FDA Proposes To Remove Orthostatic Hypotension Drug From Market

8/19/2010

Here are some highlights around pharmaceuticals-

The Wall Street Journal reported that the FDA proposed to remove brand and generic versions of low-blood pressure drug ProAmatine (midodrine hydrochloride) from the market because required post-marketing studies on the drug's effectiveness have yet to be conducted. The drug was approved under the FDA's accelerated approval program, and according to the Journal, this is the first time the agency is requesting a drug to be removed from the market because a company failed to conduct the follow-up studies that are required.

Patients who use midodrine should stop taking it and consult their doctors about other types of anti-hypotension treatment, the FDA said in a statement." Norman Stockbridge, an FDA official said, "Since, evidence to confirm the drug's benefit has not be yet provided to the FDA, it is pursuing a withdrawal of the product." Shire "has been given 15 days to respond in writing or lose its right to appeal. Makers of the generic versions of the drug were given 30 days."

The FDA "letter does not cite any safety or effectiveness problems with the drug, and suggests the action is primarily aimed at enforcing drug approval regulations that have not always been enforced." The drug was approved to treat "orthostatic hypotension."

Malaria sufferers might be able to protect themselves against life-threatening bouts of the disease by taking a single course of antibiotics, research in mice has shown.

Preventive treatment with 'needle-free' antibiotic vaccines could be used to control the infection in areas with high levels of transmission, a study published in Science Translational Medicine suggests. There are still no available vaccines against malaria. And although some antibiotics with anti-malarial properties, such as doxycycline, that kill the parasites directly are already in use as one-off, short-term prophylaxis, their prolonged use is not an option for millions of people in the developing world where malaria is endemic.

Now, azithromycin and clindamycin, two common antibiotics, have been shown to provide additional and long-term protection against malaria, even after they are no longer taken.

"The combination of the prophylactic effect with the subsequent immune-mediated protection may be enough to protect population groups at risk, such as infants and young children, from severe forms of malaria," according to Steffen Borrmann, a lead author of the study and parasitologist at the Kenya Medical Research Institute, told SciDev.Net.

The team treated mice with the antibiotics before infecting them with malaria. After taking the drugs, the mice developed vaccine-like immunity lasting at least 40 days, and almost all were protected from complications that are often lethal.

It is still not clear how long the immunity would last in humans, but Borrmann told SciDev.Net that "life-long would be the ultimate goal but we would be happy to achieve 1-2 year protection, [to last] during the most critical years in early childhood in high transmission areas".

The antibiotics work by causing small cavities in malaria parasites during their passage into the liver of the infected host. This stops the parasites from entering the blood stream, giving time for the immune system to launch a sustained defense against the parasites.This mode of action is similar to experimental vaccines that use weakened whole parasites to elicit an immune response. The tested antibiotics are available as safe, generic drugs and there are no patent issues preventing their use in clinical trials or in clinical practice. But they would likely not work in areas with low transmission levels since the degree of immunity to subsequent infections depends on the quantity of malarial parasites already infecting the patient.

Oral Contraceptives May Reduce Risk Of Death From Any Cause In Women.
"Women who have taken the Pill at any stage in their life are less likely to die from any cause -- including heart disease and all types of cancer -- than those who have never taken the oral contraceptive," according to research published online in the British Medical Journal. The study of "more than 46,000 women...revealed a slightly higher risk of dying among under-45s."

But, the slightly increased risk in younger women disappears within 10 years of stopping the pill. Researchers calculated that "there were 52 fewer deaths per 100,000 'women years' -- a composite measure of the number of women and the lengths of their lives -- among all women who had ever used the pill compared with those who had never used it. The effects may only be true for women who have taken older-style pills rather than those on newer type drugs." In younger women, "the effects...were also mainly seen in those who smoked, had high blood pressure, or were otherwise at risk of heart disease." "Women on the pill did have higher rates of violent and accidental death, through the researchers said they couldn't explain the findings." Notably, "the risk was seen in earlier analyses of the data, and has persisted through the years.

Hormonal Contraceptives May Not Be Effective In Overweight Or Obese Women.
Hormonal contraceptives may not be effective for contraception in overweight or obese women," according to a review published online in the Cochrane Database of Systematic Reviews. After performing a literature review encompassing "11 trials enrolling a total of 39,531 women," researchers found that "pregnancy risk for overweight or obese women was higher in one of three studies using BMI." In fact, "compared with women with a BMI of less than 25 kg/m2, women with a BMI of 25 kg/m2 or more had higher risk for pregnancy in this trial of two combination oral contraceptives."

Osteoporosis drug linked to irregular heart beat.
Women who take popular osteoporosis drug alendronate, known more commonly as Fosamax, are twice as likely to develop a common form of irregular heartbeat compared to those who have never taken it, suggests a new study published in the journal Archives of Internal Medicine.

Researchers analyzed data from more than 700 women who had been diagnosed with atrial fibrillation, or irregular heartbeat, in a three-year period and compared them to a control group of more than 900 randomly selected women. They found a nearly two-fold increase in risk for developing atrial fibrillation among those women who had ever taken alendronate.

The findings were compiled by researchers from Group Health and the University of Washington by analyzing records of patients enrolled in Group Health, a Seattle-based non-profit health-care centre. Alendronate is part of a family of drugs known as bisphosphonates, which are widely used to protect against bone loss and prevent bone fracture in osteoporosis patients. However, the researchers did not find a difference in risk among those who had taken Fosamax in the past versus current users. “We do not conclude that the risk is higher for past use than current use. We conclude that the risk is higher for ever use than for never use, which was our original hypothesis,” reported lead study author Dr. Susan Heckbert, a professor of epidemiology and scientific investigator in the cardiovascular health research unit at the University of Washington.

Heckbert stated that the next step would be for scientists to investigate the mechanism for how alendronate may influence the onset of atrial fibrillation. Marlene Gauthier, manager of public affairs for Merck Frosst Canada, responded to the findings by saying that a clinical trial, rather than an observational study such as this one, is the best way to evaluate a drug’s benefits and risks.

“While observational analyses are usually conducted in as rigorous a manner as possible, they are associated with inherent limitations, including factors that cannot be adequately controlled for and an ability to fully account for differences in risk factors between groups. this underscores why data from randomized, controlled clinical trials are considered to be the most reliable source of information about the efficacy and safety of medicines.” The statement continued: “We strongly recommend that if patients have concerns about Fosamax that they talk to their physician. Osteoporosis is a serious medical condition and requires appropriate treatment with physician oversight. Their physician is in the best position to understand the needs of the patient and explain the benefits and risks of any given therapy to the patient.”

“This is an observational study. It is not as strong a design as a clinical trial,” Heckbert acknowledged.

“But on the other hand, it does represent what’s happening in actual clinical medicine.” Heckbert stated that her team knew of previous study findings that suggested a link between bisphosphonates and an increased risk for atrial fibrillation. In fact, in the United States there are more than 400 cases pending against Merck in both state and federal court, in which people who have taken Fosamax claim that the drug has contributed to the development of osteonecrosis of the jaw. This happens when bone tissue dies after it loses its blood supply, and can occur after trauma to the bone, such as a dental procedure.

However, Heckbert warned that patients who take alendronate should not stop taking it due to her study’s findings. If individuals are concerned they should speak with their physician or their health-care provider. For patients who are at high risk of fracture, the benefits of alendronate or other bisphosphonates will generally outweigh the risk of atrial fibrillation.”

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