Hydrochlorothiazide/propranolol Pregnancy and Breast Feeding Warnings
Hydrochlorothiazide/propranolol is also known as: Inderide, Inderide LA
Overview
If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Propranolol/Hydrochlorothiazide while you are pregnant. Propranolol/Hydrochlorothiazide is found in breast milk. If you are or will be breast-feeding while you use Propranolol/Hydrochlorothiazide , check with your doctor. Discuss any possible risks to your baby.
Hydrochlorothiazide/propranolol Pregnancy Warnings
Propranolol-hydrochlorothiazide (HCTZ) has been assigned to pregnancy category C by the FDA. Some animal studies using high doses of propranolol (10 times the maximum recommended human dose, on a per kg basis) have revealed evidence of embryotoxicity. Propranolol has been given during pregnancy, to treat both maternal and fetal conditions, without evidence of teratogenicity. However, fetal and neonatal adverse effects have been reported. Some retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. Some experts consider the use of HCTZ during pregnancy contraindicated. There are no controlled data in human pregnancy. Propranolol-HCTZ should only be given during pregnancy when there are no alternatives and benefit outweighs risk.
Propranolol has been used safely to treat a variety of conditions during pregnancy, including hypertension and pheochromocytoma in the mother, and tachyarrhythmias in both the mother and the fetus. There are a number of abnormalities associated with the use of propranolol during pregnancy, but many of these may be attributable to underlying diseases. These abnormalities include some signs and symptoms of beta-blockade, such as bradycardia, hypoglycemia, and respiratory depression. Other abnormalities that may be due to propranolol include intrauterine growth retardation, small placentas, polycythemia, thrombocytopenia, and hypocalcemia. Structural anomalies associated with propranolol are rare, and have been reported when propranolol was used with a possible teratogen, such as an angiotensin converting enzyme inhibitor, or in the case of significant underlying maternal diseases. In short, propranolol does not appear to be teratogenic, but maternal and fetal propranolol toxicity may occur. For this reason, it is recommended that neonates of mothers who are receiving propranolol be observed for at least 48 hours for signs and symptoms of toxicity, such as bradycardia, hypotension, and hypoglycemia. Incidentally, the pharmacokinetics of propranolol do not appear to be altered during pregnancy. 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. The Michigan Medicaid surveillance study failed to show an association between either propranolol or hydrochlorothiazide (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 274 were exposed to propranolol at some time during the first trimester, and 470 were exposed to the drug at any time during pregnancy. Eleven total and 3 cardiovascular defects were observed (12 and 3 were expected, respectively). There were two cases of hypospadias. The incidence of birth defects did not achieve statistical significance. Regarding HCTZ, data were collected from two periods, one in which 390 of 104,000 pregnant women from 1980 to 1983, and one in which 567 of 229,000 pregnant women from 1985 to 1992 received 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 either propranolol or HCTZ and congenital defects. Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.
Hydrochlorothiazide/propranolol Lactation Warnings
Both propranolol and hydrochlorothiazide are excreted into human milk. Although adverse effects in the nursing infant are unlikely, the manufacturer recommends against breast-feeding while receiving hydrochlorothiazide-propranolol.
Propranolol milk to maternal plasma ratios as high as 1.5 have been reported. While no adverse effects in the nursing infant have been reported, experts advise monitoring the infant for signs and symptoms of beta-blockade and to schedule feedings at least three hours after maternal propranolol administration. In one case, a peak milk HCTZ level of 125 ng/mL was measured between 4 and 12 hours after a dose in a woman who was taking HCTZ 50 mg/day. A simultaneously measured maternal serum HCTZ level was approximately 275 ng/mL. There were no detectable drug levels or electrolyte abnormalities in the baby's blood. The authors calculated that, if a 1-month-old infant takes approximately 600 mL of milk per day, and the mean milk HCTZ level is approximately 80 ng/mL, the infant would be exposed to approximately 0.05 mg HCTZ daily. This should represent a insignificant amount of HCTZ to the infant such that adverse effects in the nursing infant are unlikely.
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