Cutting Your Drug Bill While Reducing Your Risk Of Avoidable Adverse Drug Reactions: Six Examples

A former drug company executive and physician testified before the U.S. Senate 45 years ago that the pharmaceutical industry is “...unique in that it can make exploitation appear a noble purpose.” Profiting on the decades-old charade of nobility, the pharmaceutical industry continues to sell expensive “new” patented brand name drugs that are no more effective and sometimes less safe than drugs already on the market. Remarkably, physicians prescribe them and patients pay, both groups somehow thinking (while being “flim-flammed”) that every new drug to come on the market is a “breakthrough.”

Americans who pay out-of-pocket for their prescription drugs continue to pay the highest prices in the world. In other developed countries, governments have made the deliberate decision to use cost and profit controls to ensure that their citizens have access to needed prescription drugs. The pharmaceutical industry still profits handsomely even in these other countries.

The response in the U.S. to this decades old problem — Congress held hearings on this issue as far back as 1959 — has been to ignore historical reality and to look for market-based solutions for high drug prices to ensure the public’s access to affordable prescription drugs. Some markets simply do not work: markets that involve the public’s health — including prices for prescription drugs — are examples of markets that always fail.

Congress, in its perpetual evasion of the real point, negotiated costs and profits with the pharmaceutical industry, has dreamed up to proposals that are nothing but political “gimmicks” such as reimportation of bulk quantities of brand name drugs from Canada. Imagine a country of 32 million people where healthcare is a national right rather than a business, risking the economic stability of its own system to supply drugs to a country of 300 million that does not have the political will to do the right thing. Congress would better serve the health needs of the American public if it imported the Canadian healthcare system rather than its drugs.

Despite these political “realities”, individuals can reduce their drug costs, in some cases to levels that are a fraction of what a drug would cost in Canada. One of the features of Worst Pills, Best Pills, just released in its fourth edition, is a list of 181 drugs that should never be used and corresponding alternative treatments that are equally or more effective, as safe or safer, and very often less expensive.

Many drugs are listed as DO NOT USE drugs for safety reasons; others because there are more effective alternatives. Some drugs are listed as DO NOT USE because they were developed to maintain a monopoly position in a lucrative segment of the market without any evidence of benefits. These drugs cause economic harm both to the individual and to the health care system.

This article will look at the potential savings for the individual consumer if the alternative treatments recommended in Worst Pills, Best Pills were used for six DO NOT USE drugs. All six are listed in the Drug Topics Magazine Top 200 selling drugs in U.S. in 2003. The drugs are: celecoxib (CELEBREX) used for arthritis and pain; the Alzheimer’s disease drug donepezil (ARICEPT); drospirenone with ethinyl estradiol (YASMIN 28), an oral contraceptive; esomeprazole (NEXIUM) the “new purple pill” for heartburn; montelukast (SINGULAIR), a drug approved for both asthma and hay fever; and valdecoxib (BEXTRA), an arthritis drug very similar to celecoxib.

The combined sales of these six DO NOT USE drugs was $8.1 billion with more that 75 million prescriptions dispensed in 2003.

The positive economic effect on an individual consumer who uses a Worst Pills, Best Pills recommended alternative treatment compared to one of the above DO NOT USE drugs was calculated using the retail costs found on the Web site of a popular Internet pharmacy. The results are presented as the savings that can be expected per month and per year. These results are summarized in the table at the end of this article.

In addition to the calcuable economic benefits, the positive therapeutic impact of using Worst Pills, Best Pills is incalculable; it can mean potentially avoiding serious injury or even death.

Celecoxib (CELEBREX)

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) in the same family of pain and arthritis drugs as ibuprofen (MOTRIN, ADVIL), naproxen (NAPROSYN), valdecoxib (BEXTRA), and rofecoxib (VIOXX). Rofecoxib was recently withdrawn from markets worldwide because it caused an increased risk of heart attack and stroke (see Worst Pills, Best Pills News November 2004).

Celecoxib is heavily promoted as being safer on the gastrointestinal (GI) tract than other NSAIDs, reducing the risk of ulcers and serious bleeding episodes that can be fatal. In 2003, it was the 13th most frequently dispensed drug in the U.S. with retail sales exceeding $2.2 billion. Celecoxib is no more effective for pain or arthritis than ibuprofen or naproxen. It has not been shown to be safer on the GI tract than ibuprofen. Like rofecoxib, it is associated with an increased risk of heart attack and strokes.

We listed celecoxib as a DO NOT USE drug in the April 2001 Worst Pills, Best Pills News. The alternative treatments recommended in the new edition of Worst Pills, Best Pills are plain aspirin or ibuprofen.

The potential savings are substantial in the treatment of rheumatoid arthritis, for example, by switching from celecoxib to ibuprofen. The maximum recommended dose for celecoxib to treat rheumatoid arthritis is 400 milligrams a day. At a popular Internet pharmacy, the retail cost for 60 celecoxib capsules, enough for 30 days, is $159.98. The maximum dose for ibuprofen is 3,200 milligrams per day. The retail cost of 120 tablets in the 800-milligram strength, again enough for one month, is $14.98 at the same Internet pharmacy. This is a difference of $145.00 per month. Over one year, this adds up to a savings of $1,740.00.

Donepezil (ARICEPT)

Donepezil belongs to the family of drugs known as acetylcholinesterase inhibitors that also includes rivastigmine (EXELON), galantamine (REMINYL), and tacrine (COGNEX). These drugs increase the level of acetylcholine, a brain transmitter, with the assumption that this might improve Alzheimer’s-associated dementia.

Donepezil was approved by the FDA in November. In 2003, more than 3.2 million prescriptions were dispensed for the drug with retail sales of more than $480 million. It was first listed as a DO NOT USE drug in the 1999 edition of Worst Pills, Best Pills. This recommendation was made at the time:

“At this time, there are no safe and effective treatments that substantially alter the progression of Alzheimer’s disease.”

The conclusion of the editors of the highly respected Medical Letter on Drugs and Therapeutics in their 1997 review of donepezil was typical of independent drug information sources about the drug:

“There is no evidence that use of either donepezil or tacrine leads to substantial functional improvement or prevents the progression of the disease.”

More recently, a study published in the June 26, 2004 issue of the medical journal The Lancet found that long term treatment with donepezil was ineffective (see Worst Pills, Best Pills News September 2004). The authors of the study concluded that:

Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than cholinesterase inhibitors are needed for Alzheimer’s disease.

A one month supply of donepezil, 30 tablets in the 10 milligram strength, is $155.99 at the Internet pharmacy and over a year the retail cost would be $1,871.88.

Unfortunately, donepezil is being deceptively oversold to physicians and patients, perpetuating the exploitation of patients with Alzheimer’s disease and their families and wasting hundred of millions of dollars a year.

Drospirenone and Ethinyl Estradiol (YASMIN 28)

This combination oral contraceptive of the progestin drospirenone with the estrogen ethinyl estradiol was approved by the FDA in April 2001. Drospirenone is a close chemical cousin of spironolactone (ALDACTONE), a diuretic (water pill) that causes the body to retain potassium. Spironolactone is known as a potassium-sparing diuretic and a 3-milligram dose of drospirenone (the amount in a daily pill) is equivalent to 25 milligrams of spironolactone.

In 2003, prescriptions for Yasmin exceeded six-million and retail sales were over $230 million.

Two facts form the basis for listing Yasmin as a DO NOT USE drug. First, drospirenone causes elevated blood levels of potassium that may cause serious heart and other health conditions, such as change in the acid balance of the blood and muscle weakness. Second, there is no evidence that Yasmin is superior in any way to older contraceptive products in preventing pregnancy.

It is not yet known if the risk of developing blood clots, an adverse effect of oral contraceptives, is higher or lower in women using Yasmin than it is in women using older oral contraceptives. The Netherlands Pharmacovigilance Centre has reported five cases of blood clots possibly being linked to the use of Yasmin. (see Worst Pills, Best Pills News May 2003)

Yasmin was listed as a DO NOT USE drug in the April 2002 Worst Pills, Best Pills News. The alternative oral contraceptive recommended in the new edition of Worst Pills, Best Pills is one of the older second generation pills such as the combination of levonorgestrel with ethinyl estradiol (AVIANE).

The cost of a one month supply of Yasmin 28 on the Internet pharmacy is $40.39, while a month’s supply of Aviane at the same pharmacy is $26.99. This is a difference of $13.40 per month, adding up to a savings of $160.80 per year. The added benefit is reducing the risk of developing high blood levels of potassium.

Esomeprazole (NEXIUM)

The remarkable economic success of esomeprazole, an old drug sold as being new, may be the marketing coup of the decade.

Esomeprazole is member of the proton pump inhibitor (PPI) family of drugs used for the treatment of various forms of ulcers and gastroesophageal reflux disease (GERD), which often manifests as nighttime heartburn. It was the fifth drug in the PPI family, the others being lansoprazole (PREVACID), omeprazole (PRILOSEC), pantoprazole (PROTONIX), and rabeprazole (ACIPHEX). In 2003, esomeprazole was the 15th most frequently prescribed drug in the U.S. Over 18 million prescriptions were dispensed and retail sales exceeded $2.7 billion.

Esomeprazole was approved by the FDA in February 2001. In November 2001, we told Worst Pills, Best Pills News readers to save their money and not buy this drug. It is essentially nothing more than omeprazole, which has been on the market since September 1989.

The FDA Medical Officer who evaluated esomeprazole wrote in no uncertain terms:

The sponsor’s [esomeprazole’s manufacturer AstraZeneca] comparisons of H 40 [esomeprazole 40 milligrams] vs O 20 [omeprazole 20 milligrams] do not yield valid conclusions about the superiority of H [esomeprazole] over O [omeprazole], although these comparisons are adequate to demonstrate that H is active in the assessed indications. Therefore, the sponsor’s conclusion that H 199/18 [esomeprazole] has been shown to provide a significant clinical advance over omeprazole in the first-line treatment of patients with acid-related disorders is not supported by data .

The recommended dose of esomeprazole for the management of symptomatic GERD is 20 milligrams once daily. The retail cost at the Internet pharmacy for a one month supply, 30 capsules, is $122.99. The retail cost for the same quantity and dose of generic omeprazole, the same drug, is $93.99. This is a savings of $29.00 per month or $348.00 per year.

A much bigger savings is realized if you buy non-prescription, or over-the- counter omeprazole. The retail cost of 30 is $21.42. This would save a consumer $101.57 per month, or $1,218.84 per year.

If esomeprazole is being prescribed for simple heartburn and not the more serious GERD our recommendations include to first, avoid food, and particularly alcohol, within two or three hours of bedtime. Elevate the head of the bed about six inches or sleep with extra pillows. Try to avoid foods that trigger your condition, such as fatty foods, onions, caffeine, peppermint and chocolate. Avoid alcohol, smoking, and tight clothing.

You should also avoid drugs known to aggravate ulcers, especially aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) (see the new edition of Worst Pills, Best Pills or www.worstpills.org). Ask your doctor if acetaminophen (TYLENOL) could be substituted for these drugs. Check with your doctor about other medications that aggravate the esophagus such as alendronate (FOSAMAX), a drug used to treat osteoporosis.

If these steps are not effective, try simple over-the-counter (OTC) antacids such as a generic aluminum hydroxide and magnesium hydroxide product (MAALOX, MAALOX TC). Be aware that long-term use of antacids also has risks: aluminum can cause bone damage, and antacids containing magnesium can cause severe diarrhea. Too much calcium and sodium also cause problems. If symptoms worsen or bleeding occurs, call your doctor.

If this does not relieve your symptoms, one of the family of stomach-acid blocking drugs known as histamine-blockers can be tried. This family includes cimetidine (TAGAMET), famotidine (PEPCID), nizatidine (AXID), and ranitidine (ZANTAC). Histamine-blockers are available in both OTC and prescription strengths. If the OTC histamine-blockers do not give adequate relief of your symptoms after 14 days, it is time to consult your physician.

Following the above advice would result in even greater savings than over-the-counter omeprazole compared to the cost of the new purple pill.

Montelukast (SINGULAIR)

Montelukast is a member of the leukotriene inhibitor family of drugs. It is approved by the FDA for both the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age and older and for the relief of symptoms of seasonal allergic rhinitis (hay fever) in adults and children. Montelukast was the 17th most frequently prescribed drug in the U.S. in 2003. Over 17 million prescriptions were dispensed and retail sales amounted to over $1.6 billion.

Montelukast was approved by the FDA in February 1998 for asthma. It was first listed as a DO NOT USE drug in the 2002 Companion to the 1999 edition of Worst Pills, Best Pills for two primary reasons. First, the National Institutes of Health’s 1997 Guidelines for the Diagnosis and Management of Asthma said of the leukotriene inhibitors that “further clinical experience and study are needed to establish their roles in therapy.” At this time, the role of the leukotriene inhibitors in the management of asthma is still far from established.

Second, the leukotriene inhibitors are promoted as useful in helping patients reduce their dosages of steroid drugs, for example triamcinolone (AZMACORT). Inhaled steroid drugs such as triamcinolone are the recommended treatment for chronic asthma. The Cochrane Database of Systematic Reviews published a meta-analysis of existing clinical trial data in 2002. Their analysis found, in comparing leukotriene inhibitors to placebo in people also using steroids, that the dosage of inhaled steroids can be safely reduced without requiring the use of leukotriene inhibitors. Furthermore, the dose of leukotriene inhibitors required to achieve a significant reduction in steroid dosage is several times the currently approved maximum dosage.

Montelukast was approved for hay fever in adults and pediatric patients two years of age and older in January 2003. Four of the five trials used to approve the drug found montelukast to be superior to an inactive placebo. In the fifth trial, montelukast was compared to an active antihistamine, loratadine (CLARITIN). In this trial, the score for loratadine was superior to that of montelukast.

The Medical Letter On Drugs and Therapeutics reviewed the use of montelukast for hay fever in their March 17, 2003 issue. The Medical Letter, a highly respected independent source of drug information written for health professionals, concluded:

Montelukast (Singulair) might be as effective as an oral antihistamine for treatment of seasonal allergic rhinitis (more data are needed), but it is less effective than an intranasal corticosteroid, and more expensive than either.

The retail cost of a one month supply (30 tablets) of montelukast in the 10 milligram strength is $89.99 at the Internet pharmacy, or $1,079.88 per year. The retail cost of a one month supply of over-the-counter chlorpheneramine (CHLOR-TRIMETON), an antihistamine that it is recommended in Worst Pills, Best Pills, is $8.10. The savings in one year is $982.68.

Valdecoxib (BEXTRA)

Valdecoxib is a nonsteroidal anti-inflammatory drug (NSAID) in the same family of pain and arthritis drugs as ibuprofen (MOTRIN, ADVIL), naproxen (NAPROSYN), celecoxib (CELEBREX) and rofecoxib (VIOXX). Rofecoxib was recently withdrawn from markets worldwide because it caused an increased risk of heart attack and stroke (see Worst Pills, Best Pills News November 2004).

In 2003, more than nine million prescriptions were filled for valdecoxib, and retail sales were greater than $905 million. Valdecoxib was first listed as a DO NOT USE drug in the 2002 Companion to the 1999 edition of Worst Pills, Best Pills. The alternative treatments to valdecoxib recommended in the new edition of Worst Pills, Best Pills are plain aspirin or ibuprofen.

The FDA reviews of the safety and effectiveness of valdecoxib completed before the drug was marketed revealed that valdecoxib was not approved for the treatment of acute pain because it caused an increase in heart attacks and strokes in post-surgical patients (see Worst Pills, Best Pills News September 2004). An increase in the risk of heart attack and stroke is the reason that the similar drug rofecoxib was removed from the worldwide market on September 30, 2004.

The FDA announced on December 10, 2004 that a black box warning had been added to valdecoxib’s professional product labeling, or package insert, concerning an increased risk of fatal skin reactions with the use of this drug. Warnings were also required about an increased risk of heart attack, stroke, deep surgical infections, and wound complications.

Valdecoxib is clearly a drug that should not be on the market.

The recommended dose for valdecoxib for the treatment of rheumatoid arthritis is 10 milligrams per day. The retail cost of a one month supply in the 10 milligram strength, 30 tablets, is $104.99 at the Internet pharmacy. This amounts to $1,259.88 per year. The maximum dose for ibuprofen is 3,200 milligrams per day. The retail cost of 120 tablets in the 800-milligram strength, again enough for one month, is $14.98 at the same Internet pharmacy. This is a difference of $90.01 per month. Over one year, this adds up to a savings of $1,080.12.

Valdecoxib is no better, and in some respects more dangerous, than drugs already on the market, including ibuprofen. Ibuprofen is available over-the-counter in non-prescription strengths.

The amount of money being wasted on valdecoxib is extraordinary. The biggest burden falls on those patients who suffer an avoidable adverse reaction from this drug and must pay out-of-pocket for their drugs.

What You Can Do

You can reduce your prescription drug costs while at the same time reducing your risk of preventable adverse drug reaction by using the information found in Worst Pills, Best Pills News, the new edition of Worst Pills, Best Pills, and online at www.worstpills.org.