NEW DRUG FOR DIABETES APPROVED
Appropriate for both type 1 and type 2.
A new and unique injectable drug has been approved for the control of hyperglycemia in patients with diabetes. Pramlintide (Symlin) is a synthetic analog of human amylin, a hormone that, like insulin, is secreted by the beta cells of the pancreas and works in conjunction with insulin to control postprandial glucose levels by suppressing glucagon secretion. Pramlintide is used to treat adults with type 1 or type 2 diabetes who have not achieved glucose control despite taking insulin at mealtimes. Because the drug also slows the movement of food through the gastrointestinal tract, patients with gastroparesis shouldn't take it.
Pramlintide is intended to serve as an adjunct to insulin therapy, not as a replacement for it. When taken concurrently with insulin prior to a meal, the drug helps to prevent hyperglycemia for three hours afterward, producing less fluctuation in daily glucose levels, providing better long-term glucose control (as measured by glycosylated hemoglobin AIc), and promoting weight loss better than insulin alone does. However, pramlintide increases the risk of insulin-induced hypoglycemia during the three hours after injection, and severe hypoglycemia is possible, especially in patients with type 1 diabetes. The risk of hypoglycemia is even greater if the patient administers more insulin or pramlintide than prescribed, does not eat after taking pramlintide, has a low glucose level before taking the drug, or drinks alcohol. Nausea, the most common adverse effect of pramlintide, is usually present at the beginning of therapy but dissipates quickly. The incidence and severity of nausea is reduced if the drug is initiated at low doses and gradually increased to the maintenance dose.
Pramlintide is administered by subcutaneous injection into the abdomen or thigh. Because drug absorption is too variable with injection into the arm, that site is avoided. Because of the possibility of a drug interaction, pramlintide must be administered separately from insulin and should not be injected near the site of the insulin injection.
The dose of pramlintide is determined according to the type of diabetes; a higher dose is used in type 2. Therapy is begun at a low dose and then gradually increased, according to the directions on the drug label and in the medication guide. At the initiation of the drug therapy, it's important that the dose of insulin taken before meals be reduced by half. If pramlintide is discontinued for a period of time, such as when the patient is not eating during an illness, it should be recommenced at the initial low dose and again increased gradually until the recommended dose has been achieved.
Because of the risk of hypoglycemia, patients who take pramlintide must adhere to the therapy regimen and work closely with the prescriber to achieve glucose control. Patients who are unable to discern when they are hypoglycemic should not take the drug. Patients should be informed that they must eat a meal that has at least 250 kcal or 30 g carbohydrate and that if they are unable to eat, they should refrain from taking the drug. Patients should be instructed to keep a source of fast-acting sugar at hand, such as glucose tablets or juice, in the event that hypoglycemia develops. Patient education should emphasize that a medication guide is provided with each refilled prescription, and that it should be read in its entirety each time, as the information may have changed--the success of pramlintide therapy is contingent upon the patient's participation in his own care. Education should also emphasize testing the blood sugar before each meal, two hours afterward, and at bedtime, at least initially, during titration of the dose.
Pramlintide has been tested and approved for use in only adult patients with type 1 or type 2 diabetes who take insulin at mealtimes; the use of the drug in other populations, such as children or pregnant or nursing women, carries unknown risks. That fact, together with the possibility of significant adverse effects of the drug, is the reason that off-label prescribing of it should be avoided.
Because of the unique action and special administration requirements of pramlintide, the possibility of the incidence of medication error is high. The risk of administering an incorrect dose of the drug seems possible, for example, because it's measured in micrograms while the manufacturer recommends the use of an insulin syringe that measures units. A conversion chart supplied in the medication guide, available to both health care providers and patients, indicates that a pramlintide dose of 60 micrograms is equal to 10 units of the drug in such a syringe--a misreading of the order, or an error in the prescription, might result in the administration of 60 units, putting the patient at risk for severe hypoglycemia.
In patients who don't inject themselves, pramlintide doses should be checked by two nurses prior to administration, to prevent a dosing error.
U.S. Food and Drug Administration. FDA talk paper: FDA approves new drug to treat type 1 and type 2 diabetes. 2005. http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01345.html; Amylin Pharmaceuticals. Symlin. 2005. http://www.symlin.com.
NEWS FROM THE FDA
Brief updates issued by the Food and Drug Administration.
Entecavir.
A new drug, entecavir (Baraclude), which has been approved for the treatment of chronic hepatitis B virus (HBV) infection, slows progression of the disease by interfering with viral reproduction. The adverse effects produced by the drug are the same as those produced in other HBV drug therapy and include severe, acute exacerbation of hepatitis B after the cessation of therapy, headache, gastrointestinal problems (abdominal pain, diarrhea), fatigue, and dizziness. The liver function in patients taking the drug should be monitored periodically.
Zoledronic acid.
A new warning has been added to the labeling of zoledronic acid (Zometa), which is used to treat hypercalcemia and the metastasis of solid tumors to bone. In patients with advanced cancer in whom baseline creatinine clearance is 60 mL/min or lower, the drug may cause clinically significant deterioration in renal function. Single doses shouldn't exceed 4 mg and should be infused over at least a 15-minute interval to minimize that risk. Serum creatinine should be assessed before each dose is administered, and the dose withheld if there is evidence of renal deterioration.
Rosuvastatin.
The labeling of rosuvastatin (Crestor), a lipid-lowering statin, has been revised and a public health advisory concerning the drug issued, after an extensive U.S. Food and Drug Administration (FDA) review of all pertinent clinical trial data and postmarketing reports revealed that it carries a risk of causing rhabdomyolysis that is comparable to other statin drugs. Overall, the incidence of the disease among patients taking the drug has been found to be slight. It has been revealed in pharmacokinetic studies that Asian patients are likely to have circulating levels of rosuvastatin twice as high as those found in white patients, posing a greater risk of rhabdomyolysis.
Because higher dosing (at 40 mg) appears to be related to a higher incidence of rhabdomyolysis, the label has been revised to emphasize this risk, bearing the recommendation that 5 mg be used as the initial dose in patients in whom aggressive cholesterol reduction is not necessary or in those in whom there is a predisposing factor for myopathy, such as Asians, patients taking cyclosporine, and those with severe renal insufficiency. While case reports have documented kidney failure of various types in patients treated with rosuvastatin, comorbidities (diabetes, hypertension, atherosclerosis, or heart failure) place such patients at greater risk for it already. It's not possible at this time to determine whether statins in general or rosuvastatin in particular causes or worsens kidney failure. But nurses should monitor kidney function carefully in all patients at risk for developing kidney failure, including those taking statins.
Temozolomide.
A new indication has been approved for temozolomide (Temodar), a drug already approved for the treatment of anaplastic astrocytoma, a type of brain tumor, in adult patients. The new indication is the use of the drug concurrently with radiotherapy in adult patients who have a different type of brain cancer, glioblastoma multiforme, a usage that has been found to increase the median survival of such patients by two and a half months, a slight but significant benefit.
Albuterol.
Finally, the FDA has announced that after December 31, 2008, albuterol (Proventil and others) metered-dose inhalers using chlorofluorocarbons can no longer be produced, marketed, or sold in the United States, since newer, more environmentally friendly propellants are expected to be available in sufficient quantities by that date. Although the new metered-dose inhalers are expected to be more expensive, their manufacturers are implementing programs to help low-income patients to acquire them (giveaways, price-reduction coupons, and assistance programs based on financial need).
U.S. Food and Drug Administration. FDA talk paper: FDA approves new treatment for chronic hepatitis B. 2005. http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01348.html; U.S. Food and Drug Administration. Zometa. 2004. http://www.fda.gov/medwatch/SAFETY/2005/Zometa_deardoc_12202005.pdf; U.S. Food and Drug Administration. Zometa [revised label]. 2004. http://www.fda.gov/medwatch/SAFETY/2005/Zometa_PI_nov2004.pdf; U.S. Food and Drug Administration. FDA news: FDA provides updated patient and healthcare provider information concerning Crestor. 2005. http://www.fda.gov/bbs/topics/news/2005/NEW01159.html; U.S. Food and Drug Administration. FDA public health advisory on Crestor (rosuvastatin). 2005. http://www.fda.gov/cder/drug/advisory/crestor_3_2005.htm; U.S. Food and Drug Administration. Rosuvastatin calcium (marketed as Crestor) information. 2005. http://www.fda.gov/cder/drug/infopage/rosuvastatin/default.htm; U.S. Food and Drug Administration. FDA talk paper: Temodar approved for glioblastoma multiforme. 2005. http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01344.html; U.S. Food and Drug Administration. FDA talk paper: FDA publishes final rule on chlorofluorocarbons in metered dose inhalers. 2005. http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01349.html; U.S. Food and Drug Administration. Questions and answers on final rule of albuterol MDI's. 2005. http://www.fda.gov/cder/mdi/mdifaqs.htm.