Midazolam and nitrazepam in the maternity ward: milk concentrations and clinical effects.

1. In a randomized study of 22 patients in a maternity ward, the residual concentrations of two hypnotics, midazolam 15 mg p.o. and nitrazepam 5 mg p.o., in early breast milk and plasma were measured 7 h after intake on day 2 to day 6 postpartum. Milk pH, milk fat and binding to plasma proteins were also investigated. Sleep variables were scored on questionnaires. 2. No measurable (less than 10 nmol l-1) concentrations of drug in milk were found in the group receiving 15 mg midazolam at night, either after the first night or after the fifth night. Additional investigations in two mothers demonstrated that midazolam and its hydroxymetabolite disappeared rapidly from milk with undetectable levels after 4 h. The mean (s.d.) milk to plasma ratio for midazolam was 0.15 (0.06) in six paired samples. It may be assumed that practically no midazolam is transferred via early milk to the baby if the baby is nursed more than 4 h after tablet intake. 3. Milk nitrazepam concentrations increased significantly from the first (30 nmol l-1) to the fifth morning (48 nmol l-1) in the group receiving 5 mg nitrazepam at night. The mean (s.d.) milk to plasma ratio of nitrazepam after 7 h was 0.27 (0.06) in 32 paired samples, and did not vary from day 1 to day 5. Plasma protein binding of nitrazepam in puerperal women was found to be lower than that in plasma of healthy controls. The average amount of nitrazepam received by the breast-fed baby in the morning was calculated to increase from 1 to 1.5 micrograms 100 ml-1 breast milk, from days 1 to 5. In the mothers nitrazepam was associated with better hypnotic effect, but a higher incidence of complaints than midazolam. 4. Milk pH, assuming anaerobic conditions, was found in 10 women to average 6.91 +/- 0.09 (s.d.) on days 2-6 postpartum, which is less than previously reported. 5. It is concluded that both hypnotics may be used safely for a few days in the maternity ward. However, possible long-term effects in the suckling infant of small doses of benzodiazepines ingested with breast milk remain to be investigated.

RCT Entities:   Population Interventions Outcomes