FORTZAAR

LOSARTAN/HYDROCHLOROTHIAZIDE ARROW LAB is indicated in the treatment of essential arterial hypertension in patients whose blood pressure is not sufficiently controlled by losartan or hydrochlorothiazide monotherapy.

Pregnancy

Angiotensin II receptor antagonists (ARBs)

The use of ARBs is not recommended during the 1st trimester of pregnancy (see section 4.4).

The use of ARBs is contraindicated in the 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).

Available epidemiological data concerning the risk of malformation after exposure to ACE inhibitors during the 1st trimester of pregnancy do not allow for a conclusion. However, a small increase in the risk of congenital malformation cannot be excluded. There are no available epidemiological studies concerning the use of ARBs; however, a risk similar to that of ACE inhibitors could exist with this class. Unless treatment with angiotensin II receptor antagonists is considered essential, it is recommended to modify antihypertensive treatment in patients planning pregnancy to a medication with an established safety profile during pregnancy. In case of diagnosis of pregnancy, treatment with angiotensin II receptor antagonists must be discontinued immediately and, if necessary, an alternative treatment must be started.

Exposure to ARA II treatment during the 2nd and 3rd trimesters of pregnancy is known to cause fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of skull bones) and toxicity in the newborn (renal failure, hypotension, hyperkalaemia) (see section 5.3).

In case of exposure to angiotensin II receptor antagonists from the 2nd trimester of pregnancy, it is recommended to perform a fetal ultrasound to check renal function and the bones of the skull vault.

Newborns of mothers treated with angiotensin II receptor antagonists should be monitored for blood pressure (see sections 4.3 and 4.4).

Hydrochlorothiazide

Data concerning the use of hydrochlorothiazide during pregnancy, and particularly during the 1st trimester, are limited. Animal studies are insufficient.

Hydrochlorothiazide crosses the placental barrier. Given the pharmacological mechanism of action of hydrochlorothiazide, its use during the 2nd and 3rd trimesters of pregnancy may decrease foeto-placental perfusion and lead to foetal and neonatal effects such as jaundice, electrolyte imbalance and thrombocytopenia.

Hydrochlorothiazide must not be used to treat gestational oedema, gestational hypertension or pre-eclampsia, due to the risk of decreased blood volume and placental hypoperfusion, without beneficial effect on the progression of the disease.

Hydrochlorothiazide must not be used to treat essential arterial hypertension in pregnant women, except in rare cases where no other treatment is possible.

Breastfeeding

Angiotensin II receptor antagonists (ARBs)

Due to the absence of available information on the use of losartan/hydrochlorothiazide during breastfeeding, losartan/hydrochlorothiazide is not recommended and it is preferable to use other treatments with a well-established safety profile during breastfeeding, particularly in the newborn or premature infant.

Hydrochlorothiazide

Hydrochlorothiazide is excreted in human milk in small amounts. High-dose thiazide diuretics causing intense diuresis may prevent lactation. The use of losartan/hydrochlorothiazide during breastfeeding is not recommended. If losartan/hydrochlorothiazide is used during breastfeeding, doses should be the lowest possible.

The adverse effects below are listed, if appropriate, by organ class and frequency according to the following convention:

Very frequent: ≥ 1/10

Frequent: ≥ 1/100 to < 1/10

Uncommon: ≥ 1/1 000 to < 1/100

Rare: ≥ 1/10 000 to < 1/1 000

Very rare: ≤ 1/10 000

Frequency unknown: cannot be estimated on the basis of available data

In clinical trials conducted with losartan potassium and hydrochlorothiazide, no adverse effect specific to this combination was observed. The adverse effects were limited to those described previously with losartan potassium and/or hydrochlorothiazide.

In controlled clinical studies conducted in essential hypertension, dizziness was the only drug-related adverse effect reported with a frequency higher than placebo in at least 1 % of patients treated with losartan and hydrochlorothiazide.

In addition to these effects, the adverse effects reported since the marketing of the drug are as follows:

The adverse effects reported with one of the individual components could be adverse effects observed with the losartan potassium/hydrochlorothiazide combination. These are as follows:

Losartan

The following adverse effects have been reported with losartan in clinical studies and since marketing:

Hydrochlorothiazide

Description of certain adverse effects

Non-melanoma skin cancer: based on available data from epidemiological studies, a cumulative dose-dependent association between hydrochlorothiazide and NMSC has been observed (see also sections 4.4 and 5.1).

Reporting of suspected adverse effects

Reporting suspected adverse effects after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/