Lercanidipine - instructions for use, dose, side effects, contraindications

The "slow" calcium channel blocker, a dihydropyridine derivative, inhibits the transmembrane current of calcium ions into the cells of the smooth muscles of the vessels. The mechanism of hypotensive action is caused by a direct relaxing action on the smooth muscle cells of the vessels, as a result of which the overall peripheral resistance of the vessels decreases. Has a prolonged antihypertensive effect due to the high selectivity to the smooth muscle cells of the vessels. Negative inotropic effect is absent.

Despite a relatively short half-life from plasma, lercanidipine has a prolonged antihypertensive effect due to the high membrane distribution coefficient.Due to high vascular selectivity does not have a negative inotropic effect. Acute arterial hypotension with reflex tachycardia occurs rarely due to the gradual development of vasodilation with lercanidipine.

Lercanidipine is a racemic mixture of (+) R- and (-) S-enantiomers. The antihypertensive effect of lercanidipine is primarily due to the S-enantiomer.

The duration of the therapeutic action is 24 hours.

Pharmacokinetics:

Lercanidipine is completely absorbed after ingestion. C_max in blood plasma is achieved after 1.5-3 hours and is 3.3 ± 2.09 ng / ml and 7.66 ± 5.90 ng / ml after taking 10 and 20 mg of lercanidipine, respectively.

The (+) R- and (-) S-enantiomers of lercanidipine exhibit a similar pharmacokinetic profile: they have the same time to reach C_max, the same half-life; the C_maxand AUC is 1.2 times higher for the (-) S-enantiomer. The pronounced effect of "first passage" through the liver. Absolute bioavailability of lercanidipine after ingestion after eating is approximately 10%, when taken on an empty stomach, the bioavailability is reduced by 30%. When lercanidipine is taken no later than 2 hours after the intake of fatty foods, its bioavailability increases 4-fold, so the drug should not be taken after meals.When oral lercanidipine is used, its concentration in the blood plasma is not directly proportional to the dose taken (nonlinear kinetics). Saturation of presystemic metabolism occurs gradually. Thus, bioavailability increases with increasing doses.

The distribution of blood plasma into tissues and organs occurs quickly and extensively. Binding to plasma proteins exceeds 98%.

Lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme with the formation of inactive metabolites.

About 50% of the accepted dose is excreted by the kidneys (about 50% is excreted by the intestine). Elimination occurs mainly through biotransformation. Average half-life is 8-10 hours.

Cumulation of lercanidipine with repeated ingestion is not observed.

Indications:

Essential hypertension I-II severity.

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

Contraindications:

Chronic heart failure in the stage of decompensation; unstable angina; aortic stenosis; within one month after the transferred myocardial infarction; severe liver dysfunction; impaired renal function (creatinine clearance less than 10 ml / min);lactose intolerance; galactosemia; syndrome of impaired glucose / galactose absorption; pregnancy; lactation period (breastfeeding); Women of childbearing age who do not enjoy reliable contraception; children and adolescents under 18; hypersensitivity to the components of the drug; hypersensitivity to other dihydropyridine derivatives.

Carefully:

Renal and / or hepatic insufficiency, advanced age, sinus node weakness syndrome (without a pacemaker), coronary heart disease, left ventricular dysfunction.

Pregnancy and lactation:

Contraindicated in pregnancy and during breastfeeding.

The category of FDA recommendations is not defined.

Dosing and Administration:

Inside, in the morning, at least 15 minutes before meals, without chewing, squeezed with enough water. Assign 10 mg once a day. The dose may be increased to 20 mg (in the event that the expected effect is not achieved with 10 mg administration). The therapeutic dose is selected gradually, increasing the dose to 20 mg is carried out 2 weeks after the start of the drug.

Side effects:

From the cardiovascular system: the effects associated with vasodilator action - peripheral swelling, a sensation of blood flushes to the face, palpitation, tachycardia, chest pain, lowering of arterial pressure, angina pectoris, myocardial infarction, asthenia, fatigue, headache, dizziness were rarely noted.

From the digestive system: very rarely - dyspepsia, nausea, vomiting, epigastric pain, diarrhea, reversible increase in hepatic enzyme activity, gingival hyperplasia.

Other: very rarely - polyuria, skin rash, drowsiness, myalgia.

Overdose:

Symptoms: peripheral vasodilation with a marked decrease in blood pressure and reflex tachycardia, an increase in the frequency and duration of angina attacks, myocardial infarction.

Treatment: symptomatic therapy.

Interaction:

The drug should not be taken concomitantly with CYP3A4 inhibitors (the cytochrome P450 isoenzyme of the liver), such as ketoconazole, itraconazole, erythromycin (increase the concentration of lercanidipine in the blood and lead to a potentiation of the antihypertensive effect).

Contraindicated simultaneous reception of lercanidipine with cyclosporine, as this leads to an increase in the content of both substances in the blood plasma. Lercanidipine It should not be taken with grapefruit juice, as this leads to inhibition of lercanidipine metabolism and potentiation of the antihypertensive effect.

Admission of the drug with midazolam in the elderly leads to an increase in the absorption of lercanidipine and a decrease in the rate of absorption.

Metoprolol reduces the bioavailability of lercanidipine by 50%, the bioavailability of metoprolol remains unchanged. This effect can occur due to a decrease in hepatic blood flow, which is caused by beta-blockers, so it can also appear when used with other drugs in this group.

Cimetidine 800 mg per day does not lead to significant changes in the concentration of lercanidipine in the blood plasma, but special caution is required since at higher doses of cimetidine, the bioavailability of lercanidipine and its antihypertensive effect may increase.

Ethanol can enhance the antihypertensive effect of lercanidipine.

Special instructions:

The drug is well tolerated.Effects associated with the vasodilating properties of the drug are rare. In elderly patients, dose adjustments are not required. In the presence of renal or hepatic insufficiency of mild or moderate severity, as a rule, dose correction is not required, the initial dose is 10 mg, then caution should be taken to increase the dose to 20 mg.

During the treatment period, care must be taken when performing work requiring increased attention when driving vehicles, especially at the beginning of treatment and with increasing doses of the drug (risk of drowsiness, headache and dizziness).

Instructions

Lercanidipine (Lercanidipinum)