The FDA is reviewing the safety of angiotensin-receptor blockers after a recent meta-analysis suggested a small increase in new cancer diagnoses in patients using the drugs.
The agency will update the public with its conclusions as soon as the review is complete. In the meantime, it says the benefits of ARBs outweigh any potential risks, and it advises that the drugs continue to be used as recommended.
Clinicians should report any ARB-related adverse events to the FDA's MedWatch program.
Friday, July 16, 2010
lorcaserin new weight loss drug
Lorcaserin, a selective serotonin 2C receptor agonist, helps patients both lose weight and maintain their weight loss, according to a phase III study conducted by the drug's manufacturer and published in the New England Journal of Medicine.
Some 3200 overweight or obese adults were randomized to take lorcaserin or placebo twice daily for a year, after which lorcaserin recipients continued the drug or switched to placebo for another year. All participants also received nutrition and exercise counseling.
At 1 year, more patients in the lorcaserin group than placebo group had lost at least 5% of their body weight (48% vs. 20% of patients; mean weight loss: 5.8 kg vs. 2.2 kg). In addition, lorcaserin patients who stayed on the drug for a second year were more likely to maintain their weight loss than those who switched to placebo.
Serious adverse events did not differ between lorcaserin and placebo recipients. Unlike some other serotonergic agents, lorcaserin did not increase risk for valvular heart disease.
Some 3200 overweight or obese adults were randomized to take lorcaserin or placebo twice daily for a year, after which lorcaserin recipients continued the drug or switched to placebo for another year. All participants also received nutrition and exercise counseling.
At 1 year, more patients in the lorcaserin group than placebo group had lost at least 5% of their body weight (48% vs. 20% of patients; mean weight loss: 5.8 kg vs. 2.2 kg). In addition, lorcaserin patients who stayed on the drug for a second year were more likely to maintain their weight loss than those who switched to placebo.
Serious adverse events did not differ between lorcaserin and placebo recipients. Unlike some other serotonergic agents, lorcaserin did not increase risk for valvular heart disease.
Wednesday, July 14, 2010
vitamin e/beta carotene may increase cvd
A systematic review of antioxidants for primary prevention of cardiovascular disease identified four RCTs of vitamin E; the review found no benefits for vitamin E [1). One of the RCTs identified in the review found that vitamin E may increase death from subarachnoid hemorrhage [2). The review also identified six RCTs of beta-carotene; the review found no benefit for beta-carotene. Pooled analysis of four of these six RCTs found that beta-carotene may increase cv mortality
asa lowers MI but increases stroke
The role of aspirin in primary prevention remains uncertain. In a meta-analysis of five RCTs, Foster and colleagues found that aspirin slightly reduced the risk of a serious vascular event (odds ratio, 0.86; 95% CI: 0.80–0.90) and reduced the relative risk of myocardial infarction by about a third (OR, 0.71; 95% CI: 0.60–0.80], but had an uncertain effect on stroke (OR, 1.05; 95% CI: 0.90–1.20) [1]. The meta-analysis found that there were 0.1 excess intracranial bleeds per 1,000 patients treated per year with aspirin, and 0.7 major extracranial bleeds per 1,000 patients treated per year with aspirin. The authors found “insufficient evidence from RCTs to identify which individuals would benefit overall and which would be harmed by regular treatment with aspirin, although those at high and intermediate rather than low risk would be more likely to gain benefit.” ...More
up regulation and down regulation
down-regulation - A reduction in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged excess of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.
up-regulation - An increase in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged decrease of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.
up-regulation - An increase in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged decrease of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.
fibrates may lower coronary events not mortality, stroke or HF
Fibrates appear to lower the risk for coronary events, according to a meta-analysis in the Lancet.
Researchers examined data from 18 placebo-controlled trials of fibrates for primary or secondary prevention; some 45,000 adults were included. Overall, coronary events were significantly less common in patients taking fibrates than in those on placebo (8.7% vs. 11.6%). Fibrates were also associated with significant reductions in coronary revascularization, progression of albuminuria, and retinopathy.
There was no benefit in terms of stroke, mortality, or heart failure. Serious drug-related events, including rhabdomyolysis, were not increased with fibrates.
The authors conclude: "The magnitude of effect is moderate, but in high-risk individuals and in those with combined dyslipidemia, clinically meaningful reductions in risk could be achieved."
Researchers examined data from 18 placebo-controlled trials of fibrates for primary or secondary prevention; some 45,000 adults were included. Overall, coronary events were significantly less common in patients taking fibrates than in those on placebo (8.7% vs. 11.6%). Fibrates were also associated with significant reductions in coronary revascularization, progression of albuminuria, and retinopathy.
There was no benefit in terms of stroke, mortality, or heart failure. Serious drug-related events, including rhabdomyolysis, were not increased with fibrates.
The authors conclude: "The magnitude of effect is moderate, but in high-risk individuals and in those with combined dyslipidemia, clinically meaningful reductions in risk could be achieved."
Tuesday, July 13, 2010
confidence intervals of brand vs generics
For example, the ratio of test drug to reference drug AUC (test/reference AUC) for Drug A in six subjects results in the following values:
120%, 120%, 110%, 110%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 102 to 117. This means that there is 90% probability that the true mean lies between 102% and 117%. -ME-IT EITHER DOES OR DOES'T LIE IN THIS INTERVAL=> 9 OUT OF TEN TIMES IT WILL-Therefore, the drug passes the bioequivalence test and is considered bioequivalent to the reference drug.
In another example, the test/reference AUC for Drug B in six subjects results in the following values:
110%, 190%, 30%, 130%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 75 to 145. Although the average test/AUC ratio of the drug (110%) is the same as drug A, there is a 90% probability that the true mean lies between 75% and 145%. The confidence intervals are too wide and therefore, Drug B fails to establish bioequivalence with the reference drug.
As illustrated above, the confidence interval range of 80% to 125% does not mean that drug levels can vary up to 20% between referenced (brand) drug and the test (generic) drug. If drug levels vary by more than 10%, the range of possible values within the 90% confidence interval will likely become too broad and the drug will fail to establish bioequivalence with the reference drug. 12 In fact, in a study using the FDA bioequivalence criteria, the first 224 post-1962 drugs approved over the two year period after the Waxman Hatch amendments were passed, including some narrow therapeutic index drugs, showed a mean bioavailability variation between the generic and brand products of only 3.5%.
120%, 120%, 110%, 110%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 102 to 117. This means that there is 90% probability that the true mean lies between 102% and 117%. -ME-IT EITHER DOES OR DOES'T LIE IN THIS INTERVAL=> 9 OUT OF TEN TIMES IT WILL-Therefore, the drug passes the bioequivalence test and is considered bioequivalent to the reference drug.
In another example, the test/reference AUC for Drug B in six subjects results in the following values:
110%, 190%, 30%, 130%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 75 to 145. Although the average test/AUC ratio of the drug (110%) is the same as drug A, there is a 90% probability that the true mean lies between 75% and 145%. The confidence intervals are too wide and therefore, Drug B fails to establish bioequivalence with the reference drug.
As illustrated above, the confidence interval range of 80% to 125% does not mean that drug levels can vary up to 20% between referenced (brand) drug and the test (generic) drug. If drug levels vary by more than 10%, the range of possible values within the 90% confidence interval will likely become too broad and the drug will fail to establish bioequivalence with the reference drug. 12 In fact, in a study using the FDA bioequivalence criteria, the first 224 post-1962 drugs approved over the two year period after the Waxman Hatch amendments were passed, including some narrow therapeutic index drugs, showed a mean bioavailability variation between the generic and brand products of only 3.5%.
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