The concentration of maternal sacubitril/valsartan transferred into human milk is negligible.

Background: Peripartum cardiomyopathy (PPCM) is a common cause of heart failure (HF) in the peripartum. Some medications are considered safe while breastfeeding. However, sacubitril/valsartan (Entresto), while efficacious, is not recommended in breastfeeding women due to concerns about adverse infant development, and no published data suggest otherwise. Objectives: This study aimed to assess the transfer of sacubitril/valsartan into human milk and evaluate the infant's risk of drug exposure. Methods: The InfantRisk Human Milk Biorepository released samples and corresponding health information from five breastfeeding maternal-infant dyads exposed to sacubitril/valsartan. Sacubitril, valsartan, and LBQ657 (sacubitril active metabolite) concentrations were determined using liquid chromatography-mass spectrometry (LC/MS/MS) from timed samples 0, 1, 2, 4, 6, 8, 10, and 12 h following medication administration at steady state conditions. Results: Valsartan levels were below the detection limit of 0.19 ng/mL in all milk samples. Sacubitril was measurable in all milk samples of the five participants, peaking 1 h after drug administration at a mean concentration of 1.52 ng/mL for a total infant dose of 0.00049 mg/kg/12 h and a relative infant dose (RID) calculated at 0.01%. The maximum concentration of its active metabolite LBQ657 in the milk samples was observed 4 h after medication administration and declined over the remaining 12-h dosing interval, for an average concentration of 9.5 ng/mL. The total infant dose was 0.00071 mg/kg/12 h, and the RID was 0.22%. Two mothers reported continuing to breastfeed while taking sacubitril/valsartan; both mothers stated observing no negative effects in their breastfed infants. Conclusion: The transfer of sacubitril/valsartan into human milk is minimal. These concentrations are unlikely to pose a significant risk to breastfeeding infants, with a combined calculated RID of <0.25%, which is far lower than the industry safety standards (RID <10%).

Low Nirmatrelvir and Ritonavir Exposure through Breastmilk: Analyzing Milk Concentrations and Infant Risk.

This research study investigates the intricate relationship among COVID-19, maternal and infant health, and breastfeeding practices, with a specific focus on assessing the transfer of nirmatrelvir and ritonavir into human milk. Our aim is to provide critical insights to those managing COVID-19 treatment in lactating individuals. The InfantRisk Center Human Milk Biorepository contained human milk and corresponding health information for eight mother-infant dyads exposed to standard doses of maternal nirmatrelvir with ritonavir (300 mg nirmatrelvir and 100 mg ritonavir taken orally twice daily for 5 days). The primary outcomes measured were drug levels in milk using liquid chromatography-mass spectrometry and reporting the tolerance of the breastfed infant. Nirmatrelvir with ritonavir was measurable in all participants at a mean concentration of 33.48 ng/mL (ritonavir) and 729 ng/mL (nirmatrelvir). The estimated infant dose via milk was 0.0024 mg/kg/12 h (ritonavir) and 0.054 mg/kg/12 h (nirmatrelvir). The estimated relative infant dose was 0.19% (ritonavir) and 1.43% (nirmatrelvir) well under the standard 10% safety threshold. Among the eight infants exposed in this study, there were no reported adverse events. Nirmatrelvir with ritonavir is the recommended treatment for ambulatory COVID-19 patients with mild-to-moderate COVID-19 infection at high risk for progression to severe disease. Although its use is recommended in lactating women, there are no previous studies on the transfer of nirmatrelvir into human milk. The study findings endorse the current approach of nirmatrelvir/ritonavir use in lactating women and encourage healthcare providers to consider prescribing this treatment irrespective of lactation status when indicated.

Alleviating anxiety while breastfeeding: evaluating buspirone transfer into human milk.

PURPOSE: Buspirone, an anxiolytic with minimal risk of dependence or respiratory depression, lacks extensive published data on its transfer into human milk during lactation. The objective of this study was to 1) quantify the transfer of buspirone and its active metabolite 1-pyrimidinylpiperazine (1-PP) into human milk, allowing for an estimation of maternal drug exposure to the breastfed infant, and 2) report observations of the infants exposed to buspirone via breastmilk. METHODS: Milk samples and health histories were collected from nine lactating mothers who donated milk samples to the InfantRisk Human Milk Biorepository while taking buspirone. The drug concentration-time profile of buspirone and 1-PP was determined using liquid chromatography-mass spectrometry. RESULTS: Buspirone was below the detection level of 1.5 ng/mL in all milk samples with dosages ranging from 7.5 to 30 mg twice daily. However, low levels of active metabolite 1-PP were observed at 7.5 mg twice daily up to 30 mg twice daily. The relative infant dose (RID) calculated ranged from 0.21 to 2.17%, which is below the standard 10% threshold for infant safety. There were no reports of adverse effects in the exposed infants. CONCLUSION: The levels of buspirone observed in all participants' milk samples were exceedingly low. The subsequently low relative infant dose (RID) in the range of 0.21% to 2.17% is below the 10% threshold for infant safety, suggesting that the transfer of maternal buspirone and its active metabolite (1-PP) into human milk is clinically insignificant and poses minimal risk to a breastfed infant.

Pharmacokinetics of Ketamine Transfer Into Human Milk.

PURPOSE/BACKGROUND: Ketamine is an N -methyl- d -aspartate-antagonistic dissociative anesthetic infused intermittently for off-label management of treatment-resistant depression, acute suicidality, and postpartum depression. Despite the prevalence of postpartum depression nearing upward of 15% of deliveries, almost no research has been done to evaluate its safety during lactation. METHODS: In this study, human milk samples were released from the InfantRisk Center's Human Milk Biorepository of 4 participants treated with intermittent ketamine infusions (49-378 mg) to determine the levels of the drug and its active norketamine metabolite using liquid chromatography-mass spectrometry. RESULTS: The absolute infant dose of ketamine from human milk was 0.003 to 0.017 mg/kg per day, and norketamine was 0.005 to 0.018 mg/kg per day. The relative infant dose (RID) for ketamine ranged from 0.34% to 0.57%. The RID for norketamine ranged from 0.29% to 0.95%. There were no reported infant adverse effects. CONCLUSION: The findings of this study suggest that the transfer of ketamine, as well as its active metabolite, norketamine, into human milk is minimal, as estimated by RIDs less than 1% in all participants. These relative doses are well below standardly accepted safety thresholds.

The Transfer of Domperidone into Human Milk Remains Low at High Doses.

Domperidone is a dopamine-2 (D2) receptor antagonist that stimulates the release of stored prolactin in the anterior pituitary. It is prescribed off-label in Canada and Australia to promote lactation in prolactin-deficient women. The case of a 43-year-old woman taking a high daily dose of domperidone (160 mg) is described from the InfantRisk Center Human Milk Biorepository. Milk samples were analyzed using a high-performance liquid chromatography-mass spectrometry method, detecting an average domperidone concentration of 7.0 ng/mL (range 6.2 to 8.4 ng/mL). Even at high doses, the transfer of domperidone into breast milk was negligible with a relative infant dose (RID) of 0.05%. The RID estimates the infant's potential exposure to a drug via lactation as a percentage of the weight-adjusted maternal dose. The standard threshold for reasonable infant exposure is an RID of 10%.

Transfer of Injected Triamcinolone into Human Milk of a Lactating Patient Suffering from Idiopathic Granulomatous Mastitis.

Background: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory condition of the mammary gland that presents as a painful mass, and it must be distinguished from both infectious mastitis and breast cancer. When diagnosed during lactation, it can result in significant distress and early weaning. Injection of triamcinolone has been used as a successful treatment method, but safety in breastfed infants has not been established. Methods: We present a case of a lactating patient who received a direct injection of triamcinolone (dosage 40 mg) in her breast to treat IGM after failure of oral corticosteroids. Breastmilk samples were expressed by the patient 0, 1, 4, and 24 hours after the procedure, and then daily for 1 week. All the samples were analyzed using liquid chromatography mass spectrometry. The patient was supported by a breastfeeding and lactation medicine clinic. Results: After injection of triamcinolone into the granulomatous mass, breast milk samples were collected and analyzed. No samples were found to contain triamcinolone. A temporary but significant decrease in milk production was noted after injection, though only a slight decrease had been noted with 6 weeks of systemic corticosteroids. With support, the patient rebuilt milk production and continued to breastfeed from both breasts. Conclusion: Triamcinolone was not found in any milk samples (≥0.78 ng/mL) following therapeutic injection of the affected breast. The patient was able to continue breastfeeding from the affected breast with intermittent symptoms.

Pharmacokinetics of a single dose of oclacitinib maleate as a top dress in adult horses.

The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528 kg were administered a single dose of 0.5 mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15 min, 30 min, 45 min, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean Cmax was 486 ng/ml (range 423-549 ng/ml), and Tmax was estimated to be 1.7 h (range 0.3-3.1 h). The estimated T1/2 was 7.5-8 h.

Human Milk Endocannabinoid Levels as a Function of Obesity and Diurnal Rhythm.

The endocannabinoid system is involved in the regulation of a variety of physiological and cognitive processes. While the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA) have been found in breast milk, their role(s) have yet to be determined. This study determined the normal concentration ranges of endocannabinoids (2-AG and AEA) in breast milk and the influences, if any, of obesity and diurnal rhythms on their levels. Milk samples were collected from 36 breastfeeding mothers at 4-8 weeks postpartum at each feed over a 24-h period, and further stratified into three groups based on body mass index (BMI). The samples were analyzed using liquid chromatography mass spectrometry. AEA was below the limit of detection and 2-AG levels averaged 59.3 ± 18.3 ng/mL (± SD) in women with normal BMI. Wide-ranging 2-AG concentrations in the overweight (65.5 ± 41.9 ng/mL) /obese (66.1 ± 40.6 ng/mL) groups suggest BMI may be a contributing factor influencing its levels. Following a diurnal pattern, there was a significantly higher 2-AG concentration observed during the day, as compared to night time samples. In conclusion, our study clearly suggests that appropriate milk collection and storage conditions are critical. Further, body weight and diurnal rhythm appear to influence levels of 2-AG. Based on these results, future studies are underway to determine what specific roles endocannabinoids may play in human milk and how elevated levels of 2-AG may modulate infant appetite and health.

Dexmedetomidine Levels in Breast Milk: Analysis of Breast Milk Expressed During and After Awake Craniotomy.

Background: Dexmedetomidine is an α2-adrenoreceptor agonist with utility in sedation and analgesia for the perioperative or intensive care patient. The literature regarding the safety of dexmedetomidine in lactating patients is very limited. Methods: We present a case of a lactating patient who received dexmedetomidine bolus and infusion as part of her intraoperative sedation during an awake craniotomy. Breast milk samples were expressed by the patient twice intraoperatively and twice postoperatively. All samples collected were analyzed using liquid chromatography mass spectrometry. Results: Dexmedetomidine concentrations in the breast milk were measured at various intervals and were 88 and 50 pg/mL intraoperatively, and 89 and 15 pg/mL postoperatively. Conclusion: Levels of dexmedetomidine in breast milk were exceedingly low. Interruption of breastfeeding and/or discarding expressed breast milk may not be necessary after dexmedetomidine in breastfeeding mothers. Further investigation with a larger sample size is warranted to describe safety profile of dexmedetomidine in breastfeeding infants.

Transfer of the Serotonin Modulator Vortioxetine into Human Milk: A Case Series.

Background: Vortioxetine (Trintellix) is a serotonin modulator used in the treatment of major depressive disorder in adults. There are no data presently published on the transfer of vortioxetine into human breast milk. Case Report: The present study determined the drug concentration-time profile of vortioxetine in milk samples collected from three lactating mothers, two consuming 10 mg once daily and one consuming 20 mg once daily. Milk levels were measured using liquid chromatography mass spectrometry. At a dose of 10 mg/day, the maximum concentration of vortioxetine in milk was 13.89 ng/mL. At a dose of 20 mg/day, the maximum concentration in milk was 52.32 ng/mL. The relative infant dose was calculated to be 1.1% for 10 mg dose and 1.7% for 20 mg dose. Conclusion: In these three cases, we found the levels of vortioxetine in breast milk to be low and dose proportional. However, both RID's for 10 and 20 mg doses (1.1% and 1.7%, respectively) fall below the 10% theoretical level of concern and no adverse effects were reported by the mothers. As this is a small patient sample, caution should be exercised until further studies report the safety profile of vortioxetine in breastfeeding infants.

Cladribine transfer into human milk: A case report.

BACKGROUND: Cladribine is an antimetabolite used for the treatment of relapsing-remitting multiple sclerosis. At present, there are no data available on its use in breastfeeding mothers and its transfer in human milk. OBJECTIVE: We present a case of a lactating mother who donated her milk samples to study the transfer of cladribine following a 20-mg oral dose. METHODS: Analysis was done using liquid chromatography-mass spectrometry. RESULTS: The relative infant dose calculated in this study was 3.06%. CONCLUSION: This is the first case report suggesting the transfer of cladribine in human milk in measurable quantities. However, caution should be advised during lactation.

Maternal Transfer of Cetirizine Into Human Milk.

INTRODUCTION: Cetirizine hydrochloride is a second-generation H1 histamine antagonist with Food and Drug Administration approval for treatment of allergic rhinitis and urticaria. Currently, the Food and Drug Administration does not recommend use of cetirizine during breastfeeding, as there are insufficient studies on both the transference of cetirizine into human milk and the effects of cetirizine in infants. MAIN ISSUE: To determine the concentration of cetirizine in human milk, samples were analyzed using high performance liquid chromatography mass spectrometry. MANAGEMENT: Based on calculations, relative infant dose was found to be 1.77% at 24 hr. In addition, there were no reported adverse effects seen in the infants. CONCLUSION: We suggest that transfer of cetirizine into human milk is minimal and unlikely to pose a significant risk to the breastfeeding infant. This is the first report presenting the transfer of cetirizine in human milk.

Dimethyl fumarate transfer into human milk.

Dimethyl fumarate (DMF) is approved for the treatment of relapsing-remitting multiple sclerosis. It is unknown whether DMF or its primary metabolite monomethyl fumarate (MMF) are excreted into human milk. We present two cases of lactating patients who donated milk samples to study the transfer of MMF into human milk following a week of 2 × 240 mg daily oral dose. Samples were analyzed using liquid chromatography mass spectrometry. The calculated relative infant dose was 0.019% and 0.007%. This is the first study to demonstrate that MMF is transferred into human milk, with only limited exposure to an infant.

Transfer of Dicloxacillin into Human Milk.

Background: Dicloxacillin is a beta-lactam antibiotic that is commonly used in the treatment of lactational mastitis in breastfeeding women. Although penicillins have long been considered safe for breastfeeding mothers and their infants, there is almost no data on the transfer of dicloxacillin into human breast milk despite the fact that it is commonly used for mastitis. Case Report: This study determined the drug concentration-time profile of dicloxacillin in milk samples collected from three lactating mothers consuming 500 mg dicloxacillin taken every 6 hours for treatment of mastitis. Milk levels were measured using liquid chromatography mass spectrometry. The maximum concentration of dicloxacillin in milk was 67.6 ng/mL. The relative infant dose (RID) was calculated to be 0.03%. This value is well below the theoretical level of concern of 10%. Discussion: The limited transfer of dicloxacillin into human milk is probably explained by the high plasma protein binding of dicloxacillin and its subsequent poor penetration into human milk. Conclusion: In this case series, the level of dicloxacillin in milk was found to be very low, and the RID to be only 0.03% of the maternal dose. Although the levels detected were low, dicloxacillin does transfer into breast milk. Caution should be exercised in infants with hypersensitivity to penicillins.

Rivaroxaban Treatment in Two Breastfeeding Mothers: A Case Series.

Background: Rivaroxaban (Xarelto) is a reversible direct factor Xa inhibitor used for the treatment and prevention of coagulation in numerous syndromes. There is very limited information available on the transfer of rivaroxaban into human breast milk. Case Report: This study determined the drug concentration-time profile of rivaroxaban in milk samples collected from two lactating mothers consuming 15 mg twice daily. After 21 days, each mother transitioned to 20 mg once daily. Levels in milk were measured using liquid chromatography mass spectrometry and analysis was done for both dosages. The maximum concentration of rivaroxaban observed for the 15 mg dose was 0.3 ± 0.02 µg/mL and that for the 20 mg dose was 0.26 ± 0.01 µg/mL. The relative infant dose (RID) was calculated to be 5% and 4%, respectively. Discussion: This relatively low infant dose is probably explained by the high plasma protein binding of rivaroxaban and its subsequent poor penetration into human milk. The results indicate that rivaroxaban receded to minimum concentration over a period of 12 hours. Conclusions: In these two cases, we found the levels of rivaroxaban in milk to be quite low, and the RID to be 5% of the maternal dose. Although the levels detected were low, rivaroxaban does transfer into breast milk. Caution should be exercised until further studies are conducted and report the safety profile of rivaroxaban in breastfeeding infants.

Balancing the Use of Medications While Maintaining Breastfeeding.

Breast milk is the most beneficial nutrition a mother can give her infant. Fortunately, the dose of most drugs transferred into milk is small and does not lead to clinically significant effects on the infant. In almost all instances, the mother should be advised to continue breastfeeding. Certain medications are absolutely contraindicated, including anticancer agents, radioactive drugs, and those that inhibit milk production. However, most medications can be used safely. An improved understanding of the relationship between maternal and infant exposure to medications would provide a more enlightened understanding of the risk and benefit analysis for individual drugs.