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Chlorthalidone / clonidine Pregnancy and Breastfeeding Warnings

Chlorthalidone / clonidine is also known as: Clorpres

Chlorthalidone / clonidine Pregnancy Warnings

Clonidine crosses the placenta. Limited data from 10 pregnant women have shown that the average umbilical cord to maternal plasma clonidine concentration ratio averages 0.9. No adverse fetal effects in human pregnancy have been observed, but data on the use of clonidine during the first trimester of pregnancy are limited. Data from the Michigan Medicaid Birth Defects Study (MMBDS) has revealed an unexpectedly high incidence of birth defects associated with the use of clonidine, although the number of exposures to the drug is too small to make definite conclusions (written communication, Franz Rosa, MD, Food and Drug Administration, 1994). The MMBDS is a retrospective study of 229,101 pregnancies from 1985 to 1992, of which 59 were exposed to clonidine during the first trimester of pregnancy. Of the 59 pregnancies that were exposed to clonidine, there were 3 total and 2 cardiovascular defects observed (2.0 and 0.5 were expected, respectively). Cleft palate, spina bifida, polydactyly, limb reduction/syndactyly, or hypospadias were not observed. Because of the low numbers of exposures, no definite conclusions may be made. The MMBDS showed no association between some thiazide diuretics and congenital defects. With regard to thiazide diuretics, two patients populations were reviewed--one in which 390 of 104,000 pregnant women from 1980 to 1983, and one in which 567 of 229,101 pregnant women from 1985 to 1992 received a related drug, hydrochlorothiazide (HCTZ). In the first study 28 total defects and 6 cardiovascular defects were observed (25 and 4 were expected, respectively). In the second study, 24 total defects and 7 cardiovascular defects were observed (22 and 6 were expected, respectively). Cleft palate was not observed in either study. These data do not support an association between HCTZ and congenital defects, and are considered pertinent to other thiazide diuretics. A series of 211 pregnant women who were given chlorthalidone to prevent toxemia of pregnancy has been reported. Patients were entered into the study at gestation week 16, and were given chlorthalidone 50 mg once a day or placebo in a single-blinded fashion. There were significant decreases in serum sodium and potassium in the treated patients, especially between gestation months four through nine. There appeared to be no benefit from the drug since there were no significant differences in blood pressure or the incidence of edema or proteinuria between the groups. The average height and weight of the offspring of treated patients was significantly higher; there were no deaths and no malformations. Placental weights were significantly greater among women who received chlorthalidone, but there were no differences in the amount or nature of amniotic fluid, placental calcification, or number of placental infarctions. The authors speculated whether the increased placental size in the treated group was related to alterations in glycogen metabolism. The Collaborative Perinatal Project monitored 50,282 mother-child pairs, of whom 233 were exposed to thiazide or related diuretics during the first trimester. An increased risk of malformations was found for thiazide diuretics. Use of thiazides after the first trimester does not seem to carry this risk. Thiazide diuretics may, however, pose metabolic risks to the mother and fetus (hyponatremia, hypokalemia, thrombocytopenia, hyperglycemia), and may have a direct effect on smooth muscle, resulting in inhibition of labor. Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

Clonidine-chlorthalidone has been assigned to pregnancy category C by the FDA. Animal studies have failed to reveal evidence of teratogenicity associated with either component of the drug, although an increased incidence of fetal resorption associated with clonidine has been demonstrated in some species. Some retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. There are no controlled data in human pregnancy studies. Clonidine-chlorthalidone should only be given during pregnancy when benefit outweighs risk.

Chlorthalidone / clonidine Breastfeeding Warnings

Chlorthalidone and clonidine are excreted into human milk. The manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Limited data indicate that the average concentration of clonidine in human milk is approximately twice that observed in the maternal plasma. In one case, in which the mother was taking clonidine 37.5 mcg twice a day, the milk and maternal plasma clonidine levels were 0.60 and 0.33 ng/mL, respectively, while the infant's plasma level was undetectable. No adverse effects were observed in the nursing infant. The authors calculated that, if the nursing infant consumed 150 mL/kg, the infant would have ingested 90 ng/kg of clonidine per day. This is miniscule compared to the maternal drug dosage of 1320 ng/day (maternal weight, 57 kg). Therefore, the infant's relative clonidine dosage would have been 6.8% of the mother's. Two other reports of the use of clonidine during breast-feeding are found. In one, the infant's plasma clonidine levels were 60% to 80% of the maternal plasma. Prenatal exposure to clonidine has been associated with transitory hypertension during the first three days of life and with hyperactivity and sleep disturbances in six-year-old children. While hypotension has not been observed in nursing infants whose mothers were taking up to 0.4 mg of clonidine per day, data from long term exposure to nursing infants are unavailable. There are no data on the safety of chlorthalidone during breast-feeding. In general, thiazides are known to be excreted into human milk in insignificant concentrations.

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