Lercamen 20,20 mg 60 pcs

Pharmacodynamics

A selective slow calcium channel blocker with predominant effect on blood vessels, dihydropyridine derivative. Inhibits the transmembrane flow of calcium ions into vascular smooth muscle cells. The mechanism of antihypertensive action of lercanidipine is due to a direct relaxant effect on vascular smooth muscle cells, resulting in reduction of RPS.

In spite of relatively short plasma elimination half-life, lercanidipine has prolonged antihypertensive effect due to high membrane distribution coefficient. Due to high vascular selectivity, it has no negative inotropic effect. Acute arterial hypotension with reflex tachycardia occurs rarely due to the gradual development of vasodilation when taking 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 therapeutic action is 24 h.

Pharmacokinetics

Intake

Lercanidipine is completely absorbed after oral administration. Cmax in plasma is reached after 1.5-3 hours and is 3.3±2.09 ng/mL and 7.66±5.90 ng/mL after administration of 10 and 20 mg of lercanidipine, respectively.

The (+)R- and (-)S-enantiomers of lercanidipine demonstrate a similar pharmacokinetic profile: they have the same time to reach Cmax, the same T1/2; the Cmax and AUC values are 1.2 times higher for the (-)S-enantiomer. No interconversion of enantiomers was observed in in vivo experiments.

Because of the “first pass-through” effect through the liver, the absolute bioavailability of lercanidipine is approximately 10% when taken orally after a meal; the bioavailability decreases by 1/3 when taken on an empty stomach. When taking lercanidipine within 2 hours after a fatty meal its bioavailability increases 4 times, therefore the drug Lercamen® should not be taken after meal. During oral administration of lercanidipine its plasma concentration is not directly proportional to the dose taken (nonlinear kinetics). The saturation of presystemic metabolism, occurs gradually. Thus, bioavailability increases with increasing dose.

Distribution

Distribution from plasma to tissues and organs is rapid and extensive. Binding to plasma proteins exceeds 98%.

Metabolism and excretion

Lercanidipine is metabolized with participation of CYP3A4 isoenzyme to form inactive metabolites.

About 50% of the dose taken is excreted by the kidneys (about 50% is excreted in the intestine). Elimination occurs mainly by biotransformation. The average T1/2 is 8-10 hours.

Cumulation of lercanidipine is not observed with repeated oral administration.

Pharmacokinetics in special clinical cases

. The pharmacokinetics of lercanidipine in elderly patients, patients with renal impairment (CK greater than 30 mL/min), and patients with mild to moderate hepatic impairment have been shown to be similar to those observed in the general patient population.

In patients with renal impairment (CKR less than 30 mL/min) and in patients on hemodialysis, plasma concentrations of lercanidipine were higher (approximately 70%).

In patients with severe renal and/or hepatic impairment, due to decreased plasma protein concentrations, the free fraction of lercanidipine may increase.

In patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely increased because lercanidipine is metabolized primarily in the liver.

Indications

Essential hypertension of degree I-II severity.

Active ingredient

Composition

Active substances:

Lercanidipine hydrochloride 20 mg.

Associates:

Lactose monohydrate – 60 mg,

Microcrystalline cellulose – 78 mg,

Sodium carboxymethyl starch (type A) – 31 mg,

Povidone K30 – 9 mg,

Magnesium stearate – 2 mg.

Composition of the shell:

Opadray 02F25077 – 6 mg (hypromellose – 3.825 mg, talc – 0.3 mg, titanium dioxide – 1.2 mg, macrogol 6000 – 0.6 mg, iron oxide (III) – 0.075 mg).

How to take, the dosage

The drug is taken orally at least 15 minutes before a meal, preferably in the morning, without chewing, with plenty of water.

The drug is prescribed in 10 mg 1 time per day. Depending on individual tolerance of the patient, the dose can be increased up to 20 mg.

The therapeutic dose is adjusted gradually, because the maximum antihypertensive effect develops approximately 2 weeks after starting the drug. It is unlikely that the efficacy of the drug will increase with increasing doses over 20 mg/day, at the same time increasing the risk of side effects.

The pharmacokinetic profile and data from clinical studies show that no dose adjustment of Lercamen® is required in elderly patients. However, caution should be exercised during the initial phase of treatment with Lercamen® in this group of patients.

Lercamen® In patients with mild to moderate renal and hepatic impairment, caution should be exercised.

In patients with renal failure (CKD greater than 30 ml/min) or mild to moderate hepatic failure, the initial dose is 10 mg and then the dose is increased to 20 mg/day with caution.

The antihypertensive effect may be enhanced in patients with mild to moderate hepatic impairment and dose adjustment (reduction) may be required.

Lercamen® is contraindicated in renal failure (CKD less than 30 ml/min) and in severe hepatic failure.

Interaction

Lercanidipine may be used concomitantly with beta-adrenoblockers, diuretics, ACE inhibitors.

In concomitant use with metoprolol, the bioavailability of lercanidipine decreases by 50%. This effect may also occur with concomitant use with other beta-adrenoblockers; therefore, adjustment of the dose of lercanidipine may be required to achieve the therapeutic effect with this combination.

Lercanidipine is metabolized with participation of CYP3A4 isoenzyme, therefore inhibitors and inducers of this isoenzyme, when used simultaneously, may affect the metabolism and excretion of lercanidipine. Concomitant use of lercanidipine with CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) is not recommended.

The concomitant use of cyclosporine and lercanidipine is not recommended because an increase in plasma concentrations of both substances is observed.

Precautions should be taken when using lercanidipine concomitantly with other CYP3A4 substrates (terfenadine, astemizole, class III antiarrhythmic drugs such as amiodarone, quinidine).

The bioavailability of lercanidipine at a dose of 20 mg with midazolam may increase by approximately 40% in elderly patients.

Lercanidipine should be used with caution in conjunction with CYP3A4 inducers, e.g., anticonvulsants (phenytoin, carbamazepine) and rifampicin, because the antihypertensive effect of the drug may decrease. Regular BP control is necessary.

. At concomitant use of 20 mg dose of lercanidipine no pharmacokinetic interaction was observed in patients continuously taking beta-methyldigoxin, while in healthy volunteers treated with digoxin there was increase in Cmax value for digoxin by 33% on average after fasting 20 mg of lercanidipine, with little change in AUC and renal clearance. It is necessary to monitor for signs of digoxin intoxication in patients taking digoxin and lercanidipine concomitantly.

The concomitant use of lercanidipine with cimetidine (up to 800 mg) does not cause significant changes in plasma concentrations of lercanidipine. The bioavailability and antihypertensive effect of lercanidipine may be increased with high doses of cimetidine.

When using lercanidipine (20 mg) and simvastatin (40 mg) concomitantly, AUC value for simvastatin increased by 56%, and the same value for its active metabolite – β-hydroxy acid – by 28%. When taking the drugs at different times of the day (lercanidipine in the morning, simvastatin in the evening) unwanted interaction can be avoided.

In concomitant use of lercanidipine 20 mg and warfarin in healthy volunteers no changes in warfarin pharmacokinetics were observed.

Concomitant use with fluoxetine (CYP2D6 and CYP3A4 inhibitor) in elderly patients showed no clinically significant changes in the pharmacokinetics of lercanidipine.

The antihypertensive effect may be enhanced with concomitant administration of grapefruit juice and lercanidipine.

Ethanol may potentiate the antihypertensive effect of lercanidipine.

Special Instructions

Impact on ability to drive vehicles and other mechanisms requiring increased concentration

As therapy with Lercamen® may cause dizziness, asthenia, fatigue, and rarely drowsiness dizziness, asthenia, fatigue and in rare cases drowsiness may occur, during the period of using the drug the patients should be especially careful to drive vehicles and engage in other potentially dangerous activities which require high speed of psychomotor reactions.

Contraindications

Side effects

Possible side effects are listed below in descending frequency of occurrence:

Nervous system disorders: infrequent – headache, dizziness; rarely – drowsiness.

Cardiovascular system: infrequent – palpitations, tachycardia, “rushes” of blood to the face; rarely – angina pectoris, pain behind the chest; very rare – fainting, in patients with angina pectoris may increase the frequency, duration and severity of attacks.

Digestive system disorders: Rarely – nausea, dyspepsia, diarrhea, epigastric pain, vomiting.

Skin and subcutaneous tissue: rarely – skin rash.

Muscular system disorders: rarely – myalgia.

Since the urinary system: rarely – polyuria.

From the immune system: very rarely – hypersensitivity reactions.

From the body in general: frequently – peripheral edema; rarely – asthenia, increased fatigue.

There have been reports of the following adverse very rare ( < 1/10,000) phenomena: myocardial infarction, gum hyperplasia, reversible increase in “hepatic” transaminases activity, marked BP decrease, pollakiuria (increased frequency of urination), chest pain.

Overdose

In case of lercanidipine overdose, symptoms similar to those of other dihydropyridine derivatives will presumably be observed: peripheral vasodilation with marked BP decrease and reflex tachycardia.

Treatment:conducting symptomatic therapy; in case of marked BP decrease, loss of consciousness cardiovascular therapy is indicated, in bradycardia – intravenous injection of atropine.

There have been data on 3 cases of overdose when taking lercanidipine in doses of 150 mg, 280 mg and 800 mg for the purpose of suicide.

Drowsiness has been observed in cases in which 150 mg of lercanidipine + alcohol (unspecified amount) was taken.

Treatment:Gastric lavage, administration of activated charcoal.

In case of administration of 280 mg of lercanidipine + 5.6 mg of moxonidine the following symptoms were observed: cardiogenic shock, severe myocardial ischemia, mild renal failure.

Treatment:cardiac glycosides, diuretics (furosemide), high-dose catecholamines, plasma substitutes. If 800 mg of lercanidipine was taken, nausea and a marked decrease in BP were observed.

Treatment: administration of activated charcoal and laxatives, IV dopamine.

In all overdose cases, all patients survived. There is no information on dialysis efficacy for lercanidipine. It is most likely that due to the high binding of lercanidipine to plasma proteins, dialysis may not be effective.

Pregnancy use

The use of the drug Lercamen® in pregnancy and during breastfeeding, as well as in women of childbearing age in the absence of reliable contraception is contraindicated.

Preclinical studies showed no teratogenic effects of lercanidipine in rats and rabbits, and reproductive function in rats was unchanged.

In the absence of clinical experience with lercanidipine in pregnancy and during breastfeeding, and because other dihydropyridine derivatives are known to have teratogenic effects in animals, lercanidipine is not recommended for use in pregnancy and in women of childbearing age who do not use reliable methods of contraception.

Due to the high lipophilicity of lercanidipine, its penetration into breast milk can be assumed, so the drug is not recommended during breastfeeding.

Similarities