FDA Moves to Head Off Shortages of 2 Cancer Drugs

TUESDAY, Feb. 21 (HealthDay News) -- The U.S. Food and Drug Administration announced Tuesday what it called a series of steps to ensure the continued availability of vital cancer drugs that have been in dangerously short supply.

One of the drugs, methotrexate, is used in combination with other drugs to combat -- and in many cases cure -- acute lymphoblastic leukemia (ALL), the most common type of cancer in children. It typically strikes kids aged 2 to 5.

And another drug, Lipodox, will be temporarily imported from a pharmaceutical company in India to ease a shortage of the chemotherapy drug Doxil (doxorubicin), which is used to treat ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma. Lipodox is similar in chemical makeup to Doxil; there are no generic versions of Doxil.

"Through the collaborative work of [the] FDA, industry and other stakeholders, patients and families waiting for these products or anxious about their availability should now be able to get the medication they need," FDA Commissioner Dr. Margaret A. Hamburg said in a news release.

The FDA also said it was issuing guidelines to the drug industry that spell out detailed requirements for "both mandatory and voluntary notifications" to the agency of potential problems that could result in a drug shortage or supply disruption.

Methotrexate is a cornerstone in the treatment of children with acute lymphoblastic leukemia. In high doses, the generic drug has been successful in curing patients and beneficial in preventing recurrence. Without the drug, a patient's chance for a cure is reduced while the risk of recurrence rises, oncologists said.

Some cancer doctors had warned last week that supplies of methotrexate could be exhausted within two weeks.

To offset the shortage of methotrexate, the FDA said Tuesday that it has worked with several drug manufacturers to help maintain supplies to meet all patient needs. Preservative-free methotrexate is needed for the intrathecal (injection into the fluid surrounding the brain and spinal cord) treatment of children with ALL, the agency said.

The FDA said the steps taken with methotrexate included approving a preservative-free version of the generic drug manufactured by APP Pharmaceuticals, of Schaumburg, Ill. Those supplies should become available in March and continue indefinitely, the agency said.

Second, Illinois-based Hospira Inc., which already manufactures methotrexate, has sped up additional supplies, producing 31,000 new vials of the drug -- enough for more than one month's supply. Those additional vials are being shipped Tuesday to hundreds of U.S. hospitals and treatment centers, the FDA said.

The FDA also noted that it continues to work with other manufacturers of methotrexate that have also stepped up production. Those manufacturers include Mylan Inc., of Canonsburg, Pa., and Sandoz US Inc., of Princeton, N.J.

At a midday news conference Tuesday, one of the speakers was Sara Stuckey, mother of 6-year-old Nate Stuckey, who has been on methotrexate since he was diagnosed with ALL in 2009.

"It is hard enough to hear your child has cancer, but to hear that the treatment that is successfully working is suddenly not available is devastating," she said. "My husband and I pray the recommended drugs to fight his cancer will be available when it's time for Nate's next treatment. And we hope that in the future no more families have to go through the stress of wondering whether proven, lifesaving treatments will be out of reach when they need it the most."

Speaking at the news conference, Hamburg said: "There are too many families like the Stuckeys who worry they won't have the medication they need for their next treatment and are understandably anxious about switching to a medication that may have more side effects or may be less effective. Clearly this is not acceptable."

"We are making progress," Hamburg added. "There were 195 drug shortages prevented in 2011 and 114 drug shortages prevented since October 2011 when we made the call for early notification" of potential shortages.

As for the ovarian cancer drug Lipodox, the FDA said it will allow the temporary importation of the drug made by Sun Pharma Global FZE. The agency said in its news release that "temporary importation of unapproved foreign drugs is considered only in rare cases when there is a shortage of an approved drug that is critical to patients and the shortage cannot be resolved in a timely fashion with FDA-approved drugs."

The shortages of methotrexate and Doxil are just the latest in a series of drug shortages that have existed for several years.

In 2011, prescription drug shortages in the United States hit an all-time high. Last fall, some 200 drug shortages had been reported, compared to 178 in all of 2010, the FDA reported.

Many of the scarce drugs are injectables, such as cytarabine and cisplatin, used to treat serious conditions such as cancer. Some are only given in hospitals and are "absolutely critical," Valerie Jensen, associate director of the FDA's drug shortage program, said during a news conference last September.

More than half (54 percent) of shortages in 2010 were due to quality issues, such as drug impurities. Some were caused by delays or manufacturing capacity problems, while 11 percent were caused by discontinuation of a drug and 5 percent resulted from raw material shortages, Jensen said.

Jensen also said the shortages tend to occur in drugs that aren't "economically attractive." This could mean that only one company produces the drug, making it harder to find alternatives if the supply dries up.

A lot of the problems are tied to generic drugs, health experts explained, because few manufacturers make them and profit margins aren't as high as for brand-name drugs still under patent protection.

On Oct. 31, 2011, President Barack Obama signed an executive order designed to help ease the drug shortages. The order directed the FDA to "take action" to prevent and reduce worsening prescription drug shortages.

In response to Tuesday's announcement, Dr. Armand Keating, president of the American Society of Hematology (ASH), said in a statement: "ASH is encouraged by the steps FDA is taking to alleviate drug shortages that have significantly affected so many patients with hematololgic malignancies under our members' care. The measures announced today are consistent with the Society's recommendations to FDA, Congress and the Obama Administration to expand the agency's authority to prevent drug shortages by requiring manufacturers to provide early notification of impending shortages and importing drugs in critical supply."

"While ASH applauds the specific actions announced today," Keating added, "we also realize that these measures represent only a portion of a solution to a much larger problem. In addition to these steps, additional measures -- such as developing a national drug registry and providing economic incentives to manufacturers to produce a steady supply of generics -- must be implemented to permanently prevent shortages. Until a complete solution is in place, treatment will be delayed and care will be rationed for critically ill patients."

More information

For more on drug shortages, visit the U.S. Food and Drug Administration.

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Doctors: Myanmar desperate for HIV and TB drugs

BANGKOK (AP) — Some 85,000 HIV-infected people in Myanmar are not getting treatment due to a lack of funding, despite renewed international engagement with the government amid a wave of political reform, a medical aid group said Wednesday.

Doctors Without Borders warned in its report that the situation in Myanmar could worsen after the Global Fund to Fight AIDS, Tuberculosis and Malaria cut funding worldwide because of a shortfall in donations.

The money was expected to provide HIV drugs for 46,500 people in Myanmar and help treat another 10,000 sickened by drug-resistant tuberculosis, the report said.

Cases of tuberculosis — a major killer of HIV patients — in Myanmar are nearly triple the global rate, as difficult-to-treat forms of the disease that do not respond to common treatment surge.

In 2009, the U.N. estimated 240,000 people were infected with HIV and about 18,000 were dying from it annually in Myanmar, which has one of the world's worst health systems.

Doctors Without Borders provides antiretroviral drugs to about 23,000 people at 23 clinics nationwide, funding more than half of all HIV treatment being provided to nearly 40,000 patients, said Peter Paul de Groote, who heads the organization's Myanmar operation.

Myanmar receives a fraction of the international aid provided elsewhere, largely because many nations did not support the former reclusive military government that ruled for nearly half a century. But last year, a nominally civilian government took office and launched unexpected reforms that have been applauded by the international community.

"Regardless of what is happening in the country, the people that are in need of treatment, need treatment," de Groote said by phone. "Of course, we all hope that the developments as they seem to be going in that direction will lead to more money into the country, but, in general, I think this money should be coming in regardless of what the situation is."

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Few rheumatoid arthritis clinical trials compare drugs: study

NEW YORK (Reuters Health) - To test whether a new drug is an improvement over existing treatments, the ideal clinical trial would compare the medications head to head, but few trials of rheumatoid arthritis treatments happen that way, according to a new study.

Instead, researchers found that for certain new rheumatoid arthritis medications, subjects in the comparison groups were often assigned to continue taking a drug that didn't help them or to take a fake drug called a placebo -- in both cases effectively depriving those patients of treatment for their disease.

"Of course it's easier to compare to a placebo than an active treatment but in no way can it justify exposing patients to irreversible morbidity," said Dr. Candice Estellat at the French national medical research institute, INSERM, who led the study.

Her concern is that if studies don't compare a new drug to other effective ones, people's conditions will persist or even worsen throughout the study.

Additionally, without so-called head-to-head trials, doctors will have little evidence to go on to determine whether one treatment is better than another, Estellat said.

Rheumatoid arthritis is an autoimmune disease that causes inflammation and damage to joints.

About 1.5 million adults have the painful disorder, and they typically require lifelong treatment with physical therapy or medications, such as methotrexate.

The newest forms of rheumatoid arthritis medications to become available are called biologic disease-modifying antirheumatic drugs (DMARDs).

These include the brand-name medications Enbrel and Humira. They come in the form of an injection, and cost around $15,000 per year.

Estellat and a colleague gathered information on all clinical trials of biologic DMARDs registered with the U.S. government's clinicaltrials.gov website and that were ongoing between 2002 and 2009.

She said they decided to do the study after hearing from specialists about the lack studies comparing these new drugs against other biologic DMARDs.

Of the 91 trials they identified, just five studies compared one biologic medication to another.

"Unfortunately we were not surprised as it confirms rheumatologists' feeling(s)," Estellat said.

The remaining trials will not provide doctors and patients with information for making evidence-based decisions, she and her coauthor write in the Archives of Internal Medicine.

"There (are) plenty of studies to show that A is better than placebo, B is better than placebo, C is better than placebo but so few to know which one is the best between A, B or C," Estellat told Reuters Health by email.

Not only are placebo-compared experiments less useful in understanding how well a drug works compared to others, but, the report points out, they may violate international ethical research standards and specific guidelines from the American College of Rheumatology if people are not given treatment for a serious condition like rheumatoid arthritis.

The 91 trials included 102 comparisons of a biologic medication against something else -- in most cases that something else was a placebo or a treatment previously shown not to work for them.

"Despite recommendations to give biologic treatments to patients with an inadequate response to conventional treatment, 9,879 patients were or will be randomized to control arms to receive no treatment or their previous ineffective treatment," Estellat said.

Studies on humans have to go through ethical scrutiny by independent bodies called institutional review boards, and in the U.S. they must also be approved by the Food and Drug Administration.

A spokesperson for the pharmaceutical trade group, PhRMA, wrote in an email to Reuters Health that "much of that decision-making is done under the guidance of FDA, whose experts are able to work with companies to evaluate the pros and cons of different types of trials."

Dr. Steven Pearson, the president of the Institute for Clinical and Economic Review in Boston, explained the possible reasons for not using head-to-head trials for certain drugs in an editorial accompanying Estellat's study.

He agreed that using placebos is a less desirable trial design to ultimately help physicians determine which medication they should prescribe for their patients, but said it's a trade-off for making an experiment less difficult.

"For one, having an active agent against a comparator would require many more patients," he told Reuters Health.

"In order to be able to get clear signals of the safety and effectiveness of new agents it's going to be easiest to compare it to a placebo, in terms of costs and duration," Pearson added.

To be most useful to patients and physicians, clinical trials need to compare one drug to another, and Pearson said that companies, regulators and researchers should think of creative ways to do so without having the studies become prohibitively expensive or unwieldy.

"I think the study is helpful to (the Food and Drug Administration) and others to take stock and see if there are other innovative study designs and approaches that allow more head-to-head trials," Pearson said.

Estellat said that people involved in clinical studies "have to imagine original designs to conciliate ethics and scientific requirements."

SOURCE: http://bit.ly/yh1orf Archives of Internal Medicine, February 13, 2012.

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Women in the U.K. May Lose Access to Important Breast Cancer Drugs

SALT LAKE CITY (Reuters) - Elizabeth Smart, who was kidnapped at age 14 from her Utah home and held for what she described as "nine months of hell," exchanged vows on Saturday with her boyfriend of the past year at a private wedding in Hawaii, her uncle told Reuters. Smart, 24, and Matthew Gilmour, whom she met while she …

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EU agency says weight-loss drugs risk acceptable

LONDON (Reuters) - The European Medicines Agency has decided that the benefits of orlistat-containing weight loss drugs, including GlaxoSmithKline's Alli and Roche's Xenical, outweigh the risk of very rare liver-related side effects.

The regulator launched a review of the drugs in September in light of some rare cases of severe liver injury among patients.

It said on Thursday that the drugs were beneficial in the treatment of obese or overweight patients with a body mass index (BMI) of 28 or above.

However, it recommended that labeling for the medicines, including nationally authorized orlistat-containing generics, was harmonized to ensure the warning about liver damage was consistent.

It stressed that cases of severe liver disease linked to the drugs were very rare.

There with 21 cases of severe liver toxicity reported where Xenical was considered a possible cause from 1997 to January 2011, it said, and nine reports of liver failure in people using Alli between May 2007, when it was first marketed, and January 2011.

To put that in context, Xenical and Alli together were estimated to have been used by over 53 million people worldwide, with over 20 million in the European Union, it said.

GlaxoSmithKline has put Alli up for sale as part of a disposal of non-core brands.

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Erectile drugs might help premature ejaculation

NEW YORK (Reuters Health) - Most studies looking at whether erectile dysfunction drugs can help men overcome premature ejaculation problems agree that the pills make a difference, but much of the research is flawed, according to a new review of the evidence.

Of the 14 studies included in the review, 11 found that the medications helped extend the length of time men could have intercourse before orgasm, but Dr. Anastasios Asimakopoulos, lead author of the report, urged caution in interpreting the findings.

"There is still inadequate evidence to propose the use of (these types of drugs) in treating (premature ejaculation)," he wrote in an email to Reuters Health.

The drugs, which go by the brand names Viagra, Levitra and Cialis, are intended to treat men who have problems getting and keeping an erection.

There's been an interest in also using them to address the problem of premature ejaculation, because one of the side effects of the drugs is a delay in ejaculation, the authors write in the Journal of Sexual Medicine.

Asimakopoulos, from the University of Tor Vergata in Rome, Italy, said that anywhere from four to 39 percent of men suffer from premature ejaculation.

His group collected data from 14 studies that measured the effect of medications on extending the time during intercourse before orgasm, technically referred to as the "intravaginal ejaculatory latency time."

Nine of the studies used an erectile dysfunction drug by itself, while four combined the drug with an antidepressant medication, and one combined the drug with behavioral therapy.

Most of the studies asked men to use a stopwatch before and after treatment, to measure if they were able to extend the time having sex.

Some also asked the men to rate changes in their anxiety and sexual satisfaction.

Asimakopoulos and his colleagues ran into problems trying to compare the studies. For one, they didn't always agree on the definition of premature ejaculation.

He said that future studies should use the definition provided by the International Society for Sexual Medicine, which says the disorder involves an inability to last longer than one minute before ejaculating, and includes problems such as frustration or avoiding sexual intimacy.

The other stumbling block to the group's analysis was that fewer than half of the studies compared the drugs to a placebo, a standard for high-quality studies that helps researchers determine whether the drug itself is responsible for any effects seen.

Among four studies, including about 300 men, that did compare an erectile dysfunction medication to a placebo, Asimakopoulos found a positive effect.

After taking a placebo, men had intercourse lasting from about a minute to a little more than a minute and a half.

Among the men who used a medication, intercourse lasted from more than two and a half minutes to about six.

Similarly, the erectile dysfunction drugs, when combined with an antidepressant, worked better than an antidepressant alone.

Asimakopoulos said the results show that these drugs have "a high impact...on prolonging ejaculatory times."

"There seems to be a global positive effect of these drugs in delaying ejaculation; however, the existing evidence is still partial and their role remains controversial," he said.

The drugs are worth further investigation for the treatment of premature ejaculation because antidepressants and topical anesthetics are the only alternatives demonstrated to be effective so far, the team notes in their report.

In future studies, Asimakopoulos said, researchers should not only use a standard definition of premature ejaculation and conduct studies comparing the drug to a placebo, but also shoot for developing a standard and more convenient method of measuring the disorder other than relying on a stopwatch.

SOURCE: http://bit.ly/zrye69 The Journal of Sexual Medicine, online January 16, 2012.

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Merck says hepatitis pill hampers HIV Drugs

(Reuters) - Merck & Co's recently approved Victrelis treatment for hepatitis C considerably lessens the effectiveness of some widely used medicines against the virus that causes AIDS, Merck and U.S. regulators said in separate reports.

"These drug interactions may be clinically significant for patients infected with both chronic hepatitis C virus and HIV by potentially reducing the effectiveness of these medicines when co-administered," Merck said in a February 6 letter to healthcare professionals.

Victrelis, approved last May, attacks the hepatitis C virus that over decades can lead to cirrhosis and liver failure. A significant percentage of hepatitis patients are also infected with the human immunodeficiency virus, or HIV, which weakens the immune system and is fatal without treatment.

The drug interactions were seen in a study among healthy volunteers who took Victrelis and the widely used HIV treatment Norvir in combination with one of three other anti-HIV pills: Reyataz (atazanavir), Prezista (darunavir) and Kaletra (lopinavir/ritonavir). All of the HIV drugs work by blocking protease, an enzyme the virus requires to replicate.

Victrelis reduced concentrations in the blood of Reyataz, Prezista and Kaletra by an average 49 percent, 59 percent and 43 percent, respectively.

Further, levels of Victrelis itself were reduced by 45 percent among volunteers who took it with Kaletra, and 32 percent among those who took it with a combination of Norvir and Prezista.

ISI Group analyst Mark Schoenebaum said 10 percent to 15 percent of patients with hepatitis C are co-infected with HIV, and the findings could crimp Victrelis sales by as much as 25 percent. But he said the setback would have little impact on Merck's earnings this year or in 2013.

The reduced prospects for Victrelis come even as its sales are being dwarfed by Vertex Pharmaceuticals Inc's Incivek, a rival protease inhibitor that was also approved last May.

The U.S. Food and Drug Administration, in an announcement of the findings that appeared on the agency's website on Wednesday, said patients should not stop taking any of their medicines without talking to healthcare professionals.

Drug interactions had previously been found between Victrelis and another HIV treatment called Sustiva (efavirenz). Sustiva belongs to a family of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Merck said it was conducting drug-interaction studies of Victrelis with other HIV drugs. They include Intelence (etravirine), which is also a NNRTI, and Isentress (raltegravir), which belongs to a class of drugs called HIV integrase inhibitors,

Merck shares slid 14 cents to $38.28 in afternoon trading on the New York Stock Exchange.

(Reporting By Ransdell Pierson; editing by John Wallace and Maureen Bavdek)

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Illicit Drugs Bought Off Internet May Be Poisons, Experts Warn

THURSDAY, Feb. 9 (HealthDay News) -- A case study of two men who were poisoned and turned blue after ingesting what they thought was a recreational drug that they had bought on the Internet highlights the dangers of such purchases, a new report claims.

The case study appears in the Feb. 10 issue of the Morbidity and Mortality Weekly Report, which is published by the U.S. Centers for Disease Control and Prevention.

The term "research chemicals" is a phrase used to illegally sell stimulants on the Internet, to avoid regulations that ban their use, the report authors said.

The authors described the case of two Oregon men who believed they had bought the designer amphetamine derivative 2C-E online. But the product they actually received was aniline, a highly toxic industrial chemical.

Even though these research chemicals all carry a warning label that they are "not for human consumption," the two men ingested the chemical. They quickly suffered a severe reaction as their hemoglobin was converted to methemoglobin, a molecule that prevents red blood cells from carrying oxygen.

The men's skin turned blue due to the lack of oxygen in their blood and one of them lost consciousness, said report author Dr. Shana Kusin and colleagues from the Oregon Poison Center.

The men were saved after poison center and health department officials rapidly identified the chemical and the proper treatment.

The incident illustrates the potentially life-threatening risks of buying so-called "research chemicals" over the Internet, the report authors concluded.

More information

The U.S. National Institute on Drug Abuse has more about drug abuse and addiction.

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Erectile drugs might help premature ejaculation

NEW YORK (Reuters Health) - Most studies looking at whether erectile dysfunction drugs can help men overcome premature ejaculation problems agree that the pills make a difference, but much of the research is flawed, according to a new review of the evidence.

Of the 14 studies included in the review, 11 found that the medications helped extend the length of time men could have intercourse before orgasm, but Dr. Anastasios Asimakopoulos, lead author of the report, urged caution in interpreting the findings.

"There is still inadequate evidence to propose the use of (these types of drugs) in treating (premature ejaculation)," he wrote in an email to Reuters Health.

The drugs, which go by the brand names Viagra, Levitra and Cialis, are intended to treat men who have problems getting and keeping an erection.

There's been an interest in also using them to address the problem of premature ejaculation, because one of the side effects of the drugs is a delay in ejaculation, the authors write in the Journal of Sexual Medicine.

Asimakopoulos, from the University of Tor Vergata in Rome, Italy, said that anywhere from four to 39 percent of men suffer from premature ejaculation.

His group collected data from 14 studies that measured the effect of medications on extending the time during intercourse before orgasm, technically referred to as the "intravaginal ejaculatory latency time."

Nine of the studies used an erectile dysfunction drug by itself, while four combined the drug with an antidepressant medication, and one combined the drug with behavioral therapy.

Most of the studies asked men to use a stopwatch before and after treatment, to measure if they were able to extend the time having sex.

Some also asked the men to rate changes in their anxiety and sexual satisfaction.

Asimakopoulos and his colleagues ran into problems trying to compare the studies. For one, they didn't always agree on the definition of premature ejaculation.

He said that future studies should use the definition provided by the International Society for Sexual Medicine, which says the disorder involves an inability to last longer than one minute before ejaculating, and includes problems such as frustration or avoiding sexual intimacy.

The other stumbling block to the group's analysis was that fewer than half of the studies compared the drugs to a placebo, a standard for high-quality studies that helps researchers determine whether the drug itself is responsible for any effects seen.

Among four studies, including about 300 men, that did compare an erectile dysfunction medication to a placebo, Asimakopoulos found a positive effect.

After taking a placebo, men had intercourse lasting from about a minute to a little more than a minute and a half.

Among the men who used a medication, intercourse lasted from more than two and a half minutes to about six.

Similarly, the erectile dysfunction drugs, when combined with an antidepressant, worked better than an antidepressant alone.

Asimakopoulos said the results show that these drugs have "a high impact...on prolonging ejaculatory times."

"There seems to be a global positive effect of these drugs in delaying ejaculation; however, the existing evidence is still partial and their role remains controversial," he said.

The drugs are worth further investigation for the treatment of premature ejaculation because antidepressants and topical anesthetics are the only alternatives demonstrated to be effective so far, the team notes in their report.

In future studies, Asimakopoulos said, researchers should not only use a standard definition of premature ejaculation and conduct studies comparing the drug to a placebo, but also shoot for developing a standard and more convenient method of measuring the disorder other than relying on a stopwatch.

SOURCE: http://bit.ly/zrye69 The Journal of Sexual Medicine, online January 16, 2012.

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Certain Cancer Drugs May Have Fatal Side Effects: Analysis

MONDAY, Feb. 6 (HealthDay News) -- Treatment with three relatively new cancer drugs may be linked to a slightly increased risk of death, a new analysis suggests.

While the risk is low, it should be taken into account by doctors and patients, according to Dana-Farber Cancer Institute scientists and colleagues.

The investigators analyzed the findings of 10 clinical trials that included nearly 4,700 patients treated with sorafenib (Nexavar) for kidney and liver cancer; sunitinib (Sutent) for kidney cancer and gastrointestinal stromal tumor; or pazopanib (Votrient) for kidney cancer.

These so-called "targeted" drugs are used to stop the growth or spread of cancer by blocking the vascular endothelial growth factor tyrosine kinase receptors in cancer cells, the researchers explained in a Dana-Farber news release.

The analysis of the clinical trials revealed that the incidence of fatal complications was 1.5 percent in patients who received any of the three drugs, compared with 0.7 percent in patients who received standard treatments or placebos.

Bleeding, heart attack and heart failure were the most common fatal side effects noted in the clinical trials. In addition, liver failure was also reported, according to the report published in the Feb. 6 edition of the Journal of Clinical Oncology.

"There is no doubt for the average patient, these drugs have benefits and are [U.S. Food and Drug Administration]-approved for these indications," study leader Dr. Toni Choueiri said in the news release. "While the absolute incidence of these fatal side effects is very small, the relative risks are higher and patients and practitioners need to be aware of it."

More information

The U.S. National Cancer Institute has more about targeted cancer therapies.

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