Ranitidine (ZANTAC) Removed from Market By FDA

Ranitidine is an H-2 receptor blocker marketed in the United States as Zantac. It is sold over the counter (OTC) without a prescription at the 20 mg dosage and with a prescription at the 40 mg dosage. It is used for peptic ulcer treatment, gastritis treatment, heartburn, gastroesophageal reflux and other diseases in which gastric acid causes inflammation of the lining of the stomach and discomfort.

It is being recalled because when manufacturing this product, new techniques are apparently inadvertently producing a probable carcinogen known as NDMA (N-Nitrosdimethylamaine). The longer the ranitidine sits around, the more NDMA is found. None of the levels measured are believed to be toxic.

Ranitidine is a relatively inexpensive blocker of histamine-2 receptor sites resulting in less digestive acid secretion in the stomach. The NDMA in the production product is the same chemical that resulted in the blood pressure medicine losartan and similar products being recalled. There are several alternative H-2 receptor blocker drugs on the market to replace ranitidine or Zantac. NDMA has not been found in Pepcid (famotidine), Tagamet (cimetidine), omeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).

Globalization started during the Clinton administration, and encouraged by subsequent Republican and Democratic administrations, has resulted in pharmaceutical manufacturers moving their plants to Asia and other overseas areas where labor is cheaper, and regulations are less rigid. Ronald Reagan eliminated the Food and Drug Administration’s testing lab which set the gold standard for protecting Americans against tainted drugs. Prior to this action, no pharmaceutical product ever reached the American market and had to be recalled.

Subsequent administrations reduced the funding for the FDA, especially in the inspection department. With production now overseas, and virtually unregulated, we are dependent on the goodwill of foreign governments, and the liability attorneys for big pharma, to protect us from tainted products. Almost all antibiotics, both oral and intravenous, and all IV solutions are produced overseas in addition to most of the oral generics we are forced to take by our insurer every day.

We are currently living in a civilization altering pandemic with Coronavirus COVID-19. When this plague is under control, the country will need to reset our economy. My hope is that the big pharmaceutical firms will be legally forced to bring the pharmaceutical manufacturing back to U.S. soil. At the same time, the FDA inspection division needs to be funded fully to ensure that the products we need and ingest are safe and pure!

Sunscreen Ingredients are Absorbed says FDA

For years public health officials, dermatologists and primary care physicians have been encouraging people to apply sunscreen before going out into the outdoors to reduce the risk of sunburn and skin cancers.  We are taught to apply it in advance of exposure by about 30 minutes and to reapply it every few hours especially if we are sweating and swimming.   Living in South Florida, sun exposure is a constant problem so we tend to wear long sleeve clothing with tight woven fabrics to reduce sun exposure.  My 15-month old grandson, visiting last weekend was smeared with sunscreen by his well-meaning parents before we went out to the children’s playground nearby.

These precautions seemed reasonable and sensible until an article appeared in JAMA Dermatology recently.  An article authored by M. Mata, PhD. evaluated the absorption of the chemical constituents of sunscreen after applying it as directed four times per day.  The article was accompanied by a supporting editorial from Robert M. Cliff M.D., a former commissioner in the FDA and now with Duke University School of Medicine and K. Shanika, M.D., PhD.

The study applied sunscreen four times a day to 24 subjects. Blood levels were drawn to assess absorption of the sunscreen products avobenzene, oxybenzone and octocrylene.  The results of the blood testing showed that the levels of these chemicals far exceeded the recommended dosages by multiples. The problem is that no one has evaluated these chemicals to see if at those doses it is safe or toxic causing illness?

The editorial accompanying the findings encourages the public to keep using sunscreen but cautions that the FDA and researchers must quickly find out if exposure to these levels is safe for us?  We do know that the chemical oxybenzone causes permanent bleaching and damage to coral reefs in the ocean from small amounts deposited by swimmers coated with sunscreen. The state of Hawaii has actually banned sunscreens containing oxybenzone to protect their coral reefs.

The fact that these chemicals have been approved and are strongly absorbed with no idea of the consequences is solely the result of elected officials wanting “small government” and reducing funding to the oversight organizations responsible for making sure what we use is not toxic.  It is a classic example of greed and profit over public safety.  The research on the safety of these chemicals must be funded and addressed soon. The American Academy of Pediatrics and Dermatology need to advise parents of youngsters whose minds and bodies are in the development and growth stages what is best to do for their children – sooner rather than later.

Marijuana, Pain Relief and the Facts

On a daily basis patients of mine come in for office visits complaining of wear and tear injuries, as well as aches and pains, and their methods of dealing with chronic pain. As we all know, aging is a part of the normal life process.

For instance, as we approach 70 years old we typically lose three quarters of our functioning kidney cells (nephrons) but do well with our limited reserve as long as we do not constantly call on that reserve. When we take nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen to relieve pain we are challenging that reserve leading seniors to look for alternatives. Opioids, even when appropriate, have become taboo so alternatives are being searched for.

Medical marijuana has become a very hot topic recently.  It is being heavily marketed as a pain relief alternative in several forms.  However, what little legitimate research has been conducted indicates it is not very good at relieving non cancer related chronic pain.

Not a day goes by when several patients reveal they are using cannabis products obtained out of state for pain relief with no consideration of how it interacts with the medications they are already taking. Recently, strong public relations campaigns for legalizing medical marijuana have led to its legalization in different forms, in various states, even if it doesn’t work. A select group of investors have positioned themselves to make vast sums of money from a product with little documented upside and potentially unknown downsides.

At the same time that medical marijuana enters mainstream medicine there is a similar legislative and marketing push to legalize marijuana for recreational use. Once again, a well-financed lobby of investors is trying to sell the concept of marijuana being less troublesome than legalized tobacco or alcohol. In the last few weeks there have been several articles appearing in reputable medical journals and periodicals such as the Wall Street Journal, New York Times and New Yorker magazine all examining the known results of liberalizing marijuana use in three states.

First of all, today’s marijuana is far stronger and potent than the “love generation’s” weed of the 1960’s with a higher percentage of the hallucinogen THC. To that point, states that have legalized marijuana have seen a tripling of visits to the emergency department for psychotic behavior. Also, violent crime and murders have tripled in many jurisdictions. A growing body of evidence indicates auto accidents have increased as a direct result of marijuana’s use.

Medically speaking, there is little research evaluating marijuana as a drug. Many questions remain.  What is the minimal dosage to create an effect? What is the dosage that can cause medical illness? How does the mechanism of delivery affect the final effects such as smoking versus vaping versus eating the product? Beyond the stoners’ credo of “start low and go slow” there is little data to evaluate the product as a pharmaceutical drug and or how it can interact with other drugs prescribed for you.

I am far from an anti-marijuana critic. I’d just like to know what I’d be getting in to before I consider hallucinating. It seems to me that before we liberalize marijuana use, the product needs to be put through the type of research and scrutiny the old Food and Drug Administration (FDA) put a product through before it was approved for public use.

More on Shingrix, the Shingles Vaccine

Recently, the FDA approved a new shingles vaccine called Shingrix. It is a two shot series with the suggestion made that the second shot should be taken 2 – 6 months after the first one. Shingrix will replace the original shingles vaccine Zostavax. Shingrix is recommended in all patients over 50 years old.

For those of you who have had the original shot, Zostavax, the new vaccine is still recommended. It is covered by Medicare Part D which means you must take it in a pharmacy or walk in center not in your doctor’s office. While this makes NO sense, it is the rule. If you have had shingles it is still recommended you take the new vaccine (Shingrix).

Shingles is a skin rash and painful skin condition caused by the chicken pox virus Varicella. When you have chicken pox and complete the infection course you are immune but the virus remains alive forever, living in sensory nerve endings along the spinal cord. One third of adults will have an outbreak of this varicella virus which will appear along the path of a sensory nerve or dermatome on one side of your body. It will go through the full cycle of rash, pustule and then scab that the chicken pox did. A significant number of patients will continue to have pain over the involved skin for prolonged time periods in what we call post herpetic neuralgia. The pain is described as severe as an eye scrape, passing a kidney stone or going through labor and delivery.

The original shingles vaccine, Zostavax, protected against the rash 51% of the time and against post herpetic neuralgia 67% of the time. This efficacy dropped to about 30% after four years. The new vaccine, Shingrix protects against the rash over 90% of the time and against the pain syndrome 85-90% of the time while lasting for more than four years.

Only five percent (5%) of patients receiving Shingrix develop side effects. The most common are fever, myalgia and chills. In view of this, I am suggesting to my patients we allow the vaccine to be on the U.S. market for a year to see the adverse event profile and, if safe, we then start the series of shots.

Globalization, Corporate Control and Shortages of Medication

One of my online medical information websites carried a letter from the head of the Food and Drug Administration (FDA) trying to explain why there is a shortage of standard intravenous fluids to administer at hospitals and medical clinics in the United States. The author cited an extremely busy influenza season causing patients to use Emergency Departments in record numbers plus a loss of manufacturing capabilities due to damage to a production facility in Puerto Rico during a seasonal hurricane. No more, no less.

Doctors, nurses and patients are expected to believe that there is only one production center for our intravenous fluids nationally located in Puerto Rico. If it is unable to produce and ship product then health care as we know it has to change?

If this is in fact the truth, and the only reason for the lack of available IV fluids, what exactly does it have to say about our planning and leadership at the level of the FDA and CDC? Might it in fact indict the corporate model of efficiency and productivity? Is there not a Plan B and C for supplies of intravenous fluid if one source cannot supply our needs? If this is in fact the only production source then why wasn’t it a post storm FEMA national priority similar to if the NORAD intercontinental ballistic missile system had been damaged due to Hurricane Irma or Maria and we could not monitor North Korean launches?

At the same time we have a shortage of intravenous fluids, we have a shortage of injectable narcotics for pain relief. Morphine and dilaudid are in short supply. My hospital pharmacy committee and chief medical officer are now limiting injectable pain medications to immediate post-surgical cases.

Pain elsewhere in the institution should be treated with the oral pain pills we read about causing the opioid epidemic and crisis in America. There apparently is no shortage of injectable heroin on the streets of Palm Beach County, Florida. The Mexican cartels have found a way to meet the demand of its customers unlike organized healthcare which seems unable to do so.

I do not know who is responsible for insuring that we have enough materials and medications available to care for our nation. I do know they are doing a very poor job of it and would love to know who is responsible.

New Non Live Shingles Vaccine Approved by FDA and ACIP

For several years the Advisory Committee on Immunization Practices (ACIP) has been encouraging adults to receive the shingles vaccine or Zostavax. Shingles is a recurrence of chicken pox which we had as children. The virus lives within the nerve endings near the spinal cord and recurs following sensory nerves at unexpected times producing a chicken pox like (herpetic) rash with pain on one side of your body. The lesions follow the pattern of the chicken pox with pustules crusting over the course of a week. During the rash, patients are contagious and can transmit the chicken pox virus to people not immunized against it or those people whose immunity is diminished. As the rash subsides, a large percentage of the patients continue to have pain along the path of that sensory nerve which can last forever in a post herpetic neuralgia.

Zostavax will prevent an outbreak of shingles in about 2/3 of those who receive the shot. It prevents the post rash pain syndrome in a much higher percentage of the recipients. It was this quality that made it easy for me to recommend the vaccine to my patients and to take it myself.

The shot’s major drawback was that it involved receiving an attenuated or modulated live virus. This prevented individuals on chemotherapy or with a weakened immune system from receiving this vaccine.

To address that issue Glaxo Smith Kline developed Shingrix which is a non-live, recombinant subunit vaccine injected into the muscle on two occasions. It is touted to prevent shingles in 90% of the recipients over a four year period. It will replace Zostavax as the shingles vaccine of choice. For those of us who already received Zostavax they are recommending that we boost our immunity by receiving this new vaccine as well.

I have always been quite conservative on recommending new pharmaceutical products until they have been on the US market for at least one year. With the decreased funding of the FDA, I will wait at least a year until I see what adverse reactions occur in the US population. In the meantime I will price the product and try and learn if private insurers and/or Medicare will pay for its administration.

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.

High Disability and Death Rates in Bleeds Associated with New Oral Anticoagulants

In the trailer for the movie Jaws 2 they show a swimmer in the ocean with a deep voice saying, “Just when you thought it was safe to go back into the water…” followed by the classic music associated with a shark attack and a big fin approaching the unsuspecting swimmer. I feel much the same way upon reading a Medpage Today online journal review of an article in JAMA Neurology published on December 14, 2015. Jan C. Purrucker, MD and colleagues looked at 61 consecutive patients with non-trauma related cerebral hemorrhages due to the newer oral anticoagulants Pradaxa, Xarelto and Eliquis. Overall there was a death rate of 28% at three months and “two out of 3 survivors had an unfavorable outcome.”

In October of 2015 the FDA approved the use of the antibody fragment idarucizumab (Praxbind) to reverse anticoagulation in patients bleeding from the administration of the oral anticoagulant Pradaxa. There are currently no medications to reverse the bleeding from the drugs Xarelto or Eliquis but we are promised that new products are in development. The article goes on to discuss how physicians have been forced to improvise when patients on these medications show up bleeding. They have tried fresh frozen plasma, 3-factor, 4-factor and activated prothrombin complex concentrates prothrombin complex concentrates, recombinant factor VIIa and cryoprecipitate alone or in combination with marginal success at best.

Despite there being no antidote to these blood thinners, the massive direct to consumer advertising continues on television prime time and magazines as if the products are no more dangerous than an antacid for heartburn. Coumadin or warfarin is the prototype anticoagulant working by inhibiting vitamin K dependent clotting factors. Its effects are reversible with administration of Vitamin K and clotting factors if bleeding occurs. Coumadin requires periodic blood tests (INR) to check on its efficacy and there is a long list of medications and foods that need to be avoided or adjusted while taking it. It is less convenient but safer in the sense that its effects can be reversed with medication.

The newer oral anticoagulants were championed by several studies that suggested that they were more effective in preventing embolic strokes in patients with the heart rhythm atrial fibrillation. Many experts in the field felt that those conclusions were flawed because the Coumadin group was not tightly regulated to keep their INR in a therapeutic non-clotting range thus unfairly biasing the results in favor of the newer agents.

There is no question that the newer agents are more convenient than warfarin treatment, but until there are readily available antidotes, complications seem to be more difficult to limit and control.

FDA Approves Coronary Artery Disease Screening Test

MedPage Today, the online medical journal of the University of Pennsylvania School of Medicine, announced that the FDA has ” cleared a blood test ” to screen for heart disease known as Lp-PLA2 or lipoprotein associated phospholipase A2. This test is an individual marker of vascular inflammation produced within atherosclerotic plaques. Its use was cleared for screening in all adults with no history of coronary artery disease.

In a National Institute of Health study, known as Reasons for Geographic and Racial Differences in Stroke, it was shown in a review of 4,598 people, aged 45 – 92, that individuals above the threshold level for Lp-PLA2 were more than twice as likely as others to have an event, heart attack or stroke, 7% versus 3.3 %. The study was particularly helpful when looking at black women as a group. An Lp-PLA2 level > 225nmol/min/mL is considered elevated.

This test has been available to patients in our practice through the Cleveland Heart Labs screening panel. It plus the myeloperoxidase level, CRP and other markers have been felt by the Cleveland Clinic cardiology division to have predictive value. These tests are currently available but in many cases require private pay because Medicare and private insurers do not yet cover them all.

Testosterone Therapy and Low T – “Does Anybody Really Know What Time It Is?”

The Food and Drug Administration (FDA) will now be requiring pharmaceutical manufacturers to label testosterone products with a warning that says that the use of this product is associated with an increased risk of blood clots in the veins. These venous emboli can break off and travel downstream causing lung emboli (pulmonary emboli) and even strokes. It had long been known that in men with polycythemia, a thickening of the blood due to increased red blood cells which is a side effect of testosterone therapy, have an increased risk of venous thrombosis.

The study of the effect of testosterone on veins is independent of the current FDA evaluation of the effect of testosterone on arterial clots, coronary artery disease and stroke. A Veterans Affair (VA) study showed a 29% increased risk of those events in veterans taking testosterone. A 2.19 fold higher risk of heart attack in older men and a 2.90 fold elevated risk in younger men with pre-existing heart disease was noted in another VA study. This data was refuted by testosterone advocates in their industry in an observational study suggesting a decreased risk of heart disease in users.

Testosterone supplementation is clearly indicated in criteria outlined by the American College of Endocrinology for hypogonadism. This requires measurement of the patient’s early morning testosterone level on 2 separate occasions. If the value is below a certain level supplementation is appropriate to restore your testosterone to normal functional levels. The problem is that anti-aging advocates have created a fire storm of outpatient enhancement clinics blitzing neighborhoods with advertising that supplementing your low but within the normal range testosterone enhances your quality of life, reduces unwanted body fat and invigorates the patient. There have been insufficient randomized controlled trials to answer the question of whether this practice makes you feel better but is detrimental to your health or if this is something aging men need to think about trying. The FDA investigation is now being joined by the European Medicine Agency to try and assess benefits versus risk of this form of therapy. At the recent meeting of the American Academy of Urology a lively panel debate was held reviewing what is known about testosterone therapy and whether current usage had reached abusive levels? There was broad agreement that more research is needed and until then the guidelines of the American College of Endocrinology should be the gold standard for initiating testosterone therapy safely.