Co-Diroton tablets 10mg + 12.5mg, No. 30

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

Inside.
1 tablet of the drug Co-Diroton containing 10 mg of lisinopril + 12.5 mg of hydrochlorothiazide or 20 mg + 12.5 mg once a day. If the proper therapeutic effect is not achieved within 2-4 weeks, the dose of the drug can be increased to 2 tablets of the drug Co-Diroton, used once a day.

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

Previous diuretic therapy:
Symptomatic arterial 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 prior diuretic treatment. Therefore, it is necessary to stop taking diuretics 2-3 days before starting treatment with the drug (see the SPECIAL INSTRUCTIONS section).

Tablets 12.5 mg + 10 mg
Active ingredients:
12.5 mg of hydrochlorothiazide and 10 mg of lisinopril in the form of 10.89 mg of lisinopril dihydrate;
Excipients: mannitol 50 mg, aluminum varnish based on indigotine dye (E 132) 0.2 mg, pregelatinized starch 2.25 mg, corn starch 31 mg, calcium hydrogen phosphate dihydrate 136.8 mg, partially pregelatinized starch 2.25 mg, magnesium stearate 5 mg.

• Hypersensitivity to lisinopril, other ACE inhibitors or hydrochlorothiazide and excipients,

• angioedema (including a history of Quincke's edema associated with the use of ACE inhibitors),

• anuria,

• severe renal failure (creatinine clearance (CC) less than 30 ml / min.),

• hemodialysis using high-flow membranes,

• hypercalcemia,

• hyponatremia,

• porphyria,

• precom,

• hepatic coma,

• severe forms of diabetes mellitus,

• age up to 18 years (efficacy and safety have not been established).

Carefully

Aortic stenosis / hypertrophic cardiomyopathy, bilateral renal artery stenosis, stenosis of a solitary kidney artery with progressive azotemia, condition after kidney transplantation, renal failure (CC more than 30 ml / min.), Primary hyperaldosteronism, arterial hypotension, bone marrow hypoplasia (hyponatremia the development of arterial hypotension in patients on a low-salt or salt-free diet), hypovolemic conditions (including diarrhea, vomiting), connective tissue diseases (including systemic lupus erythematosus, scleroderma), diabetes mellitus, gout, suppression of bone marrow hematopoiesis, hyperuricemia , hyperkalemia, ischemic heart disease, cerebrovascular diseases (including cerebral circulation insufficiency), severe chronic heart failure,liver failure, advanced age.

Trade name : Ko-Diroton

Grouping name : hydrochlorothiazide + lisinopril

Dosage form : tablets

Composition for 1 tablet

Tablets 12.5 mg + 10 mg
Active ingredients:
12.5 mg of hydrochlorothiazide and 10 mg of lisinopril in the form of 10.89 mg of lisinopril dihydrate;
Excipients: mannitol 50 mg, aluminum varnish based on indigotine dye (E 132) 0.2 mg, pregelatinized starch 2.25 mg, corn starch 31 mg, calcium hydrogen phosphate dihydrate 136.8 mg, partially pregelatinized starch 2.25 mg, magnesium stearate 5 mg.

Tablets 12.5 mg + 20 mg
Active ingredients:
12.5 mg of hydrochlorothiazide and 20 mg of lisinopril in the form of 21.77 mg of lisinopril dihydrate;
Excipients: mannitol 50 mg, aluminum varnish based on indigotine dye (E 132) 0.2 mg, iron dye yellow oxide (E 172) 0.1 mg, pregelatinized starch 2.25 mg, corn starch 31 mg, calcium hydrogen phosphate dihydrate 136.7 mg, partially pregelatinized starch 2.25 mg, magnesium stearate 5 mg.

Description

Tablets 12.5 mg + 10 mg:
Round, flat-cylindrical, beveled, light blue in color with a few blotches of a darker color. The symbol C 43 is engraved on one side.
Tablets 12.5 mg + 20 mg:
Round, flat-cylindrical, beveled, light green in color with a few blotches of a darker color. The symbol C 44 is engraved on one side.

Pharmacotherapeutic group : antihypertensive combined agent (angiotensin-converting enzyme (ACE) inhibitor + diuretic).

ATX code : [—09¬ј03]

Pharmacological properties

Pharmacodynamics
Hypotensive combined drug. It has antihypertensive and diuretic effects.
Lisinopril
ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the total peripheral vascular resistance, blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute blood volume and an increase in stress tolerance in patients with chronic heart failure. Expands arteries more than veins. Some of the effects are attributed to the effect on tissue renin-angiotensin systems. With prolonged use, the severity of hypertrophy of the myocardium and the walls of the resistive arteries decreases. Improves blood supply to the ischemic myocardium.ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins in about 6 hours and lasts for 24 hours. The duration of the effect also depends on the size of the dose. The onset of action is after 1 hour. The maximum effect is determined after 6-7 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, a stable effect develops after 1-2 months.The antihypertensive effect begins in about 6 hours and lasts for 24 hours. The duration of the effect also depends on the size of the dose. The onset of action is after 1 hour. The maximum effect is determined after 6-7 hours. With arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months.The antihypertensive effect begins in about 6 hours and lasts for 24 hours. The duration of the effect also depends on the size of the dose. The onset of action is after 1 hour. The maximum effect is determined after 6-7 hours. With arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months.
With a sharp withdrawal of the drug, a pronounced increase in blood pressure is not observed.
In addition to lowering blood pressure, lisinopril reduces albuminuria. In patients with hyperglycemia, it helps to normalize the function of the damaged glomerular endothelium.
Lisinopril does not affect the blood glucose concentration in patients with diabetes mellitus and does not lead to an increased incidence of hypoglycemia.
Hydrochlorothiazide
Thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium, water ions in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties; the hypotensive effect develops due to the expansion of arterioles. Has practically no effect on the normal level of blood pressure. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours. The antihypertensive effect occurs after 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.
Lisinopril and hydrochlorothiazide, if used simultaneously, have an additive antihypertensive effect

Pharmacokinetics of
Lisinopril. After taking lisinopril inside, the maximum serum concentration is reached after 7 hours. It weakly binds to plasma proteins. The average degree of absorption of lisinopril is about 25%, with significant interindividual variability (6-60%). Food does not affect the absorption of lisinopril. Lisinopril is not metabolized and is excreted unchanged exclusively by the kidneys. After repeated administration, the effective half-life of lisinopril is 12 hours.
Impaired renal function slows down the elimination of lisinopril, but this slowdown becomes clinically significant only when the glomerular filtration rate decreases below 30 ml / min. Elderly patients have, on average, 2 times higher levels of maximum drug concentration in the blood and AUC (area under the plasma concentration-time curve), compared with younger patients.
Lisinopril is excreted from the body by hemodialysis.
To a small extent, it penetrates the blood-brain barrier.
Hydrochlorothiazidedoes not undergo metabolism, but undergoes rapid excretion through the kidneys. The half-life of the drug ranges from 5.6 to 14.8 hours. At least 61% of the ingested drug is excreted unchanged within 24 hours. Hydrochlorothiazide penetrates the placental barrier, but does not penetrate the blood-brain barrier.

Indications for use

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

Contraindications

• Hypersensitivity to lisinopril, other ACE inhibitors or hydrochlorothiazide and excipients,

• angioedema (including a history of Quincke's edema associated with the use of ACE inhibitors),

• anuria,

• severe renal failure (creatinine clearance (CC) less than 30 ml / min.),

• hemodialysis using high-flow membranes,

• hypercalcemia,

• hyponatremia,

• porphyria,

• precom,

• hepatic coma,

• severe forms of diabetes mellitus,

• age up to 18 years (efficacy and safety have not been established).

Carefully

Aortic stenosis / hypertrophic cardiomyopathy, bilateral renal artery stenosis, stenosis of a solitary kidney artery with progressive azotemia, condition after kidney transplantation, renal failure (CC more than 30 ml / min.), Primary hyperaldosteronism, arterial hypotension, bone marrow hypoplasia (hyponatremia the development of arterial hypotension in patients on a low-salt or salt-free diet), hypovolemic conditions (including diarrhea, vomiting), connective tissue diseases (including systemic lupus erythematosus, scleroderma), diabetes mellitus, gout, suppression of bone marrow hematopoiesis, hyperuricemia , hyperkalemia, ischemic heart disease, cerebrovascular diseases (including cerebral circulation insufficiency), severe chronic heart failure,liver failure, advanced age.

Pregnancy and lactation

The use of lisinopril during pregnancy is contraindicated. When pregnancy is established, the drug should be discontinued as early as possible. Taking ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (a pronounced decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, intrauterine death are possible). There is no data on the negative effects of the drug on the fetus when used during the first trimester. For newborns and infants who have been exposed to intrauterine exposure to ACE inhibitors, it is recommended to be monitored for the timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia.
During the period of drug treatment, it is necessary to cancel breastfeeding.

Method of administration and dosage

Inside.
1 tablet of the drug Co-Diroton containing 10 mg of lisinopril + 12.5 mg of hydrochlorothiazide or 20 mg + 12.5 mg once a day. If the proper therapeutic effect is not achieved within 2-4 weeks, the dose of the drug can be increased to 2 tablets of the drug Co-Diroton, used once a day.

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

Previous diuretic therapy:
Symptomatic arterial 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 prior diuretic treatment. Therefore, it is necessary to stop taking diuretics 2-3 days before starting treatment with the drug (see the SPECIAL INSTRUCTIONS section).

Side effect

The most common side effects are dizziness, headache.
Other side effects:
On the part of the cardiovascular system: a marked decrease in blood pressure, chest pain, rarely - orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, atrioventricular conduction disturbance, myocardial infarction.
From the digestive tract: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, taste changes, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice.
On the part of the skin: urticaria, increased sweating, photosensitivity, pruritus, hair loss.
From the side of the central nervous system:mood lability, impaired concentration, paresthesia, fatigue, drowsiness, convulsive twitching of the muscles of the limbs and lips, rarely - asthenic syndrome, confusion.
From the respiratory system: dyspnea, dry cough, bronchospasm, apnea.
From the hematopoietic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decreased hemoglobin concentration, hematocrit, erythrocytopenia).
Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx (see the SPECIAL INSTRUCTIONS section), skin rashes, itching, fever, vasculitis, positive reactions to antinuclear antibodies, increased ESR, eosinophilia.
From the genitourinary system:uremia, oliguria / anuria, impaired renal function, acute renal failure, decreased potency.
Laboratory indicators: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypercalcemia, hyperuricemia, hyperglycemia, increased levels of urea and creatinine in the blood plasma, hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, decreased tolerance to glucose, especially in patients with glucose tolerance a history of kidney disease, diabetes mellitus and renovascular hypertension.
Others: arthralgia, arthritis, myalgia, fever, impaired fetal development, exacerbation of gout.

Overdose

Symptoms: a marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability.
Treatment: symptomatic therapy, intravenous fluid administration, blood pressure control; therapy aimed at correcting dehydration and violations of the water-salt balance. Control of urea, creatinine and serum electrolytes, as well as urine output.

Interaction with other medicinal products

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. Therefore, they can be co-administered only on the basis of an individual decision of the physician with regular monitoring of serum potassium and renal function.
With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol - an increase in the hypotensive effect.
With simultaneous use with non-steroidal anti-inflammatory drugs (NSAIDs) (indomethacin and others), estrogens - a decrease in the antihypertensive effect of lisinopril.
With simultaneous use with lithium preparations - slowing down the elimination of lithium from the body (increasing the cardiotoxic and neurotoxic effects of lithium).
With simultaneous use with antacids and cholestyramine - a decrease in absorption in the gastrointestinal tract.
The drug enhances the neurotoxicity of salicylates, weakens the effect of hypoglycemic drugs for oral administration, norepinephrine, epinephrine and anti-gout drugs, enhances the effects (including side effects) of cardiac glycosides, the effect of peripheral muscle relaxants, and reduces the excretion of quinidine.
Reduces the effect of oral contraceptives. Ethanol enhances the hypotensive effect of the drug. With the simultaneous administration of methyldopa, the risk of hemolysis increases.

special instructions

Symptomatic arterial hypotension
Most often, a pronounced decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, a decrease in the amount of salt in food, dialysis, diarrhea or vomiting (see sections INTERACTION WITH OTHER DRUGS and SIDE EFFECTS). In patients with chronic heart failure with or without concurrent renal failure, a pronounced decrease in blood pressure is possible. It is more often detected in patients with severe class of chronic 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 the strict supervision of a physician. Similar rules should be followed when prescribing to patients with ischemic heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.
Transient arterial hypotension is not a contraindication for further administration of the drug.
Before starting treatment, if possible, the sodium concentration should be normalized and / or the lost volume of fluid should be replenished, the effect of the initial dose of the drug on the patient should be carefully monitored.
Impaired renal function
In patients with chronic heart failure, a pronounced decrease in blood pressure after starting treatment with ACE inhibitors can lead to a further deterioration in renal function. Cases of acute renal failure have been reported.
In patients with bilateral stenosis of the renal arteries or stenosis of an artery of a single kidney, who received ACE inhibitors, there was an increase in serum urea and creatinine, usually reversible after discontinuation of treatment. More common in patients with renal failure.
Hypersensitivity / Angioedema
Angioneurotic edema of the face, extremities, lips, tongue, epiglottis and / or larynx was rarely observed in patients treated with ACE inhibitors, including lisinopril, which can occur during any period of treatment. In this case, treatment with lisinopril should be stopped as soon as possible and the patient should be monitored until the symptoms completely regress. In cases where swelling of only the face and lips has occurred, the condition most often goes away without treatment, however, it is possible to prescribe antihistamines.
Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis or larynx are covered, airway obstruction may occur, therefore appropriate therapy (0.3-0.5 ml of epinephrine (adrenaline) solution 1: 1000 subcutaneously) and / or measures to ensure airway patency should be carried out immediately.
Patients who already have a history of angioedema not associated with previous treatment with ACE inhibitors may be at increased risk of developing it during treatment with an ACE inhibitor.
Cough Cough has been reported
with the use of an ACE inhibitor. The cough is dry, prolonged, which disappears after stopping treatment with an ACE inhibitor. In the differential diagnosis of cough, it is necessary to take into account the cough caused by the use of an ACE inhibitor.
Patients on hemodialysis
Anaphylactic reaction has also been observed in patients undergoing hemodialysis using high permeability dialysis membranes (AN69Ѓ) who are simultaneously taking ACE inhibitors. In such cases, consideration should be given to using a different type of dialysis membrane or other antihypertensive agent.
Surgery / General anesthesia
Lisinopril can block the formation of angiotensin II when using drugs that lower blood pressure in patients with major surgery or during general anesthesia.
A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by increasing the volume of circulating blood.
Before surgery (including dentistry), the anesthesiologist should be warned about the use of ACE inhibitors.
Serum potassium Hyperkalemia has been
reported in some cases.
Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, taking potassium supplements or drugs that increase the concentration of potassium in the blood (eg, heparin), especially in patients with impaired renal function.
In patients who are at risk of symptomatic hypotension (on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, the above conditions must be compensated (loss of fluid and salts) before starting treatment.
Metabolic and endocrine effects
Thiazide diuretics can affect glucose tolerance, so it is necessary to adjust the dose of hypoglycemic agents for oral administration.
Thiazide diuretics can reduce renal calcium excretion and cause hypercalcemia. Severe hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended that treatment with thiazide diuretics be discontinued before the test to assess the function of the parathyroid glands.
During the period of drug treatment, regular monitoring of potassium, glucose, urea, and lipids in the blood plasma is required.
During the period of treatment, it is not recommended to consume alcoholic beverages, since alcohol enhances the hypotensive effect of the drug.
Caution should be exercised during exercise, hot weather (risk of dehydration and an excessive decrease in blood pressure due to a decrease in circulating blood volume).

Impact on the ability to drive vehicles and work with equipment

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

Release form

Tablets, 12.5 mg + 10 mg.
Tablets, 12.5 mg + 20 mg.
10 tablets in a PVC - aluminum foil blister. 1 or 3 blisters in a cardboard box along with instructions for use.

Storage conditions

At a temperature not higher than 25 ? C.
Keep out of the reach of children!

Shelf life

2 years.
Do not use after the expiration date printed on the package.

Conditions of dispensing from pharmacies

On prescription.