A 31-year-old woman in the early stages of pregnancy has been prescribed minoxidil (Regaine) becaus

Fråga: A 31-year-old woman in the early stages of pregnancy has been prescribed minoxidil (Regaine) because of diffuse loss of hair. It is however unclear whether the patient has already started the treatment. Is there any risk of teratogenicity?

Sammanfattning: Minoxidil is a potent vasodilatator that is used orally in treatment of hypertension. When the drug is administered orally for periods in excess of one month, hyperthrichosis occurs as a side-effect in a majority of patients. Consequently, topical minoxidil has been developed and is available as Regaine to treat male alopecia. Information on the use of minoxidil during human pregnancy is very limited and we have only found four cases of fetal exposure to minoxidil in oral doses of 5 to 10 mg daily during pregnancy. Some of these cases resulted in serious fetal malformations and stillbirths. However, conclusive data on monotherapy with minoxidil during pregnancy are lacking and we have found no case reports of topical minoxidil treatment in pregnant woman.

In spite of the low percutaneous absorption, topical treatment with minoxidil should be avoided in pregnant women. In this case the potential exposure has occurred at an early stage of pregnancy and it is assumed that exposure to potentially teratogenic drugs in this early phase will either not affect the fetus or will induce a spontaneous miscarriage. The risk for teratogenicity in this case should be regarded as insignificant.

Svar: Minoxidil is a potent resistance vessel dilatator that is used orally in the treatment of severe hypertension. Regaine liniment (20 mg/ml) also contains minoxidil, with male alopecia androgenetica as the approved indication. About 90 per cent of minoxidil is metabolised to an active metabolite in the liver, predominantly by conjugation with glucuronic acid. The elimination half-life is three to four hours and the volume of distribution is large (200-500 liters). The protein binding is negligible (1,2,3). When used topically, as in the present case, the dose of one ml (not to be exceeded) should be applied to affected areas twice daily.

In clinical trials in patients with alopecia areata or alopecia androgenetica, following topical application of one, three and five per cent lotions once or twice daily, the absorption through intact skin was very low. Following a single application or repeated administration for nine days with minoxidil lotion (one or five per cent) to the scalp of healthy subjects, less than five per cent of the administered dose was recovered in the urine and none was found in faeces. However, these trials only relate to application of a lotion formulation of minoxidil and could not be extrapolated to other formulations such as the liniment used in this case. Also, the proportion of propylene glycol to alcohol differs between formulations which could affect the absorption.

Information on the use of minoxidil in human pregnancy is very limited. We have found only four cases of fetal exposure after oral administration. In one case, oral minoxidil was used throughout gestation and no effect was seen in the healthy newborn (4). In the second case a 26-year-old woman with a history of renal artery stenosis and malignant hypertension had three midgestation stillbirths of five pregnancies. In two of these three stillbirths no information of the medication was available. The third stillbirth involved a 500 gram male infant with low-set ears but no gross anomalies and in this case the mother had, among other drugs, been treated with minoxidil orally. In the fifth pregnancy she was also treated with oral minoxidil (10 mg daily) and the infant, delivered by Cesarean section at 38 weeks gestation, had multiple abnormalities, including an omphalocele, pronounced hypertrichosis, depressed nasal bridge, low-set ears, bilateral fifth finger clinodactyly, undescended testes, a circumferential midphallic constriction, a large ventriculoseptal defect, and a brain defect (5). In the third case report a 22-year-old pregnant woman with severe uncontrolled renal hypertension, treated with oral minoxidil (among other antihypertensive drugs), delivered an infant with manifested cyanotic heart disease who died on the second day. Autopsy revealed transposition of the great vessels and pulmonic bicuspid valvular stenosis. In the last case report a 23-year-old woman took oral minoxidil (5 mg daily), metoprolol and prazosin throughout her pregnancy. The female newborn delivered near term had hypertrichosis that gradually disappeared over the following two to three months. No other abnormalities were noted (6).

We have found no cases of topical minoxidil treatment in pregnant women.