Niperten combi pills 5mg/5mg №30

Description

pharmachologic effect

The drug Niperten® Combi has a pronounced antihypertensive and antianginal effect due to the complementary action of two active substances: the blocker of the “slow” Calcium channels (BCCA) - Amlodipine and the selective beta 1-adrenergic blocker - Bisoprolol.

The mechanism of action of amlodipine

Amlodipine blocks the "slow" calcium channels and reduces the transmembrane current of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

The antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in total peripheral vascular resistance (OPSS).

The mechanism of antianginal action is studied to the end of ns, presumably it is associated with two effects:

- expansion of peripheral arterioles reduces the round focal disease (afterload). Due to the lack of reflex tachycardia, myocardial energy and oxygen consumption is reduced.
- the expansion of the large coronary arteries and coronary arterioles improves the delivery of oxygen to both normal and ischemic myocardial areas, including spasm of the coronary arteries (Prinzmetal angina or unstable angina).

In patients with arterial hypertension, taking amlodipine once a day causes a clinically significant decrease in blood pressure (BP) in the “lying” and “standing” position for 24 hours. Due to the slow development of the antihypertensive effect of amlodipine does not cause a sharp decrease in blood pressure. In patients with stenocardia, taking amlodipine 1 time per day increases the total exercise time, the time before the onset of an attack of stenocardia and to significant depression of the ST segment, and also reduces the frequency of strokes and the need for Nitroglycerin (short-acting forms).

No negative effect of amlodipine on plasma lipid, glucose and uric acid concentrations was detected.

The mechanism of action of bisoprolol

Bisoprolol is a selective beta 1-blocker, which does not have its own sympathomimetic activity and membrane-stabilizing action and is characterized by only a slight affinity for the beta2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as to the beta2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol has virtually no effect on the resistance of the respiratory tract and metabolic processes that are mediated through exposure to beta 2 -adrenoreceptors. The selective effect of bisoprolol on beta1-adrenoreceptors is maintained outside the therapeutic range. Bisoprolol ns has a pronounced negative inotropic effect.The maximum effect is achieved within 3-4 hours after ingestion. Even with the appointment of bisoprolol I once a day, its therapeutic effect lasts for 24 hours, since its half-life (T1 / 2) from blood plasma is 10-12 hours. As a rule, the maximum antihypertensive effect is achieved 2 weeks after the start of treatment. Bisoprolol reduces the activity of the sympathoadrenal system by blocking the beta1-adrenoreceptors of the heart. When taken orally in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol decreases the heart rate (HR), reduces the stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy initially increased OPS decreases. Reducing the activity of renin in the blood plasma is considered as one of the mechanisms of the antihypertensive effect of beta-blockers.

Pharmacokinetics
Amlodipine
Suction
After oral administration, amlodipine is well absorbed. The maximum concentration (Cmax) in the blood plasma is noted after 6-12 hours. Food intake does not affect the absorption of amlodipine. Absolute bioavailability ranges from 64 to 80%.
Distribution
The apparent volume of distribution is about 21 l / kg. Equilibrium plasma concentration (5-15 ng / ml) is reached 7-8 days after the start of the drug. In in vitro studies, plasma protein binding is 93-98%. Metabolism and excretion

Amlodipine is actively metabolized in the liver. About 90% of the dose taken is converted to inactive pyridine derivatives. Approximately 10% of the dose taken out at night in unchanged form. Approximately 60% of inactive metabolites are excreted by the kidneys, 20-25% through the intestines. The decrease in the concentration of amlodipine in the blood plasma occurs in two phases. The final T1 / 2 is approximately 35-50 hours, which allows you to take the drug 1 time per day. Total clearance is 7 ml / min / kg (25 l / h in a patient with a body weight of 60 kg), in elderly patients - 19 l / h.

In elderly patients and patients with renal insufficiency, no significant changes in the pharmacokinetics of amlodipine were observed. Due to decreased clearance in patients with hepatic insufficiency, lower initial doses should be used.
Bisoprolol
Suction
Bisoprolol is almost completely (more than 90%) absorbed in the gastrointestinal tract (GIT). Its bioavailability due to low biotransformation during "primary passage" through the liver (about 10%) is about 90% after ingestion. Food intake does not affect bioavailability. The pharmacokinetics of bisoprolol is linear in the dose range of 5-20 mg. Cmax in blood plasma is achieved in 2-3 hours.
Distribution
Bisoprolol is distributed fairly widely. The volume of distribution is 3.5 l / kg. Communication with plasma proteins is about 30%.
Metabolism
Metabolized by the oxidative pathway without subsequent conjugation.All metabolites are polar (water soluble) and excreted by the kidneys. The major metabolites found in plasma and urine do not possess pharmacological activity. In vitro studies on human liver microcircuits have shown that bisoprolol is primarily metabolized using the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.
Removal
The clearance of bisoprolol is determined by the balance between kidney excretion in unchanged form (about 50%) and metabolism in the liver (about 50%) with the formation of metabolites, which are also excreted by the kidneys. Total clearance is 15 l / h.

Indications

Arterial hypertension (for the replacement of amlodipine and bisoprolol in the same doses when used in monotherapy).

Contraindications

mlodipine
- Unstable stenocardia (with the exception of Prinzmetal stenocardia).
- Hemodynamically unstable heart failure after myocardial infarction.
- Clinically significant aortic stenosis.
Bisoprolol
- Acute heart failure or chronic heart failure in the decompensation stage, requiring inotropic therapy.
- Atrioventricular block (AV) of II and III degree without pacemaker.
- Sick sinus syndrome.
- Sinoatrial blockade.
- Severe bradycardia (heart rate less than 60 beats / min).
- Severe forms of bronchial asthma (BA) or chronic obstructive pulmonary disease (COPD).
- Severe disorders of peripheral arterial circulation or Raynaud's syndrome.
- Pheochromocytoma (without simultaneous use of alpha-blockers).
- Metabolic acidosis.
Amlodipine / bisoprolol combination
- Hypersensitivity to amlodipine, other dihydropyridine derivatives, bisoprolol and / or any excipients.
- Severe arterial hypotension (systolic blood pressure less than 100 mm Hg. Art.).
- Shock (including cardiogenic).
- Children's age up to 18 years (efficiency and safety of ns are established).
Carefully:
CHF (including non-ischemic etiology of III-IV functional class according to NYHA classification), liver failure, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations in plasma glucose concentrations, AV block I degree, Prinzmetal angina, occlusive peripheral artery disease, psoriasis (including history), starvation (strict diet), pheochromocytoma (with simultaneous use of alpha-blockers), BA and COPD, while conducting desensitizing therapy, total and estezii, application in elderly patients, hypotension, type 1 diabetes, aortic stenosis, mitral stenosis, acute myocardial infarction (after 28 days).
Pregnancy and lactation:
Use of the drug Niperten® Kombi during pregnancy is possible if the benefit to the mother exceeds the risk of side effects in the fetus and newborn.

If necessary, the use of the drug Niperten® Kombi during lactation breastfeeding should be stopped.
Amlodipine
In experimental studies, the embryotoxic and fetotoxic effects of the drug have not been established. However, the use of amlodipine during pregnancy is possible if the potential benefit to the mother outweighs the possible risk to the fetus. There is no data on the removal of amlodipine with breast milk. However, it is known that other BMPC - dihydropyridine derivatives, are derived from breast milk. If necessary, treatment with amlodipine during lactation is recommended to stop breastfeeding.
Bisoprolol
The use of bisoprolol during pregnancy is possible if the potential benefit to the mother outweighs the possible risk to the fetus.

Beta-blockers reduce the blood supply to the placenta and can affect the development of the fetus. It is necessary to monitor the blood flow in the placenta and uterus, as well as the growth and development of the fetus. In case of occurrence of adverse events in relation to pregnancy and / or the fetus, alternative therapy should be prescribed. It is necessary to carefully examine the newborn; in the first 3 days of life, symptoms of hypoglycemia and bradycardia may appear.

There is no data on removal of bisoprolol with breast milk. If necessary, treatment with bisoprolol during lactation is recommended to stop breastfeeding.