Pregnancy: Amlodipine: The safety of amlodipine in human pregnancy has not been established. In animal studies, reproductive toxicity was observed at high doses (see Pharmacology: Toxicology: Preclinical safety data under Actions). Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus.
Valsartan: The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first trimester of pregnancy (see Precautions). The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy (see Contraindications and Precautions).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and if appropriate, alternative therapy should be started.
Exposure to AIIRAs therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see Contraindications and Precautions).
Hydrochlorothiazide: There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient.
Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.
Amlodipine/valsartan/hydrochlorothiazide: There is no experience on the use of Exforge HCT in pregnant women. Based on the existing data with the components, the use of Exforge HCT is not recommended during first trimester and contra-indicated during the second and third trimester of pregnancy (see Contraindications and Precautions).
Breast-feeding: No information is available regarding the use of valsartan and/or amlodipine during breast-feeding. Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit milk production. The use of Exforge HCT during breast-feeding is not recommended. If Exforge HCT is used during breast-feeding, doses should be kept as low as possible. Alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Fertility: There are no clinical studies on fertility with Exforge HCT.
Valsartan: Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m2 basis (calculations assume an oral dose of 320 mg/day and a 60-kg patient).
Amlodipine: Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).