Fozicard N tablets 20mg + 12.5mg, No. 28

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

Inside, regardless of the time of the meal, drinking plenty of fluids. The dose is selected individually. The usual dose is 1 tablet once a day.

When creatinine clearance is less than 30 ml / min, the drug is not recommended to be used.

Loop diuretics are prescribed for patients with severe renal impairment.

For mild to moderate renal impairment (creatinine clearance more than 30 ml / min, serum creatinine approximately 3 mg / dL or 265 ?mol / L), the usual dose of Fosicard N. is recommended.

If liver function is impaired, dose adjustment is not required. Elderly patients may be more sensitive to the effects of the drug due to slow metabolism.

Each tablet contains:
Active ingredients: sodium fosinopril 20 mg and hydrochlorothiazide 12.5 mg.
Excipients: lactose monohydrate, sodium croscarmellose, pregelatinized starch (starch 1500), glycerol dibehinate, pigment mixture PB-23601: titanium dioxide, lactose monohydrate, iron oxide yellow, iron oxide red.

Hypersensitivity to the components of the drug or other ACE inhibitors, to sulfonamide derivatives, including thiazides. Genetically determined or idiopathic angioedema (including from the use of other ACE inhibitors in history), severe renal failure (creatinine clearance less than 30 ml / min. / 1.73 m2), anuria, gout, severe electrolyte imbalance, pregnancy , lactation period, age up to 18 years (efficacy and safety have not been established).

Carefully:arterial hypotension, connective tissue diseases (including systemic lupus erythematosus, scleroderma), liver dysfunction or progressive liver disease (small changes in water and electrolyte balance can cause hepatic coma), metabolic acidosis, renal impairment, renal artery stenosis or stenosis arteries of a single kidney (possibly an increase in the concentration of urea nitrogen and serum creatinine), impaired hematopoiesis (agranulocytosis, neutropenia), conditions accompanied by a decrease in circulating blood volume (diarrhea, vomiting), aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, chronic heart failure, salt-restricted diet, condition after kidney transplantation, diabetes mellitus,elderly age.

Trade name of the drug: FOSICARD N

Dosage form:

pills

Composition
Each tablet contains:
Active ingredients: sodium fosinopril 20 mg and hydrochlorothiazide 12.5 mg.
Excipients: lactose monohydrate, sodium croscarmellose, pregelatinized starch (starch 1500), glycerol dibehinate, pigment mixture PB-23601: titanium dioxide, lactose monohydrate, iron oxide yellow, iron oxide red.

Description
Light orange, round, flat, tablets with 'FH' engraving on one side, marbling allowed.

Pharmacotherapeutic group:

combined antihypertensive agent (ACE inhibitor + diuretic).

ATX code - —09 DA

Pharmacological properties
Pharmacodynamics
Fosinopril belongs to prodrugs. In the body, an active metabolite, fosinoprilat, is formed from fosinopril, which prevents the conversion of angiotensin I into angiotensin II. The drug has a hypotensive, vasodilating, diuretic and potassium-sparing effect. Reduces total peripheral resistance and systemic arterial pressure (BP). The drug inhibits the synthesis of aldosterone, inhibits tissue ACE.

Hydrochlorothiazide affects the mechanism of electrolyte reabsorption in the renal tubules, increasing the release of sodium and chlorine ions to approximately the same extent, as well as potassium and bicarbonate ions. Increases the activity of blood plasma renin, the secretion of aldosterone and reduces the concentration of potassium ions in the blood serum. Fosinopril and hydrochlorothiazide are additive.

Fosinopril reduces the loss of potassium ions caused by taking hydrochlorothiazide.

After oral administration, a decrease in blood pressure begins after 1 hour, reaching maximum values ??after 2-6 hours. The decrease in blood pressure after 24 hours is 60-90% of the maximum decrease in blood pressure, which allows you to take the drug once a day.

Pharmacokinetics The
pharmacokinetics of fosinopril and hydrochlorothiazide when taken simultaneously does not differ from that when administered separately. After oral administration, the absorption of fosinopril is approximately 30-40%, of which only 50-100% is hydrolyzed in the liver to fosinoprilat. The degree of absorption of fosinopril does not depend on food intake, but the rate of absorption may be slowed down. In case of impaired liver function, the rate of hydrolysis can be slowed down, while the degree of hydrolysis does not change noticeably.

The maximum concentration of fosinoprilat in blood plasma is reached after approximately 3 hours and does not depend on the dose of fosinopril taken. Fozinopril has linear pharmacokinetics. Fosinoprilat binds to a high degree with blood plasma proteins (90-95%) and to a small extent binds to the cellular components of the blood. Has a relatively small volume of distribution. In hypertensive patients with normal renal and hepatic function, the elimination half-life of fosinoprilat is approximately 11.5 hours.

After oral administration, the absorption of hydrochlorothiazide is 60-80%. The maximum concentration of hydrochlorothiazide in the blood is reached within 1-5 hours after ingestion. Plasma protein binding is 64%. Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. The half-life is 5-15 hours.

Renal failure: in renal failure, absorption, bioavailability and binding of the drug to blood plasma proteins do not change significantly. The total clearance of fosinoprilat in patients with renal insufficiency is almost 50% lower than in patients with normal renal function. Since excretion through the liver with bile partially compensates for the decrease in excretion through the kidneys, the clearance of fosinoprilat does not differ significantly in patients with moderate renal failure from that in patients with severe renal failure. In patients with renal failure of varying degrees, including renal failure in the terminal stage (creatinine clearance less than 10 ml / min. / 1,73 m 2), there is a moderate increase in the area under the concentration-time curve (AUC) (less than 2 times compared with that in patients with normal renal function). The clearance of fosinoprilat during hemodialysis and peritoneal dialysis is on average 2% and 7% compared to the clearance of urea.

Hepatic failure: The degree of hydrolysis of fosinoprilat in patients with alcoholic or biliary cirrhosis decreases insignificantly, despite the fact that the rate of hydrolysis may be reduced. The maximum concentration and AUC of fosinoprilat are higher in patients with hepatic impairment after taking the first dose, however, with the introduction of repeated doses, this difference has no clinical significance.

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

Contraindications
Hypersensitivity to the components of the drug or other ACE inhibitors, to sulfonamide derivatives, including thiazides. Genetically determined or idiopathic angioedema (including from the use of other ACE inhibitors in history), severe renal failure (creatinine clearance less than 30 ml / min / 1.73 m2), anuria, gout, severe electrolyte imbalance, pregnancy , lactation period, age up to 18 years (efficacy and safety have not been established).

Carefully:arterial hypotension, connective tissue diseases (including systemic lupus erythematosus, scleroderma), liver dysfunction or progressive liver disease (small changes in water and electrolyte balance can cause hepatic coma), metabolic acidosis, renal impairment, renal artery stenosis or stenosis arteries of a single kidney (possibly an increase in the concentration of urea nitrogen and serum creatinine), impaired hematopoiesis (agranulocytosis, neutropenia), conditions accompanied by a decrease in circulating blood volume (diarrhea, vomiting), aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, chronic heart failure, salt-restricted diet, condition after kidney transplantation, diabetes mellitus,elderly age.

Method of administration and dosage
Inside, regardless of the time of the meal, with a sufficient amount of liquid. The dose is selected individually. The usual dose is 1 tablet once a day.

When creatinine clearance is less than 30 ml / min, the drug is not recommended to be used.

Loop diuretics are prescribed for patients with severe renal impairment.

For mild to moderate renal impairment (creatinine clearance more than 30 ml / min, serum creatinine approximately 3 mg / dL or 265 ?mol / L), the usual dose of Fosicard N. is recommended.

If liver function is impaired, dose adjustment is not required. Elderly patients may be more sensitive to the effects of the drug due to slow metabolism.

Side effect
Side effects with the use of Fozicard N are similar to the side effects observed with the use of each drug separately.

Most often (in 2% of patients) there are: dizziness, headache, cough, musculoskeletal pain, feeling of fatigue.

General: chest pains, fatigue, chills.

From the side of the cardiovascular system: orthostatic hypotension, 'hot flushes' of blood to the skin of the face, fainting, edema, heart rhythm disturbances.

From the endocrine system: decreased sexual function, changes in libido.

From the immune system: angioedema.

From the digestive tract: nausea, vomiting, diarrhea, heartburn, abdominal pain, gastritis, esophagitis.

Musculoskeletal system: muscle pain, cramps.

Respiratory system: sinus congestion, pharyngitis, rhinitis.

From the urinary system: increased urination, dysuria.

From the side of the central nervous system: drowsiness, depression, paresthesia.

From the senses: hearing loss.

From the side of the skin: rash, including urticaria, itching.

On the part of laboratory indicators: a decrease in the concentration of potassium, sodium, chlorine, magnesium, glucose ions, an increase in the concentration of calcium ions, uric acid in the blood, an increase in cholesterol and triglycerides, neutropenia.

Side effects described when using fosinopril:
From the cardiovascular system: decreased blood pressure, orthostatic collapse, tachycardia, palpitations, arrhythmia, angina pectoris, myocardial infarction.

From the digestive tract: nausea, diarrhea, intestinal obstruction, pancreatitis, hepatitis, cholestatic jaundice, abdominal pain, vomiting, constipation, loss of appetite, stomatitis, glossitis.

From the respiratory system: dry cough, pulmonary infiltrates, bronchospasm, shortness of breath, rhinorrhea, pharyngitis, dysphonia. Allergic, toxic-allergic and immunopathological reactions.

From the side of the central nervous system: stroke, cerebral ischemia, dizziness, headache, weakness; when used in high doses, insomnia, anxiety, depression, confusion, disorders of the vestibular apparatus, paresthesia.

From the senses: hearing and visual impairment, tinnitus.

On the part of laboratory parameters: an increase in the concentration of urea, an increase in the activity of 'hepatic' enzymes, hypercreatininemia, hyperbilirubinemia, hyperkalemia, hyponatremia; a decrease in the concentration of hemoglobin and hematocrit, an increase in the erythrocyte sedimentation rate (ESR).

Side effects described with hydrochlorothiazide:
Dry mouth, nausea, vomiting, diarrhea; weakness, increased fatigue, dizziness, headache, palpitations, calf muscle cramps, hypokalemia, hypomagnesemia, hyponatremia, hyperuricemia, hypercalcemia, hyperglycemia; exacerbation of gout, thrombosis, thromboembolism, hypercreatininemia, acute interstitial nephritis, vasculitis, progression of myopia, neutropenia, thrombocytopenia, hemorrhagic pancreatitis, acute cholecystitis (against the background of cholelithiasis), orthostatic hypotension, allergic dermatitis.

Overdose
Symptoms: marked decrease in blood pressure, bradycardia, shock, imbalance in water and electrolyte balance, acute renal failure, stupor.
Treatment: place the patient in a 'lying' position with raised legs. In mild cases of overdose - induce vomiting and / or gastric lavage, administration of adsorbents and sodium sulfate within 30 minutes after ingestion. With a decrease in blood pressure, intravenous administration of catecholamines, angiotensin II; with bradycardia - the use of a pacemaker. The drug is not excreted during hemodialysis and peritoneal dialysis.

Interaction with other drugs
Potassium preparations, potassium-sparing diuretics (spironolactone, amiloride, triamterene) increase the risk of hyperkalemia. It is necessary to control the level of potassium in the blood serum (once every 2-3 weeks).

Antihypertensive drugs, diuretics, narcotic analgesics, agents for general anesthesia enhance the hypotensive effect of Fozicard N.

When taken simultaneously with lithium salts, an increase in the concentration of lithium in the blood serum and the risk of developing lithium toxicity are possible.

The drug enhances the hypoglycemic effect of sulfonylurea derivatives, insulin, the risk of leukopenia when used simultaneously with allopurinol, cytostatic JIC, immunosuppressants, procainamide.

Drugs for the treatment of gout. You may need to increase the dose of probenecid or sulfinpyrazone used to treat gout because hydrochlorothiazide can increase the concentration of uric acid in the blood.

Non-steroidal anti-inflammatory drugs reduce the severity of the hypotensive effect.

Alcohol, barbiturates and narcotic analgesics can reduce the hypotensive effect of the drug.

Colestyramine resin and colestipol may reduce the absorption of hydrochlorothiazide. Fozicard N should be taken at least 1 hour before or 4-6 hours after taking the indicated funds.

Calcium salts. Hydrochlorothiazide can increase the concentration of calcium ions in the blood serum by reducing its excretion from the body. With simultaneous use with Fozicard N, a decrease in the dose of calcium preparations may be required. The bioavailability of the drug when used simultaneously with chlorthalidone, nifedipine, propranolol, cimetidine, metoclopramide, propantheline bromide, digoxin, acetylsalicylic acid and warfarin does not change. The absorption of hydrochlorothiazide increases with the simultaneous administration of drugs that reduce the motility of the gastrointestinal tract.

Antacids (aluminum or magnesium hydroxide, simethicone and others) can reduce the absorption of Fozicard N. These funds should be taken at intervals of at least 2 hours.

Special instructions
To start therapy with Fozikard N should be with the adjustment of the water-electrolyte balance. Fosinopril can cause symptomatic arterial hypotension, which is most likely in patients with reduced circulating blood volume as a result of long-term previous treatment with diuretics, restriction of salt intake, dialysis, diarrhea or vomiting.

Arterial hypotension is not an absolute contraindication for the further use of Fozicard N. The maximum decrease in blood pressure is observed in the early stages of treatment and usually stabilizes at 2 weeks of therapy. With further use of the drug, a decrease in its therapeutic efficacy is not observed.

With the use of ACE inhibitors, including fosinopril, angioedema may develop. With swelling of the tongue, pharynx, larynx, airway obstruction may develop. Patients should stop taking the drug and immediately inform their doctor about the appearance of edema on the face, eyes, lips and tongue, spasm of the muscles of the larynx or shortness of breath.

In such cases, it is necessary to quickly take emergency measures. Care should also be taken when treating patients with ACE during desensitization procedures.

During hemodialysis through highly permeable membranes, as well as during apheresis of low density lipoproteins with adsorption to dextran sulfate, anaphylactic reactions may occur. In these cases, a different type of dialysis membrane or other medication should be used.

In patients with impaired renal function, especially in the presence of systemic connective tissue diseases, agranulocytosis and suppression of bone marrow function may develop. In this case, you should monitor the content of white blood cells in such patients. Such patients should be warned about the need to report any signs of infection - fever, sore throat, etc.

Care should be taken when prescribing the drug to patients with severe renal impairment. In patients with arterial hypertension with renal artery stenosis of one or both kidneys, as well as with the simultaneous use of diuretics during treatment with ACE inhibitors, the level of blood urea nitrogen and serum creatinine may increase. These effects are reversible and disappear after stopping treatment. In such patients, it is necessary to monitor kidney function during the first 2 weeks of treatment. A dose reduction may be required.

In patients with severe heart failure, oliguria and / or progressive azotemia in the presence or absence of renal failure, treatment with ACE inhibitors can cause an excessive hypotensive effect, which can increase oliguria or azotemia, and in rare cases, lead to death. Therefore, in such patients, drug treatment should be started with minimal therapeutic doses and under strict control of blood pressure, especially during the first 2 weeks of treatment.

Hydrochlorothiazide can cause hypokalemia, hyponatremia, and hypochloremic alkalosis. In the presence of fosinopril sodium, the risk of hypokalemia is reduced. Hydrochlorothiazide helps to reduce the excretion of calcium ions from the body, increase the excretion of magnesium ions in the urine, which can lead to hypomagnesemia. Periodic monitoring of the concentration of electrolytes in serum is necessary.

The concentration of uric acid in the blood may rise, and some people taking thiazide diuretics may develop an acute attack of gout. In patients with diabetes mellitus, the need for insulin may change, latent forms of diabetes mellitus may acquire a manifest form against the background of the use of thiazides. An increase in the concentration of triglycerides and cholesterol is associated with treatment with thiazide diuretics.

The cough caused by ACE inhibitors, including fosinopril, is usually nonproductive and persistent and resolves when the drug is stopped. ACE inhibitor cough should be considered as one of the options in the differential diagnosis of cough.

In rare cases, the use of ACE inhibitors can lead to the appearance of cholestatic jaundice with the development of fulminant necrosis of hepatocytes.

The efficacy and safety of the drug in children has not been established.

Release form
Tablets.

7 tablets in a PVC / aluminum foil blister; 2 blisters with instructions for use in a cardboard box.

7 tablets in a PVC / aluminum foil blister; 4 blisters with instructions in a cardboard box.

10 tablets in a PVC / aluminum foil blister; 1 blister with instructions in a cardboard box.

10 tablets in a PVC / aluminum foil blister; 3 blisters with instructions in a cardboard box.

14 tablets in a PVC / aluminum foil blister; 1 blister with instructions in a cardboard box.

14 tablets in a PVC / aluminum foil blister; 2 blisters with instructions in a cardboard box.

Storage conditions
At a temperature not exceeding 25 ? —.
Keep out of the reach of children!

Shelf life is
2 years.
The drug should not be used after the expiry date indicated on the package.

Terms of dispensing from pharmacies
On prescription.