Search

Aims: Information on breastfeeding and safety of biologics in infants is lacking due to difficulties in case collection. We evaluated methods for determining the concentration of biologics in breast milk using a dry filter method that can simplify the collection, storage and transport of breast milk. Methods: To generate dried filter paper (DFP) samples, approximately 30 μL of breast milk was placed onto a Whatman 903 card and punched out. After extraction, the supernatant was measured using an enzyme‐linked immunosorbent assay. Three concentrations of each drug were prepared in liquid breast milk (LBM) and DFP samples to determine their stability up to 28 days after storage at 2–8°C or −20°C for LBM and 25 ± 5°C for DFP. LBM and DFP samples were also provided by nursing mothers using biologics during lactation, and drug concentrations in both samples were compared. The agreement between the two measurement methods was confirmed by Bland–Altman analysis. Results: Breast milk was provided by 12 mothers who used biologics (tocilizumab, abatacept, etanercept, golimumab, sarilumab and belimumab). The coefficients of variation for within‐run and between‐run precision for the six drugs were within 15% for both LBM and DFP, and accuracy was within 90%–110% of the quality controls. After 28 days, concentrations remained at more than 90%. The difference between the values obtained by each method was within the acceptable range of error (−12.1 to +16.6 ng/mL). Conclusions: A method for determining the concentration of biologics using DFP is expected to help improve pharmacotherapy for lactating women. [ABSTRACT FROM AUTHOR]

The demand for tocilizumab is increasing in women who wish to bear children and who have active rheumatoid arthritis. Described here is a woman with rheumatoid arthritis who discontinued her tocilizumab therapy at the end of the first trimester and resumed it after delivery and where tocilizumab levels in maternal serum, infant serum, and the breast milk were measured. Tocilizumab was not detected in maternal serum just before delivery, or in umbilical cord blood or infant serum after birth. Tocilizumab levels in colostrum after intravenous injection were 0.57% of those in serum. Tocilizumab treatment in the first trimester was not associated with a significant drug level in the fetus at delivery and no fetal complications were noted. [ABSTRACT FROM AUTHOR]

Aims: Tocilizumab (TCZ), a humanized anti‐interleukin‐6 receptor monoclonal antibody, is used to treat rheumatic diseases. There is limited information about the administration of TCZ during lactation. The dried spot method, a simple technique for processing biological samples which involves placement of a drop of specimen onto filter paper, has been used in clinical pharmacology to determine various drug concentrations. This study examined the feasibility of sample collection using the dried milk spot (DMS) method for obtaining data about the transfer of TCZ into breast milk. Methods: Concentrations of TCZ determined using DMSs prepared by patients were compared with those using liquid breast milk. Results: In an enzyme‐linked immunosorbent assay of TCZ in DMSs, the accuracy ranged from 93.0% to 113.8% and the precision ranged from 0.3% to 8.4%. All concentrations of TCZ were within 15% of the reference value when analyzed on separate days. TCZ in DMSs at room temperature, 4°C, and −20°C were stable for 28 days. Extracted TCZ concentrations from patient‐prepared DMSs were strongly correlated with those of liquid samples (r = 0.996). In a pharmacokinetic study, the median (range) maximum and minimum concentrations were 113 ng/mL (68‐205) and 8.5 ng/mL (4.8‐13.4), respectively. The milk‐to‐serum ratio at the trough TCZ concentration of 3 lactating mothers were 0.0015, 0.00082 and 0.0014. Conclusions: The DMS method for measuring TCZ transfer into breast milk may be reliable and feasible, and should contribute to evaluating the safety of breast‐fed infants whose mothers receive TCZ during lactation. [ABSTRACT FROM AUTHOR]

Objective To confirm the current state of Japanese women’s perception of the teratogenic risk of medication exposure during pregnancy, and to assess the effect of counseling by　Japan Drug Information Institute in Pregnancy. Methods We used VAS to monitor the sentiments of pregnant women, before and after face-to-face counseling, about their own teratogenic risk perception, and their intention to continue pregnancy. Pregnancy outcomes were investigated by mailed questionnaires. Results Among 681 pregnant women, the median estimation of the risk of having a baby with a birth defect was 33.0% (interquartile range 16.0–50.0%) prior to counseling and 5.0% after counseling (2.0–11.0%). The median intention to continue pregnancy increased from 86.0% to 100.0% after counseling. The actual outcome survey revealed that almost all participants (97.1%) continued their pregnancies. Conclusions Pregnant women tend to overestimate the fetal risks of medication exposure during pregnancy. Counseling would prevent unnecessary termination. [ABSTRACT FROM AUTHOR]

The article discusses a study that measured abatacept concentrations in the breast milk of a 41-year-old nursing mother with rheumatoid arthritis and examined the safety of her breastfed infant. Highlights include the approval of the study by the ethics committee of the National Center for Child Health and Development, her treatment with tocilizumab and certolizumab pegol before switching to abatacept treatment, and the infant Apgar scores at one and five minutes.

The article discusses research which investigated safety of tocilizumab use during pregnancy and lactation. Topics explored include the intravenous tocilizumab dosage administered to a pregnant woman with adult-onset Still's disease (AOSD), measurement of tocilizumab concentrations in maternal serum, cord blood, and breast milk, and the health condition of the infant following exposure to tocilizumab.

What is known and objective: Statins are associated with improved pregnancy outcomes in patients with preeclamptic antiphospholipid syndrome (APS) and intrauterine foetal death. Several studies showed that statins are not teratogenic. However, data characterizing placental transfer and excretion of pravastatin into breast milk are limited. Case summary: We experienced two patients diagnosed with APS received 10 mg of pravastatin from the first trimester until delivery to prevent pre‐eclampsia. Pravastatin concentrations in maternal serum, infant serum and cord blood were evaluated. The estimated maternal‐foetal transfer ratios of pravastatin in the two patients were 25.5% and 23.8% respectively. Pravastatin was eliminated from neonatal serum within 2 days. Both infants developed normally with no drug‐related adverse effects. Pravastatin was not detected in either patient's breast milk at 3 days after the last dose. What is new and conclusion: The infants delivered from the mothers who were treated with pravastatin during pregnancy had no apparent adverse effects. [ABSTRACT FROM AUTHOR]

Safety information on diazoxide for pregnant and lactating women with hypoglycemia is limited. In this case report, we assessed diazoxide concentrations in maternal and infant blood, cord blood, and breast milk. We described a 30-year-old pregnant woman diagnosed with hypoglycemia due to nesidioblastosis at 4 months of age. Before becoming pregnant, she was treated with oral diazoxide (75–375 mg). All medications were discontinued after she was discovered to be pregnant. During gestational week 25, diazoxide treatment was resumed at 150–175 mg daily for repeated hypoglycemic episodes. Diazoxide administration was continued in combination with diet treatment until delivery. Glucose levels were well controlled. During gestational week 40, a male infant weighing 3069 g was delivered via spontaneous vaginal delivery with no pregnancy or neonatal complications. Diazoxide concentrations detected in maternal serum at 2.5–11.6 h after oral treatment ranged from 12.4 to 32.7 µg/mL. In cord blood, the diazoxide concentration was 18.5 µg/mL at 7.2 h after the last dose. During lactation, no hypoglycemia or hyperglycemia was observed. The approximate calculated ratio of diazoxide in breast milk and maternal serum was 0.09. The calculated daily infant dose was 0.47 mg/kg/day. The relative infant dose via breast milk ranged from 3.1% to 5.9%. Diazoxide transferred from maternal blood to the fetus across the placenta. It also transferred into breast milk, but there were no harmful effects on the infant. [ABSTRACT FROM AUTHOR]

The infant dose I via i breast milk was 0.95% of the maternal daily dose, that was considered to be acceptable,8 even though the drug information states that etizolam use should be avoided during breastfeeding.5 To clarify more accurate information about etizolam excretion into breastmilk, a detailed etizolam concentration profile including maximum concentration in breastmilk following oral etizolam administration will be required. Anxiety disorders may require pharmacological treatment, and it has been estimated that 10% to 26% of pregnant women with these disorders are prescribed benzodiazepines or benzodiazepine-like hypnotic drugs.1,2 These medications cross the placental and blood-brain barriers, may affect fetal growth and development,3 and have been associated with increased risks of preterm birth, low Apgar score, neonatal intensive care unit admission, and neonatal respiratory distress syndrome.4 Etizolam, a benzodiazepine-class anxiolytic, is prescribed for the treatment and management of agitation, tension, insomnia and anxiety.5 Due to the limited market distribution and use of etizolam worldwide, only one report from Japan published the information on etizolam transfer into breast milk.6 Furthermore, the information on etizolam transfer into the fetal circulation is limited. Benzodiazepine concentrations in the breast milk and plasma of nursing mothers: Estimation of relative infant dose. [Extracted from the article]