Women's Health News: FDA Approves PIVYA (pivmecillinam) for uncomplicated UTI

NEW: As of April 24, 2024 the FDA has approved a new drug application for PIVYA (pivmecillinam)  by Utility Therapeutics for the treatment of uncomplicated UTI (uUTI) caused by the following: E. Coli, P. mirabilis, and/or S. saprophyticus. This means that the drug is now ready to hit the market, and certainly will become a useful tool within our small toolkit for treatment of UTI.

What is PIVYA (pivmecillinam)?

Pivmecillinam is a beta-lactam antibiotic, which is within the same drug class as penicillin, amoxicillin, cephalosporins. This drug class is significant not only because of the commonality of hypersensitivity (a significant or life-threatening allergy) to any drug within the list of beta-lactams, but also the prevalence of antimicrobial resistance within the class.

For a full list of other beta lactam drugs, please see this publication from the National Institutes of Health (NIH), which provides a wealth of information about beta-lactam antibiotics.

What Makes PIVYA (pivmecillinam) Unique?

Don't we have enough antibiotics, already? NO! We absolutely do not have enough antibiotic options available due to the growing concerns regarding antimicrobial resistance^ In the US alone, almost 3 million antibiotic-resistant infections occur each year (2). Think about it: we have been utilizing beta lactam antibiotics, specifically penicillin, since the dawn of the 1930s - nearly 100 years ago. Think about how many opportunities a pathogen has had to mutate and develop resistance within that time frame. For reference, there are 4 known mechanisms of resistance which lead to the ability of the pathogen to evade beta lactam activity, thereby complicating treatment and limiting pharmacologic options for treatment.

Resistance to beta-lactams is an alarming and growing phenomenon and, in turn, a public health concern. (1)

PIVYA (pivmecillinam) is unique within its class for several reasons. First, PIVYA has a slightly different mechanism of action compared to its counterparts. In particular, pivmecillinam is the prodrug of mecillinam, meaning that when taken orally, pivmecillinam is absorbed in our stomach and small intestine, makes its way to the liver (where drug metabolism occurs) where it's quickly metabolized into the active form mecillinam. Due to the fact that this drug is not activated until metabolized, which is not typical of the beta lactam class, the risk of antimicrobial resistance to pivmecillinam is lower compared to other drugs within the same class, and provides a novel treatment option for pathogens which are able to evade other beta lactam drugs.

^resistance: mutations that occur within a pathogen (bacteria) that provide the pathogen the ability to evade the effects of antibiotics.

Useful Patient Information:

Contraindications

• AVOID USE if you have any known hypersensitivity to any beta lactam drugs - just because PIVYA avoids resistance, it does not avoid allergy. There are 2 other known contraindications which are both due to genetic mutations; porphyria (a rare, genetic red blood cell disorder) , as well as primary or secondary carnitine deficiency resulting due to genetic disorders of mitochondrial fatty acid oxidation/carnitine metabolism.

Warnings/Side Effects

• Common side effects of pivmecillinam include stomach upset: nausea, vomiting, diarrhea

• Rare Adverse Reactions: hypersensitivity reactions, severe cutaneous (presenting on the skin) reactions, carnitine depletion, Clostridioides difficile-associated diarrhea (C. diff) and interference with a newborn screening test for a rare metabolic disorder known as isovaleric acidemia.
  

Expanding UTI Treatment Options: A Women's Health Initiative

Did you know that:

99% of all uncomplicated UTIs are experienced by women(3)

This is due to the length and location of the urethra : a biological woman's urethra is significantly shorter than our male counterparts. Since the urethra is so short, it doesn't take much bacteria to infect the urinary tract. Additionally, a woman's urethra opening is much closer in distance to the anus, which contributes significantly to the presence of E. Coli in the area of the urethra. This is why it is so important to maintain good bathroom hygiene, and always wipe from front to back.

40% of women in the USA will develop at least 1 UTI in their lifetime (3)

With such a high number of infections, and so few effective options for outpatient treatment, the expansion of UTI treatment options is irrefutably a women's health initiative. That's why it is so important to participate in the discussion, to stay informed, and to share facts with friends, family, coworkers, etc. With UTI being such a common illness experienced almost exclusively affecting women - we have to catch up! How many pharmacologic researchers over the course of history have been women? Not nearly enough. Women, however, make up the majority of Pharmacists in the USA. We are extremely intertwined in our communities through our accessibility and profound knowledge, giving us the unique ability to spread knowledge and recommendations to those within our care.

Regardless of how much medical background you may (or may not) have, spreading this information to family, friends, or anyone in your life who's expressed frustration or concern over UTI facilitates the advancement of health for all women. Let's (wo)mansplain it to the men in our lives, and insist more research be done regarding women's health. All we have to do is spread the word; there is power in numbers, and if we all speak up, Big Pharma will be forced to listen. No matter how small, taking action through advocacy is important, and makes a significant difference by bringing attention to women's health, where more research is desperately needed.

Hopefully we see many more treatment options emerging in women's health in the near future. We'll be here to keep you informed throughout!

*Links for more information:

• FDA Press Release re: PIVYA

• Healthcare Provider Information / Phase III results

Resources:

1. Pandey N, Cascella M. Beta-Lactam Antibiotics. [Updated 2023 Jun 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545311/

2. [ Updated 2024 Apr 24 ]. FDA Approves New Treatment for Uncomplicated Urinary Tract Infections. US Food and Drug Administration; 2024 Apr-. Available from:https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-uncomplicated-urinary-tract-infections?utm_medium=email&utm_source=govdelivery

3. Existing first-line treatments have declining utility in combating UTI, highlighting the need for innovative alternatives to better serve patients. Utility Therapeutics. Available from: https://utilitytherapeutics.com/our-focus/#product-pipeline