Drug labels in the United States often omit information showing the severity of side effects or that a medicine is not very effective, two doctors said Wednesday.

The result can be a document skewed toward making a medicine seem safer and more effective than it really is, they wrote in a commentary in the New England Journal of Medicine.

“Much critical information that the Food and Drug Administration has at the time of approval may fail to make its way into the drug label and relevant journal articles,” wrote Drs. Lisa Schwartz and Steven Woloshin of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, New Hampshire.

The labels are written by the manufacturers and the wording is negotiated with the FDA, which gives final approval.

But key information can be missing, Woloshin said in a telephone interview. “How can I decide if the potential harms of this drug are worth the risk if I don’t know how well the drug works, and vice versa?” he asked.

One example is Sepracor’s four-year-old sleep drug Lunesta, promoted with an advertising campaign that cost $750,000 a day in 2007.

The company generated sales of $600 million last year and became a wholly-owned subsidiary of Dainippon Sumitomoto Pharma Co Tuesday.

The label says, without specifics, that Lunesta was superior to a placebo.

But test results submitted to the FDA showed that in the largest and longest study, “Lunesta patients still met criteria for insomnia and reported no clinically meaningful improvements in next-day alertness or functioning,” Schwartz and Woloshin wrote.

Sepracor responded that more detailed information about its products, beyond what the FDA wants, is always available to healthcare providers who ask for it, including from the company’s scientific staff.

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A similar example is Takeda Pharmaceutical Co’s insomnia drug Rozerem. Its label omitted laboratory data showing it still took 31 minutes, for adults over age 64, and 24 minutes for younger adults to fall asleep once they took the drug, compared with 38 minutes with a placebo.

In addition, volunteers reported “no subjective improvements in total sleep time, sleep quality, or the time it took to fall asleep,” the researchers said. Those data were also omitted from the label.

“Sometimes what gets lost is data on harms,” said Schwartz and Woloshin in their commentary. Novartis’ Zometa, used for cancer patients, had a warning label noting the 8- milligram dose posed a greater risk of kidney damage. But the degree of risk was not explained.

While 19 percent of the people taking the 4-milligram dose died during the study and 19 percent died taking a comparison drug, 33 percent died when given the 8-milligram dose of Zometa.

Seven years passed before the label was changed to explicitly tell doctors not to use the higher dose, but no details were given.

Novartis and Takeda had no immediate comment.

Woloshin said he and his colleagues had come up with a better format to make the scope of the risks and benefits clearer to consumers.

Last year, the FDA’s Risk Advisory Committee voted unanimously to endorse it, he said. They are scheduled to meet with the agency on the issue again next month.

The U.S. Food and Drug Administration today approved use of the vaccine Gardasil for the prevention of genital warts (condyloma acuminata) due to human papillomavirus (HPV) types 6 and 11 in boys and men, ages 9 through 26.

Each year, about 2 out of every 1,000 men in the United States are newly diagnosed with genital warts.

Gardasil currently is approved for use in girls and women ages 9 through 26 for the prevention of cervical, vulvar and vaginal cancer caused by HPV types 16 and 18; precancerous lesions caused by types 6, 11, 16, and 18; and genital warts caused by types 6 and 11.

HPV is the most common sexually transmitted infection in the United States and most genital warts are caused by HPV infection.

“This vaccine is the first preventive therapy against genital warts in boys and men ages 9 through 26, and, as a result, fewer men will need to undergo treatment for genital warts,” said Karen Midthun, M.D., acting director of the FDA’s Center for Biologics Evaluation and Research.

Gardasil’s effectiveness was studied in a randomized trial of 4,055 males ages 16 through 26 years old. The results showed that in men who were not infected by HPV types 6 and 11 at the start of the study, Gardasil was nearly 90 percent effective in preventing genital warts caused by infection with HPV types 6 and 11.

Studies were conducted to measure the immune response to the vaccine in boys ages 9 through 15. The results showed that the immune response was as good as that found in the 16 through 26 years age group, indicating that the vaccine should have similar effectiveness.

The manufacturer will conduct postmarketing studies to obtain additional information on the safety and effectiveness of Gardasil in boys and men.

Gardasil is given as three injections over a 6-month period. Headache, fever and pain at the injection site, itching, redness, swelling and bruising, were the most common side effects observed.

Gardasil is manufactured by Merck and Company Inc. of Whitehouse Station, N.J.

Sinusitis refers to inflamed sinuses normally caused by a bacterial, fungal or viral infection, the U.S. National Library of Medicine says.

The agency says these common warning signs may indicate sinusitis:
-Cold symptoms that persist for more than five to seven days.
-Inability to smell, drainage into the back of the throat, or a sore throat.
-Headache and pressure or tenderness in the face — surrounding the eyes and sometimes affecting the teeth.
-Nasal congestion, bad breath or runny nose.
-Coughing, particularly at night.
-Fever, fatigue and general feeling of illness.

The U.S. Food and Drug Administration today approved Arzerra (ofatumumab) for patients with chronic lymphocytic leukemia (CLL), a slowly progressing cancer of the blood and bone marrow.

Arzerra is approved for patients with CLL whose cancer is no longer being controlled by other forms of chemotherapy.

CLL primarily affects people older than 50 and arises from a group of white blood cells known as B-cells that are part of the body’s immune system. Each year, about 16,000 people are diagnosed with CLL and about 4,400 people die from the disease.

Arzerra is a monoclonal antibody, a type of biotechnology product. Antibodies that occur in nature are produced by the immune system in response to invaders. Arzerra binds to a specific protein found on the surface of both normal and malignant B cells, making the cells more susceptible to immune system attack.

The product was approved under the FDA’s accelerated approval process, which allows earlier approval of drugs that meet unmet medical needs. Products may receive accelerated approval based on a surrogate endpoint, such as a reduction in the size of the tumor or decrease in the number of cancerous white cells or in an enlarged spleen or lymph nodes. These indirect measures for clinical outcomes are considered reasonably likely to predict that the drug will allow patients to live longer or with fewer side effects of a disease.

“The approval of Arzerra illustrates FDA’s commitment to using the accelerated approval process to approve drugs for patients who have limited therapeutic options,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.

The accelerated approval process requires further study of the drug. The manufacturer is currently conducting a clinical trial in CLL patients to confirm that the addition of Arzerra to standard chemotherapy delays the progression of the disease.

Arzerra’s effectiveness was evaluated in 59 patients with CLL whose disease no longer responded to the available therapies.

The product’s safety was evaluated in 181 patients in two studies in patients with cancer. Common side effects included a decrease in normal white blood cells, pneumonia, fever, cough, diarrhea, lower red blood cell counts, fatigue, shortness of breath, rash, nausea, bronchitis and upper respiratory tract infections.

The most serious side effects of Arzerra are increased chance of infections, including progressive multifocal leukoencephalopathy (PML), a brain infection that is generally fatal. Patients at high risk for Hepatitis B should be screened before being treated with Arzerra. Patients with evidence of inactive hepatitis should be monitored for re-activation of the infection during and after completing treatment.

Adding insulin to standard diabetes drugs results in better blood sugar control for many with type 2 diabetes, British researchers report, and the dose and timing of insulin received can make a big difference.

Specifically, a once-a-day, long-acting dose of insulin may be the best approach for patients making the move to insulin therapy, the study found.

Keeping blood sugar under control reduces the risk of complications in type 2 diabetes. But diabetes is also a progressive disease, which disrupts insulin production. Consequently, for many diabetes patients, the drugs used to control blood sugar need to be increased repeatedly and most patients will eventually need to take insulin, the researchers said.

“Any treatment which keeps blood sugar under control will minimize risk of complications, but in the end insulin may be the only effective way of doing this,” explained lead researcher Dr. Rury Holman, a professor of diabetic medicine at the University of Oxford. “The vast majority will need insulin in the longer term.”

The report is published in the Oct. 22 online edition of the New England Journal of Medicine, to coincide with its presentation at the 20th World Diabetes Congress in Montreal. The study received funding from drug maker Novo Nordisk and the nonprofit group Diabetes UK.

For the study, Holman’s team compared different forms of insulin therapy for patients with type 2 diabetes. Insulin treatment can start with a “basal” dose that is long-acting, a “prandial” or mealtime dose of insulin that is short-acting or a so-called biphasic dose, a mixture of both short and long-acting insulin.

However, which of these regimens works best was not clear, Holman said. To find out, the researchers randomly assigned 708 patients to biphasic insulin injections twice a day (NovoMix30), mealtime insulin injections three times a day (NovoRapid) or basal insulin injected once a day (Levemir). All of the formulations are made by Novo Nordisk.

These patients had poor blood sugar control even though they were taking two common oral diabetes medications, metformin and sulfonylurea, the researchers noted.

Three years into the trial, the researchers found that slightly more than 43 percent of the patients taking basal insulin and about 45 percent of the patients taking insulin at mealtime achieved good blood sugar control, compared with about 32 percent of those taking biphasic insulin.

In addition, those on basal insulin had a lower incidence of low blood sugar, a serious side effect of insulin therapy, compared to those on biphasic or mealtime insulin, Holman’s team found. Moreover, patients on basal insulin gained less weight than people on the other two regimens.

“These findings provide clear evidence for people with type 2 that supports starting insulin therapy with a once-a-day basal insulin and subsequently adding a mealtime insulin if glycemic targets are not met,” Holman said.

Dr. Michael Roden, from the Institute for Clinical Diabetology at the German Diabetes Center at Heinrich Heine University Clinics in Dusseldorf, and author of an accompanying journal editorial, said that “you need to do a lot to control blood glucose in type 2 diabetic patients when they need insulin.”

Roden noted that while basal insulin is the place to start insulin therapy in type 2 diabetes, over time, mealtime insulin will need to be added to maintain blood sugar control.

Whether lowering blood sugar with insulin and other medications will prevent complications from diabetes, this study was too short to tell, Roden said. “The study was not powered to analyze the so-called hard endpoints, such as eye complications or, most importantly, cardiovascular problems,” he said.

However, there were fewer deaths among those in the study started on basal insulin, Roden said. “Which is only a hint, but is not a firm conclusion [of the benefit of basal insulin therapy].”