Co-Diroton, tablets 20 mg+12, 5 mg 30 pcs.

Arterial hypertension (in patients who are indicated for combination therapy).

Active ingredient

Composition

1 tablet contains lisinopril dihydrate 21.77 mg, which corresponds to lisinopril 20 mg;

hydrochlorothiazide 12.5 mg.

How to take, the dosage

Prescribe orally 1 tablet. 1 time per day. If within 2-4 weeks proper therapeutic effect is not achieved, the drug dose may be increased to 2 tablets. 1 time daily.

In patients with IQ of 30-80 ml/min the drug can be used only after adjustment of the dose of individual components of the preparation. The recommended starting dose of lisinopril in uncomplicated renal failure is 5-10 mg.

Symptomatic arterial hypotension may occur after the initial dose of the drug. Such cases occur more frequently in patients who have had fluid and electrolyte loss due to prior treatment with diuretics. Therefore, the use of diuretics should be discontinued 2-3 days prior to treatment with the drug.

Interaction

Concomitant use with potassium-saving diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium increases the risk of hyperkalemia, especially in patients with impaired renal function. Therefore they can be administered together only on the basis of an individual decision of a physician with regular monitoring of serum potassium levels and renal function.
With concomitant use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol an increase in hypotensive effect is noted.

When used concomitantly with NSAIDs (indomethacin and others), estrogens, a decrease in the antihypertensive effect of lisinopril is noted.

When used concomitantly with lithium preparations, excretion of lithium from the body is delayed (increase of the cardiotoxic and neurotoxic effects of lithium).

Concomitant use with antacids and colestiramine reduces absorption in the gastrointestinal tract.

The drug increases neurotoxicity of salicylates, reduces the effect of hypoglycemic oral agents, norepinephrine, epinephrine and antipodagric agents, increases the effects (including side effects) of cardiac glycosides, effects of peripheral myorelaxants, reduces excretion of quinidine.

Decreases the effect of oral contraceptives.

Ethanol increases the hypotensive effect of the drug.
Simultaneous administration of methyldopa increases the risk of hemolysis.

Special Instructions

More often than not, a marked decrease in BP occurs with a decrease in fluid volume caused by diuretic therapy, reduction of salt in food, dialysis, diarrhea, or vomiting.

In patients with chronic heart failure with or without concomitant renal failure, a marked decrease in BP may occur. It is more often found in patients with severe class chronic heart failure, as a consequence of using high doses of diuretics, hyponatremia or impaired renal function. In such patients the treatment should be started under strict control of a doctor. Similar rules should be followed when prescribing to patients with CHD, cerebrovascular insufficiency, in whom a sharp decrease in BP may lead to myocardial infarction or stroke.

Transient arterial hypotension is not a contraindication for further use of the drug.
Before treatment, if possible, normalize sodium concentration and/or replenish lost fluid volume and carefully monitor the effect of the initial dose of the drug on the patient.

In patients with chronic heart failure, a marked decrease in BP after initiation of treatment with ACE inhibitors may lead to further deterioration of renal function. Cases of acute renal failure have been reported.

In patients with bilateral renal artery stenosis or artery stenosis of the sole kidney receiving ACE inhibitors, there have been increased serum urea and creatinine, usually reversible after discontinuation of treatment. It was more common in patients with renal insufficiency.

The angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx has rarely been reported in patients treated with ACE inhibitors, including lisinopril, which can occur at any time during treatment. In such a case, lisinopril treatment should be discontinued as soon as possible and the patient should be monitored until the symptoms have completely resolved. In cases of edema of the face and lips only, the condition usually resolves without treatment, but antihistamines may be prescribed. Angioedema with laryngeal edema may be fatal. Airway obstruction may occur when tongue, epiglottis or larynx is involved, so appropriate therapy (0.3-0.5 ml of epinephrine (adrenaline) solution 1:1000 p/k) and/or measures to ensure airway patency should be given immediately.

In patients who already have a history of angioedema not associated with previous treatment with ACE inhibitors, there may be an increased risk of its development during treatment with an ACE inhibitor.

Cough has been noted while using an ACE inhibitor. Cough is dry, prolonged, and disappears after discontinuation of ACE inhibitor treatment. In the differential diagnosis of cough, the cough caused by ACE inhibitor use must also be considered.

Anaphylactic reactions have also been reported in patients undergoing hemodialysis using high permeability dialysis membranes (AN69®) who are simultaneously taking ACE inhibitors. In such cases, another type of dialysis membrane or another antihypertensive agent should be considered.

Lisinopril may block angiotensin II formation when BP lowering drugs are used in patients undergoing major surgery or during general anesthesia.

The marked decrease in BP, which is considered to be a consequence of this mechanism, can be corrected by increasing the RBC.

Preceding surgical procedures (including dentistry), the anesthesiologist should be warned about the use of ACE inhibitors.
In some cases, hyperkalemia has been noted. Risk factors for hyperkalemia include renal insufficiency, diabetes mellitus, taking potassium preparations or drugs that cause an increase in blood potassium concentration (e.g., heparin), especially in patients with impaired renal function.

In patients who are at risk of symptomatic hypotension (who are on a low-salt or no-salt diet) with or without hyponatremia, as well as in patients who have received high doses of diuretics, the above conditions should be compensated (fluid and salt loss) before starting treatment.

The thiazide diuretics may affect glucose tolerance, so it is necessary to adjust the doses of hypoglycemic agents for oral administration. Thiazide diuretics may decrease renal calcium excretion and cause hypercalcemia. Severe hypercalcemia may be a symptom of occult hyperparathyroidism. It is recommended to stop treatment with thiazide diuretics until parathyroid function test is performed.

Any regular monitoring of plasma potassium, glucose, urea, lipids is required during treatment with the drug.

When using the drug it is not recommended to drink alcoholic beverages because alcohol increases hypotensive effect of the drug.
Care should be taken when doing physical exercises and in hot weather (risk of dehydration and excessive decrease of BP due to reduction of BCC).

Impact on driving and operating machinery

At the time of treatment, patients should refrain from driving and engaging in potentially dangerous activities requiring increased concentration and quick psychomotor reactions because dizziness is possible, especially at the beginning of treatment.

Contraindications

Hypersensitivity (including to other ACE inhibitors and sulfonamide derivatives), anuria, angioedema (including history of use of ACE inhibitors). in anamnesis from use of ACE inhibitors), hemodialysis with high-flow membranes, hypercalcemia, hyponatremia, porphyria, precoma, hepatic coma, diabetes (severe forms), pregnancy, lactation, age under 18 years (effectiveness and safety not established).

With caution. Aortic stenosis, hypertrophic cardiomyopathy, bilateral renal artery stenosis, artery stenosis of the single kidney with progressive azotemia, condition after renal transplantation, CKD (CKD over 30 ml/min.), severe CKD (CKD less than 30 ml/min), primary hyperaldosteronism, arterial hypotension, bone marrow hypoplasia, hyponatremia (increased risk of arterial hypotension in patients on low-salt or no-salt diet), conditions accompanied by decreased BOD (including diarrhea, vomiting, diarrhea, and hypertension).including diarrhea, vomiting), connective tissue diseases (SLE, scleroderma), diabetes, gout, hyperuricemia, hyperkalemia, hepatic insufficiency, cerebrovascular insufficiency, severe CHF, elderly age.

Side effects

Frequent: dizziness, headache.

Less frequent. Cardiovascular system: marked BP decrease, chest pain, rarely – orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, AV conduction failure, myocardial infarction.

Digestive system disorders: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, change in taste, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice.

Nervous system disorders: mood lability, concentration disorders, paresthesia, fatigue, somnolence, convulsive twitching of limbs and lips, rarely – asthenic syndrome, confusion.

Respiratory system: dyspnea, bronchospasm, apnea.

Skin disorders: urticaria, sweating, alopecia, photosensitization.

Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx, skin rash, itching, fever, vasculitis, positive results for antinuclear antibodies, increased sedimentation, eosinophilia.

Hematopoietic disorders: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease of Hb, hematocrit, erythropenia).

Urogenital system disorders: uremia, oliguria/anuria, renal dysfunction, acute renal failure, decreased potency.

Laboratory findings: hyperkalemia and/or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypercalcemia, hyperuricemia, hyperglycemia, increased plasma urea and creatinine, rarely – increased activity of “liver” transaminases, hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, reduced glucose tolerance.

Others: dry cough, arthralgia/arthritis, myalgia, fetal renal impairment, gout exacerbation, vasculitis.

Overdose

Symptoms: marked BP decrease, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: symptomatic therapy, IV fluid administration, BP control; therapy aimed at correction of dehydration and water-salt balance disorders. Control of urea, creatinine and electrolytes in serum, as well as diuresis.

Pregnancy use

The use of lisinopril during pregnancy is contraindicated. If pregnancy is established, the drug should be discontinued as soon as possible.

The use of ACE inhibitors in II and III trimesters of pregnancy has adverse effects on the fetus (marked BP decrease, renal failure, hyperkalemia, skull bone hypoplasia, fetal death are possible). There is no data about the negative effect of the drug on the fetus in case of its use during the first trimester.

In newborns and infants who have had intrauterine exposure to ACE inhibitors are recommended to be monitored for timely detection of marked BP decrease, oliguria, hyperkalemia.

Breastfeeding should be discontinued during treatment with the drug.