TOP 10 PRESCRIPTION DRUGS IN THE U.S.
By Barbara Iozzia
Last year 2.8 billion prescriptions were filled in the United States. With America's population standing at 283,477,367 as of January 18, 2001, that's an average of 9.9 prescriptions filled for each person living in our nation.
Just as Mr. Blackwell releases his yearly list of "Best Dressed" and "Worst Dressed" people at the close of each year, IMS Health and Pharmacy Times magazine releases its listing of the "Top 200 Prescriptions" (by the number dispensed). With the leading 10 of these adding up to roughly 10 percent of all prescriptions filled, chances are one of them has been in your medicine cabinet over the past year.
What accounts for the popularity of the top 10 medications on the "Top 200 Prescriptions" list? Is it the sheer volume of people who use these drugs? Do these medicines outperform others in terms of effectiveness? Are brand recognition and physicians' prescribing habits factors in their success? What role does manufacturers' advertising play?
To answer these questions, HealthState asked several of our University experts to comment.
Most drugs developed over the last several centuries were naturally occurring, extracted from plants, animals and minerals. Even though British physician Thomas Sydenham first popularized the use of the quinine-containing bark of the cinchona tree as a treatment for malaria in 1666, digitalis was first used to treat heart failure in 1785, and morphine has been used to relieve pain since the early 1800s, the use of drugs to treat or cure did not hit its stride until the 1930s, when penicillin and other antibacterials were introduced. Researchers then began to produce drugs in laboratories, which provided a greater assurance of safety.
Today, drugs are used in a number of ways: to treat, prevent, or help diagnose a disease; to relieve physical or mental symptoms; to replace a natural substance such as estrogen; to stimulate the body's immune system to form antibodies; and to destroy foreign organisms such as bacteria. They are taken by mouth, injected, or used as creams, suppositories, nasal sprays, or inhalers.
PREMARIN LEADS THE LIST
Topping the list at number 1 for 1999 (figures for 2000 were not available at press time) is Premarin, the hormone replacement therapy used by millions of women to replenish estrogen after menopause, and by many younger women whose ovaries do not produce enough estrogen.
According to Gloria Bachmann, MD, associate director of women's health for UMDNJ-Robert Wood Johnson Medical School (RWJMS), Premarin has been the leading brand of hormone replacement therapy throughout the 1990s. Why? Bachmann, an obstetrician/gynecologist, cites several factors:
"Premarin has been around a long time so its name and effectiveness are well-known by physicians. When it was first prescribed in 1942, after several decades of development, a flurry of information came out about the relationship between estrogen loss and the ovarian changes that lead to menopause."
Bachmann adds that about the same time, a Boston physician correlated the loss of estrogen with long-term bone loss that can lead to osteoporosis.
The 1960s and the rise of feminism created a demand for hormone replacement therapy from women who no longer wanted to tolerate the annoying menopausal symptoms of hot flashes, vaginal dryness, sleep disturbances, and loss of libido. In the 1970s, research that proved hormone replacement therapy prevents osteoporosis and lowers the risk of uterine and cervical cancers made Premarin's popularity soar.
"In the 1980s and 1990s studies indicated that hormone replacement therapy can also prevent cardiovascular disease, Alzheimer's disease, Parkinson's disease, and macular degeneration; can promote positive skin changes, bladder continence, and sexual function; and can decrease one's risk of colon cancer and diabetes," reports Bachmann, noting more benefits for users.
An important factor for Premarin's popularity that cannot be overlooked is that the drug's pool of potential users is large and growing. Premarin's Web site states that each year approximately 5.1 million women in the 45+ age group become candidates for hormone replacement therapy.
"We are an aging society," says Bachmann, "with baby boomers entering the menopausal years in great numbers. The average life expectancy for women today is 82, which means that many of the women who are now entering menopause may live for another 30 years. And many of them will want hormone replacement therapy. Some will want to take it for the rest of their lives, some just for a short term. The good thing about hormone replacement therapy is that you can begin it at any age."
Does everyone need hormone replacement therapy? No, says Bachmann, although the majority of her post-menopausal patients do choose it. "Many women continue to make enough estrogen in organs other than the ovaries," she says. "Some patients choose to pursue lifestyle changes or alternative medications to alleviate menopausal symptoms, although in my opinion herbals alone may not be enough for relief of hot flashes and protection of bone. Herbals and low-dose estrogen may be a better option."
Current research nationwide includes clinical trials that are studying combinations of alternative medications and lifestyle changes or other non-medicinal treatments.
OVERUSE FUELS SYNTHROID'S SUCCESS
A medication to replace another hormone, called thyroid hormone T4, comes in at number 2 on the list. Synthroid is a synthetic hormone taken in pill form once a day for treatment of an underactive thyroid gland (hypothyroidism).
Synthroid matches the actions of natural thyroid hormones, which are responsible for stabilizing the body's metabolism, the rate at which the body produces energy from nutrients. Thyroid hormones affect the growth of the body's cells, the working of its muscles, the temperature of the body, reproductive functions, cholesterol level, and a person's moods, memory, and appetite. The heart, liver, kidneys, and skin need the proper amount of thyroid hormones to work effectively. Symptoms of hypothyroidism include fatigue, dry skin, weight gain, hair loss, constipation, and sensitivity to cold.
Synthroid is also used to treat benign thyroid nodules and in conjunction with surgery and radioactive iodine therapy in the management of some types of thyroid cancer.
Many of you may be surprised to learn that a synthetic thyroid hormone was number two on the list. So was Marvin Kirschner, MD. Is hypothyroidism that common a disorder among Americans?
"No," replies Kirschner, chief of endocrinology for UMDNJ-New Jersey Medical School (NJMS). He surmises that Synthroid's best-selling status points to two factors: 1. brand recognition by physicians over other generic thyroid hormone replacements, and 2. the overprescribing of thyroid hormones as a drug treatment for obesity.
"Overweight patients tell their physicians, 'I don't know why I'm so heavy, I must have a glandular problem,'" states Kirschner. "In response to these pleas, the physician prescribes Synthroid."
But does it work to control weight? No, says Kirschner. Although he says it initially increases overall metabolism and causes a temporary weight loss, the use of synthetic hormone does not rid the body of extra fat tissue. It attacks necessary muscle and bone tissue and lean body mass. Dr. Kirschner adds that Synthroid has long been discounted as a remedy for weight loss, but it is still being used improperly by probably millions of Americans.
Are there any alternatives for patients with hypothyroidism who wish to explore treatments other than Synthroid medication? Kirschner says some rely on an uncertain precursor to Synthroid called Armor's thyroid extract, which is derived from the thyroid hormones of cows.
"Trouble is," says Kirschner, "the effectiveness depends on what the cows ate. Synthroid or other forms of pure thyroxine are far more reliable and predictable as drugs for those who truly need thyroid hormone replacement."
THE LATEST AND GREATEST
Numbers 3 and 4, Lipitor and Prilosec, share a common basis for their success: They are so effective that they outperform others in their classes.
Lipitor (generic name atorvastatin) is a cholesterol-lowering drug first introduced about five years ago. It is classified as a "statin," a medication that blocks an enzyme in the liver that the body uses to make cholesterol. Lipitor's next most popular competitor is Zocor (simvastatin), number 17 on the list.
According to cardiologist Daniel Shindler, MD, an associate professor of medicine at RWJMS, part of Lipitor's appeal is that it begins to work almost immediately.
"We notice a dramatic drop in patients' cholesterol rates," he says. "This gives patients rewarding feedback and helps them to continue their cholesterol-lowering therapy."
The potential for Lipitor to garner a larger market share seems inevitable since Shindler points out that only about 30 percent of the people who could benefit from a cholesterol-lowering drug are taking one. Indeed, Lipitor is touted as "the world's number one statin with an estimated 31 percent sales growth to $3 billion in 2000."
Shindler believes that public education and awareness of the benefits of lowering one's cholesterol rate coupled with the availability of a drug with immediate feedback such as Lipitor will eventually result in more patients being diagnosed and treated. Still, because the statins are expensive drugs and routine doctors' visits and blood tests to ascertain effectiveness are required, Shindler often starts patients out on a regimen consisting of a low-fat, high-fiber diet and daily exercise.
THE POPULAR PURPLE PILL
Since first introduced in the U.S. in 1990, Prilosec swiftly rose to the top of the list, representing a major advance over Tagamet, Pepcid, and Zantac in the treatment of gastric ulcers, heartburn, and gastric esophageal reflux disease (GERD). First in its class as a proton pump inhibitor, Prilosec blocks acid-producing cells in the stomach. By decreasing acid production, Prilosec reduces the chance of acid blocking up into the esophagus and causing reflux symptoms.
Usually taken once a day before breakfast, the aggressively marketed Prilosec even has its own appropriately named Purplepill.com Web site.
In addition to being very safe and effective, first in its class, and heavily marketed, what else has led to Prilosec's popularity?
Brand recognition by doctors and the recognition by the American College of Gastroenterology that GERD can be a serious disease, speculates Louis Griffel, MD, an associate professor of medicine at RWJMS. That and "Americans' fondness for spicy and fatty foods, which can lead to gastric esophageal reflux disease."
HYDROCODONE CONTROLS PAIN
New outlooks on how to relieve and control pain are driving the prevalence of hydrocodone with APAP (acetaminophen), number 5 on the top 10 list. The drug, a synthetic opiate used to relieve moderate to severe acute pain, works by binding to receptors found throughout the central nervous system. This action causes the release of endorphins and encephalins, the body's natural painkillers.
According to physiatrist Scott Nadler, DO, director of sports medicine and an assistant professor of physical medicine and rehabilitation at NJMS, ways to treat acute and chronic pain have changed significantly over the past half-century.
"In the 1950s and 1960s, the tendency was to overtreat pain," he explains. "That gave rise to the 1970s, when everyone was afraid their patients would become addicts if they prescribed too much medication. So in the 1980s and 1990s, physicians were underdosing, with the result being that patients were living in pain for no reason. We have learned through research that people in pain are not the 'drug-seeking' population that becomes addicted. We now know we have to address the pain properly."
Nadler points out that hydrocodone is an excellent choice to treat post-operative pain and severe pain that has been unresponsive to non-steroidal anti-inflammatories, such as ibuprofen and Naprosyn. He also prescribes it in conjunction with other pain medications for neuropathic pain, which can result from trauma or secondarily to cancer or other systemic illnesses such as diabetes.
"Hydrocodone is a good, short-term mild pain medication that acts immediately," explains Nadler. "It is typically prescribed in regular dosages, with an aim toward helping patients improve their function. Patients typically take it for about one to two weeks. If more prolonged use is required, a switch to a long acting opiate medication is the next step."
An increase in the number of people, especially children, who have been diagnosed with allergies and asthma is one of the major reasons for Albuterol's and Claritin's positions, at 6 and 8, on the top 10 list.
Albuterol, the generic name for Ventolin and Proventil, is a bronchodilator, a medication that relaxes the smooth muscles of the bronchi, the air passages of the lungs, and the blood vessels that lead to them. Albuterol is used to relieve and prevent bronchospasms abnormal contractions of the bronchi that narrow and block the airways which can result from asthma and bronchitis. Albuterol can be administered via an inhaler or nebulizer.
Claritin, the world's most prescribed antihistamine since 1994, blocks the action of histamine, a natural substance released by a person's immune system during an allergic reaction. Claritin provides relief from the itchy, watery eyes, sneezing, and runny nose brought on by airborne pollens from trees, grasses, and weeds.
Allergist/immunologist Catherine Monteleone, MD, an associate professor of medicine at RWJMS, says one of the most important factors to Claritin's success is that it is non-sedating, a trait shared by only one other major-selling antihistamine, Allegra.
"People need to work, drive, and take care of their families without being drowsy," comments Monteleone. "Claritin is very effective, and it is available in several tablet and syrup forms, which can be taken safely by adults and children over age 2. The drug also benefits from a successful marketing campaign that has resulted in name recognition by physicians and patients, who appreciate its once-or twice-a-day dosing schedule. Plain Claritin is taken once a day; in combination with a decongestant it's taken twice a day."
STOPPING THE SPASMS
"The world's leading cardiovascular drug and market-leading calcium channel blocker for hypertension and angina," says the advertising about Norvasc, which holds 7th place on the top 10 list. Now in its ninth year, Norvasc is considered a "maintenance drug," a medication that a patient must take for the rest of his/her life.
Norvasc prevents calcium from entering smooth muscle cells. The drug causes the smooth muscle cells to relax, thus reducing the incidence of muscle spasms related to the cause of hypertension and chest pains or angina. With the population aging, and the number of people who will be diagnosed with high blood pressure and/or angina projected to increase, it is expected that Norvasc may hold its place on the top 10 list for a number of years, provided current concerns about calcium channel blockers are not confirmed by clincal trials now underway.
AN OLD FRIEND WITH A NEW NAME
Amoxicillin, an old standby for treating children's ear infections, is now getting new life as Trimox, the top 10 list's 9th most prescribed medication.
"Amoxicillin is the number-one recommended drug for otitis media and respiratory infections caused by bacteria in children," says Lisa Dever, MD, an associate professor of medicine at NJMS and chief of the infectious diseases clinic at the Veterans Affairs Medical Center in East Orange.
Dever, an expert on antibiotic resistance, points out that one of the major reasons for Trimox's placement on the top 10 list is due to overprescribing of the drug by physicians who inappropriately give it to patients for viral infections, which cannot be cured by an antibiotic.
"There is even a controversy now about whether using amoxicillin to treat ear infections works," says Dever. "It may relieve symptoms a day or so earlier than if nothing had been given. But the quandary physicians face is how to tell a parent who has been up all night with a baby that the child will get better if you do nothing."
Zithromax, another antibiotic, which charts at number 15 on the list, has had a phenomenal year and will probably zip up the list for the year 2000. It has been described as "the largest-selling macrolide antibiotic in the world" and promotional literature mentions its "lack of resistance in clinical practice." In addition to otitis media (ear infection), Zithromax is being marketed to treat pneumonia, bacterial bronchitis, chronic bronchitis, and sinusitis.
Dever points out that a large part of Zithromax's appeal is its dosing schedule: It is usually given once a day for only five days. As a comparison, amoxicillin usually requires dosing two or three times a day for 10 days.
When faced with giving medication to a child, most parents will opt for the ease of Zithromax, even though Dever says the majority of pediatricians still regard amoxicillin as the first drug of choice.
Dever, whose own research includes testing a number of drugs against resistant bacteria, says there is a considerable amount of antibiotics research and development going on currently.
PROZAC LIFTS MOODS
Thirty-five million people in 100 countries are taking Prozac, which tops off the list at number 10. Initially approved for the treatment of depression in the United States in 1987, Prozac was the first of a class of drugs called selective serotonin reuptake inhibitors. Scientists believe that an imbalance of a neurotransmitter in the brain, called serotonin, causes depression to develop. Prozac increases the brain's own supply of serotonin and balances the organ's activities, including the regulation of moods.
Arguably one of the most talked-about and read-about drugs, Prozac is the first and only antidepressant indicated by the U.S. Food and Drug Administration for treating depression in people aged 65 and older, a feature that may enable it to garner a larger market share in 2001.
Just as Audrey Hepburn was a perennial favorite on Mr. Blackwell's "Best Dressed List" throughout the 1960s and 1970s, there will probably always be an antibiotic or an antihistamine on the top 10 list of prescription drugs. But what other medications will make an apperance on next years's list? To find out, simply key in "Top 200 Prescription Drug List" on your Internet search engine, and you'll get your answer.
The magazine of the University of Medicine and Dentistry of New Jersey