Generics and Therapeutic Substitution – Safety and Efficacy?

Excuse me for being a “doubting Thomas,” but when I saw articles in JAMA Internal Medicine and commentaries supporting use of generics instead of brand name drugs I asked myself “Where is the proof of equivalent results and safety?”.  Generic substitution implies that the original product is no longer patented and exclusive and another firm is now producing an identical chemical version which produces the same beneficial effects on the patient.  Therapeutic substitution means your pharmaceutical insurance company or pharmacy changes the drug you are prescribed to one in the same drug class. Think of drinking Coca Cola and having the supermarket substitute a comparable brand instead.

The reason for this is simply to spend less money. Many pharmaceutical insurance companies realize if they put an obstacle in your path of obtaining your medication you likely will pay for it independently saving them money.  The authors of the JAMA articles estimate between 2010 and 2012 therapeutic substitution would have saved $73 billion. The out-of-pocket savings to the patient would have amounted to $25 billion.

I’m for saving money and spending less with certain guidelines. However; I want to know that a generic medicine is produced in a factory inspected by the Food and Drug Administration (FDA) at least as frequently as the drugs produced in North American factories. I like to know where the drug was made including country of origin, city, location and the plant’s track record for health and safety. I also want to know the generic medication produces the same drug levels and positive effects as the brand name medication and is made with no more contaminants than the original branded product.

I need reassurance that my patient isn’t receiving a counterfeit product with stolen original labeling, which has been a scam fooling pharmacists and Customs agents for years.   I would additionally like to know that the generic product, or therapeutically substituted product, works as well as the original. We know for example that Levothyroxine generics and substitutions are problematic.  We additionally know that the beta blocker carvidilol (Coreg) has certain unique properties that other beta blockers do not provide making therapeutic substitution for less expensive medications in the beta blocker class problematic.

Once this information is available it should be distributed in package inserts, online and taught in pharmaceutical, nursing and medical school courses as well as CME courses for health care professionals.

There is an abnormally perverse concern that if a pharmaceutical representative takes a health care provider out for a meal and a drink while explaining their product, we will prescribe it even if it is more expensive or doesn’t work as well.  I doubt sincerely that most physicians would do that but do believe if the cost is comparable, or less, and the efficacy is as good, they might choose the product as a viable alternative.

Antibiotic Associated Colitis Increases Risk

At least a half dozen times per week patient’s call with symptoms of a viral upper respiratory tract infection or present to the office for a visit with symptoms and signs of a cold.  These illnesses are caused by small viral particles which do not respond to antibiotic treatment.   Your body’s defense system attacks these viral particles and over a period of hours to days defeats them.   Despite years of ongoing public health announcements and handouts by doctors and nurses and attempts at patient education you find yourself negotiating with strong willed patients who want a “Z Pack” or some other antibiotic which they do not need.  “I know my body,” they argue.  “My northern or previous physician knew to always give me an antibiotic, why won’t you?”

The answer is quite simple. They do not work to shorten the course, intensity or duration of your illness. They do in fact put you at risk of developing complications of antibiotic use. When your infection requires the use of antibiotics to restore health, it is worth taking these risks. When you do not need the medication it definitely is not. This was confirmed by an article and research presented by E Erik Dubberke, MD of Washington University School of Medicine in Saint Louis, Missouri commenting on Medicare Data about the death rate associated with antibiotic related colitis infections due to Clostridia Difficile.  Bacteria normally reside in our large intestine and promote health and digestion.  When we prescribe an antibiotic it kills off the healthy and beneficial bacteria as well as the infection related bacteria. This destruction of healthy bacteria creates an environment conducive to “opportunistic “bacteria normally suppressed by the normal flora to invade and take over your gut. The resulting fever, cramping, diarrhea with blood occurs as the intestine become inflamed with colitis. One of the common opportunistic pathogens is Clostridia Difficile.

Dr. Dubberke looked at Medicare data and compared 175,000 patients older than 65 years of age and diagnosed with Clostridia difficile infection and compared them to 1.45 million control patients. He found that those with clostridia difficile infection had a 44% increased risk of death. When comparing admissions to nursing homes for treatment there was an 89% increased risk due to antibiotic related colitis care.

Antibiotics are wonderful when appropriate. They will always carry a risk of a side effect, adverse reaction or complication which is a risk worth taking in the correct setting.  It is clearly not worth the risk when your doctor tells you that it will not work.

How Often Do Screening Colonoscopies Result in a Complication?

Harlan Krumholz, MD is the director of the Yale Center for Outcomes Research and Evaluation (CORE). His team at Yale is being paid extraordinarily well to determine what works and what doesn’t in Medicare. Their data will theoretically allow Medicare to issue payment for services based on success rates of care without complications. His group is part of a national program promoted by the Center for Medicare Services (CMS) to spend less for more effective high quality care. This in my humble opinion is “voodoo” health care policy.

One of their areas of interest is trips to the emergency room or hospital within 7 – 14 days of a colonoscopy. They developed a formula to look at this problem and applied it to Medicare claims data in the year 2010 in NY, Nebraska, Florida and California. They found 1.6% of healthy individuals going for screening colonoscopy ended up at the hospital within seven days. They found wide variations in this rate coming from different facilities and different doctors. When the data is extrapolated to the 1.7 million Medicare beneficiaries undergoing screening colonoscopy annually it indicates there will be at least 27,000 unplanned hospital visits within seven days of the procedure.

Determining what causes complications of a screening procedure so we can determine a root cause and then prevent it is a good thing. However; the research needs to be done by independent groups not receiving funds from CMS which has a clear and strong conflict of interest!

We need to be looking at complications related to the choice of preparation, choice of colonoscopy, choice of anesthesia and whether polyps were removed and or biopsies taken. We additionally need to assess the definition of “low risk patient.”

Within the recommended age group for screening colonoscopies of 50-75 years old, very few patients are not taking prescription medications as well as supplements. The research needs to look at procedures such as CT Scan virtual colonoscopy and fecal immunochemical human occult blood testing as well for efficacy and complication rate.

There are currently DNA analysis tests of columnar epithelium colon cells sloughed during a normal bowel movement. Pre-cancerous polyps and colon cancer have distinctive DNA patterns that can be detected by looking at fecal material. There is no prep but the cost of $500 makes determining if it works and under what circumstances important. If it works then shouldn’t it be the screening test to determine who needs to have a colonoscopy? Yes, the research must be done but it must be done by agencies not affiliated with CMS with their stated goal of spending less for better service and better quality.

CDC and ACP: Stop Prescribing Antibiotics for Common Respiratory Infections

The Affordable Health Care Act has created patient satisfaction surveys which can affect a physician’s reimbursement for services rendered plus their actual employment by large insurers and health care systems. This has created a fear of not giving patients something or something they want at visits for colds, sore throats and other viral illnesses. Aaron M Harris, MD, MPH, an internist and epidemiologist with the CDC noted that antibiotics are prescribed at 100 million ambulatory visits annually and 41% of these prescriptions are for respiratory conditions. The unnecessary use of antibiotics has resulted in an increasing number of bacteria developing resistance to common antibiotics and to a surge in Emergency Department visits for adverse effects of these medications plus the development of antibiotic related colitis. To address the issue of overuse of antibiotics, Dr Harris and associates conducted a literature review of evidence based data on the use of antibiotics and its effects and presented guidelines for antibiotic use endorsed by the American College of Physicians and the Center for Disease Control.

1. Physicians should not prescribe antibiotics for patients with uncomplicated bronchitis unless they suspect pneumonia are present”. Acute bronchitis is among the e most common adult outpatient diagnoses, with about 100 million ambulatory care visits in the US per year, more than 70% of which result in a prescription for antibiotics.” The authors suggested using cough suppressants, expectorants, first generation antihistamines, and decongestants for symptom relief.
2. Patients who have a sore throat (pharyngitis) should only receive an antibiotic if they have confirmed group A streptococcal pharyngitis. Harris group estimates that antibiotics for adult sore throats are needed less than 2% of the time but are prescribed at most outpatient visits for pharyngitis. Physicians say it is quicker and easier to write a prescription than it is to explain to the patient why they do not need an antibiotic.
3. Sinusitis and the common cold result in overprescribing and unnecessary use of antibiotics often. Over four million adults are diagnosed with sinusitis annually and more than 80% of their ambulatory visits result in the prescribing of an antibiotic unnecessarily. “ Treatment with antibiotics should be reserved for patients with acute rhinosinusitis who have persistent symptoms for more than ten days, nasal discharge or facial pain that lasts more than 3 consecutive days and signs of high fever with onset of severe symptoms. They also suggest patients who had a simple sinusitis or cold that lasted five days and suddenly gets worse (double sickening) qualified for an antibiotic

Last year two patients in the practice who were treated with antibiotics prescribed elsewhere for situations outside the current guidelines developed severe antibiotic related colitis. They presented with fever, severe abdominal pain and persistent watery bloody diarrhea. Usual treatment with oral vancomycin and cholestyramine did not cure the illness. One patient lost thirty pounds, the other sixty pounds. Fecal transplants were required to quell the disease. At the same time community based urine infections now require a change in antibiotic selection because so many of the organisms are now resistant to the less toxic, less expensive , less complicated antibiotics that traditionally worked.

“My doctor always gives me an antibiotic and I know my body and what it needs,” can no longer be the criteria for antibiotic use.

Generic Colchicine for Gout May Soon be Available on Local Markets

Colchicine has been the gold standard drug for the treatment of acute gout flare ups for generations. It is used additionally when physicians institute uric acid lowering therapy with allopurinol to prevent an acute gouty attack that can accompany any change of our uric acid level. It has additional uses in the treatment of the very rare Mediterranean fever.

The drug was always generic and exceedingly inexpensive until 2010 when the FDA granted Takeda Pharmaceuticals copyright exclusivity production it put its version known as Colcrys through the rigorous testing and trials the FDA demands. Before Takeda engaged in the testing and evaluation of Colcrys, all of our colchicine in the USA was produced overseas in small generic factories that had no oversight or inspections by the Food and Drug Administration (FDA). As a reward for going through the oversight process to insure that our colchicine was safe and pure, Takeda Pharmaceuticals received an exclusive distribution right while the other foreign products were removed from the market. The cost of colchicine produced by Takaeda USA soared to $6-$10 per pill. This made a month’s supply too expensive for many users.

Last month, under encouragement from the FDA and consumer groups, Takeda Pharmaceuticals USA gave permission to Prasco Laboratories to distribute Colcrys as a generic product at a much lower cost. It will be sold under the Prasco name. As of 03/19/2015 it has not yet arrived in the South Palm Beach County Florida market but should be there shortly.

Viagra, Cialis and Levitra Use and Malignant Melanoma

Jiali Han, Ph.D of the Indiana University School of Public Health in Indianapolis reported in JAMA that use of Viagra or sildenafil was associated with an 84% greater risk of malignant melanoma. Their preliminary data obtained from the Health Professionals Follow-up Study (HPFS) looked at 51,529 men aged 40 – 75 years old and all health professionals. Beginning in 1986 these individuals filled out a detailed health questionnaire every other year. The researchers reached their conclusions after reviewing the 2,000 HPFS survey and excluding all participants with a history of melanoma, squamous cell cancer or basal cell skin cancer prior to calendar year 2000. They were left with 25,848 men who had a mean baseline age of 64.8 years. 5.3 % of these men (1370) reported use of sildenafil (Viagra). From 2000 until 2010 142 melanomas were reported in that group.

The authors theorize that Viagra and the other drugs promote tumor growth by inadvertently inhibiting our immune system’s ability to suppress tumor growth messages at the genetic and molecular level. They emphasize that this is a preliminary study that does not prove cause and effect but does generate enough concern to warrant the creation of a study to answer the question” Our data provide epidemiological evidence on possible skin adverse effects of PDE5A inhibitors and support continued investigation of this relationship.” There was no mention of frequency of use or dosage and development of melanoma.

The authors were clear that if the relationship does in fact hold true, it extends to all the drugs in this class. Considering the billions of dollars in pharmaceutical profit involved it is hard to imagine that the question will not be addressed in a well-planned and funded study.

Aspirin for Breast Cancer?

In an observational study published in the Journal of Clinical Oncology in 2010, Drs. Michelle Holmes and Wendy Chen of the Harvard Medical School showed that women with breast cancer who took one aspirin per week had a 50% lower chance of dying from breast cancer. They have been trying to set up a randomized blinded study of 3000 women with breast cancer to test this finding using the gold standard of research but they have been unable to raise the $10,000,000 required for a five year study. Pharmaceutical companies see no profit in aspirin and prefer to use their research money on medications that are potentially more profitable. Government agencies seem to feel the same way opting to test new cancer drugs pushed by pharmaceutical companies rather than finance an inexpensive available product.

The authors believe aspirin, if proven to be effective in randomized trials, is a less expensive alternative for women who cannot afford or cannot tolerate hormonal therapy post-surgery for five years. Great Britain, through its national health service has decided to study the effects of aspirin on four cancers, with breast cancer one of them, in a study that will not be completed until 2025. Drs. Holmes and Chen believe that with proper funding their study of women with stage 2 and 3 breast cancer, would answer the question of aspirin’s efficacy within five years.