18 Metabolic Disorders FAMILY P RACTICE N EWS • August 15, 2006 ing, presented by the Alzheimer’s Associa- cluded a blood glucose test and testing for Alzheimer’s Risk Elevated as Well tion. “And it will become more and more dementia and Alzheimer’s disease. Diabetics from page 1 important as we experience the epidemic of The mean follow-up was 5 years per per- obesity in the United States.” son. By that time, borderline diabetes had istry, who were surveyed from 1994 to 1996. were below 10%. Diabetic patients are ad- Even patients with borderline diabetes been identified in 47 subjects and 397 had The mean age at baseline was 66 years; 66% vised to keep their HbA1c below 7%. should be aware of controlling their glu- been diagnosed with dementia (307 with were white, 10% black, and the rest were Those with HbA1c levels of 12%-15% cose levels, said Dr. Laura Fratiglioni, who Alzheimer’s). Hispanic, Asian, or Native American. were 22% more likely to develop demen- presented research completed by her col- After controlling for vascular risk fac- The patients were followed until 2005. tia, while those whose levels were be- league, Dr. Weili Xu of the Karolinska In- tors, borderline diabetes was associated By then, 11% had developed new-onset de- tween 10% and 11.9% had a 16% increased stitute, Stockholm. with a 67% increased risk for developing mentias. Hemoglobin A1c (HbA1c) was sig- risk. The increased risks remained signifi- Their 9-year study tracked the incidence a dementia and a 77% increased risk for de- nificantly associated with the incidence of cant even after adjusting for age, race, gen- of dementia in 1,173 subjects older than 75 veloping Alzheimer’s, Dr. Fratiglioni said. dementia. Patients with the highest HbA1c der, weight, and diabetes treatment. years who were free of both dementia and Additional analysis found that the risk was (15% and higher) were the most likely to “This shows us that tight glycemic con- diabetes at baseline. increased yet again in those with border- develop dementia, with an elevated risk of trol continues to be as important as pa- The subjects were examined three times line diabetes who also had a systolic blood 78% compared with those whose levels tients’ age,” Dr. Whitmer said at the meet- during the study period; each exam in- pressure of 180 mm Hg or higher. ■ BRIEF SUMMARY PRECAUTIONS Administration of approximately 9 times the MRHD of 145mg/day of CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION Initial therapy: Laboratory studies should be done to ascertain that the lipid fenofibrate to female rats before and throughout gestation caused 100% of levels are consistently abnormal before instituting TRICOR therapy. Every dams to delay delivery and resulted in a 60% increase in post-implantation ® Metformin attempt should be made to control serum lipids with appropriate diet, exercise, loss, a decrease in litter size, a decrease in birth weight, a 40% surviva1 of TRICOR 48 mg and 145 mg weight loss in obese patients, and control of any medical problems such as pups at birth, a 4% survival of pups as neonates, and a 0% survival of pups to (fenofibrate tablets) diabetes mellitus and hypothyroidism that are contributing to the lipid weaning, and an increase in spina bifida. ߑ abnormalities. Medications known to exacerbate hypertriglyceridemia (beta- Administration of approximately 10 times the MRHD to female rats on days only blockers, thiazides, estrogens) should be discontinued or changed if possible 6-15 of gestation caused an increase in gross, visceral and skeletal findings in Cuts BMI in prior to consideration of triglyceride-lowering drug therapy. fetuses (domed head/hunched shoulders/rounded body/abnormal chest, CONTRAINDICATIONS Continued therapy: Periodic determination of serum lipids should be kyphosis, stunted fetuses, elongated sternal ribs, malformed sternebrae, extra TRICOR is contraindicated in patients who exhibit hypersensitivity to obtained during initial therapy in order to establish the lowest effective dose foramen in palatine, misshapen vertebrae, supernumerary ribs). fenofibrate. of TRICOR. Therapy should be withdrawn in patients who do not have an Administration of approximately 7 times the MRHD to female rats from day adequate response after two months of treatment with the maximum 15 of gestation through weaning caused a delay in delivery, a 40% decrease in At-Risk Teens TRICOR is contraindicated in patients with hepatic or severe renal dysfunction, including primary biliary cirrhosis, and patients with recommended dose of 145 mg per day. live births, a 75% decrease in neonatal survival, and decreases in pup weight, unexplained persistent liver function abnormality. Pancreatitis: Pancreatitis has been reported in patients taking fenofibrate, at birth as well as on days 4 and 21 post-partum. TRICOR is contraindicated in patients with preexisting gallbladder disease gemfibrozil, and clofibrate. This occurrence may represent a failure of Administration of fenofibrate at 9 to 18 times the MRHD to female rabbits B OSTON — Metformin was associated (see WARNINGS). efficacy in patients with severe hypertriglyceridemia, a direct drug effect, or a caused abortions in 10% to 25% of dams and death in 7% of fetuses at 18 secondary phenomenon mediated through biliary tract stone or sludge times the MRHD. with weight loss that persisted at 12 WARNINGS formation with obstruction of the common bile duct. Nursing mothers: Fenofibrate should not be used in nursing mothers. Liver Function: Fenofibrate at doses equivalent to 96 mg to 145 mg TRICOR months in obese adolescents at risk for di- Hypersensitivity Reactions: Acute hypersensitivity reactions including Because of the potential for tumorigenicity seen in animal studies, a decision per day has been associated with increases in serum transaminases [AST severe skin rashes requiring patient hospitalization and treatment with steroids should be made whether to discontinue nursing or to discontinue the drug. (SGOT) or ALT (SGPT)]. In a pooled analysis of 10 placebo-controlled trials, abetes, Dr. Dorit Koren said at the annu- have occurred very rarely during treatment with fenofibrate, including rare Pediatric Use: Safety and efficacy in pediatric patients have not been increases to > 3 times the upper limit of normal occurred in 5.3% of patients spontaneous reports of Stevens-Johnson syndrome, and toxic epidermal established. al meeting of the Endocrine Society. taking fenofibrate versus 1.1% of patients treated with placebo. necrolysis. Urticaria was seen in 1.1 vs. 0%, and rash in 1.4 vs. 0.8% of Geriatric Use: Fenofibric acid is known to be substantially excreted by the When transaminase determinations were followed either after fenofibrate and placebo patients respectively in controlled trials. kidney, and the risk of adverse reactions to this drug may be greater in patients On the basis of the results of this small discontinuation of treatment or during continued treatment, a return to normal Hematologic Changes: Mild to moderate hemoglobin, hematocrit, and white with impaired renal function. Because elderly patients are more likely to have limits was usually observed. The incidence of increases in transaminases retrospective study, metformin should be blood cell decreases have been observed in patients following initiation of decreased renal function, care should be taken in dose selection. related to fenofibrate therapy appear to be dose related. In an 8-week dose- fenofibrate therapy. However, these levels stabilize during long-term ranging study, the incidence of ALT or AST elevations to at least three times ADVERSE REACTIONS submitted to further testing as a tool in the administration. Extremely rare spontaneous reports of thrombocytopenia and the upper limit of normal was 13% in patients receiving dosages equivalent to CLINICAL: Adverse events reported by 2% or more of patients treated with agranulocytosis have been received during post-marketing surveillance prevention of diabetes in high-risk, obese 96 mg to 145 mg TRICOR per day and was 0% in those receiving dosages fenofibrate during the double-blind, placebo-controlled trials, regardless of outside of the U.S. Periodic blood counts are recommended during the first 12 equivalent to 48 mg or less TRICOR per day, or placebo. Hepatocellular, causality, are listed in the table below. Adverse events led to discontinuation of months of TRICOR administration. teens, she said. In previous studies of sim- chronic active and cholestatic hepatitis associated with fenofibrate therapy treatment in 5.0% of patients treated with fenofibrate and in 3.0% treated with Skeletal muscle: The use of fibrates alone, including TRICOR, may have been reported after exposures of weeks to several years. In extremely rare placebo. Increases in liver function tests were the most frequent events, causing ilar patients, metformin has been associat- occasionally be associated with myopathy. Treatment with drugs of the fibrate cases, cirrhosis has been reported in association with chronic active hepatitis. discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials. class has been associated on rare occasions with rhabdomyolysis, usually in Regular periodic monitoring of liver function, including serum ALT (SGPT) ed with short-term weight loss, as well as patients with impaired renal function. Myopathy should be considered in any BODY SYSTEM Fenofibrate* Placebo should be performed for the duration of therapy with TRICOR , and therapy patient with diffuse myalgias, muscle tenderness or weakness, and/or marked Adverse Event (N=439) (N=365) improvements in glucose levels, lipid ab- discontinued if enzyme levels persist above three times the normal limit. elevations of creatine phosphokinase levels. BODY AS A WHOLE Cholelithiasis: Fenofibrate, like clofibrate and gemfibrozil, may increase Patients should be advised to report promptly unexplained muscle pain, Abdominal Pain 4.6% 4.4% normalities, and hyperandrogenism. cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is tenderness or weakness, particularly if accompanied by malaise or fever. CPK Back Pain 3.4% 2.5% suspected, gallbladder studies are indicated.