Lecalpin 10 mg film-coated tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Lercanidipine hci
Available from:
Accord Healthcare Ireland Ltd.
ATC code:
C08CA; C08CA13
INN (International Name):
Lercanidipine hci
Dosage:
10 milligram(s)
Pharmaceutical form:
Film-coated tablet
Therapeutic area:
Dihydropyridine derivatives; lercanidipine
Authorization status:
Marketed
Authorization number:
PA2315/186/001
Authorization date:
2009-09-11

PACKAGE LEAFLET

Package leaflet: Information for the user

Lecalpin 10 mg film-coated tablets

Lecalpin 20 mg film-coated tablets

Lercanidipine hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What Lecalpin is and what it is used for

What you need to know before you take Lecalpin

How to take Lecalpin

Possible side effects

How to store Lecalpin

Contents of the pack and other information

1.

What Lecalpin is and what it is used for

Lecalpin belongs to a group of medicines called calcium channel blockers that block the entry of

calcium into the muscle cells of the heart and the blood vessels that carry blood away from the heart

(the arteries). It is the entry of calcium into these cells that causes the heart to contract and arteries to

narrow. By blocking the entry of calcium, calcium channel blockers decrease contraction of the heart

and dilate (widen) the arteries, and the blood pressure is reduced.

Lecalpin has been prescribed to you to treat your high blood pressure, also known as hypertension.

2.

What you need to know before you take Lecalpin

Do not take Lecalpin

if you are allergic to lercanidipine or any of the other ingredients of this medicine ( listed in

section 6).

if you have had allergic reactions to medicines that are closely related to Lecalpin tablets (such

as amlodipine, nicardipine, felodipine, isradipine, nifedipine or lacidipine)

if you are suffering from certain heart diseases:

uncontrolled cardiac failure

an obstruction to flow of blood from the heart

unstable angina (angina at rest or progressively increasing)

if you have had heart attack less than one month ago

if you have severe liver or kidney problems

If you are taking drugs that are inhibitors of CYP3A4 isoenzyme:

antifungal medicines (such as ketoconazole or intraconazole)

macrolide antibiotics (such as erythromycin or troleandomycin)

antivirals (such as ritonavir)

at the same time as another drug called ciclosporin or cyclosporin

with grapefruit or grapefruit juice

if you are pregnant, or if you wish to become pregnant or if you are a woman in child-bearing

age and do not use any contraceptive method

if you are breast-feeding

Warnings and precautions

Talk to your doctor before taking Lecalpin

if you have a heart condition known as sick sinus syndrome, and do not have a pacemaker

if you suffer from chest pain (angina pectoris), Lercandipine may in very rare cases cause

increased frequency of attacks that may last longer and become more severe. Heart attacks have

been reported in isolated cases

if you have problems with your liver or kidney, or you are on dialysis

Other medicines and Lecalpin

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines, including medicines obtained without a prescription.

Taking Lecalpin with certain other medicines (see below), may alter the effect of these medicines or

of Lecalpin.

It is especially important for your doctor to know if you are already being treated with any of the

following medicines:

phenytoin or carbamazepine (medicines for epilepsy)

rifampicin (a medicine to treat tuberculosis)

midazolam (a medicine that helps you sleep)

cimetidine, more than 800 mg (a medicine for ulcers, indigestion, or heartburn)

digoxin (a medicine to treat a heart problem)

terfenadine or astemizole (medicines for allergies)

amiodarone or quinidine (medicines to treat a fast heart beat)

metoprolol (a medicine to treat high blood pressure)

simvastatin (a medicine for high cholesterol value)

Lecalpin with food, drink and alcohol

You must not eat grapefruit or drink grapefruit juice as this may increase the effect of Lecalpin.

If you use alcohol together with Lecalpin you may experience dizziness/fainting, tiredness or

weakness. This is because the medicine may lower your blood pressure considerably together with

alcohol.

Pregnancy and breast-feeding

Ask your doctor for advice before taking any medicine.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor for advice before taking this medicine.

Do not use if you are pregnant, or if you wish to become pregnant or if you are a woman in

childbearing age and do not use any contraceptive method.

Do not use if you are breast-feeding.

Driving and using machines

Lecalpin has a negligible influence on the ability to drive or use machines. However, side effect such

as dizziness, weakness, tiredness and rarely sleepiness may occur. You should be careful until you

know how you react to Lecalpin.

Lecalpin contains lactose monohydrate

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor

before taking this medicine.

3.

How to take Lecalpin

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist

if you are not sure.

The recommended dose is one Lecalpin 10 mg film-coated tablet daily at the same time each day,

preferably in the morning at least 15 minutes before breakfast, because a high fat meal significantly

increases your blood levels of the medicine. Your doctor may decide you to increase your dose to one

Lecalpin 20 mg film-coated tablet daily, if needed.

The tablets should preferably be swallowed whole with 1/2 glass of water. The score line is only there

to help you break the tablet if you have difficulty swallowing it whole.

Use in children and adolescents

Lecalpin is not recommended for use in children and adolescents below 18 years.

If you take more Lecalpin than you should

Immediately contact a doctor, the nearest hospital casualty department or the centre for poison

information for advice.

Exceeding the correct dosage may cause blood pressure to become too low, and the heart to beat

irregularly or faster. It may also lead to unconsciousness.

If you forget to take Lecalpin

If you forget to take your tablet, take it as soon as you remember, unless it is almost time for your next

dose. Then go on as before. Do not take a double dose to make up for a forgotten dose.

If you stop taking Lecalpin

If you stop taking Lecalpin your blood pressure may increase again. Please consult your doctor before

stopping the treatment.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequencies of side effect have been listed below according to the following definitions:

Very common:

may affect more than 1 in 10 people

Common:

may affect up to 1in 10 people

Uncommon:

may affect up to 1 in 100 people

Rare:

may affect up to 1 in 1,000 people

Very rare:

may affect up to1 in 10,000 people

not known:

frequency cannot be estimated from

the available data

Uncommon:

Headache, dizziness, faster heartbeats, awareness of the beating of the heart, flushing

(transient episodic redness of the face and neck), ankle swelling.

Rare:

Sleepiness, weakness, tiredness, nausea, vomiting, diarrhoea, abdominal pain, indigestion, rash,

muscle pain, passage of large amounts of urine, angina pectoris.

Very rare, not known:

Decrease in blood pressure which may lead to fainting, allergic reaction,

swelling of gums, increase in liver enzyme blood test values, fall in blood pressure which can cause

dizziness, light-headedness or fainting, increase in the usual number of times one urinates, chest pain

and heart attack.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via

HPRA Pharmacovigilance

Website: www.hpra.ie.

By reporting side effects you can help provide more information on the safety of this medicine.

5.

How to store Lecalpin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label, carton or bottle after EXP.

The expiry date refers to the last day of that month.

Storage conditions:

Al/PVC/PVDC blister: Do not store above 30°C. Store in the original package to protect from

moisture.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Lecalpin contains

The active substance is lercanidipine hydrochloride.

One 10 mg film-coated tablet contains 10 mg lercanidipine hydrochloride, equivalent to 9.4 mg

lercanidipine.

One 20 mg film-coated tablet contains 20 mg lercanidipine hydrochloride, equivalent to

18.8 mg lercanidipine.

The other ingredients are:

Tablet core:

Magnesium stearate, povidone, sodium starch glycolate (Type A), lactose

monohydrate, microcrystalline cellulose.

Film-coating

10 mg tablets: Macrogol, polyvinyl alcohol (partly hydrolysed), talc, titanium

dioxide (E 171), yellow iron oxide (E 172).

Film-coating

20 mg tablets: Macrogol, polyvinyl alcohol (partly hydrolysed), talc, titanium

dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E172).

What Lecalpin looks like and contents of the pack

Lecalpin 10 mg tablets are yellow colored, round shaped, biconvex, coated tablets debossed with

“LT1” one one side and breakline on the other side. The diameter of the tablet is approximately

6.5mm.

Lecalpin 20 mg tablets are pink colored, round shaped, biconvex, coated tablets debossed with “LT2”

on one side and breakline on the other side. The diameter of tablet is approximately 8.5mm.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Pack sizes:

Blisters ( Al/PVC/PVDC):

Lecalpin 10 mg film-coated tablets: 14, 20, 28, 30, 50, 56, 60, 90, 98, 100 tablets

Lecalpin 20 mg film-coated tablets: 14, 20, 28, 30, 50, 56, 60, 90, 98, 100 tablets

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare Ireland Ltd,

Euro House,

Euro Business Park,

Little Island,

Cork T45 K857,

Ireland

Manufacturer

Accord Healthcare Limited

Sage house, 319 Pinner Road, Harrow, Middlesex,

HA1 4HF, United Kingdom

Accord Healthcare Polska Sp. z o.o.,

Authorization holder address:

ul. Taśmowa 7

Warszawa, Polska,

02-677 Poland

Manufacturing site address:

ul. Lutomierska 50, Pabianice,

95-200, Poland

LABORATORI FUNDACIÓ DAU,

C/ C, 12-14 Pol. Ind. Zona

Franca, Barcelona, 08040,

Spain

Accord-UK Limited,

Whiddon Valley, Barnstaple,

EX32 8NS, United Kingdom

This medicinal product is authorised in the Member States of the EEA under the following

names:

Ireland

Lecalpin 10mg Film-coated Tablets

Lecalpin 20mg Film-coated Tablets

United Kingdom

Lercanidipine hydrochloride 10mg film-coated Tablets

Lercanidipine hydrochloride 20mg film-coated Tablets

This leaflet was last revised in July 2020

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Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Lecalpin 10 mg film-coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One film‑coated tablet contains 10 mg lercanidipine hydrochloride, equivalent to 9.4 mg lercanidipine.

Excipient with known effect:

Lecalpin 10 mg film‑coated tablet: Lactose monohydrate 30 mg

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

Yellow colored, round shaped, biconvex, coated tablets debossed with "LT1" on one side and breakline on the other side. The

diameter of tablet is approximately 6.5mm.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Lecalpin is indicated for the treatment of mild to moderate essential hypertension.

4.2 Posology and method of administration

Posology

Route of administration: For oral use.

The recommended dosage is 10 mg orally once a day at least 15 minutes before meals; the dose may be increased to 20 mg

depending on the individual patient's response.

Dose titration should be gradual, because it may take about 2 weeks before the maximal antihypertensive effect is apparent.

Some individuals, not adequately controlled on a single antihypertensive agent, may benefit from the addition of lercandipine

to therapy with a beta‑adrenoreceptor blocking drug, a diuretic (hydrochlorothiazide) or an angiotensin converting enzyme

inhibitor.

Since the dose‑response curve is steep with a plateau at doses between 20‑30 mg, it is unlikely that efficacy will be improved

by higher doses; whereas side effects may increase.

Elderly

Although the pharmacokinetic data and clinical experience suggest that no adjustment of the daily dosage is required, special

care should be exercised when initiating treatment in the elderly.

Paediatric population

Lercanidipine is not recommended for use in children and adolescents below the age of 18 years as there is no clinical

experience.

Renal or hepatic insufficiency

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Special care should be exercised when treatment is commenced in patients with mild to moderate renal or hepatic dysfunction.

Although the usually recommended dose schedule may be tolerated by these subgroups, an increase in dose to 20 mg daily

must be approached with caution. The antihypertensive effect may be enhanced in patients with hepatic impairment and

consequently an adjustment of the dosage should be considered.

Lercanidipine is not recommended for use in patients with severe hepatic impairment or with severe renal impairment

(creatinine clearance < 30 ml/min).

Method of administration

The tablets should be taken with some water at least 15 minutes before a meal.

4.3 Contraindications

- Hypersensitivity to the active substance, to any dihydropyridine or to any of the excipients listed in section 6.1.

- Left ventricular outflow tract obstruction.

- Untreated congestive cardiac failure.

- Unstable angina pectoris.

- Within 1 month of a myocardial infarction.

- Severe renal or hepatic impairment.

- Co‑administration with:

- strong inhibitors of CYP3A4 (see section 4.5),

- cyclosporin (see section 4.5),

- grapefruit juice (see section 4.5).

- Women of child‑bearing potential unless effective contraception is used.

4.4 Special warnings and precautions for use

Sick sinus syndrome

Special care should be exercised when lercanidipine is used in patients with sick sinus syndrome (if a pacemaker is not in situ).

Although hemodynamic controlled studies revealed no impairment of ventricular function, care is also required in patients with

left ventricular dysfunction. It has been suggested that some short‑acting dihydropyridines may be associated with increased

cardiovascular risk in patients with ischaemic heart disease. Although lercanidipine is long‑acting caution is required in such

patients.

Angina pectoris

Some dihydropyridines may rarely lead to precordial pain or angina pectoris. Very rarely patients with pre‑existing angina

pectoris may experience increased frequency, duration or severity of these attacks. Isolated cases of myocardial infarction may

be observed (see section 4.8).

Use in renal or hepatic dysfunction:

Special care should be exercised when treatment is commenced in patients with mild to moderate renal or hepatic dysfunction.

Although the usually recommended dose schedule may be tolerated by these subgroups, an increase in dose to 20 mg daily

must be approached with caution. The antihypertensive effect may be enhanced in patients with hepatic impairment and

consequently an adjustment of the dosage should be considered.

Lercanidipine is not recommended for use in patients with severe hepatic impairment or in patients with severe renal

impairment (creatinine clearance < 30 ml/min) (see section 4.2).

Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs (see section 4.5).

CYP3A4 inducers

Inducers of CYP3A4 like anticonvulsants (e.g. phenytoin, carbamazepine) and rifampicin may reduce lercanidipine's plasma

levels and therefore the efficacy of lercanidipine may be less than expected (see section 4.5).

This medicinal product contains lactose monohydrate and therefore should not be administered to patients with Lapp lactase

insufficiency, galactosaemia or glucose/galactose malabsorption syndrome.

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4.5 Interaction with other medicinal products and other forms of interactions

Metabolic interactions

Lercanidipine is known to be metabolised by the CYP3A4 enzyme and, therefore, inhibitors and inducers of CYP3A4

administered concurrently may interact with the metabolism and elimination of lercanidipine.

CYP3A4 inhibitors

Co‑administration of lercanidipine with inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, erythromycin,

troleandomycin) should be avoided. An interaction study with a strong CYP3A4 inhibitor, ketoconazole, has shown a

considerable increase in plasma levels of lercanidipine (a 15‑fold increase of the AUC and an 8‑fold increase of the C

the eutomer S‑lercanidipine).

Increased plasma levels of both lercanidipine and ciclosporin have been observed following concomitant administration. A

study in young healthy volunteers has shown that when ciclosporin was administered 3 hours after the lercanidipine intake, the

plasma levels of lercanidipine did not change, while the AUC of ciclosporin increased by 27 %. However, the co‑administration

of lercanidipine with ciclosporin has caused a 3‑fold increase of the plasma levels of lercanidipine and a 21 % increase of the

ciclosporin AUC. Ciclosporin and lercanidipine should not be administered together.

As for other dihydropyridines, lercanidipine is sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in

its systemic availability and increased hypotensive effect. Lercanidipine should not be taken with grapefruit juice.

When concomitantly administered at a dose of 20 mg with midazolam p.o. to elderly volunteers, lercanidipine's absorption was

increased (by approximately 40 %) and the rate of absorption was decreased (t

was delayed from 1.75 to 3 hours).

Midazolam concentrations were not modified.

CYP3A4 inducers

Co‑administration of lercanidipine with CYP3A4 inducers like anticonvulsants (e.g. phenytoin, carbamazepine) and rifampicin

should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored

more frequently than usual.

CYP3A4 substrates

Co‑administration of 20 mg lercanidipine in patients chronically treated with β‑methyldigoxin showed no evidence of

pharmacokinetic interaction. Healthy volunteers treated with digoxin following dosing with 20 mg lercanidipine given fasted

showed a mean increase of 33 % in digoxin C

, while AUC and renal clearance were not significantly modified. Patients on

concomitant digoxin treatment should be closely monitored clinically for signs of digoxin toxicity.

Concomitant administration of cimetidine 800 mg daily does not cause significant modifications in plasma levels of

lercanidipine, but at higher doses caution is required since the bioavailability and the hypotensive effect of lercanidipine may

be increased.

An interaction study with fluoxetine (an inhibitor of CYP2D6 and CYP3A4), conducted in volunteers of an age of 65 ± 7 years

(mean ± s.d.), has shown no clinically relevant modification of the pharmacokinetics of lercanidipine.

The co‑administration of 20 mg lercanidipine to healthy volunteers given fasted did not alter the pharmacokinetics of warfarin.

Caution should be exercised when lercanidipine is co‑prescribed with other substrates of CYP3A4, like terfenadine, astemizole,

class III antiarrhythmic drugs such as amiodarone, quinidine.

Alcohol

Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs.

Other interactions

When lercanidipine was co‑administered with metoprolol, β‑blocker eliminated mainly by the liver, the bioavailability of

metoprolol was not changed while that of lercanidipine was reduced by 50 %. This effect may be due to the reduction in the

hepatic blood flow caused by β‑blockers and may therefore occur with other drugs of this class. Consequently, lercanidipine

may be safely administered with beta‑adrenoceptor blocking drugs, but dose adjustment may be required.

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When a dose of 20 mg of lercanidipine was repeatedly co‑administered with 40 mg of simvastatin, the AUC of lercanidipine

was not significantly modified, while simvastatin's AUC increased by 56 % and that of its active metabolite β‑hydroxyacid by

28 %. It is unlikely that such changes are of clinical relevance. No interaction is expected when lercanidipine is administered in

the morning and simvastatin in the evening, as indicated for such drug.

Lercanidipine has been safely administered with diuretics and ACE inhibitors.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of lercanidipine in pregnant women. Non‑clinical data provide no evidence of a

teratogenic effect in the rat and the rabbit and reproductive performance in the rat was unimpaired. Since other

dihydropyridine compounds have been found teratogenic in animals, lercanidipine should not be administered during

pregnancy or to women with child‑bearing potential unless effective contraception is used.

Breastfeeding

Because of high lipophilicity of lercanidipine, distribution in milk may be expected. Therefore, it should not be administered to

nursing mothers.

4.7 Effects on ability to drive and use machines

Lecalpin has no or negligible influence on the ability to drive and use machines. However, caution should be exercised because

dizziness, asthenia, fatigue and rarely somnolence may occur.

4.8 Undesirable effects

The following undesirable effects have been reported in clinical studies and in the post‑marketing phase:

Assessment of frequencies:

Very common:

≥1/10

Common:

≥ 1/100 to < 1/10

Uncommon:

≥ 1/1,000, to < 1/100

Rare:

≥ 1/10,000 to < 1/1,000

Very rare:

< 1/10,000

not known (cannot be estimated from

the available data)

System organ class

Adverse drug

reactions

Immune system

disorders

Very rare

Hypersensitivity

Psychiatric

disorders

Rare

Somnolence

Nervous system

disorders

Uncommon

Headache,

dizziness

Cardiac

disorders

Uncommon

Tachycardia,

palpitations,

peripheral

oedema

Rare:

angina pectoris

Very rare

Chest pain,

myocardial

infarction,

hypotension

Some dihydropyridines may rarely lead to precordial pain or angina pectoris. Very rarely patients with

pre‑existing angina pectoris may experience increased frequency, duration or severity of these attacks.

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Vascular

disorders

Uncommon

Flushing

Gastrointestinal

disorders

Rare

Dyspepsia,

diarrhoea,

abdominal pain,

vomiting

Very rare

gingival

hypertrophy

Skin and

subcutaneous

tissue disorders

Rare

Rash

Musculoskeletal

and connective

tissue disorders

Rare

Myalgia

Renal and

urinary

disorders

Rare

Polyuria

Very rare

Urinary

frequency

General

disorders and

administration

site conditions

Rare

Asthenia,

fatigue

Investigations

Very rare

Reversible

increases in

serum levels of

hepatic

transaminases

Lercanidipine does not appear to influence adversely blood sugar or serum lipid levels.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected

adverse reactions via the national reporting system:

HPRA Pharmacovigilance

Website: www.hpra.ie

4.9 Overdose

In the post‑marketing experience, three cases of overdose were reported (150 mg, 280 mg and 800 mg of lercanidipine,

respectively, ingested in an attempt to commit suicide).

Dose level

Signs/Symptoms

Management

Outcome

150 mg

+ undefined amount of alcohol

Sleepiness

Gastric lavage

Active charcoal

Recovered

280 mg

5.6 mg moxonidine

Cardiogenic shock

Severe myocardial ischaemia

Mild renal failure

High‑dose catecholamines

Furosemide

Digitalis

Parenteral plasma expanders

Recovered

800 mg

Emesis

Hypotention

Active charcoal

Cathartics

Dopamine i.v.

Recovered

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Overdosage might be expected to cause excessive peripheral vasodilatation with marked hypotension and reflex tachycardia. In

case of severe hypotension, bradycardia and unconsciousness, cardiovascular support could be helpful, with intravenous

atropine for bradycardia.

In view of the prolonged pharmacological effect of lercanidipine, it is essential that the cardiovascular status of patients who

take an overdose is monitored for 24 hours at least. There is no information on the value of dialysis. Since the active substance

is highly lipophilic, it is most probable that plasma levels are no guide to the duration of the period of risk and dialysis may not

be effective.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Selective calcium channel blockers with mainly vascular effects, ATC code: C08CA13

Lercanidipine is a calcium antagonist of the dihydropyridine group and inhibits the transmembrane influx of calcium into

cardiac and smooth muscle. The mechanism of its antihypertensive action is due to a direct relaxant effect on vascular smooth

muscle thus lowering total peripheral resistance. Despite its short pharmacokinetic plasma half‑life, lercanidipine is endowed

with a prolonged antihypertensive activity because of its high membrane partition coefficient, and is devoid of negative

inotropic effects due to its high vascular selectivity.

Since the vasodilatation induced by lercanidipine is gradual in onset, acute hypotension with reflex tachycardia has rarely been

observed in hypertensive patients.

As for other asymmetric 1,4‑dihydropyridines, the antihypertensive activity of lercanidipine is mainly due to its (S)‑enantiomer.

In addition to the clinical studies conducted to support the therapeutic indications, a further small uncontrolled but

randomised study of patients with severe hypertension (mean ± SD diastolic blood pressure of 114.5 ± 3.7 mmHg) showed

that blood pressure was normalised in 40 % of the 25 patients on 20 mg once daily dose and in 56 % of 25 patients on 10 mg

twice daily doses of lercanidipine. In a double‑blind, randomized, controlled study versus placebo in patients with isolated

systolic hypertension lercanidipine was efficacious in lowering systolic blood pressure from mean initial values of 172.6 ±

5.6 mmHg to 140.2 ± 8.7 mmHg.

5.2 Pharmacokinetic properties

Absorption

Lercanidipine is completely absorbed after 10‑20 mg oral administration and peak plasma levels, 3.30 ng/ml ± 2.09 s.d. and

7.66 ng/ml ± 5.90 s.d. respectively, occur about 1.5‑3 hours after dosing.

The two enantiomers of lercanidipine show a similar plasma level profile: the time to peak plasma concentration is the same,

the peak plasma concentration and AUC are, on average, 1.2‑fold higher for the (S) enantiomer and the elimination half‑lives

of the two enantiomers are essentially the same. No in vivo interconversion of enantiomers is observed.

Due to the high first pass metabolism, the absolute bioavailability of lercanidipine orally administered to patients under fed

conditions is around 10 %, although it is reduced to 1/3 when administered to healthy volunteers under fasting conditions.

Oral administration of lercanidipine leads to plasma levels of lercanidipine not directly proportional to dosage (non‑linear

kinetics). After 10, 20 or 40 mg, peak plasma concentrations observed were in the ratio 1:3:8 and areas under plasma

concentration‑time curves in the ratio 1:4:18, suggesting a progressive saturation of first pass metabolism. Accordingly,

availability increases with dosage elevation.

Oral availability of lercanidipine increases 4‑fold when lercanidipine is ingested up to 2 hours after a high fat meal. Accordingly,

lercanidipine should be taken before meals.

Distribution

Distribution from plasma to tissues and organs is rapid and extensive.

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The degree of serum protein binding of lercanidipine exceeds 98 %. Since plasma protein levels are reduced in patients with

severe renal or hepatic dysfunction, the free fraction of the drug may be increased.

Biotransformation

Lercanidipine is extensively metabolised by CYP3A4; no parent drug is found in the urine or the faeces. It is predominantly

converted to inactive metabolites and about 50 % of the dose is excreted in the urine.

In vitro‑experiments with human liver microsomes have demonstrated that lercanidipine shows some degree of inhibition of

CYP3A4 and CYP2D6, at concentrations 160- and 40‑fold, respectively, higher than those reached at peak in the plasma after

the dose of 20 mg.

Moreover, interaction studies in humans have shown that lercanidipine did not modify the plasma levels of midazolam, a

typical substrate of CYP3A4, or of metoprolol, a typical substrate of CYP2D6. Therefore, inhibition of biotransformation of

drugs metabolised by CYP3A4 and CYP2D6 by lercanidipine is not expected at therapeutic doses.

Elimination

Elimination occurs essentially by biotransformation. A mean terminal elimination half life of 8‑10 hours was calculated and the

therapeutical activity lasts for 24 hours because of its high binding to lipid membrane. No accumulation was seen upon

repeated administration.

Elderly, renal and hepatic insufficiency

In elderly patients and in patients with mild to moderate renal dysfunction or mild to moderate hepatic impairment the

pharmacokinetic behaviour of lercanidipine was shown to be similar to that observed in the general patient population;

patients with severe renal dysfunction or dialysis‑dependent patients showed higher levels (about 70 %) of the drug. In

patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely to be increased since

the drug is normally metabolised extensively in the liver.

5.3 Preclinical safety data

Safety pharmacological studies in animals have shown no effects on the autonomic nervous system, the central nervous system

or on gastrointestinal function at antihypertensive doses.

The relevant effects which have been observed in long‑term studies in rats and dogs were related, directly or indirectly, to the

known effects of high doses of Ca‑antagonists, predominantly reflecting exaggerated pharmacodynamic activity.

Lercanidipine was not genotoxic and showed no evidence of carcinogenic hazard.

Fertility and general reproductive performance in rats were unaffected by treatment with lercanidipine.

There was no evidence of any teratogenic effect in rats and rabbits; however, in rats, lercanidipine at high dose levels induced

pre- and post- implantation losses and delay in foetal development.

Lercanidipine hydrochloride, when administered at high dose (12 mg/kg/day) during labour, induced dystocia.

The distribution of lercanidipine and/or its metabolites in pregnant animals and their excretion in breast milk have not been

investigated.

Metabolites have not been evaluated separately in toxicity studies.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

Magnesium stearate

Povidone

Sodium starch glycolate Type A

Health Products Regulatory Authority

28 August 2020

CRN009V8H

Page 8 of 8

Lactose monohydrate

Cellulose, microcrystalline

Film-coating:

Macrogol

Polyvinyl alcohol, partly hydrolysed

Talc

Titanium dioxide (E 171)

Yellow iron oxide (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Blister Pack

3 years

6.4 Special precautions for storage

Al/PVC/PVDC blister: Do not store above 30°C. Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

Blister pack (Aluminium/ PVDC) with push-through foil.

Pack sizes:

Blisters ( Al/PVC/PVDC):

Lecalpin 10 mg film-coated tablets: 14, 20, 28, 30, 50, 56, 60, 90, 98, 100 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Accord Healthcare Ireland Ltd.

Euro House

Euro Business Park

Little Island

Cork T45 K857

Ireland

8 MARKETING AUTHORISATION NUMBER

PA2315/186/001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 11

September 2009

Date of last renewal: 2

July 2014

10 DATE OF REVISION OF THE TEXT

August 2020

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