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Candesartan / hydrochlorothiazide Pregnancy and Breastfeeding Warnings

Candesartan / hydrochlorothiazide is also known as: Atacand HCT

Overview

Candesartan/Hydrochlorothiazide may cause birth defects or fetal death if you take it while you are pregnant. If you think you may be pregnant, contact your doctor right away. Candesartan/Hydrochlorothiazide is found in breast milk. Do not breast-feed while taking Candesartan/Hydrochlorothiazide.

Candesartan / hydrochlorothiazide Pregnancy Warnings

Candesartan is similar to angiotensin converting enzyme (ACE) inhibitors, which are contraindicated during pregnancy. Because of the many reports of fetal deaths and malformations associated with the use of ACE inhibitors, a committee of the National Institutes of Health has recommended that these drugs be avoided during pregnancy. Drugs that act on the renin-angiotensin-aldosterone (RAA) system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking ACE inhibitors. The use of drugs that act directly on the RAA system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have been reported, although it is not clear whether these occurrences were due to exposure to the drug. These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be informed. Rarely, no alternative to a drug acting on the RAA system will be found. In these cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment. If oligohydramnios is observed, candesartan should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. 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. However, thiazide diuretics may 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. Data from the Michigan Medicaid Birth Defects Study has revealed an association between the use of HCTZ and congenital abnormalities (written communication, Franz Rosa, MD, Food and Drug Administration, 1994). This was a retrospective study of 229,101 completed pregnancies between 1985 and 1992, of which 567 were exposed to HCTZ at some time during the first trimester, and 1,173 were exposed to the drug at any time during pregnancy. Of the 567 pregnancies, there were 24 total and 7 cardiovascular birth defects (22 and 6 were expected, respectively). There were no observations of cleft palate, spina bifida, limb reduction, or hypospadias. The one instance of polydactyly did not achieve statistical significance. These data are consistent with an association between the use of HCTZ and birth defects, although other factors, including underlying disease(s) of the mother, are not accounted for. Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

Candesartan-hydrochlorothiazide has been assigned to pregnancy category C (first trimester) and category D (second and third trimesters) by the FDA. There was no evidence of teratogenicity or other adverse effects on embryo-fetal development when pregnant mice, rats or rabbits were treated orally with candesartan cilexetil alone or in combination with hydrochlorothiazide. There are no controlled data in human pregnancy. The manufacturer states that when used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. Retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. Use of candesartan-hydrochlorothiazide is considered contraindicated during pregnancy.

Candesartan / hydrochlorothiazide Breastfeeding Warnings

Animal studies have shown candesartan to be present in breast milk. In one case, a peak milk HCTZ concentration of 125 ng/mL was measured between 4 and 12 hours after a (usual daily) dose of HCTZ 50 mg in one subject. A simultaneously measured maternal serum HCTZ level was approximately 275 ng per mL. There were no detectable drug levels or electrolyte abnormalities in the baby's blood. The authors calculated that, if a one month old infant takes approximately 600 mL of milk per day, and the average milk HCTZ level is approximately 80 ng per mL, the infant would be exposed to approximately 0.05 mg HCTZ a day. This usually represents an insignificant amount of HCTZ to the infant such that adverse effects in the nursing infant are unlikely with regard to this component of this combination drug.

There are no data on the excretion of candesartan into human milk. Hydrochlorothiazide is secreted into human milk in low concentrations. Adverse effects in the nursing infant are unlikely. Hydrochlorothiazide is considered compatible with breast-feeding by the American Academy of Pediatrics. The manufacturer, however, 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.

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