Quetiapine Excretion Into Human Breast Milk.

BACKGROUND: Risk assessment of the use of quetiapine during breastfeeding is challenging owing to a paucity of data. METHODS: A pharmacokinetic study was conducted in lactating women who were taking quetiapine. The primary endpoint was to determine quetiapine concentration profiles in milk and estimated infant exposure levels. Multiple milk and a single blood quetiapine concentrations were determined using a highly sensitive liquid chromatography with tandem mass spectroscopy method. RESULTS: Nine subjects receiving fast-release quetiapine (mean dose, 41 mg/d) were analyzed at steady state. The mean milk/plasma drug concentration ratio at 2-hour postdose was 0.47 (SD, 0.50; range, 0.13-1.67). The mean milk concentration of each patient was 5.7 ng/mL (SD, 4.5; range, 1.4-13.9 ng/mL). The mean infant quetiapine dose via milk per body weight relative to weight-adjusted maternal dose was 0.16 % (SD, 0.08; range, 0.04%-0.35%). CONCLUSIONS: Infant exposure levels to quetiapine via milk are predicted to be very small.

Probiotics for infantile colic: a randomized, double-blind, placebo-controlled trial investigating Lactobacillus reuteri DSM 17938.

OBJECTIVE: To investigate the effectiveness of Lactobacillus reuteri DSM 17938 for the treatment of infantile colic in breastfed Canadian infants, compared with placebo. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial was conducted involving 52 infants with colic, according to modified Wessel criteria, who were assigned at random to receive L reuteri DSM 17938 (10(8) colony-forming units) (n = 24) or placebo (n = 28) for 21 days. Daily crying and fussing times were recorded in a structured diary, and maternal questionnaires were completed to monitor changes in infant colic symptoms and adverse events. RESULTS: Total average crying and fussing times throughout the study (from baseline to day 21) were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group (1719 ± 750 minutes [29 ± 13 hours] vs 2195 ± 764 minutes [37 ± 13 hours]; P = .028) (relative risk, 0.78; 95% CI, 0.58-0.98). Infants given L reuteri DSM 17938 showed a significant reduction in daily crying and fussing times at the end of treatment period compared with those receiving placebo (median, 60 minutes/day [IQR, 64 minutes/day] vs 102 minutes/day [IQR, 87 minutes/day]; P = .045). On day 21, a significantly higher proportion of infants in the L reuteri DSM 17938 group responded to treatment with a ≥50% crying time reduction compared with infants given placebo (17 vs 6, P = .035; relative risk, 3.3; 95% CI, 1.55-7.03). CONCLUSION: Administration of L reuteri DSM 17938 significantly improved colic symptoms by reducing crying and fussing times in breastfed Canadian infants with colic.

Relative bioequivalence of amoxicillin dissolved in breast milk.

BACKGROUND: Oral antibiotics use in infants in developing countries is challenging because liquid formulations are often unavailable. However, dissolving solid formulation of drugs in water poses a risk of gastrointestinal infection. Although mother's milk may be a potential vehicle, no evidence exists to indicate that antibiotics dissolved in human milk are bioequivalent to those dissolved in water. Therefore, we compared pharmacokinetic parameters of an orally administered antibiotic, amoxicillin, dissolved in human milk, to those of water-dissolved amoxicillin. METHODS: A pharmacokinetic study was conducted in 16 healthy adult volunteers in a randomised crossover design. Marketed amoxicillin powder for suspension was dissolved in either human milk or water at a final concentration of 50 mg/mL, and 10 mL was given orally in a fasting state. Timed blood samples were obtained and plasma amoxicillin was quantified using liquid chromatography-mass spectrometry. FINDINGS: Results showed that pharmacokinetic parameters, including area-under-the-curve, Cmax and half-life of the water-based and milk-based amoxicillin administration were not significantly different. 90% CIs of the ratios of these parameters in concomitant breast milk administration to those of water were within 89% and 116%, suggesting they are bioequivalent (defined as a range between 80% and 125%). INTERPRETATION: We conclude that oral administration of amoxicillin dissolved in human milk at 50 mg/mL results in pharmacokinetics profiles comparable to amoxicillin dissolved in water. Pharmaceutical interactions between amoxicillin and breast milk are unlikely, suggesting no need to modify dosing schedules.

Pregnancy outcomes following maternal exposure to second-generation antipsychotics given with other psychotropic drugs: a cohort study.

OBJECTIVES: Second-generation antipsychotics (SGAs), in conjunction with other psychotropic medications, are increasingly used to treat psychiatric disorders in pregnancy. The few available studies investigating the reproductive safety of SGAs did not reach conclusive results, and none have compared monotherapy with polytherapy involving other psychotropic medications. DESIGN: Descriptive cohort study using a prospectively collected database. SETTING: Motherisk Program, The Hospital for Sick Children, Toronto, Canada. PARTICIPANTS: 133 women exposed to SGAs and other psychotropic drugs and 133 matched healthy controls were assessed and analysed. Outcomes of mother-child pairs exposed to SGAs in monotherapy (N=37) were compared with those exposed to SGAs with other psychotropic medications (in polytherapy; N=96). MAIN OUTCOME MEASURES: Maternal, pregnancy, delivery and neonatal outcomes. RESULTS: 72% of exposed women received SGAs in polytherapy, and 101 women took their medications throughout pregnancy. These women had significantly higher pre-pregnancy weight, experienced more associated comorbidities and instrumental deliveries, and delivered a greater proportion of large for gestational age neonates. There were no differences in maternal weight gain in pregnancy between the exposed and comparison groups and between the monotherapy-exposed and polytherapy-exposed subgroups. The exposed neonates were more likely to be born premature, were admitted more often to the neonatal intensive care unit, presented with poor neonatal adaptation signs and had higher rates of congenital malformations. All the aforementioned neonatal outcomes were found mainly in the polytherapy subgroup. CONCLUSIONS: The use of SGAs in polytherapy was prevalent in the assessed cohort and was associated with adverse pregnancy outcomes for both the mother and the child. In utero exposure to SGA monotherapy appears to be associated with less risk to the fetus. Future research should focus on polytherapy in pregnancy in order to define its reproductive safety and to separate the effects of medication exposure, underlying psychopathology and associated comorbidities.

Toward improved pregnancy labelling.

Information about the use of a medication in pregnancy is part of overall drug labelling as prepared by the pharmaceutical company and approved by the regulators. It is aimed at assisting clinicians in prescribing, however, very few drugs are labelled for specific indications in pregnancy, since there is rarely information about the use of a drug in this condition. Recently the FDA has drafted new guidelines for the labeling of drugs in pregnancy and breastfeeding, to replace the A,B,C,D,X system that was used for more than 30 years. Here we document the use of the new system through 3 different medications; each representing a different clinical situation in pregnancy--acute infection, chronic pain, and drug use during labor. Advantages and challenges in the new system are being highlighted.