TWYNSTA

Treatment of essential arterial hypertension in adults:

Additional treatment

TELMISARTAN/AMLODIPINE ARROW 40 mg/10 mg is indicated in patients whose blood pressure is not sufficiently controlled by amlodipine 10 mg alone.

Substitution treatment

Adult patients taking telmisartan and amlodipine tablets separately may replace them with TELMISARTAN/AMLODIPINE ARROW tablets containing the same doses of active substances.

Pregnancy

There is limited data on the use of the telmisartan/amlodipine combination in pregnant women. No reproductive toxicity studies have been conducted in animals with the telmisartan/amlodipine combination.

telmisartan

The use of angiotensin II receptor antagonists (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).

Studies of telmisartan conducted in animals have shown reproductive toxicity (see section 5.3).

Available epidemiological data concerning the risk of malformation after exposure to ACEIs during the 1st trimester of pregnancy do not allow for conclusions to be drawn. However, a small increase in the risk of congenital malformations cannot be excluded. There are no controlled epidemiological data on the risk associated with ARBs; however, a similar risk may exist for this class. Unless ARB treatment is considered essential, it is recommended in patients planning a pregnancy to modify antihypertensive treatment to a medication with an established safety profile during pregnancy. In case of diagnosis of pregnancy, ARB treatment must be discontinued immediately and, if necessary, an alternative treatment will be started.

Exposure to ARBs during the 2nd and 3rd trimesters of pregnancy is known to cause fetal toxicity in humans (decreased renal function, oligohydramnios, delayed ossification of skull bones) and toxicity in the newborn (renal failure, hypotension, hyperkalemia) (see section 5.3).

In case of exposure 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 ARBs should be monitored for blood pressure (see sections 4.3 and 4.4).

amlodipine

The safety of amlodipine in pregnant women has not been established.

Studies conducted in animals have shown reproductive toxicity at high doses (see section 5.3).

Breastfeeding

Amlodipine is excreted in breast milk. The proportion of the maternal dose received by the infant has been estimated at an interquartile range of 3 to 7 %, with a maximum of 15 %. The effect of amlodipine on infants is unknown.

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

Fertility

No data from controlled clinical studies with the fixed combination or with each of the active substances taken separately are available.

No reproductive toxicity studies have been conducted specifically with the combination of telmisartan and amlodipine.

In preclinical studies, no effect of telmisartan was observed on the fertility of males and females.

In certain patients treated with calcium channel blockers, reversible biochemical changes have been reported at the level of the sperm head. Clinical data are insufficient to allow for a conclusion on the potential effect of amlodipine on fertility. In a study conducted in rats, deleterious effects on male fertility were observed (see section 5.3).

This medicine has a moderate influence on the ability to drive vehicles and use machines. Adverse effects such as syncope, drowsiness, sensations of dizziness or vertigo are sometimes observed with the intake of antihypertensives, and this must be taken into account when driving vehicles or using machines (see section 4.8). If patients present these adverse effects, they must avoid performing potentially dangerous tasks such as driving vehicles or using machines.

Summary of the safety profile

The most common adverse reactions include dizziness and peripheral oedema. Serious syncope can rarely occur (less than 1 case per 1 000 patients).

Adverse reactions previously reported with one of the individual components (telmisartan or amlodipine) may be potential adverse reactions with telmisartan/amlodipine, even if not observed in clinical trials or during the post-marketing period.

Tabulated summary of adverse reactions

The safety and tolerability of telmisartan/amlodipine have been evaluated in five controlled clinical trials in over 3 500 patients, over 2 500 of whom received telmisartan in combination with amlodipine.

Adverse reactions have been ranked under headings of frequency using the following convention: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1 000, < 1/100); rare (≥ 1/10 000, < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

1: this event may be incidental or related to a mechanism currently unknown.

2: most cases of abnormal hepatic function/hepatic disorder reported from post-marketing experience with telmisartan occurred in Japanese patients. Japanese patients are more likely to experience these adverse reactions.

3: cases of interstitial lung disease (mainly interstitial pneumonia and eosinophilic pneumonia) have been reported since the marketing of telmisartan.

Description of selected adverse reactions

Intestinal angioedema

Cases of intestinal angioedema have been reported with the use of angiotensin II receptor antagonists (see section 4.4).

Reporting of suspected adverse reactions

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