Lisoril^® (Tablets) Instructions for Use

Marketing Authorization Holder

Ipca Laboratories Ltd. (India)

ATC Code

C09AA03 (Lisinopril)

Active Substance

Lisinopril (Rec.INN registered by WHO)

Dosage Forms

	Lisoril®	Tablets 5 mg: 28 or 30 pcs.
		Tablets 10 mg: 28 or 30 pcs.
		Tablets 20 mg: 28 or 30 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (3) – cardboard packs.
14 pcs. – blister packs (2) – cardboard packs.

Excipients: starch, mannitol, dicalcium phosphate dihydrate, magnesium stearate, red iron oxide dye.

10 pcs. – blisters (3) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.

Excipients: starch, mannitol, dicalcium phosphate dihydrate, magnesium stearate, red iron oxide dye.

10 pcs. – blister packs (3) – cardboard packs.
14 pcs. – blister packs (2) – cardboard packs.

Excipients: starch, mannitol, dicalcium phosphate dihydrate, magnesium stearate, red iron oxide dye.

10 pcs. – blister packs (3) – cardboard packs.
14 pcs. – blister packs (2) – cardboard packs.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE blocker

Pharmacological Action

ACE inhibitor. Suppresses the formation of angiotensin II from angiotensin I. Reducing the content of angiotensin II leads to a direct decrease in aldosterone secretion. Reduces the degradation of bradykinin and increases the synthesis of prostaglandin. Reduces total peripheral vascular resistance, blood pressure, preload, pulmonary capillary pressure, causes an increase in cardiac output and an increase in myocardial tolerance to stress in patients with heart failure. Dilates arteries to a greater extent than veins. Some effects are explained by the impact on tissue renin-angiotensin systems. With long-term use, it reduces hypertrophy of the myocardium and walls of resistive arteries. Improves blood supply to the ischemic myocardium. ACE inhibitors prolong the life expectancy of patients with heart failure and slow the progression of left ventricular dysfunction in patients who have had a myocardial infarction without clinical manifestations of heart failure.

The onset of action is within 1 hour. The maximum effect is determined after 6-7 hours, duration is 24 hours. In arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months.

Pharmacokinetics

The bioavailability of the drug is 25-50%, weakly binds to plasma proteins. C_max in blood serum is reached after 7 hours. Food intake does not affect absorption.

Permeability through the BBB and placental barrier is low.

Lisoril^® is not metabolized and is excreted unchanged in the urine. The main part is excreted during the initial phase (effective T_1/2 – 12 hours), followed by a terminal distant phase (T_1/2 about 30 hours).

Indications

• Arterial hypertension (as monotherapy or in combination with other antihypertensive agents);
• Chronic heart failure (as part of combination therapy for the treatment of patients taking digitalis preparations and/or diuretics).

ICD codes

Dosage Regimen

Take orally before, during, or after meals.

Arterial hypertension

The initial dose of Lisoril^® is 5 mg once/day. The dose is adjusted according to changes in blood pressure. The usual dose is 10 mg/day in a single dose. If there is no adequate response, the dose can be increased to 20-40 mg/day. The maximum daily dose is 80 mg. For patients taking diuretics, the dose is selected individually.

In renal impairment, the dose is set depending on the CC values. With CC greater than 30 ml/min, the recommended initial dose of Lisoril^® is 5-10 mg/day. With CC from 30 to 10 ml/min – the initial dose is 2.5-5 mg/day. With CC less than 10 ml/min – 2.5 mg/day.

Chronic heart failure

The recommended initial dose is 2.5 mg/day. This dose is effective for some patients, but a dose of 5-20 mg/day is more often achieved.

Adverse Reactions

From the cardiovascular system: decreased blood pressure, chest pain, rarely – orthostatic hypotension, tachycardia, bradycardia, appearance of heart failure symptoms, impaired atrioventricular conduction.

From the nervous system: dizziness, headache, increased fatigue, drowsiness, convulsive twitching of limb and lip muscles, rarely – asthenic syndrome, mood lability, confusion.

From the gastrointestinal tract: nausea, dyspepsia, anorexia, taste change, abdominal pain, diarrhea, dry mouth.

From the hematopoietic organs: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decreased hemoglobin content, erythrocytopenia).

From the respiratory system: dyspnea, bronchospasm, apnea.

Allergic reactions: angioedema, skin rashes, itching.

Laboratory parameters: hyperkalemia, hyperuricemia, rarely – increased activity of liver transaminases, hyperbilirubinemia.

Other: dry cough, decreased potency, rarely – acute renal failure, arthralgia, myalgia, fever, edema (tongue, lips, limbs), impaired fetal kidney development.

Contraindications

• Hypersensitivity to lisinopril and other ACE inhibitors;
• Severe renal impairment;
• Bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia;
• Condition after kidney transplantation;
• Azotemia;
• Primary hyperaldosteronism;
• Aortic stenosis (and similar obstructions to blood flow);
• Hereditary angioedema;
• Pregnancy, lactation period;
• Age under 18 years (efficacy and safety not established).

With caution

• Arterial hypotension;
• Bone marrow hematopoiesis depression;
• Hyponatremia (increased risk of arterial hypotension in patients on a low-salt or salt-free diet);
• Systemic connective tissue diseases;
• Diabetes mellitus;
• Gout;
• Hyperuricemia;
• Coronary artery disease;
• Cerebrovascular insufficiency;
• Severe chronic heart failure;
• Hyperkalemia;
• Elderly age.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Renal Impairment

Contraindicated in severe renal impairment.

Pediatric Use

Contraindicated in children under 18 years of age (efficacy and safety not established).

Geriatric Use

Should be prescribed with caution to elderly patients.

Special Precautions

Regular medical supervision is necessary during treatment. For patients with impaired renal function, it is necessary to reduce the dose or decrease the frequency of administration of Lisoril^®.

In patients taking Lisoril^®, the development of angioedema of the face, lips, tongue, glottis, and/or larynx has been reported. In such cases, it is necessary to immediately discontinue Lisoril^®.

In patients with chronic heart failure and concomitant renal failure, a sharp decrease in blood pressure is observed after taking Lisoril^®. Treatment of such patients should be started under careful medical supervision with a minimum dose of 2.5 mg of Lisoril^®.

Drug Interactions

No significant interaction of Lisinopril with propranolol, hydrochlorothiazide, digoxin was noted.

A decrease in the hypotensive effect of Lisinopril is possible with simultaneous use with NSAIDs, estrogens, and sympathomimetics.

Hydrochlorothiazide may potentiate the antihypertensive effect of Lisinopril.

Combined use with beta-blockers, “slow” calcium channel blockers, and diuretics increases the hypotensive effect of Lisinopril.

With simultaneous use with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium, salt substitutes containing potassium, the risk of hyperkalemia increases, especially in patients with impaired renal function.

Lisinopril reduces potassium loss caused by thiazide-type diuretics.

When co-administered with lithium preparations, Lisinopril may slow the excretion of lithium from the body.

Antacids and cholestyramine reduce the absorption of Lisinopril in the gastrointestinal tract.

Storage Conditions

In a dry, light-protected place at a temperature below 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 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.