MINOXIDIL

Fetal Risk Summary

Minoxidil is a potent antihypertensive peripheral vasodilator. Information on its use in human pregnancy is very limited, with only four occurrences of fetal exposure located in the medical literature (1,2 and 3).

In one case, minoxidil was used throughout gestation, and no effect of this exposure was seen in the healthy newborn (1). A second case involved a mother with a history of renal artery stenosis and malignant hypertension who was treated throughout gestation with minoxidil, captopril, and propranolol (2). Three of her four previous pregnancies had ended in midgestation stillbirths. The most recent stillbirth, her fourth pregnancy, involved a 500-g male infant with low-set ears but no gross anomalies. The mother had been treated with the above regimen plus furosemide. In her second pregnancy, she had been treated only with hydrochlorothiazide, and she had delivered a normal term infant. No information was available on the first and third pregnancies, both of which ended in stillbirths. In her current pregnancy, daily doses of the three drugs were 10 mg, 50 mg, and 160 mg, respectively. The infant, delivered by cesarean section at 38 weeks' gestation, had multiple abnormalities, including an omphalocele (repaired on the 2nd day), pronounced hypertrichosis of the back and extremities, depressed nasal bridge, low-set ears, micrognathia, bilateral fifth finger clinodactyly, undescended testes, a circumferential midphallic constriction, a large ventriculoseptal defect, and a brain defect consisting of slightly prominent sulci, especially the basal cisterns and interhemispheric fissure. Growth retardation was not evident, but the weight (3170 g, 60th percentile), length (46 cm, 15th percentile), and head circumference (32.5 cm, 25th percentile) were disproportionate. Neurologic, skeletal, and kidney examinations were normal. Marked hypotension (30–50 mm Hg systolic) was present, which resolved after 24 hours. Heart rate, blood glucose, and renal function were normal. The infant's hospital course was marked by failure to thrive, congestive heart failure, prolonged physiologic jaundice, and eight episodes of hyperthermia (>38.5°C without apparent cause) between 2 and 6 weeks of age. The hypertrichosis, which was much less prominent at 2 months of age, is a known side effect of minoxidil therapy in both children and adults, and the condition in this infant was thought to be caused by that drug (2). The cause of the other defects could not be determined, but a chromosomal abnormality was excluded based on a normal male karyotype (46,XY) determined after a midgestation amniocentesis.

Two additional cases of in utero exposure to minoxidil were reported to the FDA and published in 1987 (3). The first infant was the product of a 32-week gestation in a 22-year-old woman with severe uncontrolled renal hypertension who was treated during pregnancy with minoxidil, methyldopa, hydralazine, furosemide, and phenobarbital. The 1770-g infant died of congenital heart disease the day after delivery. Defects noted at autopsy were transposition of the great vessels and pulmonic bicuspid valvular stenosis. Hypertrichosis was not observed. No conclusions can be drawn on the cause of the cardiac defects. The second infant, delivered near term and weighing 3220 g, was exposed throughout gestation to minoxidil (5 mg/day) plus metoprolol (100 mg/day) and prazosin (20 mg/day). The mother had severe hypertension secondary to chronic nephritis. Hypertrichosis was evident in both the mother and the newborn, but no other abnormalities were noted in the infant. The excessive hair growth, which was longest in the sacral area, gradually disappeared during the following 2–3 months. Normal development was noted at 2 years of age.

Breast Feeding Summary

Minoxidil is excreted into breast milk (1). Levels in the milk ranged from 41.7 ng/mL (1 hour) to 0.3 ng/mL (12 hours), with milk:plasma ratios during this interval varying from 0.67 to 1.0. No adverse effects were observed in the infant. The American Academy of Pediatrics considers minoxidil to be compatible with breast feeding (4).

References

1. Valdivieso A, Valdes G, Spiro TE, Westerman RL. Minoxidil in breast milk. Ann Intern Med 1985;102:135.
2. Kaler SG, Patrinos ME, Lambert GH, Myers TF, Karlman R, Anderson CL. Hypertrichosis and congenital anomalies associated with maternal use of minoxidil. Pediatrics 1987;79:434–6.
3. Rosa FW, Idanpaan-Heikkila J, Asanti R. Fetal minoxidil exposure. Pediatrics 1987;80:120.
4. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.