FDA Drug Approvals

The first generic versions of Cymbalta (duloxetine delayed-release capsules), a prescription medicine used to treat depression and other conditions, has been green-lighted by the federal government.

The U.S. Food and Drug Administration (FDA) has given approval to

Aurobindo Pharma Ltd., Dr. Reddy’s Laboratories Ltd., Lupin Ltd., Sun Pharma Global FZE, Teva Pharmaceuticals USA, and Torrent Pharmaceuticals Ltd. to market the drug in various strengths.

“Health care professionals and consumers can be assured that these FDA-approved generic drugs have met our rigorous standards,” said Kathleen Uhl, M.D., acting director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research. “Generic drugs offer greater access to health care for many people.”

Boxed warning

Duloxetine and other antidepressant drugs have a boxed warning describing the increased risk of suicidal thinking and behavior during initial treatment in children, adolescents and young adults ages 18 to 24. The warning also says data do not show this increased risk in those older than 24 years and that patients ages 65 and older who take antidepressants have a decreased risk of suicidal thinking and behavior.

The warning says depression and other serious psychiatric disorders themselves are the most important causes of suicide and that close monitoring of patients starting these medications is necessary. Duloxetine must be dispensed with a patient medication guide that describes important information about the drug’s uses and risks.

Common adverse reactions reported by people taking Cymbalta include nausea, dry mouth, drowsiness, fatigue, decreased appetite, increased sweating, and dizziness.

Generic prescription drugs approved by the FDA have the same high quality and strength as brand-name drugs. Generic prescription drug manufacturing and packaging sites must pass the same quality standards as those of brand-name drugs.

Depression is characterized by symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy once-pleasurable activities. Episodes often recur throughout a person's lifetime.

Signs and symptoms of depression include: depressed mood, loss of interest in usual activities, significant change in weight or appetite, insomnia or excessive sleeping (hypersomnia), restlessness/pacing (psychomotor agitation), increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration and suicide attempts or thoughts of suicide.

Chances are you've done this before: You go to your local pharmacy to buy medicine. You're inclined to go with the familiar brand name product -- the one you've seen in the TV commercials and other ads. But you see the generic version -- which is much less expensive -- and you think, "If it's so inexpensive, it must not be as effective or safe.”

You would be wrong -- and you're not alone.

Food and Drug Administration (FDA) pharmacist Brenda Stodart, Pharm.D., who for 14 years has answered questions on FDA's Drug Information line (1-855-543-DRUG ) says, "Every day without fail we educate consumers and health care professionals about the safety and efficacy of generic drugs."

So, what are generic drugs and how does FDA ensure they are a safe and effective alternative to name brands?

When a new, FDA-approved drug goes on the market, it may have patent or exclusivity protection that lets the manufacturer sell the drug exclusively for a period of time. When those expire or no longer serve as a barrier to approval, other companies can make it in generic form. FDA must approve the generic drug before it can be marketed.

Rigorous standards

Lawrence Yu, Ph.D., FDA acting deputy director for science in FDA's Office of Generic Drugs, explains that for a generic drug to be approved by FDA, its manufacturer must show that it is "equivalent" to the innovator drug (brand name). This means that to gain FDA approval, a generic drug must:

• contain the same active ingredients as the innovator drug. Active ingredients make the drug effective against the disease or condition it is treating.
• come in the same dosage form. If the brand name is a capsule, the generic should be a capsule, too.
• be administered the same way. If the brand name is taken orally, the generic should be taken orally, too.
• be identical in strength
• have the same conditions of use
• be bioequivalent (an equal rate and extent of drug absorbed the bloodstream)
• meet the same standards for identity, strength, purity and quality
• be manufactured under the same standards that FDA requires for the manufacture of innovator products

"Then, and only then,” says Yu, “we can assure consumers that the generic will work as well as the name brand."

Mansoor Khan, R.Ph., Ph.D., the agency's director of the Division of Product Quality Research, says the review process includes a review of scientific data on the drug's manufacturing, ingredients and performance.

Shifting gears

Sometimes, new complaints or evidence arise indicating that a generic drug may not have the same safety or effectiveness as was previously believed. "If we have reasons to believe a generic drug does not perform the same as a brand name product," Khan says, "we have the ability to perform experiments in the FDA laboratories and take a comprehensive, scientific look at the differences between the products."

This happened with the generic drug Budeprion XL 300 mg, a generic form of Wellbutrin, a drug used to treat depression. FDA's original bioequivalence evaluation had been of a lower dosage (150 mg). After receiving reports of adverse effects from consumers who used Budeprion at the 300 mg dosage level, the FDA conducted another study and determined that Budeprion XL 300 mg was not bioequivalent to the Wellbutrin XL 300 mg.

FDA requested that the manufacturers of Budeprion XL voluntarily withdraw the 300-mg version from the market, which they promptly agreed to do.

While FDA goes to great lengths to ensure that the brand and generic drugs perform equally, in very rare instances, such as Budeprion XL, these efforts do not succeed. BudeprionXL is definitely an outlier, however, Khan says, as there are literally thousands of approved generic products that perform equally without problems or complaints.

The price is right

Generic manufacturers are able to sell their products for lower prices because they are not required to develop a new drug from scratch with pre-clinical studies or to repeat the many costly clinical trials of new drugs, Khan says. Generally, they also do not pay for costly advertising, marketing and promotion.

The Congressional Budget Office estimated that from 1984 to 1994, generic drugs save consumers an estimated $8 to $10 billion a year at retail pharmacies. Even more billions are saved when hospitals use generics.

Even greater savings were found in a report from the IMS Institute for Health Care Informatics commissioned by the Generic Pharmaceutical Association in 2012. It found that generic drugs have saved over $1 trillion over the last decade, $193 billion in 2011 alone.

But not every drug has a comparable generic.

To find out if there is a generic equivalent for your brand-name drug, use Drugs@FDA. You can also search for generic equivalents by using FDA's "Electronic Orange Book." You can also consult the most recent monthly approvals for "First Generics."

This summer, generic versions of two statins, Pravachol and Zocor, will become available, at prices lower than the brand names now command. The FDA announced approval of the generic version of Pravachol earlier this week.

If you have been taking Pravachol or Zocor, switching to a generic version of the same drug makes sense, according to the May issue of the Harvard Heart Letter. Generic drugs are the same as the brand-name version in all but looks, inactive ingredients, and price. By law a generic drug must

• contain the same active ingredients as the brand-name drug
• be identical in strength, dosage, and administration
• work the same way in the body
• meet the same standards for quality
• be made by the same rules the FDA has set for the brand-name drug.

The difference? Generic drugs cost less.

What if you are taking a statin that doesnt yet have a generic equivalent, such as Crestor, Lescol, or Lipitor?

Although the statins are chemically different, they all lower total and LDL cholesterol. Insurers will almost certainly try to move people to generics. However, some statins are more powerful than others. If you need to ratchet your cholesterol way down, talk with your doctor to see if going generic makes sense.

So far, Americans haven't been that good about switching from costly brand-name drugs to less expensive but equally effective generics. With effective generic statins on the market, the Harvard Health Letter suggests maybe it's time to make the switch.

The Food and Drug Administration has told Novartis Pharmaceuticals Corporation that it wants it to suspend marketing of Zelnorm, used to treat irritable bowel syndrome. The agency said it requested the voluntary action based on recent findings of an increased risk of serious heart problems associated with use of the drug.

But Public Citizen says there's nothing recent about and notes that in March 2001, it petitioned the agency not to approve Zelnorm because it was only marginally effective and posed serious safety concerns. Besides heart problems, risks included ovarian cysts and fainting spells.

"We noted in this petition that receptors with which this drug interacts exist not only in the intestinal tract ... but also in the heart," said Dr. Sidney Wolfe, M.D., director of Public Citizen's Health Research Group.

"We pointed out that cisapride, a gastrointestinal drug which also caused fainting and was taken off the market because of cardiac arrhythmias, also affected this same receptor in the heart," Wolfe said.

"Once again, the FDA has approved a drug with marginal effectiveness in the face of serious questions about its safety -- putting at risk the millions of people who have already used it," Wolfe said.

He noted that the FDA has only asked the company to withdraw the drug from the market despite "even clearer evidence of harm.

"This again raises questions about both the adequacy of the FDA's pre-approval review and post-marketing surveillance," Wolfe said..

Zelnorm was approved by the FDA in July 2002 for short-term treatment of women with irritable bowel syndrome whose primary symptom is constipation. It was subsequently approved in August 2004 for treatment of chronic constipation for men and women under age 65. Zelnorm is currently marketed in 55 countries.

There were 2.13 million prescriptions issued for Zelnorm in 2005 alone, making it one of the top 200 drugs in the U.S., according to Public Citizen.

FDA said it advises patients who are using Zelnorm to contact their health care providers to discuss treatment alternatives. Patients who are taking Zelnorm should seek emergency medical care if they experience severe chest pain, shortness of breath, dizziness, sudden onset of weakness or difficulty walking or talking, or other symptoms of a heart attack or stroke, the FDA said.

FDA said it had only recently become aware of the drug's hazards. Its statement did not make any mention of the agency's ignoring Public Citizen's petition six years ago.

"This decision reflects the FDA's commitment to continuously monitor approved drugs throughout their marketing life, and take action when we believe the risks exceed the benefits," said Dr. Douglas Throckmorton, Deputy Director for the Center for Drug Evaluation and Research. "Here, a potential risk of very serious harm to patients who have this non-life-threatening condition was recently identified, making this action necessary."

Throughout February and March 2007, Novartis reported to FDA the results of a new analysis of 29 short-term randomized, controlled clinical trials of Zelnorm. FDA has concluded, based on these data that for most patients the benefits of this drug no longer outweigh the risks, the agency said.

The analysis included more than 11,600 patients treated with Zelnorm and over 7000 patients treated with placebo. The data showed that the risk of serious cardiovascular adverse events (e.g., angina, heart attacks, and strokes) associated with use of Zelnorm is higher than with placebo treatment.

Thirteen Zelnorm-treated patients (or 0.1%) had confirmed cardiovascular ischemic events, and only 1 placebo-treated patient (or 0.01%) with an event.

Relief could be on the way for as many as 63 million people that the National Institutes of Health estimates are affected by chronic constipation. 

The U.S. Food and Drug Administration has approved Linzess (linaclotide) to treat chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C) in adults. 

Chronic idiopathic constipation is a diagnosis given to those who experience persistent constipation and do not respond to standard treatment. An estimated 15.3 million people are affected by IBS. IBS-C is a subtype characterized mainly by abdominal pain and by hard or lumpy stools at least 25 percent of the time and loose or watery stools less than 25 percent of the time. 

The treatment 

Linzess is a capsule taken once daily on an empty stomach, at least 30 minutes before the first meal of the day. The medication helps relieve constipation by helping bowel movements occur more often. In IBS-C, it may also help ease abdominal pain. 

“No one medication works for all patients suffering from these gastrointestinal disorders,” said Victoria Kusiak, M.D., deputy director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “With the availability of new therapies, patients and their doctors can select the most appropriate treatment for their condition.” 

Safety and effectiveness 

The safety and effectiveness of Linzess for the management of IBS-C were established in two, double-blind studies. A total of 1,604 patients were randomly assigned to take 290 micrograms of Linzess or a placebo for at least 12 weeks. 

Results showed Linzess was more effective in reducing the amount of abdominal pain and increasing the number of complete spontaneous bowel movements compared with placebo. 

The safety and effectiveness of Linzess for the management of chronic idiopathic constipation also were established in two, double-blind studies. A total of 1,272 patients were randomly assigned to take Linzess at doses of 145 mcg or 290 mcg or a placebo for 12 weeks. 

Results from these studies showed patients taking Linzess experienced more complete spontaneous bowel movements than those taking the placebo. The 290 mcg dose is not approved for chronic constipation because studies indicated it was no more effective than the 145 mcg dose.

Linzess is approved with a Boxed Warning to alert patients and health care professionals that the drug should not be used in patients 16 years of age and younger. The most common side effect reported in during the clinical studies was diarrhea.

The current medication you're using to treat rheumatoid arthritis (RA) not working? You may have an alternative.

The U.S. Food and Drug Administration (FDA) has approved Xeljanz (tofacitinib) to treat adults with moderately to severely active RA who have had an inadequate response to, or who are intolerant of, methotrexate.

RA is an autoimmune disease, in which the body's immune system mistakenly attacks healthy tissue leading to inflammation of the joints and surrounding tissues. According to the Centers for Disease Control and Prevention, RA affects an estimated 1.5 million Americans. Xeljanz, a pill taken twice daily, works by blocking molecules called “Janus kinases,” which are important in the joint inflammation of RA.

A new treatment option

“Xeljanz provides a new treatment option for adults suffering from the debilitating disease of RA who have had a poor response to methotrexate,” said Badrul Chowdhury, M.D., Ph.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

Xeljanz is being approved ahead of the product’s prescription drug user fee goal date of Nov. 21, 2012, the date the agency was scheduled to complete review of the drug application.

The safety and effectiveness of Xeljanz were evaluated in seven clinical trials in adult patients with moderately to severely active RA. In all of the trials, patients treated with Xeljanz experienced improvement in clinical response and physical functioning compared to patients treated with placebo.

Risk of infection

The use of Xeljanz was associated with an increased risk of serious infections, including opportunistic infections (infections that occur primarily when the immune system is suppressed), tuberculosis, cancers and lymphoma. Xeljanz carries a Boxed Warning regarding these safety risks. Xeljanz treatment is also associated with increases in cholesterol and liver enzyme tests and decreases in blood counts.

The FDA approved Xeljanz with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a Medication Guide advising patients about important safety information and a communication plan to inform health care providers about the serious risks associated with Xeljanz.

Post-marketing study required

To study the long-term effects of Xeljanz on heart disease, cancer, and serious infections, the FDA is requiring a post-marketing study that will evaluate two doses of Xeljanz and include a group of patients on another approved treatment to serve as a comparison.

The most common adverse reactions in clinical trials were upper respiratory tract infections, headache, diarrhea, and inflammation of the nasal passage and the upper part of the pharynx.

Xeljanz is marketed by New York-based Pfizer Inc.

If you use the antibiotic azithromycin, which is sold as Zithromax or Z-Pak, you should know that it can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.

The U.S. Food and Drug Administration (FDA) says patients at particular risk for developing this condition include those with known risk factors such as existing prolongation of the QT interval -- a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, low blood levels of potassium or magnesium, a slower than normal heart rate, or use of certain drugs used to treat abnormal heart rhythms, or arrhythmias.

The FDA advisory follows a review of a study by medical researchers as well as another study by a manufacturer of the drug that assessed the potential for it to cause abnormal changes in the electrical activity of the heart.

Updated labels

The azithromycin drug labels have been updated to strengthen the Warnings and Precautions section with information related to the risk of QT interval prolongation and torsades de pointes, a specific, rare heart rhythm abnormality. Information has also been added regarding the results of a clinical QT study which showed that azithromycin can prolong the QTc interval.

Health care professionals are advised to consider the risk of fatal heart rhythms with azithromycin when considering treatment options for patients who are already at risk for cardiovascular events .

Antibacterial drugs

FDA notes that the potential risk of QT prolongation with azithromycin should be placed in appropriate context when choosing an antibacterial drug: Alternative drugs in the macrolide class, or non-macrolides such as the fluoroquinolones, also have the potential for QT prolongation or other significant side effects that should be considered when choosing an antibacterial drug.

FDA released a statement on May 17, 2012, about a New England Journal of Medicine (NEJM) study that compared the risks of cardiovascular death in patients treated with the antibacterial drugs azithromycin, amoxicillin, ciprofloxacin (Cipro), and levofloxacin (Levaquin), or no antibacterial drug.

The study reported an increase in cardiovascular deaths, and in the risk of death from any cause, in persons treated with a 5-day course of azithromycin (Zithromax) compared with persons treated with amoxicillin, ciprofloxacin, or no drug. The risks of cardiovascular death associated with levofloxacin treatment were similar to those associated with azithromycin treatment.    

Tecfidera (dimethyl fumarate) capsules has won approval from the U.S. Food and Drug Administration (FDA) to treat adults with relapsing forms of multiple sclerosis (MS).

“No drug provides a cure for multiple sclerosis so it is important to have a variety of treatment options available for patients,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Multiple sclerosis can impair movement, sensation, and thinking and have a profound impact on a person’s quality of life.”

Positive results

Results from two clinical trials showed that those taking Tecfidera had fewer MS relapses compared with people taking an inactive pill (placebo). One of the trials showed that those taking Tecfidera experienced a worsening of disability less often than patients taking a placebo.

Tecfidera may decrease a person’s white blood cell count (lymphocytes). Lymphocytes help protect the body from infection and low counts can raise the risk of infection, although no significant increase in infections was seen in patients taking Tecfidera in clinical trials. Before starting treatment, and annually thereafter, the FDA recommends that the patient’s white blood cell count be assessed by their health care provider.

Flushing (warmth and redness) and stomach problems (nausea, vomiting, and diarrhea) were the most common adverse reactions reported by patients receiving Tecfidera in clinical trials, especially at the start of therapy. These side effects may decrease over time.

Young adults at risk

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function (relapses) are initially followed by recovery periods (remissions).

Over time, recovery periods may be incomplete, leading to progressive decline in function and increased disability. MS patients often experience muscle weakness and difficulty with coordination and balance. Most people experience their first symptoms of MS between the ages of 20 and 40.

Tecfidera is made by Biogen Idec, Weston, Mass.

There's a new product on the market for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and or emphysema.

Breo Ellipta (fluticasone furoate and vilanterol inhalation powder), which has been okayed by the U.S. Food and Drug Administration (FDA), is also approved to reduce exacerbations of COPD in patients with a history of exacerbations.

Symptoms of COPD, a serious lung disease that worsens over time, can include chest tightness, chronic cough and excessive phlegm. Cigarette smoking is the leading cause of COPD which, according to the National Heart, Lung, and Blood Institute, is the third leading cause of death in the United States.

Breo Ellipta, a combination of fluticasone furoate, an inhaled corticosteroid, and vilanterol, a long-acting beta2-adrenergic agonist (LABA), works by decreasing inflammation in the lungs and helping the muscles around the airways of the lungs stay relaxed to increase airflow and reduce exacerbations in patients with COPD.

A serious problem

“COPD is a serious disease that makes breathing difficult,” said Curtis Rosebraugh, M.D., M.P.H., director, Office of Drug Evaluation II, Center for Drug Evaluation and Research, FDA. “The availability of new long-term maintenance medications provides additional treatment options for the millions of Americans who suffer with COPD.”

The safety and efficacy of Breo Ellipta were evaluated in 7,700 patients with a clinical diagnosis of COPD. Those treated showed improved lung function and reduced exacerbations compared with those who used a placebo.

Asthma warning

The drug carries a boxed warning that LABAs increase the risk of asthma-related death. The safety and efficacy of Breo Ellipta in patients with asthma have not been established, and it is not approved for the treatment of asthma.

Breo Ellipta carries a patient medication guide that includes instructions for use and information about the potential risks of taking the drug. It should not be used as a rescue therapy to treat sudden breathing problems (acute bronchospasm) and is not recommended for people younger than 18 years.

Serious side effects include increased risks of pneumonia and bone fractures. Among the most common side effects are inflammation of the nasal passage (nasopharyngitis), upper respiratory tract infection, headache and oral candidiasis (thrush).

Breo Ellipta was developed by GlaxoSmithKline in collaboration with Theravance.

Patients with previously untreated chronic lymphocytic leukemia (CLL) have a new treatment option.

The U.S. Food and Drug Administration (FDA) has approved Gazyva (obinutuzumab) for use in combination with chlorambucil.

CLL is a blood and bone marrow disease that usually gets worse slowly. According to the National Cancer Institute, 15,680 people in the U.S. will be diagnosed and 4,580 will die from the disease this year.

The approval “represents an important new addition to the treatments for patients with CLL,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval reflects the promise of the Breakthrough Therapy Designation program, allowing us to work collaboratively with companies to expedite the development, review and availability of important new drugs.”

How it works

Gazyva works by helping certain cells in the immune system attack cancer cells. Gazyva is intended to be used with chlorambucil, another drug used to treat patients with CLL.

It's the first drug with breakthrough therapy designation to receive FDA approval. This designation was requested by the sponsor and granted soon after the biologic license application to support marketing approval was submitted to the FDA.

The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

Gazyva was granted priority review because it demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. And the FDA granted Gazyva orphan product designation because it is intended to treat a rare disease.

Side effects

The most common side effects observed in participants receiving Gazyva in combination with chlorambucil were infusion-related reactions, a decrease in infection-fighting white blood cells (neutropenia), a low level of platelets in the blood (thrombocytopenia), low red blood cells (anemia), pain in the muscles and bones (musculoskeletal pain), and fever (pyrexia).

Gazyva is being approved with a boxed warning regarding Hepatitis B virus reactivation and a rare disorder that damages the material that covers and protects nerves in the white matter of the brain (progressive multifocal leukoencephalopathy).

These are known risks with other monoclonal antibodies in this class and rare cases were identified in participants on other trials of Gazyva.

Gazyva is marketed by South San Francisco-based Genentech.

The FDA has moved levonorgestrel – the contraceptive drug first sold as “Plan B One-Step” – one step closer to full over-the-counter status, by removing previous legal restrictions limiting the purchase of generic versions to buyers age 17 or older unless the buyers had a prescription.

Plan B's previous legal status was that official name-brand Plan B, produced by Teva, was available to all ages without a prescription, but the cheaper generic version was prescription-only to those age 16 and younger. The FDA's official reasoning for this restriction was that the generic version still needed to be tested on teenagers (rather than protecting Teva from low-priced generic competition).

NPR's health blog noted on March 2 that “the FDA now says the generic versions of the product must still say on their labels that they are intended for 'women 17 years of age or older,' but they may be sold directly from retail shelves without a requirement to produce proof of age.”

The Reproductive Health Technologies Project praised the FDA decision in a press release (.pdf) which noted that “in the very near future, people seeking generic emergency contraception, which tends to cost $7 less on average than the brand name product, will be able to get it directly off the shelf instead of from a pharmacist. Moving generic products to the shelf will also hopefully result in market competition that will drive down the price of EC overall.”

The FDA decision was made in compliance with a circa-2013 federal court order (also in .pdf form) requiring all “levonorgestrel-based emergency contraceptives [be] available without a prescription and without point-of-sale or age restrictions.”

Mrs. Thomas took her prescription for her heart medication to the pharmacy to have it filled. “I don’t want one of those generic drugs either,” she stated. “I want the real thing.” So, are brand name drugs really better than generic version?

According to recent information published in Consumer Reports, the answer is an emphatic no. To win approval from the Food and Drug Administration (FDA), the manufacturer of the generic medication must show that the drug has the same active ingredient and that it is identical in strength, dosage form, route of administration and labeling as the brand name drug.

The company must also demonstrate that individuals absorb and excrete the medication at the same rate. Says a pharmaceutical scientist who worked for decades at the FDA, “People may think that brand name products are better because they’re more expensive, but the body doesn’t know whether the drug came from a brand name or a generic company.”

When a medication goes off patient, other pharmaceutical manufacturers are free to create generic versions of that drug. The consumer can save considerable money by switching to the generic form of that drug. But the price of the drug does not go down immediately after the generic is released to the market.

Let’s take a mythical medication, Fat-no-more, used for weight loss, as an example. The brand’s retail price for a month’s worth of Fat-no-more is $220. Then it goes generic. After one year, the generic price is about half: $110. After 2 years on the market, it goes to $48. After 3 years, the price is $12.

Why does it take so long for the price to go down? When a drug is about to go off patent, manufacturers file lawsuits to challenge the patent. The company that wins obtains a 6-month period to sell that generic exclusively. When that period is over, other generic houses can produce that drug, forcing the prices even lower. Today, 8 out of 10 prescriptions filled in the US are for generic drugs, says the FDA. Cost is a big factor because generics can be as much as 85% cheaper than their brand counterparts.

Costs soaring

The cost of generic drugs is soaring, however.

Relatively cheap as they are compared with brand name products, the price gap between brand name drugs and generics is beginning to narrow – and it is not because proprietary drugs are getting cheaper. A 2014 article in the New England Journal of Medicine revealed that certain older drugs, many of which are generic and not protected by patents or market exclusivity, are now also extremely expensive.

Examples:

• Captopril, used for hypertension and heart failure, increased in price by more than 2,800% between November 2012 and November 2013, from 1.4 cents to 39.9 cents per tablet.
• Doxycycline, a broad-spectrum antibiotic that has been in existence since 1967, zoomed in price from 6.3 cents to $3.36 per pill.
• Clomipramine, a long-established antidepressant, has jumped in price from 22 cents to $8.32 per pill.
• Digoxin, used for atrial fibrillation (irregular heartbeat) and heart failure by millions of Americans, saw a price increase of 637% between 2002 and 2013.
• Some generic versions of codeine formulations for migraine, thyroid medicines, as well as the generic steroid prednisolone, have all more than doubled in price since last year, according to industry analyst EvaluatePharma. 

Yet, low-cost generics have saved the health care industry $209 billion in 2012, $239 billion in 2013 and almost $1.5 trillion over the past decade, according to the most recent data.

Sadly, prices have spiked for certain medications because of shortages of raw materials, supply disruptions or other factors that have led some manufacturers to stop producing those medications, resulting in a near monopoly. The number of manufacturers of digoxin, for example, has fallen from 8 to 3.

As Aaron Kesselheim, MD, assistant professor of pharmaceutical economics at Harvard Medical School, stated, “Studies show it is not until you have 4 or 5 companies manufacturing the same generic will the prices really drop.” Therefore, ask your doctor to switch your medications to another drug in that class if you are spending more money than you would like.

Mrs. Thomas’ pharmacist explained the generic process to her and she agreed that perhaps the generic form of her pricy heart medication was as good as the “real thing” and she agreed to switch to the generic. She was pleased at the money she saved, as well as the confidence she gained from her pharmacist’s counseling.

Xanodyne Pharmaceuticals Inc., the maker Darvon and Darvocet -- the brand version of the prescription pain medication propoxyphene -- has agreed to withdraw the medication from the U.S. market.

The move comes at the request of the Food and Drug Administration (FDA), which has also informed the generic manufacturers of propoxyphene-containing products of Xanodyne's decision and requested that they voluntarily remove their products as well.

Risk of heart problems

The FDA sought market withdrawal of propoxyphene after receiving new clinical data showing the drug puts users at risk of potentially serious or even fatal heart rhythm abnormalities. As a result of these data -- combined with other information, including new epidemiological data -- the agency concluded that the risks of the medication outweigh the benefits. 

"The FDA is pleased by Xanodyne's decision to voluntarily remove its products from the U.S. market," said John Jenkins, M.D., director of the Office of New Drugs in FDA's Center for Drug Evaluation and Research (CDER). "These new heart data significantly alter propoxyphene's risk-benefit profile. The drug's effectiveness in reducing pain is no longer enough to outweigh the drug's serious potential heart risks."

Doctors notified

The FDA is advising health care professionals to stop prescribing propoxyphene to their patients. Anyone currently taking the drug should contact his or her health care professional as soon as possible to discuss switching to another pain management therapy.

Propoxyphene is an opioid used to treat mild to moderate pain. First approved by the FDA in 1957, the drug is sold by prescription under various names both alone (e.g., Darvon) or in combination with acetaminophen (e.g., Darvocet).

New information

Since 1978, the FDA has received two requests to remove propoxyphene from the market. Until now, the agency had concluded that the benefits of propoxyphene for pain relief at recommended doses outweighed the safety risks of the drug.

In January 2009, the FDA held an advisory committee meeting to address the efficacy and safety of propoxyphene. After considering the data submitted with the original drug applications for propoxyphene, as well as subsequent medical literature and postmarketing safety databases, the committee voted 14 to 12 against the continued marketing of propoxyphene products.

In making this recommendation, the committee noted that additional information about the drug's cardiac effects would be relevant in weighing its risks and benefits.

European precedent

In June 2009, the European Medicines Agency (EMEA) recommended that the marketing authorizations for propoxyphene be withdrawn across the European Union. A phased withdrawal of propoxyphene is underway.

In July 2009, the FDA decided to permit continued marketing, but required that a new boxed warning be added to the drug label alerting patients and health care professionals to the risk of a fatal overdose. In addition, the agency required Xanodyne to conduct a new safety study assessing unanswered questions about the effects of propoxyphene on the heart.

Further review

The agency now has reviewed the data from that study, which show that, even when taken at recommended doses, propoxyphene causes significant changes to the electrical activity of the heart. These changes, which can be seen on an electrocardiogram (EKG), can increase the risk for serious abnormal heart rhythms that have been linked to serious adverse effects, including sudden death.

The available data also indicate that the risk of adverse events for any particular patient (even patients who have taken the drug for many years) is subject to change based on small changes in the health status of the patient, such as dehydration, a change in medications, or decreased kidney function.

"With the new study results, for the first time we now have data showing that the standard therapeutic dose of propoxyphene can be harmful to the heart," said Gerald Dal Pan, M.D., M.H.S., director of the Office of Surveillance and Epidemiology, CDER. "However, long-time users of the drug need to know that these changes to the heart's electrical activity are not cumulative. Once patients stop taking propoxyphene, the risk will go away."

Xanodyne is based in Newport, Ky.

If you liked the heparin, dog food, lead-painted toystoothpaste and truck tiresfrom China, you'll be happy to hear that Chinese-made generic drugs are making their way to the U.S.

While the development raises some safety concerns, it also holds out the prospect of even fiercer competition in the generic field. Manufacturers in the U.S., Europe, India, Israel and elsewhere are already competing for market share and more retail drug stores and supermarkets are offering discounts on popular generics.

The U.S. drug industry is watching the development with interest.

Roger Williams, chief executive of U.S. Pharmacopeia, the official standards-setting authority for all prescription and over-the-counter medicines, said China is capable of manufacturing safe and effective drugs but the U.S. Food and Drug Administration will have to be cautious before it approves the sale of any Chinese-made generics.

"We should be concerned, because the U.S. safety nets are frayed, and China has become a poster child for problems," Williams told the Newark Star-Ledger.

The use of generics continues to grow in the U.S., as brand-name prescription drugs lose their patent protection. More than 67 percent of all prescriptions in 2007 were for generics.

Teva, an Israeli company, has the biggest U.S. market share for generics, with 19 percent. It is followed by Sandoz, a company owned by European-based drugmaker Novartis; Mylan; Watson Pharmaceuticals; and Barr Pharmaceuticals, according to IMS Health.

China is already a big supplier of active ingredients used in both generic and brand-name drugs, and many over-the-counter medicines sold here are made in China..