LerkaNAN

lercanidipine

Coated tablets

Round biconvex tablets with orange yellow coating.

Each tablet contains:
Active substance: 10 mg of lercanidipine hydrochloride (corresponds to 9.4 mg of lercanidipine);
Auxiliary substances: lactose monohydrate, crospovidone, magnesium stearate, microcrystalline cellulose;
Coating composition: polyvinyl alcohol, titanium dioxide (E171), polyethylene glycol (macrogol), talc, iron oxide yellow (E172), Sunset yellow dye (E110), iron oxide black (E172).

Selective calcium channel blockers with mainly vascular effects. Dihydropyridine derivatives.

C08CA13

Lercanidipine is a dihydropyridine calcium antagonist which inhibits calcium transmembrane current into heart and smooth muscle cells. Its antihypertensive action mechanism is subject to direct relaxing effect on smooth muscles of vessels, thereby reducing the total peripheral vascular resistance. Despite its short pharmacokinetic plasma elimination half-life, lercanidipine has a prolonged antihypertensive effect due to a high membrane distribution coefficient, and it does not have a negative inotropic effect due to high vascular selectivity.

Due to gradual development of vasodilation after initiation of lercanidipine treatment, acute hypotension with reflex tachycardia is noted once in a way in patients with arterial hypertension.

Like other asymmetric 1,4-dihydropyridines, lercanidipine antihypertensive effect is mainly due to its (S)-enantiomer.

Treatment of mild and moderate essential hypertension in adults.

The recommended dose for oral administration is 10 mg once a day at least 15 minutes before meals; the dose can be increased up to 20 mg depending on the achieved therapeutic effect of the patient.

Select the therapeutic dose gradually since the maximum antihypertensive effect develops within two weeks of treatment.
If the antihypertensive agent is ineffective alone, rather a favorable effect is possible when administrating LerkaNAN in combination with beta-blockers (atenolol), diuretics (hydrochlorothiazide) or ACE inhibitors (captopril, enalapril).
Since the dose-response curve is steep and has a plateau at doses of 20-30 mg, it is unlikely that the effectiveness of the medication will increase with dose escalation, but at the same time the severity of side effects may increase.

Special population

Elderly patients
Although pharmacokinetic data and clinical experience indicate that no correction is required when choosing a daily dose, special care should be taken when initiating the treatment.

Pediatric use
Administration of LerkaNAN in children and adolescents is currently not recommended, since there is no experience of this medicinal product administration in patients under 18 years of age.

Administration in patients with renal or hepatic insufficiency
Special care should be taken when initiating treatment of patients with mild to moderate kidney or liver function disorder. Normally, this subgroup of patients can smoothly tolerate the recommended dosage regimen, but one should be careful when increasing the dose to 20 mg/day. Antihypertensive effect of the medication may increase in hepatically impaired patients; therefore, dose adjustment may be required.

LerkaNAN is not recommended for use in patients with severe hepatic impairment or with severe renal impairment (glomerular filtration rate < 30 ml/min).

Administration method
Observe precautions before using the medication:

• it is recommended to take the medication in the morning, at least 15 minutes before breakfast.

Do not take the medication in conjunction with grapefruit juice (see Sections Contra Indications and Interaction with other medications).

Approximately 1.8% of patients taking lercanidipine had concurrent reactions. The most common concurrent reactions reported in the course of controlled clinical trials were headache, dizziness, peripheral edema, tachycardia, palpitations and fluxion, while they occurred in less than 1% of patients.

Side effects incidence rate classification: very often (≥ 1/10), often (≥ 1/100, but < 1/10), infrequently (≥ 1/1000, but < 1/100), rarely (≥ 1/10000, but < 1/1000), very rarely (< 1/10000), frequency is unknown (cannot be estimated based on available data).

Immune system disorders: very rarely – hypersensitivity.

Mental disorders: rarely – drowsiness.

Nervous system disorders: Infrequently – headache, dizziness.

Cardiac disorders: infrequently – tachycardia, palpitations; rarely – angina pectoris.

Vascular disorders: infrequently – fluxion, fainting.

Gastrointestinal disorders: rarely – nausea, dyspepsia, diarrhea, abdominal pain, vomiting.

Skin and subcutaneous tissue disorders: rarely – rash.

Musculoskeletal and connective tissue disorders: rarely – myalgia.

Renal and urinary disorders: rarely – polyuria.

General disorders and disorders at the injection site: infrequently – peripheral edema, rarely – asthenia, increased fatigue.

In the course of post-marketing studies, the following undesirable effects have been reported in very rare cases: gum hypertrophy, reversible concentration increase liver transaminases in blood serum, hypotension, frequent urination and chest pain.

In rare cases some dihydropyridines can lead to heart pain or angina pectoris. Patients suffering from angina pectoris very rarely may experience increase in frequency, duration or severity of strokes. In some cases, myocardial infarction may occur.

Lercanidipine does not significantly affect the level of glucose and lipids in blood plasma.

In case of adverse reactions, including those not specified in the instruction for medical use, consult a doctor.

• hypersensitivity to lercanidipine and to any dihydropyridine or to any other component of the medicinal product,
• pregnancy and breast-feeding,
• women of reproductive age if they do not use reliable contraception,
• children and adolescents under 18 years of age (safety and administration efficiency in children under 18 years of age is not established),
• obstruction of left ventricular outflow tract,
• untreated congestive cardiac failure,
• unstable angina pectoris,
• serious kidney or liver function abnormality,
• a period of 1 month after myocardial infarction,
• simultaneous use with:
  • strong CYP3A4 inhibitors,
  • cyclosporine,
  • grapefruit juice.

If taking a larger dose than prescribed by your doctor, immediately contact specialists to provide timely medical care!

Three cases of overdose were reported (150, 280 and 800 mg of lercanidipine respectively, were taken in a suicide attempt).

Like administration of other dihydropyridines, one expects that an overdose will declare itself by excessive peripheral vasodilation with evident hypotension and reflex tachycardia. In case of severe hypotension, bradycardia and loss of consciousness, cardiovascular support with intravenous administration of atropine may be required.

Taking into account the prolonged pharmacological action of lercanidipine in case of overdose we need to monitor the cardiovascular status of such patients for at least 24 hours. There is no information on dialysis efficiency evaluation. Since the active substance is highly lipophilic, most likely its plasma concentration is not a parameter reflecting the duration of the risk period, so dialysis may be ineffective.

Do not take a double dose to compensate for skipping LerkaNAN intake. Take your usual dose of the medication immediately and continue taking it the next day as prescribed.

It is not recommended to change the prescribed dose or stop taking LerkaNAN without consulting your doctor. If you think that the effect of the medication is too weak or too strong, inform your doctor or pharmacist.

If you have any further questions about administration of this medication, consult your doctor or pharmacist/

It is known that lercanidipine is metabolized under the influence of CYP3A4 enzyme and therefore inhibitors and inducers of CYP3A4 taken in combination with lercanidipine can affect the process of its metabolism and elimination.

Avoid simultaneous administration of LerkaNAN in combination with such CYP3A4 inhibitors as ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin. The study on interaction with ketoconazole, a strong CYP3A4 inhibitor, showed that as a result of this interaction concentration of lercanidipine in plasma increased significantly (AUC value increased 15-fold and C_max value for S-lercanidipine eutomer increased 8-fold).

It is not recommended to take cyclosporine in combination with lercanidipine. Both for lercanidipine and cyclosporine an increase in plasma concentration was observed as a result of their combined use. A study with participation of young healthy volunteers showed that if cyclosporine was taken 3 hours after taking lercanidipine concentration of lercanidipine in plasma did not change, while AUC value for cyclosporine increased by 27%. However, the combined administration of lercanidipine in combination with cyclosporine causes 3-fold increase in lercanidipine concentration in plasma and AUC value increase for cyclosporine by 21%.

It is not recommended to take lercanidipine with grapefruit juice. Like other dihydropyridines lercanidipine shows particular sensitivity to inhibition of metabolism by grapefruit juice and as a result its systemic bioavailability increases as well as hypotensive effect.

With simultaneous oral administration of lercanidipine by elderly volunteers at a dose of 20 mg in combination with midazolam, lercanidipine absorption increased (by approximately 40%) and the rate of absorption decreased (t_max slowed down to 3 hours instead of 1.75 hours). Concentrations of midazolam did not change.

Be careful when using lercanidipine in combination with other CYP3A4 substrates, such as terfenadine and astemizole as well as Class III antiarrhythmic agents, such as amiodarone and quinidine.

Care should be taken when prescribing simultaneous administration of lercanidipine in combination with inducers of CYP3A4, such as anticonvulsants (e.g., phenytoin, carbamazepine) and rifampicin, since its antihypertensive effect may decrease. Blood pressure should be monitored more often than usual.

In case of simultaneous administration of lercanidipine in combination with metoprolol, a beta-blocker which eliminates mainly through the liver, metoprolol bioavailability did not change while lercanidipine bioavailability decreased by 50%. This effect takes place probably due to a decrease in hepatic blood flow caused by beta-blockers, and therefore may also occur when using other medications of this class. So lercanidipine can be safely prescribed with beta-adrenergic blockers, therefore, dose adjustment may be required.

The study on interaction with fluoxetine (CYP2D6 and CYP3A4 inhibitor) conducted on volunteers aged 65 ± 7 years showed no clinically significant changes in lercanidipine pharmacokinetics.

Simultaneous use of cimetidine at a dose of 800 mg per day does not cause significant changes in lercanidipine concentration in plasma, but be careful at higher doses since lercanidipine bioavailability and its hypotensive effect may increase.

Simultaneous prescription of lercanidipine at a dose of 20 mg to patients who have been taking beta-methyldigoxin for a long time showed no pharmacokinetic interaction. Healthy volunteers taking digoxin and lercanidipine at a dose of 20 mg on an empty stomach showed an increase in digoxin C_max value by an average of 33% without significant changes in AUC and renal clearance. Patients taking digoxin and lercanidipine simultaneously require careful clinical monitoring regarding possible signs of digoxin toxicity.

When lercanidipine was taken repeatedly at a dose of 20 mg in combination with 40 mg of simvastatin, AUC value for lercanidipine changed slightly while AUC value for simvastatin increased by 56% and the same indicator for its active β-hydroxyacid metabolite increased by 28%. It is unlikely that such changes are clinically significant. You cannot expect interactions if lercanidipine is taken in the morning and simvastatin is taken in the evening, as shown for such a medicinal product.

When healthy volunteers took warfarin in combination with 20 mg of lercanidipine on an empty stomach, no changes in warafin pharmacokinetics were observed.

Lercanidipine was safely prescribed in combination with diuretics and with angiotensin converting enzyme inhibitors.

Avoid drinking alcohol as it can potentiate the effect of vasodilatory antihypertensive medications.

Inform your doctor about all medications you are taking. Consult your doctor before you start taking any medication during treatment with LerkaNAN medicinal product.

Sick sinus syndrome
Patients with sick sinus syndrome should be especially careful when taking lercanidipine (if a pacemaker is not implanted).

Left ventricular dysfunction and ischemic heart disease
Despite the fact that hemodynamic studies have not revealed any deterioration in ventricular function, be careful when using the medicinal product in patients with left ventricular dysfunction. Some short-acting dihydropyridine derivatives may increase the risk of cardiovascular complications in patients with ischemic heart disease. Although lercanidipine has a prolonged effect you should tread carefully in such patients.

In rare cases, dihydropyridine derivatives can lead to cardialgia or angina attacks. Patients suffering from angina pectoris very rarely may experience increase in frequency, duration and severity of strokes. In some cases, myocardial infarction may occur (See Section Precautions).

Kidney or liver function abnormality
Take special care when initiating treatment of patients with mild to moderate kidney or liver function disorder. Although this subgroup of patients can smoothly tolerate the recommended dosage regimen, be careful when increasing the dose to 20 mg/day. Antihypertensive effect of the medication may increase in hepatically impaired patients; therefore, dose adjustment may be required.

LerkaNAN is not recommended for use in patients with severe hepatic impairment or with severe renal impairment (glomerular filtration rate < 30 ml/min).

Alcohol
Avoid drinking alcohol as it can potentiate the effect of vasodilatory antihypertensive medications.

Inducers of CYP3A4
Inducers of CYP3A4 such as anticonvulsants (e.g., phenytoin, carbamazepine) and rifampicin, can reduce concentration of lercanidipine in plasma, therefore lercanidipine therapeutic efficacy may be lower than expected.

Auxiliary substances
The medicinal product contains lactose, so do not use it in patients with such rare hereditary diseases as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

The tablet coating includes Sunset yellow FCF (E110) which can cause allergic reactions.

If you have one of the diseases or conditions listed above, consult your healthcare provider before taking the medicinal product.

Pregnancy
During animal studies (rats and rabbits) lercanidipine teratogenic effect was not proven and reproductive ability in rats was not impaired. However, since there is no clinical experience of lercanidipine administration in pregnant and breastfeeding women, and teratogenic effects in other dihydropyridine derivatives were detected during experimental animal studies, administration of LerkaNAN is contraindicated in pregnant women as well as in women of childbearing age who do not use reliable contraception.

Breast-feeding
Lercanidipine may exude with breast milk due to its high lipophilicity. In this regard it is not recommended to use lercanidipine during breast-feeding.

Fertility (ability to conceive)
Clinical data is not available. In some patients who take calcium channel blockers reversible biochemical changes in spermatozoid heads have been noted which can negatively affect fecundating ability.

Whenever repetitive in vitro fertilization was unsuccessful and there were no other possible explanations for this, taking calcium channel blockers should be considered as the reason.

LerkaNAN has little effect on ability to drive or use machines. However, care should be taken given the risk of dizziness, weakness, fatigue, and drowsiness (in rare cases).

Coated tablets, 10 mg.
15 or 25 tablets in a blister made of a light-tight double-layer film (PVC/PVDH) and aluminum foil. One or two blisters No.25 or two blisters No.15 together with a patient information leaflet in a carton pack.

Protect from light and moisture, at a temperature not above 25°C. Keep away from children.

2 years. Do not use after the expiration date.

State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus,
Phone / Fax +375 17 268-63-64
production@academpharm.by
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en