TWYNSTA

Treatment of essential hypertension in adults:

Add-on therapy

TELMISARTAN/AMLODIPINE ARROW 80 mg/10 mg is indicated in patients whose blood pressure is not adequately controlled by TELMISARTAN/AMLODIPINE ARROW 40 mg/10 mg or TELMISARTAN/AMLODIPINE ARROW 80 mg/5 mg.

Replacement therapy

Adult patients taking telmisartan and amlodipine tablets separately may instead receive tablets of TELMISARTAN/AMLODIPINE ARROW containing the same component doses.

Pregnancy

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

Telmisartan

The use of angiotensin II receptor antagonists (AIIRAs) is not recommended during the 1st trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).

Preclinical studies with telmisartan have shown reproductive toxicity (see section 5.3).

Epidemiological data regarding the risk of malformation following exposure to ACE inhibitors during the 1st trimester of pregnancy have not been conclusive. However, a small increase in the risk of congenital malformations cannot be excluded. There is no controlled epidemiological data on the risk associated with AIIRAs, however a similar risk could exist for this class. 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 AIIRA therapy during the 2nd and 3rd trimesters of pregnancy is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).

Should exposure to AIIRA therapy have occurred from the 2nd 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 sections 4.3 and 4.4).

Amlodipine

The safety of amlodipine in human pregnancy has not been established.

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

Breastfeeding

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 to 7 %, with a maximum of 15 %. The effect of amlodipine on infants is unknown.

As no information is available regarding the use of telmisartan during breastfeeding, the telmisartan/amlodipine combination is not recommended. It is preferable to use other treatments with an established safety profile during breastfeeding, especially when nursing a newborn or preterm infant.

Fertility

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

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 some patients treated with calcium channel blockers, reversible biochemical changes have been reported in the head of spermatozoa. Clinical data are insufficient to allow 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 frequent adverse effects include dizzy sensations and peripheral oedema. Serious syncope may rarely occur (less than 1 case per 1 000 patients).

Adverse effects previously reported for each of the active substances taken individually (telmisartan or amlodipine) may potentially occur during treatment with telmisartan/amlodipine, even if they have not been demonstrated during clinical trials or after marketing.

Summary table of adverse effects

The safety of use and tolerability of telmisartan/amlodipine were evaluated in five controlled clinical trials conducted in more than 3 500 patients, of whom more than 2 500 received telmisartan in association with amlodipine.

Adverse effects have been classified according to their frequency using the following classification: very frequent (≥ 1/10); frequent (≥ 1/100, < 1/10); uncommon (≥ 1/1 000, < 1/100); rare (≥ 1/10 000, < 1/1 000); very rare (< 1/10 000); unknown frequency (cannot be estimated on the basis of available data).

Within each frequency group, adverse effects are presented in descending order of severity.

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

2 : most cases of abnormal liver function/liver disorder reported after the marketing of telmisartan occurred in Japanese patients. Japanese patients are more likely to present these adverse effects.

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

Description of selected adverse effects

Intestinal angioedema

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

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorisation of the medicinal product is important. It allows continuous 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/