Category: Vaccines

Why is the Tdap Vaccine in Category C?

The Tdap vaccine is routinely recommended for all pregnant women, so why would it be in the FDA Category C?

The FDA has actually removed the pregnancy categories.

We should start by stating that “risk-benefit decisions regarding use of a drug during pregnancy are more complex than the category designations suggest.”

Why is the Tdap Vaccine in Category C?

Anyway, the category designations are no longer being used on new drugs and vaccines.

“In December of 2014, the FDA published the Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, referred to as the “Pregnancy and Lactation Labeling Rule” (PLLR or final rule). The PLLR removes pregnancy letter categories – A, B, C, D and X. Instead, under the final rule, narrative summaries of the risks of a drug during pregnancy and discussions of the data supporting those summaries are required in labeling to provide more meaningful information for clinicians.”

Guidelines for Vaccinating Pregnant Women

So is it still Category C?

Yes, for now. Few vaccines have converted to the new labeling system yet, which still leaves us with:

  • Pregnancy Category B: Tdap (Boostrix) – Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus during the first trimester (and there is no evidence of risk in later trimesters).
  • Pregnancy Category C: Tdap (Adacel) – Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks OR Animal reproduction studies have not been conducted and there are no adequate and well-controlled studies in humans.

Of course, the Vaccine Safety Datalink has published more than 14 studies “related to pregnancy and vaccination during pregnancy” and has used “data to study the health of children born to women who were vaccinated during pregnancy.”

And many of these studies are about the Tdap vaccine!

“There are no theoretical or proven concerns about the safety of the Tdap vaccine (or other inactivated vaccines like Tdap) during pregnancy. The shot is safe when given to pregnant women.”

Frequently Asked Questions for Pregnant Women Concerning Tdap Vaccination

This will likely be reflected when we get new labels for these vaccines, with wording that makes it clear that Tdap vaccines are safe in pregnancy.

what to know about the tdap vaccines and their category c designation

Tdap vaccines still have a Category C designation simply because their labels haven’t been updated to reflect the latest safety studies.

More on Tdap Vaccines and Category C

Dengvaxia for Dengue Fever

Dengvaxia was recently approved by the FDA after being available in other countries since about 2015.

“Indicated for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4. DENGVAXIA is approved for use in individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas.”

Wait.

Dengue is endemic throughout the tropics and subtropics, including most of the Caribbean.
Dengue is endemic throughout the tropics and subtropics, including most of the Caribbean.

It’s only for people who have already had a dengue infection before?

Dengvaxia Controversy

Unfortunately, Dengvaxia “performs differently in seropositive versus seronegative individuals.”

“In areas of 70% dengue seroprevalence, over a 5-year follow-up, for every 4 severe cases prevented in seropositive, there would be one excess severe case in seronegative per 1,000 vaccinees; for every 13 hospitalizations prevented in seropositive vaccinees, there would be 1 excess hospitalization in seronegative vaccinees per 1,000 vaccinees.”

WHO on Questions and Answers on Dengue Vaccines

If you have never had dengue before and you are vaccinated, you are at risk for a severe infection if you do get dengue. On the other hand, if you are unvaccinated, you are at even greater risk of getting dengue, a life-threatening infection. Fortunately, the first episode of dengue is usually fairly mild.

The problem occurs if your antibody levels have dropped enough, which can cause you to have a severe case of dengue the second time. The process is called antibody-dependent enhancement and has to do with antibody levels, either natural or vaccine induced. So it can occur whether or not you are vaccinated, although getting Dengvaxia, an attenuated, live vaccine, can act as a primary dengue infection.

“These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future.”

Scott Halstead on Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

It is something that dengue researcher Scott Halstead warned folks about as soon as he saw the first published study on Dengvaxia.

But why would you need a vaccine if you have already had dengue?

“In humans recovery from infection by one dengue virus provides lifelong immunity against that particular virus serotype. However, this immunity confers only partial and transient protection against subsequent infection by the other three serotypes of the virus. Evidence points to the fact that sequential infection increases the risk of developing severe dengue.”

WHO on Dengue control

There are four serotypes of dengue.

So if you aren’t vaccinated, you are at risk to get dengue multiple times.

Tragically, about 800,000 children in the Philippines were given Dengvaxia in a universal immunization program without checking to see if they had dengue first. And it likely led to some severe cases of dengue and deaths. This led to the vaccine being banned in that country and is thought to be one of the causes behind their current measles outbreak, as their Dengvaxia controversy led to more vaccine hesitancy.

And it will lead to more folks getting dengue. Instead of a ban, they should likely be more picky about who they give the vaccine to, either confirming that recipients have already had dengue (titer test) or only giving the vaccine to older kids.

Dengvaxia for Dengue Fever

Do you need Dengvaxia?

Remember, Dengvaxia is only for those living in endemic areas and in the United States, dengue is only endemic in the U.S. territories of American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands.

Do you need Dengvaxia if you are simply traveling to one of these areas?

Since Dengvaxia is not approved for those who haven’t had a dengue infection before, you likely wouldn’t get it just for traveling to an endemic area, unless perhaps you routinely travel to an endemic area and have had dengue already. A titer test can confirm a previous dengue infection, but there is no indication to get vaccinated for travel yet.

Also, while in other countries it is available for use between 9 and 45 years, in the United States, Dengvaxia is only approved for children between 9 and 16 years of age.

More on Dengvaxia for Dengue Fever

Making a Better Pertussis Vaccine

So we know that we need a better pertussis vaccine.

DTaP and Tdap just aren’t doing the job that they should be doing.

Whooping Cough is back, again.
Whooping Cough is back, again.

So when will we get one?

Making a Better Pertussis Vaccine

Since anti-vaccine folks are always talking about the 300 new vaccines in the pipeline, you would think that we would have had several new pertussis vaccines by now…

Unfortunately, we don’t.

What we do have is some good candidates, including:

  • new acellular pertussis vaccines, either with more antigens or an adjuvant
  • a new live attenuated nasal vaccine, BPZE1
  • new whole-cell vaccines with reduced endotoxin contents (so should have fewer side effects that then original whole-cell pertussis vaccine – DTP)

Before you get too excited, keep in mind that none of these vaccines will be available in your pediatrician’s office any time soon. Developing a new vaccine takes a lot of time.

BPZE1 has started phase 2a trials though.

What do we do until we get new pertussis vaccines?

“We should be more vigilant than we have been in the past to recognize and treat pertussis in all age groups so that transmission to young infants is reduced. Most important (although not discussed in this review) is to ensure that all pregnant women receive the Tdap vaccine between 27 and 36 weeks’ gestation with each pregnancy. Also, we should consider routinely administering Tdap vaccine every 3 years to all adolescents and adults who were primed with a DTaP vaccine.”

James D. Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines—Mistakes Made and Implications for the Future

We should keep using the pertussis vaccines we have!

Vaccines work, even when they aren’t as effective as we would like.

More on Making a Better Pertussis Vaccine

The Shingles Vaccine Shortage

Shingrix became the second shingles vaccine to be licensed in the United States, becoming the preferred shingles vaccine in 2017.

“Shingrix provides strong protection against shingles and PHN. Two doses of Shingrix is more than 90% effective at preventing shingles and PHN. Protection stays above 85% for at least the first four years after you get vaccinated.”

What Everyone Should Know about Shingles Vaccine

The first, Zostavax, was licensed in 2006.

Both are for older adults.

The Shingles Vaccine Shortage

Having a new and better shingles vaccine is good!

High levels of demand for shingles vaccine has lead to shortages and Shingrix manufacturing facilities are already at maximum capacity.
High levels of demand for shingles vaccine has lead to shortages and Shingrix manufacturing facilities are already at maximum capacity.

Not being able to actually get the vaccine and get vaccinated and protected isn’t so good. There has been a shortage of the vaccine due to high levels of demand since last year.

“Recombinant zoster vaccine (RZV) is recommended for the prevention of herpes zoster and related complications for immunocompetent adults aged ≥50 years.”

Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines

Fortunately, we will likely see more doses of the vaccine available this year and everyone will eventually be able to get vaccinated. In addition to your doctor or favorite pharmacy, the Shingrix Vaccine Locator might help you find a dose until the shortage is over.

More on the Shingles Vaccine Shortage