Eclamiz, tablets 5 mg+10 mg 30 pcs

Pharmacotherapeutic group: combined hypotensive agent (slow calcium channel blocker + angiotensin-converting enzyme (ACE) inhibitor)

ATX code: C09BB03

Pharmacological properties

Pharmacodynamics

Combination drug containing the active ingredients: lisinopril and amlodipine.

Lisinopril

An angiotensin-converting enzyme (ACE) inhibitor, reduces angiotensin II formation from angiotensin I. Decreased angiotensin II leads to a direct reduction in the release of aldosterone. Reduces bradykinin degradation and increases prostaglandin synthesis.

Limits total peripheral vascular resistance (PPR), blood pressure (BP), preload, pulmonary capillary pressure, causes an increase in the minute blood volume and increases myocardial exercise tolerance in patients with chronic heart failure (CHF). Dilates arteries to a greater extent than veins. Some effects are attributed to effects on the tissue renin-angiotensin-aldosterone system (RAAS). Long-term use reduces myocardial and arterial wall resistance hypertrophy. It improves the blood supply to the ischemic myocardium.

The ACE inhibitors prolong life expectancy in patients with CHF and slow the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure.

The onset of action is 1 h after oral administration. The maximum antihypertensive effect is determined after 6-7 hours and lasts for 24 hours. In arterial hypertension, the antihypertensive effect is noted in the first days after the start of treatment, the stable effect develops after 1-2 months. In case of abrupt withdrawal of the drug no marked increase in BP has been noted.

In addition to BP reduction, lisinopril decreases albuminuria. Lisinopril has no effect on blood glucose concentration in diabetic patients and does not lead to increased incidence of hypoglycemia.

Amlodipine

The dihydropyridine derivative is a “slow” calcium channel blocker with antianginal and antihypertensive effects. It blocks calcium channels, reduces transmembrane transition of calcium ions into the cell (more in vascular smooth muscle cells than in cardiomyocytes).

The antianginal action is caused by the dilation of coronary and peripheral arteries and arterioles: in angina pectoris it reduces myocardial ischemia; by dilation of peripheral arterioles it reduces myocardial hypertension and decreases post-load of the heart and myocardial oxygen demand. By dilating coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina); prevents coronary artery spasm (including that caused by smoking). In patients with stable angina a single daily dose increases exercise tolerance, slows down the development of angina and “coronary” ST-segment depression, reduces the frequency of angina attacks and the use of nitroglycerin and other nitrates.

It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilatory effect on vascular smooth muscle. In arterial hypertension, a single dose provides clinically significant reduction of blood pressure (BP) for 24 hours (in patient’s “lying” and “standing” position). Orthostatic hypotension when prescribing amlodipine is rare. It does not cause a decrease in exercise tolerance and left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy.

It does not influence myocardial contractility and conduction, does not cause reflex increase of heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria. It does not have any adverse effect on metabolism and blood plasma lipid concentration and can be used for therapy of patients with bronchial asthma, diabetes and gout. Significant decrease in BP is observed after 6-10 hours, the duration of effect is 24 hours.

Lisinopril + amlodipine

Combining lisinopril and amlodipine in one drug allows achieving comparable BP control and preventing possible adverse effects caused by one of the active substances. For example, BMCC, by directly dilating arterioles, can lead to sodium and fluid retention in the body, and therefore may activate the RAAS. An ACE inhibitor blocks this process.

Pharmacokinetics

Lisinopril

Intake. After oral administration, lisinopril is absorbed from the gastrointestinal tract (GIT) by an average of 25%, but absorption can vary from 6 to 60%. The bioavailability is 25%. Food intake does not affect the absorption of lisinopril.

Distribution. Almost no binding to plasma proteins. Maximum plasma concentration (Cmax) of 90 ng/ml is reached after 6-7 hours. Hematoencephalic and placental barrier permeability is low.

Metabolism. Lisinopril is not biotransformed in the body.

Elimination. It is excreted unchanged by the kidneys. The elimination half-life (T1/2) is 12 hours.

Pharmacokinetics in selected patient groups

In elderly patients the plasma concentration of lisinopril and the area under the curve “concentration-time” (AUC) are twice as high as in younger patients.

In patients with CHF the absorption and clearance of lisinopril are decreased, the bioavailability is 16%.

In patients with renal insufficiency, the concentration of lisinopril is several times higher than the plasma concentration in healthy volunteers, with increased time to reach Cmax and increased T1/2.

Lisinopril is excreted by hemodialysis.

Amlodipine

Intestinal absorption. After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. Bioavailability is 64-80%. Food intake has no effect on absorption of amlodipine.

Distribution. Most of the amlodipine in blood (95%) is bound to plasma proteins. Cmax is observed after 6-10 hours. Equilibrium concentrations are reached after 7-8 days of therapy. The average volume of distribution is 20 l/kg body weight, indicating that most of amlodipine is in the tissues and a smaller part in the blood.

Metabolism. Amlodipine undergoes slow but active metabolism in the liver with no significant “primary passage” effect. Metabolites have no significant pharmacological activity.

Elimination. After single administration, the T1/2 ranges from 31 to 48 h, with multiple administration the T1/2 is approximately 45 h. About 60% of oral intake is excreted by kidneys mainly as metabolites, 10% – unchanged, and 20-25% – in intestine with bile. Total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg).

Pharmacokinetics in selected groups of patients

In elderly patients (over 65 years) the excretion of amlodipine is slower (T1/2 – 65 h) compared to younger patients, but this difference has no clinical significance. The prolonged T1/2 in patients with hepatic impairment suggests that the drug cumulation in the body will be higher with long-term use (T1/2 – up to 60 h). Renal insufficiency has no significant effect on amlodipine kinetics. Amlodipine penetrates through the blood-brain barrier. It is not eliminated by hemodialysis.

Lisinopril+Amlodipine

A interaction between the active ingredients in the drug is unlikely.

The AUC, time to reach and the Cmax and T1/2 values are not changed as compared to those of each individual active substance. Food intake does not affect the absorption of the active substances. Long circulation of both active substances in the body makes it possible to take the drug once a day.

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

Special Instructions

Arterial hypotension

A marked decrease in BP with the development of clinical symptoms may be observed in patients with decreased BOD and/or sodium content due to diuretics, fluid loss or other reasons, such as excessive sweating, prolonged vomiting and/or diarrhea. In the case of arterial hypotension, the patient should be laid down, legs elevated, and fluid loss replenished (intravenous infusion of 0.9% sodium chloride solution) if necessary. Preferably, fluid and/or sodium loss should be restored before starting Eclamiz therapy. BP should be monitored after the initial dose. Such conditions apply to patients with coronary heart disease or cerebrovascular disease in whom a marked decrease in BP may result in myocardial infarction or stroke.

Aortic and mitral stenosis

As with all vasodilators, Eclamiz should be used with caution in patients with left ventricular outflow tract obstruction and mitral valve stenosis.

Renal dysfunction

Some patients with arterial hypertension without significant renovascular disease have increased serum creatinine and urea concentrations, in most cases minimal or transient, more pronounced with concomitant use of ACE inhibitors and diuretics. This is most common in patients with a history of kidney disease.

To determine the optimal maintenance dose, the dosing regimen should be determined on an individual basis, using lisinopril and amlodipine separately, with simultaneous monitoring of renal function. The Eclamiz combination drug is indicated only in patients in whom the optimal maintenance dose of amlodipine and lisinopril is titrated to 5 mg and 10 mg or 10 mg and 20 mg, respectively.

If renal function is impaired, Eclamiz should be discontinued and replaced with monotherapy with drugs at adequate doses. Dose reduction or discontinuation of diuretics may also be required.

Anhyoneurotic edema

Anhyoneurotic edema of the face, extremities, lips, tongue, vocal folds and/or larynx have been reported in patients who have taken ACE inhibitors, including lisinopril. In these cases, Eclamiz should be stopped immediately and the patient should be closely monitored until all symptoms have resolved.
Swelling of face, lips and extremities usually resolves on its own, however, antihistamines should be used to reduce symptoms.

Contraindications

Side effects

The side effects caused by Eclamiz combined are less frequent than when each component is taken alone.

The most common adverse reactions when taking the combination drugs are: headache (8%), dry cough (5%) and dizziness (3%).

The frequency of adverse reactions is shown separately for lisinopril and amlodipine.

The data are presented by system-organ class according to the MedDRA dictionary and with the following frequency: very common (≥1/10); common (≥1/100 to <1/10); infrequent (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000); frequency unknown (cannot be determined from available data).

Overdose

Pregnancy use

Similarities