Lisinoton H (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group hf. (Iceland)

Manufactured By

ZiO-Health CJSC (Russia)

ATC Code

C09BA03 (Lisinopril and diuretics)

Active Substances

Hydrochlorothiazide (Rec.INN registered by WHO)

Lisinopril (Rec.INN registered by WHO)

Dosage Forms

	Lisinoton H	Tablets 10 mg+12.5 mg: 10, 14, 28 or 30 pcs.
		Tablets 20 mg+12.5 mg: 10, 14, 28 or 30 pcs.
		Tablets 20 mg+25 mg: 10, 14, 28 or 30 pcs.

Dosage Form, Packaging, and Composition

Tablets yellow-orange in color, round, biconvex, marked “LH” on one side, without a score; marbling is allowed.

Excipients : mannitol – 18.7 mg, calcium hydrogen phosphate dihydrate – 57.14 mg, pregelatinized corn starch – 4 mg, colorant – 1.6 mg (pregelatinized corn starch – 1.488 mg, iron oxide yellow (E172) – 80 mcg, iron oxide red (E172) – 32 mcg), croscarmellose sodium – 4.4 mg, magnesium stearate – 770 mcg.

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

Tablets white in color, round, biconvex, marked “LH” on one side and with a score on the other; marbling is allowed.

Excipients : mannitol – 38.3 mg, calcium hydrogen phosphate dihydrate – 117.05 mg, pregelatinized corn starch – 10.5 mg, croscarmellose sodium – 8.4 mg, magnesium stearate – 1.47 mg.

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

Tablets yellow-orange in color, round, biconvex, marked “LH” on one side and with a score on the other; marbling is allowed.

Excipients : mannitol – 37.4 mg, calcium hydrogen phosphate dihydrate – 114.28 mg, pregelatinized corn starch – 8 mg, colorant – 3.2 mg (pregelatinized corn starch – 2.976 mg, iron oxide yellow (E172) – 160 mcg, iron oxide red (E172) – 64 mcg), croscarmellose sodium – 8.8 mg, magnesium stearate – 1.54 mg.

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

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Antihypertensive combination agent (ACE inhibitor + diuretic)

Pharmacological Action

Lisinoton H is a combination of an ACE inhibitor (Lisinopril) and a diuretic (Hydrochlorothiazide). It has antihypertensive and diuretic effects.

Lisinopril

An ACE inhibitor, it reduces the formation of angiotensin II from angiotensin I. The decrease in angiotensin II content leads to a direct reduction in aldosterone secretion. It reduces the degradation of bradykinin and increases prostaglandin synthesis. It reduces systemic vascular resistance, blood pressure, preload, pulmonary capillary wedge pressure, causes an increase in cardiac output and improves exercise tolerance in patients with heart failure.

It 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-type arteries. It improves blood supply to the ischemic myocardium. ACE inhibitors prolong the life expectancy of patients with chronic heart failure and slow the progression of left ventricular dysfunction in patients who have had a myocardial infarction without clinical manifestations of heart failure. Onset of action is within 1 hour, maximum effect is determined in 6-7 hours, duration is 24 hours. In arterial hypertension, the effect is noted in the first days after starting treatment, a stable effect develops after 1-2 months.

Hydrochlorothiazide

A thiazide diuretic, its diuretic effect is associated with impaired reabsorption of sodium, chloride, potassium, magnesium ions, and water in the distal part of the nephron; it delays the excretion of calcium ions and uric acid. It has antihypertensive properties; the hypotensive effect develops due to the dilation of arterioles. It has practically no effect on normal blood pressure. The diuretic effect occurs within 1-2 hours, reaches a maximum in 4 hours and lasts 6-12 hours. The antihypertensive effect occurs in 3-4 days, but 3-4 weeks may be required to achieve the optimal therapeutic effect.

Lisinopril and Hydrochlorothiazide, when used simultaneously, have an additive antihypertensive effect.

Pharmacokinetics

Data on the pharmacokinetics of the drug Lisinoton^® H are not provided.

Indications

• Arterial hypertension (in patients for whom combination therapy is indicated).

ICD codes

Dosage Regimen

Administered orally, once a day.

For essential hypertension, 1 tablet (10 mg+12.5 mg) once a day is prescribed. If necessary, the dose can be increased to 1 tablet (20 mg+12.5 mg) once a day.

In patients with CrCl greater than 30 and less than 80 ml/min, the drug can be used only after titration of the dose of the individual components of the drug. The recommended initial dose of lisinopril for uncomplicated renal failure is 5-10 mg.

Symptomatic hypotension may occur after taking the initial dose of the drug. Such cases are more common in patients who have had fluid and electrolyte loss due to previous diuretic therapy. Therefore, it is necessary to discontinue diuretics 2-3 days before starting treatment with Lisinoton H.

Adverse Reactions

In most patients, adverse events were mild and transient.

Most frequently dizziness, headache.

Adverse events that occurred less frequently are listed below.

From the cardiovascular system marked decrease in blood pressure, chest pain; rarely – orthostatic hypotension, tachycardia, bradycardia, appearance of symptoms of heart failure, impaired AV conduction, myocardial infarction.

From the digestive system nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, taste disturbance, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice; rarely – increased activity of liver transaminases, hyperbilirubinemia.

From the nervous system mood lability, impaired concentration, paresthesia, increased fatigue, drowsiness, convulsive twitching of limb and lip muscles; rarely – asthenic syndrome, confusion.

From the respiratory system dyspnea, bronchospasm, apnea, dry cough.

Dermatological reactions sweating, hair loss, photosensitivity.

Allergic reactions urticaria, angioedema of the face, extremities, lips, tongue, glottis and/or larynx, skin rash, itching, fever, vasculitis, positive antinuclear antibody results, increased ESR, eosinophilia.

From the hematopoietic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease in hemoglobin, hematocrit, erythrocytopenia).

From the genitourinary system uremia, oliguria/anuria, impaired renal function, acute renal failure, decreased potency.

From the musculoskeletal system arthralgia/arthritis, myalgia.

Laboratory parameters hyperkalemia and/or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hyperuricemia, hyperglycemia, increased levels of urea and creatinine; rarely – hypercholesterolemia, hypertriglyceridemia, decreased glucose tolerance.

Other impaired fetal kidney development, exacerbation of gout.

Contraindications

• Anuria;
• Severe renal failure (CrCl less than 30 ml/min);
• Angioedema (including history from ACE inhibitor use);
• Hemodialysis using high-flux membranes;
• Hypercalcemia;
• Hyponatremia;
• Porphyria;
• Precoma, hepatic coma;
• Diabetes mellitus (severe forms);
• Pregnancy;
• Lactation period;
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to the components of the drug;
• Hypersensitivity to other ACE inhibitors and sulfonamide derivatives.

With caution aortic stenosis/hypertrophic cardiomyopathy, bilateral renal artery stenosis, stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, renal failure (CrCl greater than 30 ml/min), primary hyperaldosteronism, arterial hypotension, bone marrow hypoplasia, hyponatremia (increased risk of arterial hypotension in patients on a low-salt or salt-free diet), conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting), connective tissue diseases (systemic lupus erythematosus, scleroderma), diabetes mellitus, gout, hyperuricemia, hyperkalemia, coronary artery disease, cerebrovascular insufficiency, severe chronic heart failure, hepatic insufficiency, elderly age.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

With caution hepatic insufficiency.

Use in Renal Impairment

In patients with CrCl greater than 30 and less than 80 ml/min, the drug can be used only after titration of the dose of the individual components of the drug. The recommended initial dose of lisinopril for uncomplicated renal failure is 5-10 mg.

Pediatric Use

Contraindication: age under 18 years (efficacy and safety not established).

Geriatric Use

With caution: elderly age.

Special Precautions

Marked decrease in blood pressure most often occurs with a reduction in circulating blood volume caused by diuretic therapy, reduced salt intake, dialysis, diarrhea, or vomiting. In patients with chronic heart failure with or without concurrent renal impairment, symptomatic hypotension may develop. It is more often detected in patients with severe forms of heart failure, as a result of the use of high doses of diuretics, hyponatremia, or impaired renal function. In such patients, treatment should be started under strict medical supervision. Similar rules should be followed when prescribing to patients with coronary artery disease, cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

A transient hypotensive reaction is not a contraindication for taking the next dose of the drug.

In patients with chronic heart failure, a marked decrease in blood pressure after starting treatment with ACE inhibitors can lead to further deterioration of renal function.

Cases of acute renal failure have been noted.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney receiving ACE inhibitors, an increase in serum urea and creatinine was noted, usually reversible after discontinuation of treatment. This was more common in patients with renal failure.

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx (can occur at any time during treatment) was rarely observed in patients treated with ACE inhibitors, including Lisinopril. In such a case, lisinopril treatment should be discontinued as soon as possible and the patient should be monitored until symptoms completely regress. In cases where the edema involved only the face and lips, the condition most often resolves without treatment, however, antihistamines may be prescribed. Angioedema with laryngeal edema can be fatal. When the tongue, glottis, or larynx is involved, airway obstruction may occur, so appropriate therapy (0.3-0.5 ml of epinephrine solution 1:1000 subcutaneously) and/or measures to ensure airway patency should be immediately administered.

Patients with a history of angioedema not associated with previous ACE inhibitor treatment may have an increased risk of its development during ACE inhibitor treatment.

Cough has been observed with ACE inhibitor use. The cough is dry, persistent, and disappears after discontinuation of ACE inhibitor treatment. In the differential diagnosis of cough, cough caused by ACE inhibitor use must be considered.

An anaphylactic reaction has also been noted in patients undergoing hemodialysis using high-permeability dialysis membranes who are simultaneously taking ACE inhibitors. In such cases, the possibility of using another type of dialysis membrane or another antihypertensive agent should be considered.

When using blood pressure-lowering agents in patients undergoing major surgery or during general anesthesia, Lisinopril may block the formation of angiotensin II.

Marked hypotension, considered a consequence of this mechanism, can be corrected by increasing the circulating blood volume.

Before surgery (including dentistry), the surgeon/anesthesiologist must be informed about the use of ACE inhibitors.

In some cases, hyperkalemia has been observed.

Risk factors for developing hyperkalemia include renal failure, diabetes mellitus, intake of potassium supplements or drugs that cause an increase in blood potassium concentration (e.g., heparin), especially in patients with impaired renal function. In patients at risk of symptomatic hypotension (on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who have received high doses of diuretics, the above conditions must be compensated (loss of fluid and salts) before starting treatment.

Thiazide diuretics can affect glucose tolerance, so doses of antidiabetic medications need to be adjusted.

Thiazide diuretics can reduce urinary calcium excretion and cause hypercalcemia. Marked hypercalcemia may be a symptom of latent hyperparathyroidism; it is recommended to discontinue thiazide diuretic treatment before conducting tests to assess parathyroid function.

During treatment with Lisinoton H, regular monitoring of plasma potassium, glucose, urea, lipids, and creatinine is necessary.

During treatment, it is not recommended to consume alcoholic beverages, as alcohol enhances the hypotensive effect of the drug.

Caution should be exercised during physical exercise, in hot weather (risk of dehydration and excessive decrease in blood pressure due to reduced circulating blood volume).

Effect on ability to drive vehicles and operate machinery

During treatment, patients should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as dizziness is possible, especially at the beginning of the course of treatment.

Overdose

Symptoms marked decrease in blood pressure.

Treatment induce vomiting and/or perform gastric lavage, conduct symptomatic therapy aimed at correcting dehydration and water-electrolyte balance disturbances. For arterial hypotension, administer isotonic solution. Monitor serum urea, creatinine and electrolytes, as well as diuresis.

Drug Interactions

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

With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol, the hypotensive effect is enhanced.

With simultaneous use with NSAIDs (indomethacin and others), estrogens, the antihypertensive effect of lisinopril is reduced.

With simultaneous use with lithium preparations, a slowdown in the excretion of lithium from the body is noted (increased cardiotoxic and neurotoxic effects of lithium).

With simultaneous use with antacids and cholestyramine, a decrease in absorption from the gastrointestinal tract is noted.

The drug enhances the neurotoxicity of salicylates.

The drug weakens the effect of oral hypoglycemic agents, norepinephrine, epinephrine, and antigout agents.

The drug enhances the effects (including side effects) of cardiac glycosides, the action of peripheral muscle relaxants.

The drug reduces the excretion of quinidine.

Reduces the effect of oral contraceptives.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

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.