Irbesartan and Amlodipine

Symptomatic hypotension may occur in patients with sodium/volume depletion and in those under intensive treatment with diuretics and/or salt restriction, or in hemodialysis. The depletion of volume and/or sodium should be corrected before starting treatment with irbesartan/amlodipine.

There are no adequate and well-controlled studies in pregnant women. Irbesartan/amlodipine combination is contraindicated during pregnancy. Irbesartan/amlodipine should not be used in women of childbearing potential unless effective contraceptive measures are being used. If pregnancy occurs during treatment with irbesartan/amlodipine, this should be discontinued as soon as possible.

Fetal/neonatal morbidity and mortality

Although there is no experience with irbesartan in pregnant women, it has been reported that exposure of the pregnancy product to ACE inhibitors, administered to pregnant women during the second and third quarters of pregnancy, causes injuries and death of the fetus. Therefore, as any other drug acting directly on the renin-angiotensin-aldosterone system, irbesartan/amlodipine should not be administered during pregnancy. When pregnancy is detected during treatment, irbesartan/amlodipine should be discontinued as soon as possible.

Irbesartan/amlodipine combination is contraindicated during lactation.

For irbesartan

The effect of irbesartan on the ability to drive and use machines has not been investigated. Based on its pharmacodynamic properties, it is unlikely that irbesartan will have an effect on the ability to drive or operate machines. However, it should be taken into account that patients being treated for hypertension may occasionally experience dizziness or tiredness.

For amlodipine

Amlodipine may have a mild or moderate effect on the ability to drive and use machines. If patients taking amlodipine experience dizziness, headache, fatigue or nausea, the reaction speed may be affected. Caution is advised especially when starting treatment.

Adverse events

Since clinical studies are conducted under broadly variable conditions, the incidence of adverse reactions observed in drug clinical studies cannot be directly compared to clinical studies with other medications and may not reflect the rates observed in practice.

For irbesartan

Irbesartan safety has been evaluated in clinical studies with approximately 5000 subjects, including 1300 hypertensive patients treated for 6 months and more than 400 patients treated for 1 year or more. In general, adverse events in patients receiving irbesartan were mild and transient and were not related to the dose. The incidence of adverse events was not related to age, gender, or race.

In placebo-controlled clinical trials, including 1965 patients treated with irbesartan (usual treatment duration of 1 to 3 months), the discontinuation of treatment due to any clinical or laboratory adverse event was 3.3 percent for patients treated with Irbesartan and 4.5 percent for patients treated with placebo (p=0.029).

Adverse events that have been reported in clinical studies or post-marketing with irbesartan are categorized below according to the system organ class and frequency (see Table 1).

The following CIOMS frequency rating is used, when applicable: Very common: (≥1/10); common: (≥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), unknown: cannot be estimated from available data.

The frequencies of adverse reactions from the post-marketing experience are unknown, because these reactions are reported voluntarily from a population of uncertain size.

Table 1. Adverse Events Reported in Clinical Trials with Irbesartan or in Post-marketing Reports:

^a Including all adverse events, probably or possibly related, or indefinite relationship to the therapy, whatever its incidence in patients treated with placebo
^b Including all adverse events, probably or possibly related, or indefinite relationship to the therapy, occurring with a frequency of 0.5% to <1% and in a similar or slightly higher incidence in patients treated with irbesartan compared to patients treated with placebo (none of them significantly different in statistical terms between the 2 treatment groups)

Terms marked with a star (*) refer to the adverse reactions that were additionally reported in >2% of diabetic hypertensive patients with chronic renal insufficiency and overt proteinuria and in excess of placebo.

For amlodipine

Adverse events reported in clinical studies with amlodipine are categorized below according to system organ class and frequency (see Table 2).

The following CIOMS frequency rating is used, when applicable: Very common: (≥1/10); common: (≥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), unknown: cannot be estimated from available data.

Table 2. Adverse Events Reported in Clinical Trials with Amlodipine:

In clinical studies comparing the fixed-dose combination irbesartan/amlodipine to either irbesartan or amlodipine monotherapy, the types and incidences of treatment-emergent adverse events (TEAEs) possibly related to study treatment were similar to those observed in earlier monotherapy clinical trials and postmarketing reports. The most frequently reported adverse event was peripheral edema, mainly associated with amlodipine (see Table 3).

The following CIOMS frequency rating is used, when applicable: Very common ≥10%; Common ≥1 and <10%; Uncommon ≥0.1 and <1%; Rare ≥0.01 and <0.1%; Very rare <0.01%, Unknown (cannot be estimated from available data).

Table 3. Treatment-Emergent Adverse Events Considered Possibly Related to Study Drug in Irbesartan/Amlodipine Clinical Studies (I-ADD, I-COMBINE and I-COMBO):