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

FDA - Steven Reznick, MDMedPage 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?”

Low T v2The 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.

DNA Test to Replace Pap Smear

DNAThe Pap smear or Papinicolou Cervical Cancer Test is designed to detect early cancer of the cervix. It requires expert technique in obtaining the specimen during a speculum pelvic exam, expertise in applying the swab obtained specimen to a glass slide and preparation of the slide for transport to a cytology lab for microscopic evaluation. The microscopic evaluation is supposed to be performed by a specially trained and certified cytologist but they are in very short supply. The result is that there is great variability and suspected variation of accuracy in this test.

We now know that cervical cancer is a sexually transmitted disease (STD) of the human papilloma virus particularly HPV strains 16 or 18. Roche Molecular Systems has obtained FDA approval for its HPV DNA molecular test looking for fourteen high risk HPV strains. If a woman is found to have strain 16 or 18 health care professionals are advised to proceed to testing with colposcopy. If one of the other strains is found it is suggested that a Pap smear be performed to screen for the need for colposcopy. The FDA approval came after testing 48,000 women and comparing the accuracy of Pap Smears versus the DNA testing.

The new FDA approval allows clinicians to use the HPV testing alone or in conjunction with Pap smears.

Supplement Toxicity on the Rise

VitaminsIn a report in MedPage Today, the medical newsletter of the University of Pennsylvania School of Medicine, researchers attending the meeting of the American Association of the Study of Liver Diseases reported a striking increase in the number of severe liver injuries reported in supplements between the years 2004 and 2012. They reported the number of cases increased from 7 – 20% and blamed the vast proportion of those cases on dietary and herbal supplements.  Particularly disturbing was the number of injuries in young people involved in bodybuilding.

Mary Rinella, MD of Northwestern Memorial Hospital in Chicago moderated a discussion group on the topic and mentioned what a large problem it is; “It’s made worse by the popular belief that such supplements are harmless, which leads patients to omit mentioning them when they are in a clinic or doctor’s office.”  She went on to say that, “We don’t know what’s in the products or even what’s in the bottle.” Rinella said.  “Dietary and herbal supplements are not considered drugs and so escape oversight by the FDA.”

Warren Kupin, MD, FACP of the University of Miami Miller School of Medicine division of nephrology delivered a similar message on the epidemic of kidney disease in young adults being caused by the contents of common herbs and supplements sold on our shelves with pleasant healthful sounding names. He raised the red flag on products produced in India and Asia or products containing materials from those areas which contain high levels of heavy metals such as mercury, cadmium, arsenic and others. The target market is young women of child bearing age and they expose their partners and children to these products.  He took a commonly sold supplement, opened the bottle and said that the aroma escaping contained so many heavy metals that if this was produced in a US factory OSHA would require the workers to be wearing respirators in that type of toxic environment.

Consumers need to read labels and ask questions of their doctors before they add an herb or supplement to their daily regimen.  Women of child bearing age need to be especially vigilant and discuss these supplements with their obstetricians and pediatricians before considering ingesting them. The National Institute of Health maintains a very objective website on alternative and complimentary medications at nccam.nih.gov/health/whatiscam that is a great resource and location of factual material.   

I always suggest that when you visit your doctor you bring all your medications, vitamins, minerals, herbs and supplements in a plastic bag with you so that the doctor can read the labels with you.  Accepting the advice you receive on the Internet or from the sales personnel at a vitamin and mineral store is not the most accurate way to learn the truth.  The public is injuring and maiming themselves by consuming too much of the wrong things and there is little or no government oversight and regulation of these products. Protect yourself and ask your doctor for assistance!

 

Evaluation of Blood in the Urine (Hematuria)

Speciman BottlesI recently had a long discussion with a diabetic patient about the drug Actos. This very effective and relatively safe diabetic drug has now been implicated as increasing the risk of bladder cancer. While the FDA has not removed the drug from the market, it has been removed from the market in Germany.  My patient wondered if he could continue using Actos but send his urine off for testing and evaluation regularly to detect any indication bladder cancer early. I said I preferred switching medications. 

Chance would have it that the April 11, 2013 edition of Journal Watch addressed the question indirectly.  They looked at whether or not it was safe to send urine off for cytology to look for cancerous cells in the evaluation of blood in the urine. Urine cytology, like the Pap smear, looks at cells in the urine from the bladder and tries to diagnose bladder abnormalities and cancers by identifying abnormal cells. The traditional evaluation of blood in the urine includes doing x-ray and imaging studies as well as performing an invasive procedure called a cystoscope (under anesthesia a fiber optic device is inserted into the bladder through the urethra and advanced into the upper collecting tracts.).

In a study performed in the United Kingdom at a teaching hospital, researchers reviewed the records of patients with blood in the urine. Sixty-five percent of the patients had visible bleeding while 35% had only microscopic bleeding. They all underwent imaging of the upper tract, cystoscopy and urine cytology.

A full evaluation of imaging, cystoscopy and cytology was performed on 2,507 patients. Fourteen percent of the patients were ultimately diagnosed with transitional cell cancers of the bladder. The sensitivity and specificity of abnormal cytology were 45% and 89% making cytology not “good enough” to serve as a first line test for patients with unexplained blood in the urine. More than half the patients with bladder cancers had negative cytology and about 105 of patients with negative cytology had bladder cancers.

The study supports the recommendations of the American Urologic Association’s guidelines that recommend against using urine cytology in the initial evaluation of patients with microhematuria.