147: Real-World Insights into Drug Dosing Patterns for Commonly Prescribed Drugs During Pregnancy

Statement of Purpose, Innovation or Hypothesis: In the United States, out of 52 million women aged 15-49 who have been pregnant, 50% take four or more medications, with 25% having preexisting conditions^1-6. However, there's a critical lack of data for medication dosing in pregnancy, with nearly 75% of drugs lacking pregnancy-related information on their labels and only 1.3% of pharmacokinetic (PK) studies including pregnant subjects2. This gap is problematic because physiological changes during pregnancy significantly affect drug PK^7-11. However, it is not practically feasible to conduct dedicated pregnancy PK studies for every drug.  Our project analyzes prescription data usage from 13 hospitals in pregnant women to understand current real world dosing patterns and identify 50 relevant drugs for physiologically-based PK modeling (PBPK) and simulations. The PBPK simulations will be used as a screening tool to establish a framework to prioritize medications for further PK research and guide dose adjustments.

Description of Methods & Materials: Electronic health records were collected for pregnant women with antenatal care between 2016-2022 at the 13 University of Maryland Medical System hospitals. The data was organized by maternal encounters and orders written each encounter. Encounters were separated into inpatient, outpatient, and emergent categories. Orders for medical devices, vitamins/minerals, dietary supplements, immunization, herbal remedies, over-the-counter topical medications, and non-prescription IV fluids were excluded from the database. Maternal characteristics, encounter and prescription frequency, therapeutic class, classification in pregnancy, diagnosis information, and dose prescribed were statistically and graphically summarized overall, by encounter type, and by trimester.  For women receiving the same medication across trimesters, doses were categorized as unchanged, increased, or decreased, with the percentage change noted.

Data & Results: Our final dataset included a total of 1,422,379 orders across 186,007 encounters in 39,844 pregnant women. On average, pregnant subjects received 17 unique medication orders. Medications were filtered to focus on outpatient data, in order to target those frequently used during pregnancy and relevant to dose adjustments. The most prescribed classes of medications  were: antiemetics/antiacids/laxatives (Ondansetron, Docusate, Metoclopramide), analgesics (Acetaminophen, Aspirin,  Indomethacin, Oxycodone) , antimicrobials (Metronidazole, Nitrofurantoin , Cephalexin), antidiabetics (Insulin, Metformin), antihypertensives (Nifedipine, Labetalol, Metoprolol), and corticosteroids (Betamethasone, Fluticasone, Prednisone) (Figure 1). The general distribution of drug class remains similar between first and second trimesters. In the third trimester there is a decrease in antiemetics prescribed and an increase in analgesics, antihypertensives, and antimicrobials. A total of 327 medications were given to mothers across multiple trimesters. Of those 44% had dose changes across trimesters in at least 30% of mothers. Some key cases of notable change and clinically relevant drugs can be seen in Table 1.

Interpretation, Conclusion or Significance: This study highlights the extensive use and dose variability of medications throughout pregnancy. It underscores the need for targeted drug studies within this demographic. In the next phase, the findings will guide the selection of 50 drugs for further assessment. By employing PBPK modeling, one can gain mechanistic insights into how this dosing variability impacts the safety and efficacy of drugs in this demographic. The significance of this research lies in its potential to help refine medication dosing guidelines for pregnant women, thereby enhancing maternal outcomes.

Disclosures:

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10. Stika CS. Principles of Obstetric Pharmacology. Obstetrics and Gynecology Clinics of North America. 2023;50(1):1-15. doi:10.1016/j.ogc.2022.10.012

11. Jeong H. Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes. Expert Opinion on Drug Metabolism & Toxicology. 2010;6(6):689-699. doi:10.1517/17425251003677755 

Additional Information/Authors: Authors: Brooke Langevin, Babajide Shenkoya, Qi Liu, Yuching Yang, Katrina Mark, Mathangi Gopalakrishnan