INCREASED RISK OF BIRTH DEFECTS, FOETAL AND NEONATAL MORBIDITY AND DEATH WHEN USED THROUGHOUT PREGNANCY.
Given the effects of the individual components in this combination product on pregnancy and lactation, Triplixam is not recommended during the first trimester of pregnancy. Triplixam is contraindicated during the second and third trimesters of pregnancy.
Triplixam is not recommended during lactation. A decision should therefore be made whether to discontinue nursing or to discontinue Triplixam taking account the importance of this therapy for the mother.
Pregnancy: Perindopril: 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. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.
Exposure to ACE inhibitor 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 ACE inhibitors have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension (see Contraindications and Precautions).
Indapamide: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of indapamide in pregnant women. Prolonged exposure to thiazide during the third trimester of pregnancy can reduce maternal plasma volume as well as uteroplacental blood flow, which may cause a feto-placental ischemia and growth retardation. Moreover, rare cases of hypoglycemia and thrombocytopenia in neonates have been reported following exposure near term.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
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).
Breastfeeding: Triplixam is not recommended during lactation.
Perindopril: Because no information is available regarding the use of perindopril during breastfeeding, perindopril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Indapamide: There is insufficient information on the excretion of indapamide/metabolites in human milk. Hypersensitivity to sulfonamide-derived medicines and hypokalaemia might occur. A risk to newborns/infants cannot be excluded.
Indapamide is closely related to thiazide diuretics which have been associated, during breast-feeding, with a decrease or even suppression of milk lactation.
Amlodipine: Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3 - 7%, with a maximum of 15%. The effect of amlodipine on infants is unknown.
Fertility: Common to perindopril and indapamide: Reproductive toxicity studies showed no effect on fertility in female and male rats (see Pharmacology: Toxicology: Preclinical safety data under Actions). No effects on human fertility are anticipated.
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).