Lisinopril + Hydrochlorthiazidum

General characteristics. Structure:

Active ingredients: 10 or 20 mg of lisinopril, 12,5 mg of Hydrochlorthiazidum in each tablet.

Excipients: mannitol, corn starch, starch 1500 (starch corn partially prezhelatinizirovanny), calcium hydrophosphate dihydrate, понсо 4R, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. The combined anti-hypertensive drug. Has anti-hypertensive and diuretic effect.

Lisinopril. Inhibitor of an angiotensin-converting enzyme (APF), reduces formation of II angiotensin of angiotensin I. Decrease in content of angiotensin II leads to direct reduction of allocation of Aldosteronum. Reduces degradation of bradikinin and increases synthesis of prostaglandins. Reduces the general peripheric vascular resistance (GPVR), the arterial pressure (AP), preloading, pressure in pulmonary capillaries, causes increase in minute volume of blood and increase in tolerance to loadings in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by influence on fabric a renin-angiotenzinovuyu system. At prolonged use expressiveness of a hypertrophy of a myocardium and walls of arteries of resistive type decreases. Improves blood supply of an ischemic myocardium.

APF inhibitors extend life expectancy at patients with chronic heart failure, slow down progressing of dysfunction of a left ventricle at the patients who had a myocardial infarction without clinical displays of heart failure. The anti-hypertensive effect begins approximately in 6 h and remains during 24 h. Effect duration also depends on dose size. The beginning of action – in 1 h. The maximum effect is defined by 6 – 7 h. At arterial hypertension the effect is noted in the first days after an initiation of treatment, stable action develops in 1 – 2 month.

At sharp drug withdrawal the expressed increase in the ABP is not observed.

In addition to decrease in the ABP lisinopril reduces an albuminuria. At patients with a hyperglycemia contributes to normalization of function of the damaged glomerular endothelium.

Lisinopril does not influence concentration of glucose in blood at patients with a diabetes mellitus and does not lead to increase of cases of a hypoglycemia.

Hydrochlorthiazidum. Thiazide diuretic which diuretic effect is connected with disturbance of a reabsorption of ions of sodium, chlorine, potassium, magnesium, water in distal department of nephron; removal of calcium ions, uric acid detains. Has anti-hypertensive properties; hypotensive action develops due to expansion of arterioles. Practically does not exert impact on the ABP normal level.

The diuretic effect develops in 1 – 2 h, reaches a maximum in 4 h and remains for 6 – 12 h. Anti-hypertensive action comes in 3 – 4 days, but for achievement of optimum therapeutic effect 3 – 4 weeks can be required.

Lisinopril and Hydrochlorthiazidum if are applied at the same time, render the additive anti-hypertensive effect.

Pharmacokinetics. Absorption. After reception of lisinopril in Cmax in plasma it is reached in 7 h. Average extent of absorption of lisinopril makes about 25%, at considerable interindividual variability (6-60%). Food does not influence lisinopril absorption.

Distribution. Lisinopril poorly contacts proteins of plasma. In small degree gets through the blood-brain barrier (BBB).

Hydrochlorthiazidum gets through a placental barrier, but does not get through GEB.

Metabolism and removal. Lisinopril is not exposed to metabolism and is removed in not changed look only by kidneys. After repeated introduction effective T½ of lisinopril makes 12 h.

Hydrochlorthiazidum is not exposed to metabolism, but is quickly removed by kidneys. T1/2 fluctuates of 5,6 h to 14,8 h. Not less than 61% of Hydrochlorthiazidum accepted inside are removed in not changed look during 24 h.

Pharmacokinetics in special clinical cases. The renal failure slows down lisinopril removal, but this delay becomes clinically significant only at a glomerular filtration rate less than 30 ml/min.

At patients of advanced age is Cmax and AUC lisinopril is on average twice higher, in comparison with patients of younger age.

Lisinopril is removed from an organism by a hemodialysis.

Indications to use:

Arterial hypertension (at patients to whom the combination therapy is shown).

Route of administration and doses:

Arterial hypertension. Adults. Use of the combined drug with the fixed dose does not approach to start therapy. The combined drug with the fixed dose can replace a combination of 10 mg or 20 mg of lisinopril and patients whose condition was stabilized against the background of therapy by separate active agents in the same dosages appointed in the form of separate drugs have 12,5 mg of a hydrochlorothiazide. A usual dose — 1 tablet of 1 times a day. As well as any other medical supplies which accept   1 time a day the medicine (M) Lisinopril + Hydrochlorthiazidum should be accepted approximately in one and too time every day.

If it is not possible to reach the desirable therapeutic effect within 2–4 weeks of treatment, the dose can be raised to 2 tablets of 1 times a day.

The previous therapy by diuretics. After reception of the first dose of HP Lisinopril + Hydrochlorthiazidum can develop symptomatic hypotension; development of this state is more probable at patients with exhaustion of a reserve of liquid and/or salt as a result of the previous therapy by diuretics. Therapy by diuretics should be stopped in 2–3 days prior to therapy of HP Lisinopril + Hydrochlorthiazidum. If it is impossible, it is necessary to begin treatment with separate components in a low dose (lisinopril in a dose of 5 mg).

Patients with a renal failure. The HP Lisinopril + Hydrochlorthiazidum cannot be applied as initial therapy at patients with a renal failure.

At patients with a slight or moderate renal failure (clearance of creatinine> 30 and <80 ml/min.) the HP Lisinopril + Hydrochlorthiazidum can be applied only after titration of a dose of separate components. In this case the recommended dose of the lisinopril appointed in the form of separate drug makes 5–10 mg.

Patients of advanced age. It is known that efficiency and portability of lisinopril and Hydrochlorthiazidum at their co-administration were identical both at patients of advanced age, and at younger patients with the arterial hypertension (AH). In the range of dosages from 20 mg to 80 mg elderly people (65 years and are more senior) had an identical efficiency of lisinopril and younger patients with AG. At patients of advanced age with AG monotherapy by lisinopril was also effective concerning decrease in the diastolic ABP, as well as monotherapy by Hydrochlorthiazidum or atenololy. If at the patient of advanced age depression of function of kidneys is revealed, it is necessary to correct an initial dose of lisinopril. (see the subsection "Patients with a Renal Failure").

Dividing risk on a tablet it is intended only for medicine reception simplification by the patient and does not serve for division into equal doses.

Features of use:

Symptomatic hypotension. Most often the expressed decrease in the ABP arises at decrease in volume of the circulating blood caused by therapy by diuretics, reduction of amount of salt in food, dialysis, diarrhea or vomiting (see. "Interaction with other medicines" and "Side effect"). At patients with chronic heart failure with a simultaneous renal failure or without it, development of symptomatic hypotension is possible. It comes to light at patients with severe forms of heart failure, as a result of use of high doses of diuretics, a hyponatremia or an impaired renal function more often. At such patients treatment should be begun under strict control of the doctor. The similar rules should follow at appointment as the patient with coronary heart disease, cerebrovascular insufficiency at which sharp decrease in the ABP can lead to a myocardial infarction or a stroke.

Tranzitorny hypotensive reaction is not a contraindication for reception of the following dose of drug.

Renal failure. At patients with chronic heart failure, the expressed decrease in the ABP after an initiation of treatment with APF inhibitors can lead to further deterioration in renal function.

Cases of an acute renal failure are noted.

Patients with a bilateral stenosis of renal arteries or a stenosis have arteries of the only kidney, the receiving APF inhibitors, increase in urea and creatinine in blood serum, usually reversible after the treatment termination was noted. Met at patients with a renal failure more often.

The increased sensitivity / the Quincke's disease. The Quincke's disease of the person, extremities, lips, language, an epiglottis and/or a throat (can arise during any period of treatment) was noted seldom at the patients treated by APF inhibitors including lisinopril. In that case treatment by lisinopril needs to be stopped as soon as possible and for the patient to establish observation before full regression of symptoms. The state most often undergoes in cases when hypostasis arose only on a face and lips, without treatment, however, perhaps purpose of antihistaminic drugs.

Ангионевротическй hypostasis with hypostasis of a throat can be fatal. When are captured language, the epiglottis or a throat can occur obstruction of respiratory tracts therefore it is necessary to carry out immediately the corresponding therapy (0,3-0,5 ml solution of Epinephrinum (adrenaline) 1:1000 subcutaneously) and/or measures for ensuring passability of respiratory tracts.

At patients who in the anamnesis already had a Quincke's disease which is not connected with the previous treatment by APF inhibitors the risk of its development can be increased during treatment by APF inhibitor (see the section "Contraindications").

Cough. At use of APF inhibitor cough was noted. Cough dry, long which disappears after the treatment termination by APF inhibitor. At the differential diagnosis of cough, it is necessary to consider also the cough caused by APF inhibitor use.

The patients who are on dialysis. Anaphylactic reaction is noted also at the patients subjected to a hemodialysis with use of dialysis membranes with high-permeability which at the same time accept APF inhibitors. In such cases it is necessary to consider the possibility of use of other type of a membrane for dialysis or other anti-hypertensive means.

Surgery / General anesthesia. At use of means, the reducing ABP, for patients at extensive surgical intervention or during the general anesthesia, lisinopril can block formation of angiotensin II.

The expressed decrease in the ABP which is considered the investigation of this mechanism can be eliminated with increase in volume of the circulating blood.

Before surgical intervention (including stomatology) it is necessary to warn the surgeon/anaesthesiologist about use of APF inhibitors.

Potassium in serum. The hyperpotassemia was in certain cases noted. Risk factors for development of a hyperpotassemia include a renal failure, a diabetes mellitus, administration of drugs of potassium or the drugs causing increase in potassium concentration in blood (for example, heparin), especially at patients with disturbance with function of kidneys.

At patients who have a risk of symptomatic hypotension (being on a low-salt or electrolyte-deficient diet) with or without hyponatremia, and also at patients who received high doses of diuretics the above-named states before an initiation of treatment need to be compensated (loss of liquid and salts).

Metabolic and endocrine effects. Thiazide diuretics can influence tolerance to glucose therefore it is necessary to adjust doses of antidiabetic medicines.

Thiazide diuretics can reduce releases of calcium with urine and cause a hypercalcemia. The expressed hypercalcemia can be a symptom of the hidden hyperparathyreosis, it is recommended to stop treatment by thiazide diuretics before test according to function of epithelial bodies.

During treatment of HP Lisinopril + Hydrochlorthiazidum is necessary regular control in a blood plasma of potassium, glucose, urea, fats and creatinine.

During treatment it is not recommended to take alcoholic beverages as alcohol strengthens hypotensive effect of drug.

It is necessary to be careful when performing physical exercises, hot weather (risk of development of dehydration and excessive decrease in the ABP because of decrease in volume of the circulating blood).

Laboratory indicators. Drug can influence results of the following laboratory analyses: Hydrochlorthiazidum in a blood plasma can reduce the level of the iodine connected with proteins (treatment by Hydrochlorthiazidum should be stopped before carrying out laboratory inspection for epithelial body function assessment) and to increase concentration of free bilirubin in a blood plasma.

Use during pregnancy and feeding by a breast. Use of APF inhibitors is not recommended in the I trimester of pregnancy (see sections of "Precautionary measure" and "Contraindication"). Use of APF inhibitors is contraindicated in II and III trimesters of pregnancy (see sections of "Precautionary measure" and "Contraindication").

The available data on risk of development of teratogenic effect at influence of APF inhibitors in the I trimester of pregnancy were not final; however it is impossible to exclude slight increase of this risk. While therapy continuation by APF inhibitors is considered necessary, the patients planning pregnancy have to be transferred to the alternative anti-hypertensive therapy including the drugs having the established safety profile for use during pregnancy. If pregnancy occurred, treatment by APF inhibitors has to be immediately stopped and if it is possible, alternative therapy has to be begun (see the section "Contraindications").

Use of APF inhibitors in II and III trimesters of pregnancy, as we know, causes fetotoksichesky effects in the person (depression of function of kidneys, олигогидрамнион, delay of ossification of bones of a skull) and neonatal toxicity (a renal failure, hypotension, a hyperpotassemia). If in the III trimester of pregnancy APF inhibitors were applied, ultrasonic monitoring of bones of a skull and function of kidneys is recommended. Newborns whose mothers accepted APF inhibitors have to be under careful observation in connection with possible development of arterial hypotension (see sections of "Contraindication" and "Use").

Use of diuretics for healthy pregnant women is not recommended as the woman and a fruit are exposed to unnecessary danger, including possible development of jaundice of a fruit and the newborn, thrombocytopenia and other side reactions, similar, noted at adult patients.

Hydrochlorthiazidum cannot be applied to treatment of hypostases, AG or a preeclampsia at pregnant women as instead of beneficial effect on the course of a disease it increases risk of reduction of volume of plasma and worsens uteroplacental blood supply.

The lisinopril which got through a placenta was removed from a blood-groove of newborns by peritoneal dialysis that gave a certain clinical advantage. Theoretically he can be brought from an organism by means of exchange hemotransfusion. Experience of removal from a blood-groove of newborns of Hydrochlorthiazidum which also gets through a placenta, no.

Use of HP Lisinopril + Hydrochlorthiazidum contraindicated during feeding by a breast (see the section "Contraindications"). Lisinopril gets into breast milk of rats. It is unknown whether lisinopril gets into breast milk of the person, and also whether Hydrochlorthiazidum in quantity which, presumably, even in therapeutic doses can influence the child gets into it.

Children. Lisinopril + Hydrochlorthiazidum is not intended to HP for use for children. Safety and efficiency of its reception at children and teenagers (aged up to 18 years) are not established.

Influence on ability to manage vehicles and to service mechanisms: during treatment patients should refrain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions since dizziness, especially at the beginning of a course of treatment is possible.

Cautions and special instructions. Double blockade renin-angiotensin-aldosteronovoy Double system blokadarenin-angiotensin-aldosteronovoy of system is associated with the increased risk of development of hypotonia, a hyperpotassemia and renal failures (including an acute renal failure) in comparison with monotherapy. Double blockade of RAAS about use of IAPF, SCONCE of II, or Aliskirena cannot be recommended to any patient, especially patients with a diabetic nephropathy.

In some cases, when joint by use of IAPF and SCONCE of II it is absolutely shown, careful observation of the specialist and obligatory monitoring of function of kidneys, water and electrolytic balance, arterial pressure is necessary. It belongs to purpose of a kandesartan or valsartan as additional therapy to APF inhibitors at patients with chronic heart failure. Carrying out double blockade of RAAS under careful observation of the specialist and obligatory monitoring of function of kidneys, water and electrolytic balance and arterial pressure, is possible at patients with chronic heart failure at intolerance of antagonists of Aldosteronum (Spironolactonum) at whom the persistirovaniye of symptoms of chronic heart failure, despite performing other adequate therapy is observed.

Side effects:

Against the background of reception of separate components it was reported about side reactions which can potentially develop also against the background of reception       of HP Lisinopril + Hydrochlorthiazidum.

The side effects caused by lisinopril and other APF inhibitors.

From blood and lymphatic system: lymphadenopathy, anemia, agranulocytosis, oppression of function of marrow, hemolitic anemia, leukopenia, thrombocytopenia, neutropenia, autoimmune diseases.

From cardiovascular system: a heart consciousness, tachycardia, arterial hypotension (including orthostatic hypotension), disturbance of cerebral circulation, Reynaud's phenomenon, balance disturbance, a myocardial infarction or a stroke, perhaps, owing to the expressed arterial hypotension at patients of group of high risk.

Mental disturbances: change of mood, sleep disorder, confusion of consciousness, disorientation.

From a nervous system: dizziness, balance disturbance, paresthesia, headache, taste disturbance, disturbance of sense of smell.

From an acoustic organ and balance: вертиго.

From respiratory system, bodies of a thorax and a mediastinum: cough, bronchospasm, short wind, rhinitis, sinusitis, allergic alveolitis, eosinophilic pneumonia, upper respiratory tract infections.

From a GIT: diarrhea, vomiting, nausea, dryness in a mouth, a glossitis, pancreatitis, a Quincke's disease of intestines, abdominal pain, digestion disturbance, a loss of appetite, a lock.

From gepatobiliarny system: hepatitis, hepatocellular or cholestatic jaundice, liver failure **.

From skin and hypodermic cellulose: rash, hypersensitivity, a Quincke's disease, a symptom complex, an alopecia, a small tortoiseshell, an itch, psoriasis, the strengthened sweating, feeling of heat, a dermahemia, skin disturbances (a pempigus, a toxic epidermal necrolysis, Stephens-Johnson's syndrome, a multiformny erythema, a skin pseudo-lymphoma).

Disturbances of metabolism and food: hypoglycemia.

From a musculoskeletal system and connecting fabric: muscular spasm, muscular weakness.

From endocrine system: disturbance of secretion of antidiuretic hormone.

From kidneys and urinary tract: oliguria/anury, dysfunction of kidneys, acute renal failure (ARF), proteinuria.

Complications of the general character: increased fatigue, an adynamy, discomfort in a breast.

From reproductive system and mammary glands: impotence, gynecomastia.

Laboratory indicators: increase in activity of liver enzymes, increase in concentration of creatinine of a blood plasma, increase in urea of blood, decrease in a hemoglobin content, decrease in a hematocrit, blood plasma bilirubin.

The cough caused by therapy by APF inhibitors is characterized as constant, unproductive, disappears at drug withdrawal. It should be considered when carrying out differential diagnosis of cough.

Very seldom messages on patients at which undesirable development of hepatitis led to a liver failure took place. Patients at whom against the background of therapy jaundice developed or there was a substantial increase of activity of liver enzymes, have to stop reception of HP Lisinopril + Hydrochlorthiazidum and undergo appropriate medical examination.

It was reported about isolated cases of a Quincke's disease of the person, extremities, lips, language, a glottis and/or throat (see Precautionary measures).

It was reported about development of a symptom complex which can include one or more of the following symptoms: fever, vasculitis, mialgiya, arthralgia/arthritis, positive antinuclear antibodies (ANA), increase SOE, eosinophilia and leukocytosis, rash, photosensitization or other dermatological manifestations.

Slight increase of concentration of creatinine and urea of a blood plasma is noted. These phenomena are usually reversible at the termination of administration of drug. It was reported about insignificant decrease in values of hemoglobin and a hematocrit. It was reported about oppression of marrow that it is shown by anemia and/or thrombocytopenia. Revealed hyper - or a hypopotassemia and a hyponatremia. It was reported about isolated cases of increase in activity of liver enzymes and/or contents of the bilirubin of a blood plasma, but communication with administration of drug containing lisinopril and Hydrochlorthiazidum it is not established.

It was reported about isolated cases of the development to a syncope and a stethalgia, but communication with administration of drug containing lisinopril and Hydrochlorthiazidum it is not established.

There are messages on development of neuropathy against the background of reception of APF inhibitors.

The side effects caused by Hydrochlorthiazidum

Infections and invasions: sialadenitis.

From immune system: hypersensitivity reactions, including anaphylactic reactions, shock.

From blood and lymphatic system: leukopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anemia, hemolitic anemia, oppression of function of marrow.

Disturbance of metabolism and food: anorexia; hyperglycemia; glucosuria; a hyperuricemia which can provoke gouty attacks at patients with the asimptomny course of a disease; disturbance of balance of electrolytes, including a hyponatremia and a hypopotassemia; hypomagnesiemia; hypercalcemia; increase in level of lipids of blood; gout; decrease in a glyukozotolerantnost which can cause manifestation of a latent diabetes mellitus; a gipokhloremichesky alkalosis which can induce hepatic encephalopathy or a hepatic coma.

Mental disturbances: concern, depression, changes of mood, sleep disorder, confusion of consciousness, disorientation, drowsiness, nervousness.

From a nervous system: dizziness, headache, spasms, paresthesia.

From an organ of sight: xanthopsia, temporary vision disorder.

From an acoustic organ and balance: вертиго.

From cardiovascular system: arrhythmia, orthostatic arterial hypotension.

From respiratory system, bodies of a thorax and a mediastinum: a respiratory distress syndrome, including a pneumonitis and a fluid lungs.

From a GIT: irritation of a mucous membrane of a stomach, a lock, dryness in a mouth, thirst, nausea, vomiting.

From gepatobiliarny system: jaundice (the jaundice caused by an intra hepatic cholestasia), pancreatitis, cholecystitis.

From skin and hypodermic cellulose: vasculitis, necrotizing angiitis, toxic epidermal necrolysis, Stephens-Johnson's syndrome, photosensitivity reactions, rash, eczema, skin volchanochnopodobny reactions, reactivation of skin manifestations of a system lupus erythematosus, small tortoiseshell, purpura.

From a musculoskeletal system and connecting fabric: muscular spasm and pain.

From kidneys and urinary tract: renal failure, dysfunction of kidneys and intersticial nephrite.

From generative organs: sexual frustration.

Complications of the general character: exhaustion.

Interaction with other medicines:

Diuretics. If during therapy by lisinopril to add diuretic, the additional anti-hypertensive effect will be gained.

After reception of the first dose of HP Lisinopril + Hydrochlorthiazidum can develop symptomatic hypotension; emergence of this state is more probable at patients with deficit of liquid and/or salt in an organism because of the previous therapy by diuretics. Therapy by diuretics has to be stopped prior to therapy of HP Lisinopril + Hydrochlorthiazidum (see the section "Precautionary measures").

The nutritional supplements containing the potassium, kaliysberegayushchy diuretics or substitutes of salt containing potassium. Removal of potassium from an organism against the background of reception of thiazide diuretics is usually weakened by kaliysberegayushchy effect of lisinopril. Use of the nutritional supplements containing potassium of the kaliysberegayushchy substances or substitutes of salt containing potassium, especially at patients with an impaired renal function can lead to significant increase in content of potassium in a blood plasma. If simultaneous use of HP Lisinopril + Hydrochlorthiazidum and the use of any of these substances is obviously necessary, they have to be used with care against the background of frequent control of content of potassium in a blood plasma (see the section "Precautionary measures").

Tricyclic antidepressants / antipsychotic drugs / anesthetics. Simultaneous use of some anesthetics, tricyclic antidepressants or antipsychotic drugs and APF inhibitors can lead to additional decrease in the ABP (see the section "Precautionary measures").

Narcotic drugs / antipsychotic drugs. Against the background of reception of APF inhibitors orthostatic arterial hypotension can develop.

Barbiturates or drugs. There can be strengthening of orthostatic hypotension.

Non-steroidal anti-inflammatory drugs (NPVP). Prolonged use of NPVP (the selection TsOG-2 inhibitors, acetylsalicylic acid> of 3 g/days and non-selective NPVP) can reduce hypotensive action both APF inhibitor, and a tiazid. Simultaneous use of NPVP and APF inhibitors can worsen function of kidneys. This effect is usually reversible. In rare instances OPN, first of all at patients with an impaired renal function as it happens at people of advanced age and at patients to dehydration can develop.

At some patients reception of NPVP can reduce diuretic, natriuretic and anti-hypertensive effects of diuretics.

It was reported about the increase in level of potassium in a blood plasma caused by NPVP and APF inhibitors that can lead to a renal failure.

Sympathomimetics. Sympathomimetics can reduce expressiveness of hypotensive effect of APF inhibitors.

Other anti-hypertensive drugs. The anti-hypertensive effect of HP Lisinopril + Hydrochlorthiazidum can be strengthened at simultaneous use of other medicines that is probably capable to cause orthostatic hypotension. Simultaneous use of glyceryl of trinitrate and other nitrates or other vazodilatator can reduce in addition the ABP.

Acetylsalicylic acid, trombolitik, blockers of β-adrenoceptors, nitrates. The HP Lisinopril + Hydrochlorthiazidum can be applied along with acetylsalicylic acid (in cardiological doses), trombolitika, blockers of β-adrenoceptors and/or and/or nitrates.

Antidiabetic drugs. It is known that simultaneous use of APF inhibitors and antidiabetic drugs (insulin, peroral hypoglycemic drugs) can lead to strengthening of antihyperglycemic action with risk of development of a hypoglycemia. The possibility of development of this phenomenon is more probable during the first 2 weeks of a combination therapy and at patients with an impaired renal function.

Decrease in a glyukozotolerantnost therefore there can be a need for change of dosing of antidiabetic medicine is possible.

Anti-gouty means (пробенецид, Sulfinpyrazonum and Allopyrinolum). Simultaneous use of APF inhibitors and Allopyrinolum increases risk of injury of kidneys and can lead to increase in risk of development of a leukopenia.

There can be a need for dose adjustment of uricosuric means as Hydrochlorthiazidum can increase the level of uric acid in a blood plasma. Perhaps, there will be a need for increase in a dose of a probenetsid or Sulfinpyrazonum. At simultaneous use of tiazid increase in frequency of reactions of hypersensitivity to Allopyrinolum is possible.

Cyclosporine. Simultaneous use of APF inhibitors and cyclosporine increases risk of injury of kidneys and a hyperpotassemia.

Lovastatin. Simultaneous use of APF inhibitors and a lovastatin increases risk of a hyperpotassemia.

Cytostatics, immunosuppressants, procaineamide. Simultaneous use with APF inhibitors can lead to increase in risk of a leukopenia.

Gold. Nitritoidny reactions (vazodilatation symptoms, including a hyperemia, nausea, dizziness and arterial hypotension which can be shown in a severe form) owing to gold injections (for example sodium ауротиомалат) are noted more often at patients who at the same time accept lisinopril.

B Amphotericinum (parenterally), карбеноксолон, glucocorticoids, AKTG or the stimulating laxatives. Hydrochlorthiazidum can aggravate disturbances of water and electrolytic balance, especially a hypopotassemia.

Cardiac glycosides. There is an increased risk of overdose of cardiac glycosides in connection with the hypopotassemia caused by tiazida.

Colestyraminum and колестипол. Can reduce or worsen absorption of Hydrochlorthiazidum therefore the HP Lisinopril + Hydrochlorthiazidum should be taken at least for 1 h or in 4–6 h after reception of these medicines.

Not depolarizing muscular relaxants (for example tubocurarine). Hydrochlorthiazidum can strengthen effect of these drugs.

The medicines causing tachycardia on type a pirouette. Owing to risk of development of a hyperpotassemia simultaneous use of Hydrochlorthiazidum and drugs which effects are influenced by changes of level of potassium in a blood plasma and which can cause ventricular tachycardia on type a pirouette should be carried out with care. Periodic monitoring of level of potassium in a blood plasma and ECG inspection is recommended if Hydrochlorthiazidum is accepted along with drugs which effects are influenced by changes of level of potassium in a blood plasma and the following drugs causing polymorphic tachycardia like pirouette (ventricular tachycardia), including some antiarrhytmic means:

- antiarrhytmic means of the class Ia (for example quinidine, hydroquinidine, Disopyramidum);

- antiarrhytmic means of a class III (for example Amiodaronum, соталол, дофетилид, ибутилид);

- some neuroleptics (for example, thioridazine, Chlorpromazinum, levomepromazinum, трифторперазин, циамемазин, Sulpiridum, сультоприд, амисульпирид, тиаприд, Pimozidum, haloperidol, Droperidolum);

- other medicines (for example, bepridit, цизаприд, difemanit, erythromycin for in/in introductions, галофантрин, мизоластин, pentamidine, терфенадин, Vincaminum for in/in introductions).

Sotalol. The hypopotassemia caused by tiazida can increase risk of development of the arrhythmia caused sotaloly.

Lithium drugs. Lithium drugs are usually not appointed along with diuretics or APF inhibitors. Diuretic drugs and APF inhibitors reduce renal clearance of lithium and increase risk of intoxication lithium. If after all there is a need of use of this combination of drugs, the level of lithium should be controlled carefully (see the section of the Precautionary measure).

Trimethoprimum. Simultaneous use of APF inhibitors and tiazid with Trimethoprimum increases risk of a hyperpotassemia.

Corticosteroids, AKTG. The strengthened loss of electrolytes, especially a hypopotassemia.

Pressor amines (for example Epinephrinum). Decrease in the response to influence of pressor amines, but not so is possible to stop their use.

Alcohol. Alcohol can strengthen hypotensive effect of any anti-hypertensive drugs.

Antacids. Reduce bioavailability of APF inhibitors.

Metforminum. Apply with care, considering risk of lactat acidosis at the expense of the possible functional renal failure caused by Hydrochlorthiazidum.

Anticholinergics (atropine, Biperidinum). Because of easing of motility of the digestive tract (DT) and reduction in the rate of evacuation from a stomach bioavailability of diuretics of thiazide type increases.

Cytotoxic means (for example, cyclophosphamide, methotrexate). Tiazida can reduce removal of cytotoxic drugs kidneys and exponentiate their miyelosupressorny effect.

Methyldopum. It was reported about isolated cases of developing of hemolitic anemia at simultaneous use of Hydrochlorthiazidum and Methyldopums.

Influence on results of laboratory analyses. By means of influence on exchange of calcium of a tiazida can influence results of assessment of function of epithelial body.

Carbamazepine. Considering risk of a symptomatic hyponatremia, it is necessary to carry out clinical and biological monitoring.

Iodinated contrast means. In case of dehydration induced by diuretics the risk of development of OPN increases, it is preferential at use of high doses of iodinated contrast means. Patients need a regidratation before administration of iodinated drugs.

Blockers of β-adrenoceptors and diazoxide. Simultaneous use of thiazide diuretics, including Hydrochlorthiazidum, and blockers of β-adrenoceptors can increase risk of a hyperglycemia. Thiazide diuretics, including Hydrochlorthiazidum, can strengthen hyper glycemic effect of diazoxide.

Amantadin. Tiazida, including Hydrochlorthiazidum, can increase risk of development of the side effects caused amantadiny.

Double blockade system renin-angiotensin-aldosteronovoy

On the basis of the available data, double blockade of RAAS using IAPF, the SCONCE of II or Aliskiren cannot be recommended to any patient, especially patients with a diabetic nephropathy.

At patients with a diabetes mellitus or a moderate / heavy renal failure (SKF <60 ml/min. / 1,73 sq.m) simultaneous use of Aliskiren with IAPF or BRAII is contraindicated.

In some cases, when joint by use of IAPF and SCONCE of II it is absolutely shown, careful observation of the specialist and obligatory monitoring of function of kidneys, water and electrolytic balance, arterial pressure is necessary.

Contraindications:

— a Quincke's disease (including the Quincke's edema in the anamnesis connected using APF inhibitors);

— anury;

— the expressed renal failure (the clearance of creatinine (CC) less than 30 ml/min.);

— a hemodialysis with use of high-flowing membranes;

— hypercalcemia;

— hyponatremia;

— porphyria;

— prekoma;

— hepatic coma;

— severe forms of a diabetes mellitus;

— age up to 18 years (efficiency and safety are not established);

— hypersensitivity to drug components;

— hypersensitivity to other APF inhibitors.

Simultaneous use of inhibitors of an angiotensin-converting enzyme or blockers of receptors of AT2 with Aliskiren at patients with a diabetes mellitus or a moderate/heavy renal failure (SKF <60 ml/min. / 1,73 sq.m) is contraindicated.

With care: an aortal stenosis / a hypertrophic cardiomyopathy, a bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney with the progressing azotemia, a state after transplantation of kidneys, a renal failure (KK more than 30 ml/min.), primary hyper aldosteronism, arterial hypotension, a marrow hypoplasia, a hyponatremia (the increased risk of development of arterial hypotension in the patients who are on a low-salt or electrolyte-deficient diet), hypovolemic states (including diarrhea, vomiting), diseases of connecting fabric (including a system lupus erythematosus, a scleroderma), a diabetes mellitus, gout, oppression of a marrowy hemopoiesis, a hyperuricemia, a hyperpotassemia, the coronary heart disease (CHD), cerebrovascular diseases (including insufficiency of cerebral circulation), heavy chronic heart failure, a liver failure, advanced age.

Overdose:

There is no special information on treatment of overdose of lisinopril/Hydrochlorthiazidum.

Lisinopril. Symptoms. The most probable symptoms of overdose are arterial hypotension, disturbance of electrolytic balance, a renal failure, circulator shock, a hyperventilation of lungs, tachycardia (cardiopalmus), bradycardia, dizziness, concern and cough.

Hydrochlorthiazidum. The signs and symptoms caused by elimination of electrolytes (a hypopotassemia, a hypochloraemia, a hyponatremia) and dehydration owing to excessive reception of diuretics are most often noted: spasms; paresis; renal failure; consciousness oppression, including a coma.

Symptoms. Tachycardia, shock, weakness, confusion of consciousness, dizziness, a spasm of muscles, paresthesia, exhaustion, disorders of consciousness, nausea, vomiting, thirst, a polyuria, an oliguria, an anury, a hypopotassemia, a hyponatremia, a hypochloraemia, an alkalosis, the increased urea nitrogen level in blood (generally renal failure). At co-administration of cardiac glycosides the hypopotassemia can strengthen cardiac arrhythmia.

Treatment. A symptomatic treatment and supporting. Therapy of HP Lisinopril + Hydrochlorthiazidum has to be stopped, and also it is necessary to establish careful observation of a condition of the patient. Therapeutic measures depend on character and weight of symptoms. It is necessary to take measures for prevention of absorption and to use elimination acceleration methods.

In case of development of heavy arterial hypotension of the patient it is necessary to lay on a back with the raised lower extremities and to quickly begin infusion of normal saline solution. It is possible to consider the possibility of treatment by angiotensin II (if it is available). As well as all APF inhibitors, lisinopril it can be removed from the general blood-groove by a hemodialysis (see the section "Pharmacological Properties"). It is necessary to avoid use of a poliakrilnitrilovy dialysis membrane with high hydraulic permeability. It is necessary to control electrolytes and creatinine of a blood plasma. For treatment of resistant bradycardia installation of a pacemaker is shown. It is necessary to carry out frequent monitoring of the main vital signs, electrolytes and creatinine of a blood plasma.

If as a result of these actions do not achieve desirable result, it is necessary in/in introduction of catecholamines. Bradycardia can be also reduced by means of atropine use.

Storage conditions:

In the place protected from light and moisture at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Medicine cannot be used after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging. 3 or 6 blister strip packagings together with a leaf insert place in a pack from a cardboard (No. 10х3, No. 10х6).