiazolidinedione (TZD) therapy, in patients with type 2 diabetes using diet and exercise who have not achieved adequate glycemic control on insulin glargine alone. A double-blind, placebo-controlled clinical trial found that use of exenatide in combination with insulin glargine with or without metformin and/or a TZD was associated with lowered A1c compared with placebo. No increase in hypoglycemia or weight gain was noted. The most common adverse effects included nausea, diarrhea, vomiting, headache, and constipation.
For more information, see FDA Okays Exenatide as Adjunct to Insulin Glargine.
Juvisync™, the combination of sitagliptin and simvastatin (MSD International GmbH Clonmel, Co.; Tipperary, Ireland), was approved by the FDA on October 7, 2011. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to improve glycemic control in patients with type 2 diabetes; simvastatin is a hydroxymethylglutaryl coenzyme A reductase inhibitor used to reduce low-density lipoprotein cholesterol. Juvisync is indicated for adults in whom use of both agents is appropriate. The recommended usual starting dosage is 100 mg/40 mg once daily in the evening. Prescribing information will inform clinicians of the potential for statins to increase blood sugar levels in patients with type 2 diabetes; however, the risk appears to be very small and is outweighed by the benefits of statins for reducing heart disease in patients with diabetes.
For more information, see FDA Approves Diabetes and Cholesterol-Lowering Drug Combo
New indications for the fully human monoclonal antibody Prolia® (denosumab; Amgen Manufacturing Limited; Thousand Oaks, California) were approved on September 16, 2011. Prolia is approved to increase bone mass in patients at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer. Prolia is administered subcutaneously every 6 months; patients should take calcium 1000 mg and at least 400 IU of vitamin D daily. The most common adverse effects in patients with bone loss due to hormone ablation for cancer were back pain and arthralgia.
For more information, see FDA Approves Denosumab for Patients With Cancer.
Simvastatin 80 mg (Zocor®; Merck & Co., Inc.; Whitehouse Station, New Jersey) should not be used in new patients or in patients already taking lower doses of simvastatin according to the FDA Drug Safety Communication issued June 8, 2011. Due to risk for myopathy, use of 80 mg should be limited to patients who have tolerated the dose for 1 year without muscle symptoms. Patients taking amiodarone, verapamil, or diltiazem should not receive more than 10 mg of simvastatin. Patients taking amlodipine or ranolazine should not receive more than 20 mg of simvastatin. Revised product labeling will reflect changes to dosing and drug interactions.
For more information, see FDA Restricts Use of Simvastatin 80 mg.
The FDA issued a Drug Safety Communication on September 1, 2011 stating that Reclast® (zoledronic acid injection; Novartis Pharmaceuticals Corporation; East Hanover, New Jersey) is contraindicated in patients with creatinine clearance less than 35 mL/min or with evidence of acute renal impairment. Cases of acute renal failure requiring dialysis or having a fatal outcome have been associated with this injectable used to prevent and treat osteoporosis. Clinicians should screen patients for risk prior to administration and monitor renal function during therapy. The medication guide is being updated to inform patients about this risk, and a Dear Healthcare Provider letter will be issued.
For more information, see FDA Strengthens Kidney Risk Warning for Reclast.
Product labeling has been updated for pioglitazone (Actos®; Takeda Pharmaceuticals North America, Inc.; Deerfield, Illinois). Use of pioglitazone for more than 1 year may be associated with an increased risk for bladder cancer. Pioglitazone should not be used in patients with active bladder cancer or in patients with a history of bladder cancer. Instruct patients to alert their healthcare professionals for hematuria and signs and symptoms of bladder cancer, such as urinary urgency or dysuria.
For more information, see New Pioglitazone Label Highlights Bladder-Cancer Risk.
After evaluating cancer risk associated with angiotensin receptor blockers (ARBs), medications commonly used to treat hypertension, on June 2, 2011 the FDA released their conclusion of no increased risk for cancer in patients who have taken ARBs. The FDA’s trial-level meta-analysis included 31 trials involving about 156,000 patients and an average follow-up of 39 months.
For more information, see FDA Review Concludes: No Cancer Risk With ARBs.
On July 21, 2011 the FDA announced that it was continuing to review data in regard to the risk for esophageal cancer associated with oral bisphosphonate use. Due to conflicting data, the FDA stressed that it has not concluded that patients taking oral bisphosphonates are at increased risk for esophageal cancer. According to the FDA, the benefit of oral bisphosphonates to reduce the risk for osteoporosis currently outweighs the risk. The alert notes that esophageal cancer is rare, particularly in women. Patients should be instructed to follow administration directions carefully to minimize the risk for adverse events. Additionally, the alert notes that there is not enough evidence to support endoscopic screening in asymptomatic patients.
For more information, see FDA Studying Link Between Bisphosphonates, Esophageal Cancer.