Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants

Study Overview
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Brief Summary
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Over half of women in the US who are breastfeeding their infants take prescription drugs. You are being asked to participate in this study because you are breastfeeding your infant and are currently taking, as part of your medical care, at least one of the drugs we are studying. We are interested in studying drugs commonly prescribed to women who are breastfeeding so we can learn more about the amount of drug that is transferred to breastmilk and estimate how much of drug that is consumed by breastfed infants.

Detailed Description
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The purpose of this study is to understand if the study drugs of interest are found in breastmilk and how much; to estimate the amount of drug that is consumed by breastfed infants and what effect this may have on infants; and to share what we learn with other researchers. The study drugs of interest have Food and Drug Administration (FDA) approval, but there is little or no information about the amount of drug found in the breastmilk of mothers who take them; the amount of drug that may be transferred to their infant's through breastmilk; or the effects this transfer may have on their infants. During this study we will ask to collect breastmilk and blood from mothers, and blood from infants, to measure the amount of study drug of interest in these body fluids. Results from this study will help researchers better understand how much of the study drug of interest is in your blood and breastmilk, and how much of the study drug of interest may be in your infant's blood because of breastfeeding.

Official Title
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Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants

Conditions
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Lactating Women on Select DOI, Breastfed Infants of Mothers on Select DOI

Intervention / Treatment
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* Other: Tranexamic acid (TXA)
* Other: labetalol
* Other: metformin
* Other: nifedipine
* Other: clindamycin
* Other: oxycodone
* Other: azithromycin
* Other: escitalopram
* Other: sertraline
* Other: ondansetron
* Other: Ciprofloxacin
* Other: Doxycycline
* Other: Levofloxacin
* Other: Methylphenidate
* Other: Sumatriptan
* Other: Citalopram
* Other: Cyclobenzaprine
* Other: Furosemide
* Other: Gabapentin
* Other: Hydrochlorothiazide
* Other: Hydroxyurea
* Other: Rosuvastatin
* Other: Topiramate
* Other: Trazodone
* Other: Valganciclovir
* Other: Venlafaxine
* Other: Verapamil
* Other: Remdesivir
* Other: Anakinra
* Other: Tocilizumab
* Other: Fluvoxamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lactating women who are receiving at least one DOI per SOC who are ≤180 days postpartum, and their infants (≤180 days of age) who receive maternal breastmilk. Informed consent/HIPAA obtained, according to local IRB/REB/IEC guidelines, prior to any study-related procedures. Lactating women who are not legal adults and their breastfed infants may be enrolled if they assent to participate in the study and consent is obtained from their legal guardian according to local IRB/REB/IEC guidelines. Exclusion Criteria: Any concomitant condition which, in the opinion of the physicians providing patient care or the principal investigator conducting the study, would preclude a subject's participation in the study. Known pregnancy during PK sampling.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tranexamic acid (TXA)<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Tranexamic acid (TXA)<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| labetalol<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: labetalol<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| metformin<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: metformin<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| nifedipine<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: nifedipine<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| clindamycin<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: clindamycin<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| oxycodone<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: oxycodone<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| azithromycin<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: azithromycin<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| escitalopram<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: escitalopram<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| sertraline<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: sertraline<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| ondansetron<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: ondansetron<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Ciprofloxacin<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Ciprofloxacin<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Doxycycline<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Doxycycline<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Levofloxacin<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Levofloxacin<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Methylphenidate<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Methylphenidate<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Sumatriptan<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Sumatriptan<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Citalopram<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Citalopram<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Cyclobenzaprine<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Cyclobenzaprine<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Furosemide<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Furosemide<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Gabapentin<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Gabapentin<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Hydrochlorothiazide<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Hydrochlorothiazide<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Hydroxyurea<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Hydroxyurea<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Rosuvastatin<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Rosuvastatin<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Topiramate<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Topiramate<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Trazodone<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Trazodone<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Valganciclovir<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Valganciclovir<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Venlafaxine<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Venlafaxine<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Verapamil<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Verapamil<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Remdesivir<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Remdesivir<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Anakinra<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Anakinra<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Tocilizumab<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Tocilizumab<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|
| Fluvoxamine<br>No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose. | Other: Fluvoxamine<br>* Understudied drugs will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| M/P ratio | Characterize the pharmacokinetics using maternal milk/plasma exposure ratio is calculated by dividing the BMS01 drug of interest breastmilk concentration by the BMS01 drug of interest in maternal plasma concentration. | Until the infant becomes 180 days of age | 
| DID | Pharmacokinetics is characterized by estimated daily infant dose-daily infant dose which estimates the quantity of drug delivered to an infant via breastmilk in a given day. | Until the infant becomes 180 days of age | 
| RID | Pharmacokinetics is characterized by relative infant dose is a method of relating the potential dose of the drug delivered to the infant to the typical therapeutic dose given to the mother. | Until the infant becomes 180 days of age | 
| I/M ratio | Pharmacokinetics is characterized using infant maternal/exposure ratio. IM ratio is calculated using the average infant plasma concentration of the BMS01 drug of interest and historical value of clearance in infants. | Until the infant becomes 180 days of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile of commonly used drugs in infants exposed to drugs in breastmilk | see Cohort 1-31 for listing of drugs | Until the infant becomes 180 days of age | 
| AE | Safety profile of commonly used drugs in infants exposed to drugs in breastmilk is characterized by Adverse Events(AE) which are collected at each time point when the study-specific procedure occurred and up until 1 hour after. | Up until 180 days of age | 
| SAE | Safety profile of commonly used drugs in infants exposed to drugs in breastmilk is characterized by Serious Adverse Events which are directly related to study procedures and were recorded from participants (infant or mother) at each time point when the study-specific procedure occurred and up until 1 hour after. | Up until 180 days of age | 
| ESI | Safety profile of commonly used drugs in infants exposed to drugs in breastmilk is characterized by Events of Special Interest(ESI) which include any pre-specified safety event that could be related to BMS01 drug of interest exposure. ESI's are only assessed for infants and only at study visits from the time the BMS01 DOI was initiated in mother and infant began breast milk feeding through the end of the study / infant age ≤ 180 days | Until the infant becomes 180 days of age |