Teldipin tablets 10 mg + 80 mg No. 30

Instructions for Teldipin tablets 10 mg + 80 mg No. 30

Composition

active ingredients: telmisartan, amlodipine;

1 tablet contains 80 mg of telmisartan and 10 mg of amlodipine (as amlodipine besylate);

Excipients: meglumine, sodium hydroxide, povidone K30, lactose monohydrate, sorbitol (E 420), iron oxide yellow (E 172), magnesium stearate, sodium stearyl fumarate, mannitol (E 421), colloidal anhydrous silicon dioxide, stearic acid.

Dosage form

Pills.

Main physicochemical properties:

Teldipine, 80 mg/10 mg tablets: oval, slightly biconvex, two-layer tablets, brownish-yellow on one side, marbled, white to off-white on the other side, engraved with K1.

Pharmacotherapeutic group

Angiotensin-II receptor blockers, combinations. Telmisartan and amlodipine. ATC code C09D B04.

Pharmacological properties

Pharmacodynamics

Telmisartan.

Mechanism of action.

Telmisartan is a specific and effective antagonist of angiotensin II receptors (type AT1). Telmisartan displaces angiotensin II with very high affinity at its binding sites on the AT1 receptor subtype, which are responsible for the activity of angiotensin II. Telmisartan does not exhibit any partial agonist effect on the AT1 receptor. Telmisartan selectively binds the AT1 receptor. Binding is long-lasting. Telmisartan does not exhibit affinity for other receptors, including AT2 and other, less studied AT receptors. The functional role of these receptors is unknown, as is the effect of their possible "overstimulation" by angiotensin II, the level of which increases under the influence of telmisartan. Telmisartan reduces plasma aldosterone levels. Telmisartan does not inhibit human plasma renin, does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), an enzyme that also degrades bradykinin. Therefore, potentiation of bradykinin-mediated side effects should not be expected.

In humans, telmisartan at a dose of 80 mg almost completely inhibits the increase in blood pressure induced by angiotensin II. The blocking effect is maintained for 24 hours and remains significant for up to 48 hours.

Clinical efficacy and safety

Treatment of essential hypertension

After the first dose of telmisartan, antihypertensive activity gradually develops within 3 hours. The maximum reduction in blood pressure is achieved 4-8 weeks after the start of treatment and is maintained during long-term therapy.

The antihypertensive effect is maintained continuously for 24 hours after administration of the drug, including the last 4 hours before the next dose, as confirmed by ambulatory blood pressure monitoring. This was confirmed by the ratio of the blood pressure reduction before the next dose to the maximum blood pressure reduction of more than 80% after taking 40 and 80 mg of telmisartan in placebo-controlled clinical trials. There is a clear relationship between dose and time to recovery to baseline systolic blood pressure. Similar data for diastolic blood pressure are contradictory.

In patients with arterial hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting pulse rate. The influence of the diuretic and natriuretic effects of the drug on its hypotensive effect has not yet been determined. The antihypertensive efficacy of telmisartan is comparable to that of drugs belonging to other classes of antihypertensive drugs (demonstrated by clinical studies comparing telmisartan with amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril).

When treatment with telmisartan is abruptly discontinued, blood pressure gradually returns to pre-treatment values within a few days, without withdrawal symptoms.

In clinical trials comparing two antihypertensive drugs, the incidence of dry cough was significantly lower in patients taking telmisartan than in patients taking ACE inhibitors.

Prevention of cardiovascular diseases

The ONTARGET study (Ongoing International Trial of Telmisartan Alone and in Combination with Ramipril) compared the effects of telmisartan, ramipril, and the combination of telmisartan and ramipril on cardiovascular outcomes in 25,620 patients aged 55 years and older with coronary heart disease, stroke, transient ischemic attack, peripheral arterial disease, or type 2 diabetes with target organ damage (e.g., retinopathy, left ventricular hypertrophy, macro- or microalbuminuria). These patients were at risk for cardiovascular disease.

The effect of telmisartan was similar to that of ramipril in reducing the primary composite endpoint of cardiac death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for congestive heart failure. The incidence of the primary endpoint was similar in the telmisartan (16.7%) and ramipril (16.5%) groups. The hazard ratio for telmisartan compared with ramipril was 1.01 (97.5% CI 0.93-1.10, p (no benefit) = 0.0019 at a cut-off value of 1.13). The all-cause mortality rate was 11.6% and 11.8% for patients receiving telmisartan and ramipril, respectively.

Telmisartan was non-inferior to ramipril on the pre-specified secondary endpoint (fatal cardiovascular event, non-fatal myocardial infarction, and non-fatal stroke) [0.99 (97.5% CI 0.90-1.08), p (no benefit) = 0.0004], the primary endpoint in the pivotal HOPE (The HeartOutcomes Prevention Evaluation Study) study comparing ramipril with placebo.

In the TRANSCEND study, patients with ACE-I intolerance were randomized to telmisartan 80 mg (n=2954) or placebo (n=2972), with the same inclusion criteria as in the ONTARGET study. Both drugs were used in addition to standard therapy.

The median follow-up was 4 years and 8 months. There was no significant difference in the incidence of the primary composite endpoint (cardiac death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for congestive heart failure) [15.7% for telmisartan and 17% for placebo, with a relative risk of 0.92 (95% CI 0.81–1.05, p = 0.22)]. There was evidence of superiority of telmisartan over placebo for the pre-specified secondary composite endpoint (cardiac death, non-fatal myocardial infarction, and non-fatal stroke [0.87 (95% CI 0.76–1.00, p = 0.048)]). There was no evidence of benefit in terms of cardiovascular mortality (relative risk 1.03, 95% CI 0.85 – 1.24).

Cough and angioedema were reported less frequently in patients taking telmisartan than in patients taking ramipril, although hypotension was reported more frequently with telmisartan.

The combination of telmisartan and ramipril did not provide a better effect compared to ramipril or telmisartan used separately. With the combination of drugs, cardiovascular mortality and all-cause mortality were quantitatively higher. In addition, a significantly higher incidence of hyperkalemia, renal failure, hypotension and dizziness was recorded in the combination treatment group. Therefore, the use of the combination of telmisartan and ramipril is not recommended for this population.

In the Preventive Treatment to Effectively Prevent Re-Stroke (PRoFESS) study, in patients aged 50 years and older with a recent stroke, sepsis was more common with telmisartan compared to placebo, 0.70% and 0.49% respectively [RR 1.43 (95% confidence interval 1.00-2.06)]; the incidence of fatal sepsis was higher in patients taking telmisartan (0.33%) compared to patients taking placebo (0.16%) [RR 2.07 (95% confidence interval 1.14-3.76)].

The established increased incidence of sepsis with telmisartan may be coincidental or depend on a mechanism that has not yet been established.

Two large randomized controlled trials (ONTARGET and VA NEPHRON-D (Diabetic Nephropathy in the Elderly Study)) examined the use of a combination of ACE inhibitors with angiotensin II receptor blockers.

The ONTARGET study was conducted in patients with cardiovascular and cerebrovascular diseases or type 2 diabetes with evidence of target organ damage. The VA NEPHRON-D study was conducted in patients with type 2 diabetes and diabetic nephropathy.

These studies did not show a strong positive effect on the kidneys and/or cardiovascular system and a reduction in mortality, but there was an increased risk of hyperkalemia, acute renal failure and/or hypotension compared with monotherapy.

Given their similar pharmacodynamic properties, these results also apply to other ACE inhibitors and angiotensin II receptor blockers.

Therefore, ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

The ALTITUDE (Aliskiren in Type 2 Diabetes Using Kidney and Cardiovascular Endpoints) trial assessed the benefit of adding aliskiren to standard therapy with ACE inhibitors or angiotensin II receptor blockers in patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, or both. The trial was stopped early due to an increased risk of adverse events.

Amlodipine.

Amlodipine is a calcium ion flux inhibitor belonging to the dihydropyridine group (slow calcium channel blocker or calcium ion antagonist) and blocks the transmembrane flow of calcium ions into myocardial and vascular smooth muscle cells.

The mechanism of antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle. The exact mechanism by which amlodipine reduces angina is not fully understood, but amlodipine reduces overall exercise ischemia through the following actions:

Amlodipine dilates peripheral arterioles and thus reduces total peripheral resistance (afterload). Since the heart rate is unchanged, the reduction in workload on the heart reduces myocardial energy consumption and oxygen demand; amlodipine also partially contributes to the dilation of the main coronary arteries and coronary arterioles in both intact and ischemic areas of the myocardium. This dilation increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal's angina or variant angina).

In patients with hypertension, once-daily administration of amlodipine provides clinically significant reductions in supine and standing blood pressure over 24 hours. Due to its slow onset of action, amlodipine does not cause acute hypotension.

In patients with angina, once-daily administration of amlodipine increases total exercise time, time to angina attack, and time to 1 mm ST-segment depression, reduces the frequency of angina attacks, and reduces the need for nitroglycerin.

Amlodipine is not associated with any negative metabolic effects or changes in plasma lipid levels, so it can be used in patients with asthma, diabetes, and gout.

Patients with coronary heart disease (CHD)

The efficacy of amlodipine in preventing clinical events in patients with coronary heart disease (CHD) was evaluated in an independent, multicenter, randomized, double-blind, placebo-controlled trial involving 1997 patients, CAMELOT (Comparison of Amlodipine and Enalapril in Limiting Thrombosis). Over 2 years, 663 patients received amlodipine 5–10 mg, 673 patients received enalapril 10–20 mg, and 655 patients received placebo in addition to standard therapy with statins, β-blockers, diuretics, and aspirin. The main efficacy results are shown in Table 1. The results indicate that treatment with amlodipine was associated with fewer hospitalizations for angina and fewer revascularization procedures in patients with CHD.

Use in patients with heart failure

Haemodynamic studies and exercise-controlled clinical trials in patients with heart failure, NYHA functional class II–IV, have shown that amlodipine did not lead to clinical deterioration in terms of exercise tolerance, left ventricular ejection fraction, and clinical symptoms.

The aim of the placebo-controlled PRAISE trial was to evaluate the effect of amlodipine in patients with NYHA functional class III–IV heart failure who were receiving digoxin, diuretics, and ACE inhibitors. The study showed that amlodipine did not increase the risk of mortality or morbidity/mortality related to heart failure.

Study (ALLHAT) – evaluating different types of treatments to prevent heart attacks

The ALLHAT (Antihypertensive and Lipid-lowering Treatment for Heart Attack Prevention) randomized, double-blind, morbidity/mortality trial was conducted to compare current therapeutic agents: amlodipine 2.5–10 mg/day (calcium channel blocker) or lisinopril 10–40 mg/day (ACE inhibitor) as first-line therapy and the thiazide diuretic chlorthalidone 12.5–25 mg/day in patients with mild to moderate hypertension.

The study included 33,357 hypertensive patients aged 55 years or older who were followed for a mean of 4.9 years. Patients had at least one additional cardiovascular risk factor, including: previous myocardial infarction or stroke >6 months before study entry or evidence of other atherosclerotic cardiovascular disease (overall 51.5%), type 2 diabetes (36.1%), dyslipidemia with high-density lipoprotein (HDL) <35 mg/dL (11.6%), left ventricular hypertrophy as determined by electrocardiogram or echocardiography (20.9%), and smoking (21.9%).

The primary endpoint was a composite of fatal CHD or nonfatal myocardial infarction. There was no statistically significant difference in the primary endpoint between amlodipine-based and chlorthalidone-based therapy: relative risk 0.98 95% CI (0.90–1.07) p=0.65. Among the secondary endpoints: the incidence of heart failure (component of the composite cardiovascular endpoint) was significantly higher in the amlodipine group compared with the chlorthalidone group (10.2% vs. 7.7%, relative risk 1.38, 95% CI [1.25–1.52] p<0.001). However, there was no significant difference in all-cause mortality between amlodipine-based therapy and chlorthalidone-based therapy (relative risk 0.96, 95% CI [0.89–1.02] p=0.20).

Pharmacokinetics

Absorption.

Telmisartan is rapidly absorbed, but the amount absorbed is variable. The mean absolute bioavailability of telmisartan is approximately 50%. When telmisartan is administered with food, the area under the concentration-time curve (AUC) for telmisartan decreases from approximately 6% (40 mg dose) to approximately 19% (160 mg dose). 3 hours after administration, plasma concentrations are similar to those observed when telmisartan is administered in the fasted state.

Linearity/nonlinearity.

It is believed that a slight decrease in AUC does not reduce the therapeutic efficacy of the drug. There is no linear relationship between doses and plasma levels. The maximum plasma concentration (Cmax) and, to a lesser extent, the AUC increase disproportionately at doses above 40 mg.

Distribution.

Telmisartan is highly bound to plasma proteins (more than 99.5%), mainly to albumin and alpha-1-acid glycoprotein. The mean volume of distribution (Vss) at steady state is approximately 500 l.

Biotransformation.

Telmisartan is metabolized by conjugation to the glucuronide of the parent compound, which has no pharmacological activity.

Breeding.

Telmisartan is characterized by a biexponential pharmacokinetic curve with a terminal half-life of more than 20 hours. The maximum plasma concentration (Cmax) and, to a lesser extent, the AUC increase disproportionately with dose. When using telmisartan at recommended doses, no clinically significant accumulation has been observed. Plasma concentrations are higher in women than in men, without a corresponding effect on efficacy.

After oral and intravenous administration, telmisartan is almost completely excreted in the feces, mainly unchanged. Cumulative urinary excretion is less than 1% of the dose. Total plasma clearance (Cltot) is high (approximately 1000 ml/min) compared with hepatic blood flow (approximately 1500 ml/min).

Special categories of patients.

Sex.

There was a difference in plasma concentrations depending on gender, with Cmax and AUC being 3- and 2-fold higher in women compared to men, respectively.

Elderly patients.

The pharmacokinetics of telmisartan do not differ in elderly patients and patients under 65 years of age.

Patients with impaired renal function.

In patients with mild, moderate and severe renal impairment, plasma concentrations of telmisartan were doubled. However, lower plasma concentrations were observed in patients with renal failure undergoing dialysis. Telmisartan is highly bound to plasma proteins in patients with renal failure and is not removed by dialysis. The elimination half-life is not altered in patients with renal impairment.

Patients with liver dysfunction.

Pharmacokinetic studies in patients with hepatic impairment have shown an increase in absolute bioavailability of almost 100%. The elimination half-life is not altered in these patients.

Amlodipine

Absorption, distribution, binding to plasma proteins.

After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels occurring 6–12 hours after administration. Absolute bioavailability is 64–80%.

Food intake does not affect the bioavailability of amlodipine.

Biotransformation/excretion.

The terminal half-life of amlodipine from plasma is approximately 30–50 hours, which corresponds to once-daily dosing. Amlodipine is extensively metabolized in the liver to inactive metabolites. 10% of the parent amlodipine and 60% of the metabolites of amlodipine are excreted in the urine.

Special categories of patients.

Patients with liver dysfunction.

Clinical data on the use of amlodipine in patients with hepatic impairment are limited. In patients with hepatic impairment, amlodipine clearance is reduced, resulting in a prolonged half-life and an increase in AUC by approximately 40-60%.

Elderly patients.

The time to reach maximum plasma concentrations of amlodipine is similar in young and elderly patients. In elderly patients, amlodipine clearance tends to be reduced, resulting in an increase in AUC and half-life. The increase in AUC and prolongation of half-life in patients with congestive heart failure were within the expected range for patients of the age group studied.

Indication

Teldipine is indicated as replacement therapy for the treatment of patients with arterial hypertension who are already treated with telmisartan and amlodipine, administered simultaneously at the same dose as in the combination.

Contraindication

Hypersensitivity to the active substance or to any of the components of the drug; pregnancy or planning to become pregnant (see section "Use during pregnancy and breastfeeding"); biliary obstructive disorders; severe liver function disorders; severe arterial hypotension; shock (including cardiogenic); obstruction of the left ventricular outflow tract (e.g. due to severe aortic stenosis); hemodynamically unstable heart failure after acute myocardial infarction;

The simultaneous use of Teldipine with aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR < 60 ml/min/1.73 m2) (see sections “Interaction with other medicinal products and other types of interactions”, “Pharmacodynamics”).

Interaction with other medicinal products and other types of interactions

No interactions between the two components of this fixed combination were observed during clinical studies.

Interactions inherent to the combination.

No studies have been conducted on interactions with other drugs.

This should be taken into account when used concomitantly.

Other antihypertensive drugs. The blood pressure lowering effect of Teldipine may be enhanced by concomitant use of other antihypertensive drugs.

Medicinal products with blood pressure lowering potential. Based on the pharmacological properties, it can be expected that some medicinal products may enhance the hypotensive effects of all antihypertensive medicinal products, including Teldipine, e.g. baclofen, amifostine. Furthermore, orthostatic hypotension may be exacerbated by alcohol, barbiturates, narcotics or antidepressants.

Corticosteroids (systemic use). Decreased antihypertensive effect.

Interactions associated with telmisartan.

Concomitant use is not recommended.

Potassium-sparing diuretics or potassium supplements. Angiotensin II receptor antagonists such as telmisartan attenuate diuretic-induced potassium loss. Potassium-sparing diuretics such as spironolactone, eplerenone, triamterene or amiloride, potassium supplements or potassium-containing salt substitutes may lead to significant increases in serum potassium. If concomitant use is indicated because of documented hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.

Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, including telmisartan. If the combination is considered necessary, serum lithium levels should be closely monitored during concomitant use.

Other antihypertensive agents acting on the renin-angiotensin-aldosterone system (RAAS): Clinical data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) with a combination of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of adverse events such as hypotension, hyperkalaemia and decreased renal function (up to acute renal failure) compared with the use of a single RAAS-acting agent (see sections 4.4, 4.3 and 5.1).

Concomitant use requires caution.

In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the combination of angiotensin II receptor antagonists and cyclooxygenase inhibitors may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, this combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated; in addition, renal function should be monitored after initiation of combination therapy and periodically thereafter.

Ramipril: In one study, the combination of telmisartan and ramipril was reported to result in a 2.5-fold increase in AUC0-24 and Cmax of ramipril and ramiprilat. The clinical significance of this observation is unknown.

This should be taken into account when used concomitantly.

Digoxin: When telmisartan was co-administered with digoxin, an increase in mean peak (49%) and trough (20%) plasma digoxin concentrations was observed. Digoxin levels should be monitored at the start of treatment, during dose adjustments and when telmisartan therapy is discontinued to maintain them within the therapeutic range.

Interactions related to amlodipine.

Concomitant use requires caution.

CYP3A4 inhibitors.

Concomitant administration of the CYP3A4 inhibitor erythromycin in young patients and diltiazem in elderly patients increased plasma concentrations of amlodipine by 22% and 50%, respectively. However, the clinical significance of this observation has not been determined. It cannot be excluded that potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir) may increase plasma concentrations of amlodipine to a greater extent than diltiazem. Amlodipine should be used with caution in combination with CYP3A4 inhibitors. However, no adverse events consistent with such an interaction have been reported.

CYP3A4 inducers: When used concomitantly with known CYP3A4 inducers, the plasma concentration of amlodipine may change. Therefore, blood pressure should be monitored and the dose adjusted both during and after concomitant use, particularly with potent CYP3A4 inducers (such as rifampicin, St. John's wort).

Grapefruit or grapefruit juice. Co-administration of 240 ml of grapefruit juice with a single oral dose of 10 mg amlodipine in 20 healthy volunteers did not show any significant effect on the pharmacokinetics of amlodipine. The concomitant use of amlodipine with grapefruit or grapefruit juice is still not recommended because bioavailability may be increased in some patients, leading to increased antihypertensive effect.

This should be taken into account when used concomitantly.

Tacrolimus: There is a risk of increased blood levels of tacrolimus when co-administered with amlodipine, but the pharmacokinetic mechanism of this interaction is not fully established. To avoid tacrolimus toxicity, tacrolimus blood levels should be monitored regularly and the dosage adjusted if necessary when amlodipine is co-administered in patients taking tacrolimus.

Cyclosporine: Interaction studies between cyclosporine and amlodipine have not been conducted in healthy volunteers or other populations, except in renal transplant patients, where a variable increase in cyclosporine trough concentrations (mean 0-40%) was observed. In renal transplant patients receiving amlodipine, monitoring of cyclosporine concentrations should be considered and, if necessary, a reduction in the cyclosporine dose.

Simvastatin: Coadministration of multiple doses of amlodipine 10 mg and simvastatin 80 mg resulted in a 77% increase in simvastatin exposure compared to simvastatin alone. For patients taking amlodipine, the dose of simvastatin should be limited to 20 mg daily.

Others. Amlodipine has been safely used with digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide, magnesium hydroxide, simethicone), cimetidine, cyclosporine, antibiotics, and oral hypoglycemic drugs. When amlodipine and sildenafil were combined, each drug independently exerted its own blood pressure-lowering effect.

Application features

Pregnancy: Angiotensin II receptor antagonists (ARBs) should not be initiated during pregnancy. Unless continued ARB 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, ARBs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.8).

In patients with hepatic impairment, the half-life of amlodipine is prolonged and AUC values are increased: dosage recommendations for such patients have not been established. Therefore, Teldipine should be used with caution in patients with mild to moderate hepatic impairment.

Renal hypertension: There is an increased risk of severe hypotension and renal failure when patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney are treated with drugs that affect the renin-angiotensin-aldosterone system.

Renal insufficiency and kidney transplantation. When taking Teldipine in patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. There is no experience of the safe use of Teldipine in patients with recent kidney transplantation. Telmisartan and amlodipine are not removed by dialysis.

Intravascular hypovolemia. Symptomatic hypotension, especially after the first dose, may occur in patients with reduced fluid volume and/or sodium due to diuretic therapy, dietary salt restriction, diarrhea or vomiting. Such conditions should be corrected before using telmisartan. If hypotension occurs while taking Teldipine, the patient should be placed in the horizontal position and, if necessary, an intravenous infusion of saline solution should be given. After stabilization of blood pressure, treatment can be continued.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS).

There is evidence that the concomitant use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (up to acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see sections "Interaction with other medicinal products and other forms of interaction" and "Pharmacological properties").

If dual blockade is considered absolutely necessary, it should only be performed under specialist supervision and with continuous close monitoring of renal function, electrolytes and blood pressure.

ACE inhibitors and angiotensin II receptor blockers should not be prescribed simultaneously in patients with diabetic nephropathy.

Other conditions requiring stimulation of the renin-angiotensin-aldosterone system: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with congestive heart failure or severe renal disease, including renal artery stenosis), treatment with other medicinal products that affect the renin-angiotensin-aldosterone system, such as telmisartan, may be associated with acute hypotension, hyperazotemia, oliguria or, rarely, acute renal failure (see section 4.8).

Primary aldosteronism: Patients with primary aldosteronism generally do not respond to antihypertensive drugs that act by blocking the renin-angiotensin system. Therefore, the use of Teldipine is not recommended.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy. As with other vasodilators, special caution is required when treating patients with aortic and mitral valve stenosis or obstructive hypertrophic cardiomyopathy.