Sakure^® (Tablets) Instructions for Use

Marketing Authorization Holder

FP Obolenskoe, JSC (Russia)

ATC Code

C08CA09 (Lacidipine)

Active Substance

Lacidipine (Rec.INN registered by WHO)

Dosage Forms

	Sakure^®	Film-coated tablets, 2 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42 or 56 pcs.
		Film-coated tablets, 4 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42 or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets, white or almost white, round, biconvex in shape; the inner layer is white or almost white on the cross-section.

	1 tab.
Lacidipine	2 mg

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, potato starch, copovidone, talc, magnesium stearate.

Shell composition: hypromellose (hydroxypropyl methylcellulose), macrogol 6000 (polyethylene glycol 6000), titanium dioxide, talc.

7 pcs. – blisters (1) – carton packs.
7 pcs. – blisters (2) – carton packs.
7 pcs. – blisters (3) – carton packs.
7 pcs. – blisters (4) – carton packs.
10 pcs. – blisters (1) – carton packs.
10 pcs. – blisters (2) – carton packs.
10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (4) – carton packs.
14 pcs. – blisters (1) – carton packs.
14 pcs. – blisters (2) – carton packs.
14 pcs. – blisters (3) – carton packs.
14 pcs. – blisters (4) – carton packs.

Film-coated tablets, white or almost white, round, biconvex in shape; the inner layer is white or almost white on the cross-section.

	1 tab.
Lacidipine	4 mg

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, potato starch, copovidone, talc, magnesium stearate.

Shell composition: hypromellose (hydroxypropyl methylcellulose), macrogol 6000 (polyethylene glycol 6000), titanium dioxide, talc.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

Lacidipine is a slow calcium channel blocker from the dihydropyridine derivatives group.

It reduces the entry of calcium through voltage-dependent calcium channels (mainly L-type) into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries; in high doses, it reduces the release of calcium from intracellular stores.

It uncouples the processes of excitation and contraction in the myocardium and vascular smooth muscles, mediated by tropomyosin, troponin, and calmodulin.

In therapeutic doses, it normalizes the transmembrane calcium current, does not affect venous tone, the sinoatrial and atrioventricular nodes, does not have a negative inotropic effect, and causes dilation of peripheral arterioles and a decrease in total peripheral vascular resistance.

Lacidipine dilates peripheral arterioles, reduces total peripheral vascular resistance, and lowers blood pressure. It has an antiatherogenic effect.

When using lacidipine at a dose of 4 mg, minimal prolongation of the QT interval is observed.

In kidney transplant patients taking cyclosporine, Lacidipine eliminates the cyclosporine-induced decrease in renal blood flow and glomerular filtration rate.

Lacidipine does not affect the automaticity of the sinoatrial node and does not slow down the conduction of excitation through the atrioventricular node.

There is no data indicating that Lacidipine impairs glucose tolerance or reduces the effectiveness of hypoglycemic therapy.

Pharmacokinetics

Absorption

After oral administration, Lacidipine is rapidly but minimally absorbed from the gastrointestinal tract and undergoes intensive metabolism during the “first pass” through the liver. The absolute bioavailability of lacidipine is approximately 10%.

The maximum concentration of lacidipine in blood plasma is reached in 30-150 minutes. Lacidipine has a very high (more than 95%) ability to bind to blood plasma proteins (albumin and α1-acid glycoprotein).

Metabolism

Lacidipine is metabolized mainly in the liver to form four main metabolites with minor pharmacological activity.

Liver metabolism occurs with the participation of the CYP3A4 isoenzyme. There is no data confirming the ability of lacidipine to induce or inhibit cytochrome P450 isoenzymes.

Excretion

Approximately 70% of the orally administered dose of lacidipine is excreted as metabolites through the intestines, and the remaining part of the dose is excreted as metabolites through the kidneys.

At steady-state concentration, the T_1/2 of lacidipine varies from 13 to 19 hours.

Indications

Arterial hypertension.

Lacidipine is used as monotherapy or in combination with other antihypertensive drugs, for example, beta-blockers, diuretics, or ACE inhibitors (angiotensin-converting enzyme).

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
I10	Essential [primary] hypertension

ICD-11 code	Indication
BA00.Z	Essential hypertension, unspecified

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Orally, preferably in the morning, regardless of meal time. The initial dose is 2 mg once a day.

When treating arterial hypertension, it is necessary to focus on the severity of the disease and the individual patient’s response to treatment.

If necessary, the dose can be increased to 4 mg per day and even to 6 mg per day after the time required to achieve a therapeutic effect.

Usually, in clinical practice, this period is at least 3-4 weeks, unless the patient’s condition requires a faster dose increase.

In elderly patients, patients with impaired renal and liver function, dose adjustment of the drug is not required.

Adverse Reactions

Some patients may experience mild side effects associated with peripheral vasodilation.

The most common side effects are headache, dizziness, facial flushing, and palpitations.

They are usually transient and, as a rule, disappeared during further therapy while continuing the use of lacidipine at the recommended dose.

Rare side effects include asthenia, skin rashes (including erythema and itching), functional stomach disorders, nausea, polyuria, and gingival hyperplasia.

Like other dihydropyridine drugs, in a small number of patients, the drug causes an exacerbation of angina, usually at the beginning of treatment.

This side effect is most likely in patients with clinically significant coronary heart disease.

The drug does not cause significant changes in blood and biochemical parameters.

In very rare cases, a reversible increase in the level of alkaline phosphatase in the blood plasma is observed.

Nervous system disorders: headache, dizziness, tremor, depression, mood lability.

Cardiovascular system disorders: palpitations, tachycardia, facial flushing, worsening of concomitant angina (detected in a small number of patients usually at the beginning of treatment, more likely in patients with clinically significant coronary heart disease), syncope, pronounced decrease in blood pressure.

Gastrointestinal disorders: stomach discomfort, nausea, constipation, hypertrophic gingivitis.

Skin and subcutaneous tissue disorders: allergic reactions, skin rash (including erythema and itching), angioedema, urticaria.

Renal and urinary tract disorders: polyuria.

Effect on laboratory and instrumental test results: reversible increase in alkaline phosphatase activity.

General disorders: asthenia, peripheral edema, weakness.

If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Contraindications

Hypersensitivity to lacidipine, other dihydropyridine derivatives, and other components of the drug;
Severe aortic stenosis;
Acute myocardial infarction (within 1 month after an acute myocardial infarction);
Congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (the drug contains lactose);
Pregnancy, lactation period;
Age under 18 years (efficacy and safety have not been established).

With caution

In patients with intracardiac conduction disorders, with low cardiac output, with unstable angina, with congenital and acquired (documented) QT interval prolongation, with simultaneous use of drugs that can cause QT interval prolongation, such as class I and III antiarrhythmic drugs, tricyclic antidepressants, some antipsychotics, antibiotics (for example, erythromycin) and some H1-histamine receptor blockers (for example, terfenadine).

Caution should be exercised when using lacidipine in patients with impaired liver function, including patients with hepatic insufficiency (10 points or more on the Child-Pugh scale), since the antihypertensive effect of the drug may be more pronounced in them.

Considering the possibility of slow calcium channel blockers to affect the function of the sinoatrial and atrioventricular nodes, Lacidipine should be used with caution in patients with concomitant conduction disorders.

Use in Pregnancy and Lactation

The use of the drug during pregnancy and breastfeeding is not recommended. If it is necessary to use the drug during breastfeeding, breastfeeding should be discontinued.

Use in Hepatic Impairment

Patients with impaired liver function should exercise caution.

Use in Renal Impairment

In patients with impaired renal function, dose adjustment is not required.

Pediatric Use

The drug is contraindicated in children under 18 years of age (efficacy and safety have not been established).

Geriatric Use

In elderly patients, dose adjustment is not required.

Special Precautions

During treatment, caution should be exercised when engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

During treatment, standard measures should be taken to control the functional activity of the myocardium and blood pressure.

If angina attacks appear or if angina worsens after starting therapy with Sakure^®, as well as in case of severe arterial hypotension, the drug should be discontinued.

Effect on the ability to drive vehicles and mechanisms

It causes dizziness, therefore, caution should be exercised when driving vehicles or moving mechanisms.

Overdose

Symptoms: pronounced decrease in blood pressure, tachycardia (associated with prolonged peripheral vasodilation), impaired sinoatrial and atrioventricular conduction, bradycardia, confusion, stupor, nausea, vomiting, metabolic acidosis, hyperglycemia.

Most likely, an overdose of lacidipine may manifest with symptoms of prolonged vasodilation: arterial hypotension and tachycardia.

Treatment: symptomatic (there is no specific antidote).

Drug Interactions

Combined use of lacidipine and other antihypertensive drugs, for example, diuretics, β-blockers or ACE inhibitors, is possible.

No interactions of lacidipine with digoxin, tolbutamide, and warfarin have been identified. The concentration of lacidipine in blood plasma may increase with simultaneous use of cimetidine.

Grapefruit juice reduces the metabolism and bioavailability of lacidipine, as well as other dihydropyridine drugs. Lacidipine should not be taken with grapefruit juice.

Since Lacidipine is metabolized by the CYP3A4 isoenzyme, inducers and inhibitors of this isoenzyme may affect the metabolism and excretion of lacidipine. The antihypertensive effect of lacidipine is weakened by NSAIDs (sodium retention and blockade of prostaglandin synthesis by the kidneys) and estrogens (sodium retention).

In patients taking cyclosporine, Lacidipine eliminates the cyclosporine-induced decrease in renal blood flow and glomerular filtration rate.

Concomitant use of lacidipine with corticosteroids and tetracosactide may reduce the antihypertensive effect of the drug.

Storage Conditions

In a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer