une 8, 2011 (Silver Spring, Maryland) — The Food and Drug Administration is recommending that physicians restrict prescribing high-dose simvastatin (Zocor, Merck) to patients, given an increased risk of muscle damage [1]. The new FDA drug safety communication, issued today, states that physicians should limit using the 80-mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.
"Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug," the agency states.
In addition, the FDA is requesting that additional changes be made to the drug's label. The label will be changed to include the new dosing recommendations, as well as warnings not to use the drug with various medications, including itraconazole (Sporanox, Jannsen Pharmaceutica), ketoconazole (Nizoral by Ortho-McNeil Pharmaceutical), posaconazole (Noxafil, Merck), erythromycin, clarithromycin, telithromycin (Ketek, Sanofi-Aventis), HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, and danazol.
In addition, the 10-mg dose should not be exceeded in patients taking amiodarone, verapamil, and diltiazem, and the 20-mg dose should not be exceeded with amlodipine (Norvasc, Pfizer) and ranolazine (Ranexa, Gilead).
The changes to the label are based on the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a study reported by heartwire . In that trial, 52 patients taking the 80-mg dose developed myopathy compared with one patient treated with the 20-mg dose. In addition, 22 patients treated with the high dose of simvastatin developed rhabdomyolysis compared with none treated with the 20-mg dose.
The FDA notes that the risks of myopathy and rhabdomyolysis were highest in the first year and that older age and female sex increased the risks.
In statement released today following the FDA alert [2], Merck notes that it has launched a new information website and is encouraging patients who think the prescribing changes might affect them to speak with their doctors.
Dr Steven Nissen (Cleveland Clinic, OH), who wrote an editorial accompanying the 2004 publication of the A to Z trial, a study that tested high-dose simvastatin in acute coronary syndrome patients, who was critical of the high rate of myopathy in that study, called the FDA decision "appropriate" but said it comes late.
"Most knowledgeable lipid experts stopped administering the 80-mg dosage of simvastatin years ago," he said in an email to heartwire . "Unfortunately, once again the FDA has been too slow to react to a serious drug safety problem. We currently have more than two million Americans taking an unsafe dosage of simvastatin when there are safer alternatives. I'm glad the FDA acted but wish they hadn't taken so long."
References
Food and Drug Administration. FDA drug safety communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. June 8, 2011. Available here.
Merck. US prescribing information for simvastatin revised to include new limits on the use of the highest dose--80 mg--and updated drug interaction information [press release]. June 8, 2011. Available here.
Friday, July 8, 2011
Friday, July 1, 2011
Trial of Niacin to Increase HDL in High-Risk Patients Stopped Early After Showing No Benefit
A major government study has been stopped early because it showed no benefit to raising HDL levels with niacin in patients at high risk for cardiovascular events, the National Heart, Lung, and Blood Institute announced Thursday.
In the AIM-HIGH trial, the rate of MI, stroke, hospitalization for acute coronary syndrome, or revascularization among some 3400 patients did not differ between a group taking statin plus high-dose niacin and one taking statin plus placebo during 32 months' follow-up. All patients had well-controlled LDL levels at entry, but had low HDL levels and high triglycerides.
Asked to comment, Dr. Harlan Krumholz of Journal Watch Cardiology wrote: "This study reinforces that medications that change a risk factor do not necessarily change patient risk. Niacin, fibrates, and ezetimibe have so far failed to show that they improve patient outcomes in patients on statins. Be on guard for claims that are based only on how an intervention affects a risk factor — we need studies that show us the effect of these drugs on outcomes that patients experience."
In the AIM-HIGH trial, the rate of MI, stroke, hospitalization for acute coronary syndrome, or revascularization among some 3400 patients did not differ between a group taking statin plus high-dose niacin and one taking statin plus placebo during 32 months' follow-up. All patients had well-controlled LDL levels at entry, but had low HDL levels and high triglycerides.
Asked to comment, Dr. Harlan Krumholz of Journal Watch Cardiology wrote: "This study reinforces that medications that change a risk factor do not necessarily change patient risk. Niacin, fibrates, and ezetimibe have so far failed to show that they improve patient outcomes in patients on statins. Be on guard for claims that are based only on how an intervention affects a risk factor — we need studies that show us the effect of these drugs on outcomes that patients experience."
Thursday, June 23, 2011
Add-On Drugs Compared for Uncontrolled Type 2 Diabetes
In the treatment of type 2 diabetes not controlled by metformin and a sulfonylurea, no add-on drug has an obvious advantage over another, according to an Annals of Internal Medicine network meta-analysis.
Researchers examined 18 trials comprising 4500 participants with uncontrolled diabetes. (The add-on treatments were thiazolidinediones, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, insulins, and acarbose.) The following effects were noted:
No drug class had an advantage in controlling glycated hemoglobin levels.
Insulins and thiazolidinediones were associated with weight gain.
Glucagon-like peptide-1 agonists were associated with weight loss.
Insulins were associated with a doubled frequency of hypoglycemic episodes.
The authors acknowledge the limitations of network meta-analysis, in which some treatments are compared indirectly. They conclude that, in choosing a third drug, an individual patient's clinical features such as weight and hypoglycemia need to be considered.
Researchers examined 18 trials comprising 4500 participants with uncontrolled diabetes. (The add-on treatments were thiazolidinediones, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, insulins, and acarbose.) The following effects were noted:
No drug class had an advantage in controlling glycated hemoglobin levels.
Insulins and thiazolidinediones were associated with weight gain.
Glucagon-like peptide-1 agonists were associated with weight loss.
Insulins were associated with a doubled frequency of hypoglycemic episodes.
The authors acknowledge the limitations of network meta-analysis, in which some treatments are compared indirectly. They conclude that, in choosing a third drug, an individual patient's clinical features such as weight and hypoglycemia need to be considered.
3-Month Treatment for Latent TB Infection as Effective as 9-Month Treatment
In patients with latent tuberculosis, a shorter treatment regimen may be as safe and effective as a longer course in preventing active disease, according to a CDC study presented on Monday at the American Thoracic Society conference.
Researchers studied some 8000 patients with latent TB who lived in countries with low to medium incidence of TB — mostly from the U.S. and Canada. Patients were randomized to either the standard treatment (9 months of self-administered daily isoniazid) or a shorter regimen (3 months of supervised weekly rifapentine and isoniazid). Over roughly 3 years' follow-up, seven patients on the shorter regimen developed TB disease, compared with 15 on standard treatment. The shortened-therapy group had a significantly higher rate of treatment completion (82% vs. 69%).
CDC Director Dr. Thomas Frieden called the findings "one of the biggest developments in TB treatment in decades." The CDC stresses that the results are only applicable to countries with low to moderate levels of latent infection
Researchers studied some 8000 patients with latent TB who lived in countries with low to medium incidence of TB — mostly from the U.S. and Canada. Patients were randomized to either the standard treatment (9 months of self-administered daily isoniazid) or a shorter regimen (3 months of supervised weekly rifapentine and isoniazid). Over roughly 3 years' follow-up, seven patients on the shorter regimen developed TB disease, compared with 15 on standard treatment. The shortened-therapy group had a significantly higher rate of treatment completion (82% vs. 69%).
CDC Director Dr. Thomas Frieden called the findings "one of the biggest developments in TB treatment in decades." The CDC stresses that the results are only applicable to countries with low to moderate levels of latent infection
lower dose asa appears to lower gi bleeds
Long-term use of aspirin and the risk of gastrointestinal bleeding.
Am J Med. 2011; 124(5):426-33 (ISSN: 1555-7162)
Huang ES; Strate LL; Ho WW; Lee SS; Chan AT
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
BACKGROUND: In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear.
METHODS: We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion.
RESULTS: During a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (≥2 standard [325 mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week (P(trend)<.001). Similar dose-response relationships were observed among short-term users (≤5 years; P(trend)<.001) and long-term users (>5 years; P(trend)<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding (P(trend) = .28).
CONCLUSION: Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short- and long-term users.
Am J Med. 2011; 124(5):426-33 (ISSN: 1555-7162)
Huang ES; Strate LL; Ho WW; Lee SS; Chan AT
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
BACKGROUND: In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear.
METHODS: We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion.
RESULTS: During a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (≥2 standard [325 mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week (P(trend)<.001). Similar dose-response relationships were observed among short-term users (≤5 years; P(trend)<.001) and long-term users (>5 years; P(trend)<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding (P(trend) = .28).
CONCLUSION: Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short- and long-term users.
FDA: 5-Alpha Reductase Inhibitors Associated with Increased Risk for High-Grade Prostate Cancer Diagnosis
The labels of 5-alpha reductase inhibitors (5-ARIs) are being changed to note an increased risk for being diagnosed with high-grade prostate cancer, the FDA announced on Thursday. The drugs (finasteride and dutasteride) are approved to treat benign prostatic hyperplasia and male pattern hair loss.
The announcement came after the FDA reviewed data from two prostate cancer prevention trials. In one, finasteride (given daily for 7 years) was associated with a higher frequency of prostate cancers with Gleason scores between 8 and 10, compared with placebo (1.8% vs. 1.1%). In the other, dutasteride (given daily for 4 years) was also associated with more high-grade cancers relative to placebo (1% vs. 0.5%).
The FDA recommends that physicians rule out prostate cancer before prescribing 5-ARIs for benign prostatic hyperplasia. Also, because these drugs lower prostate-specific antigen values, clinicians should be aware that if PSA increases while a patient is taking a 5-ARI — even if it is within the normal range — it may indicate the presence of prostate cancer
The announcement came after the FDA reviewed data from two prostate cancer prevention trials. In one, finasteride (given daily for 7 years) was associated with a higher frequency of prostate cancers with Gleason scores between 8 and 10, compared with placebo (1.8% vs. 1.1%). In the other, dutasteride (given daily for 4 years) was also associated with more high-grade cancers relative to placebo (1% vs. 0.5%).
The FDA recommends that physicians rule out prostate cancer before prescribing 5-ARIs for benign prostatic hyperplasia. Also, because these drugs lower prostate-specific antigen values, clinicians should be aware that if PSA increases while a patient is taking a 5-ARI — even if it is within the normal range — it may indicate the presence of prostate cancer
Friday, April 15, 2011
Phentermine plus Topiramate Leads to Significant Weight Loss at 1 Year
A combination of phentermine and topiramate appears to be an effective obesity treatment, according to a phase III, industry-conducted trial published in the Lancet.
Some 2500 patients who were overweight or obese and had at least two comorbidities were randomized to placebo or low- or high-doses of phentermine plus topiramate. All patients received diet and lifestyle counseling. At 56 weeks, patients in the treatment groups lost more weight than controls (high-dose, 10.2 kg; low-dose, 8.1 kg; placebo, 1.4 kg). A higher proportion of patients in the treatment groups also achieved 10% weight loss (high-dose, 48%; low-dose, 37%; placebo, 7%).
Patients in the treatment groups reported higher rates of dry mouth, constipation, and paresthesia. In addition, a dose-related increase was observed in depression- and anxiety-related adverse events.
Some 2500 patients who were overweight or obese and had at least two comorbidities were randomized to placebo or low- or high-doses of phentermine plus topiramate. All patients received diet and lifestyle counseling. At 56 weeks, patients in the treatment groups lost more weight than controls (high-dose, 10.2 kg; low-dose, 8.1 kg; placebo, 1.4 kg). A higher proportion of patients in the treatment groups also achieved 10% weight loss (high-dose, 48%; low-dose, 37%; placebo, 7%).
Patients in the treatment groups reported higher rates of dry mouth, constipation, and paresthesia. In addition, a dose-related increase was observed in depression- and anxiety-related adverse events.
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