Expiration date: 09/2025

Release form and composition:

Tablets light orange, round, flat, engraved FH on one side, allowed the presence of marbling.

1 tablet contains:

sodium fosinopril 20 mg

hydrochlorothiazide 12.5 mg

Excipients: lactose monohydrate, sodium croscarmellose, starch pregelatinized (starch 1500), glycerol dibehenate, pigment RV-23601 (titanium dioxide, lactose monohydrate, iron oxide yellow, iron oxide red).

14 PCs. - blisters (2) - packs of cardboard.

Pharmacological action:

Antihypertensive combination drug. Fosinopril - ACE inhibitor. In the body of fosinopril formed active metabolite-fosinoprilat, which prevents the conversion of angiotensin I to angiotensin II. It has antihypertensive, vasodilating, diuretic and potassium-sparing effect. Reduces round and AD. Inhibits the synthesis of aldosterone, inhibits tissue ACE.

Hydrochlorothiazide is a thiazide diuretic. Affects the mechanism of reabsorption of electrolytes in the renal tubules, increasing the release of sodium and chlorine ions to about the same extent, as well as potassium and bicarbonate ions. Increases plasma renin activity, aldosterone secretion and reduces the concentration of potassium ions in the blood serum.

Fosinopril and hydrochlorothiazide have an additive effect. Fosinopril reduces the loss of potassium ions caused by the intake of hydrochlorothiazide.

The antihypertensive effect is seen after 1 h of ingestion, reaches a maximum value after 2-6 h. the Decline in AD 24 hours is 60-90% of your maximum AP reduction that allows you to take the drug 1 time/day.

Pharmacokinetics:

Pharmacokinetics of fosinopril and hydrochlorothiazide while receiving no different from that in their separate appointment.

Fosinopril

Pharmacokinetics fosinoprila is linear.

Suction

After oral absorption from the gastrointestinal tract is approximately 30-40%. The degree of absorption does not depend on the meal, but the rate of absorption can be slow. Fosinoprilata Cmax in plasma is reached after approximately 3 h and does not depend on the dose fosinoprila.

Distribution

Fosinoprilat highly bound to plasma proteins (90-95%) and slightly associated with cellular blood components. Has a relatively small Vd.

Metabolism

50-100% absorbirowawrzayasa fosinoprila is hydrolyzed in the liver to fosinoprilata. With impaired liver function, the rate of hydrolysis can be slowed down, while the degree of hydrolysis does not change significantly.

Breeding

In patients with hypertension in normal renal and liver function T1/2 fosinoprilata is approximately 11.5 no.

Pharmacokinetics in special clinical cases

In renal insufficiency, absorption, bioavailability and binding of fosinopril to plasma proteins does 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 the 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 an average degree of renal failure from that in patients with severe renal failure. In renal insufficiency of varying degrees, including end-stage renal insufficiency (CC less than 10 ml/min/1.73 m2), there is a moderate increase in AUC (less than 2 times compared with that in patients with normal renal function). Fosinoprilat clearance in hemodialysis and peritoneal dialysis is on average 2% and 7% compared to urea clearance.

The degree of hydrolysis of fosinoprilat in alcoholic or biliary cirrhosis decreases slightly, despite the fact that the rate of hydrolysis can be reduced. Cmax and AUC fosinoprilata higher in patients with liver failure after the first dose, but with the introduction of repeated doses, this difference has no clinical significance.

Hydrochlorothiazide

Suction and distribution

After oral absorption from the gastrointestinal tract is 60-80%. Cmax in plasma is achieved through 1-5 h after oral administration.

The plasma protein binding is 64%.

Metabolism and excretion

Hydrochlorothiazide is not metabolized and is rapidly excreted in the urine. T1/2 is 5-15 hours

Indications:

• arterial hypertension (in cases where combination therapy is indicated).
  

Dosage regimen:

The dose is selected individually. Average dose - 1 tablet 1 time / day.

Tablets are taken orally, regardless of the time of meal, with a sufficient amount of liquid.

In mild to moderate renal impairment (CC more than 30 ml / min, serum creatinine approximately 3 mg/DL or 265 µmol / l), a normal dose of Nosicarda is recommended. When QC less than 30 ml / min drug is not recommended. In severe renal impairment administered loop diuretics.

In violation of liver function dose adjustment is not required.

When prescribing the drug to elderly patients, it should be borne in mind that they may be more sensitive to the action of the drug due to slow metabolism.

Side effect:

Side effects observed when applying Fozikard N similar with the side effects observed when applying each drug separately.

From the Central and peripheral nervous system: the most common (2% of patients) - dizziness, headache, fatigue sometimes - drowsiness, depression, paresthesia, hearing loss.

From the respiratory system: the most common (2% of patients) - cough sometimes - nasal congestion, pharyngitis, rhinitis.

From the musculoskeletal system: the most common (2% of patients) - musculoskeletal pain sometimes-cramps.

From the cardiovascular system: orthostatic hypotension, blood flow to the skin, fainting, swelling, heart rhythm disorders, chest pain.

From the sexual system: decrease in sexual function, change in libido.

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

From the urinary system: increased urination, dysuria.

Dermatological reactions: rash, itching.

On the part of laboratory parameters: reducing the concentration of potassium ions, sodium, chlorine, magnesium, glucose, increasing the concentration of calcium ions, uric acid in the blood, increasing cholesterol and triglycerides, neutropenia.

Allergic reactions: angioedema, urticaria.

Other: chills.

Side effects described in the application of fosinopril:

From the cardiovascular system: decrease in blood PRESSURE, orthostatic collapse, tachycardia, palpitations, arrhythmia, angina, myocardial infarction.

From the digestive system: nausea, diarrhea, intestinal obstruction, pancreatitis, hepatitis, cholestatic jaundice, abdominal pain, vomiting, constipation, decreased appetite, stomatitis, glossitis, increased activity of liver enzymes, hyperbilirubinemia.

From the respiratory system: dry cough, pulmonary infiltrates, bronchospasm, shortness of breath, rhinorrhea, pharyngitis, dysphonia.

CNS and peripheral nervous system: stroke, cerebral ischemia, dizziness, headache, weakness, disturbances of hearing and vision, tinnitus when used in high doses - insomnia, anxiety, depression, confusion, disorders of the vestibular apparatus, paresthesia.

From the laboratory parameters: increase of urea concentration, hypercreatininemia, hyperkalemia, hyponatremia, decrease in the concentration of hemoglobin and hematocrit, increased erythrocyte sedimentation rate.

Side effects described in the application of hydrochlorothiazide:

From the digestive system: dry mouth, nausea, vomiting, diarrhea, hemorrhagic pancreatitis, acute cholecystitis (due to cholelithiasis).

CNS: weakness, fatigue, dizziness, and headache.

From the cardiovascular system: palpitations, orthostatic hypotension, thrombosis, thromboembolism, vasculitis.

Laboratory parameters: hypokalemia, hypomagnesemia, hyponatremia, hyperuricemia, hypercalcemia, hyperglycemia, neutropenia, thrombocytopenia.

From the urinary system: hypercreatinemia, acute interstitial nephritis.

Allergic reactions: dermatitis.

Other: cramps of calf muscles, exacerbation of gout, progression of myopia.

Contraindications:

• hereditary or idiopathic angioedema (including after taking other ACE inhibitors history)
  
• severe renal failure (Cct30 ml / min / 1.73 m2))
  
• anuria
  
• gout
  
• expressed violations of electrolyte balance
  
• pregnancy
  
• lactation (breastfeeding) period)
  
• child and adolescence to 18 years
  
• hypersensitivity to fosinopril and other components of the drug, other ACE inhibitors, to sulfonamide derivatives, including thiazides.
  

With caution, the drug should be prescribed for hypotension, connective tissue diseases (including SLE, scleroderma), hepatic impairment or progressive liver disease (small changes in fluid and electrolyte balance may cause hepatic coma), metabolic acidosis, impaired renal function, renal artery stenosis or stenosis of artery only kidneys (may increase the concentration of urea nitrogen and serum creatinine blood), violations of blood (agranulocytosis, neutropenia), conditions, accompanied by a decrease in BCC (diarrhea, vomiting), aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary artery disease, chronic heart failure, with a diet with salt restriction, conditions after kidney transplantation, diabetes, as well as elderly patients.

Pregnancy and lactation:

The drug is contraindicated in pregnancy and lactation.

Special instruction:

Before starting therapy with Fostermom N it is necessary to conduct correction of fluid and electrolyte balance. Fosinopril can cause symptomatic hypotension, which is most likely in patients with reduced BCC as a result of prolonged prior treatment with diuretics, limiting salt intake, dialysis, diarrhea or vomiting.

Hypotension is not an absolute contraindication for further use of the Nosicardium. The maximum decrease in blood PRESSURE is noted in the early stages of treatment and is stabilized usually at 2 weeks of therapy. With further use of the drug, a decrease in its therapeutic effectiveness is not observed.

When using ACE inhibitors, including fosinopril, angioedema may develop. With edema of the tongue, pharynx, larynx, airway obstruction may develop. Patients should stop taking the drug and immediately inform the doctor about the appearance of swelling on the face, eyes, lips and tongue, spasm of the larynx muscles or difficulty breathing. In such cases, urgent action is needed quickly.

You should also exercise caution when assigning Fozikard N during the procedures of desensitization.

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

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

In patients with 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 after cessation of treatment. In such patients, it is necessary to monitor renal function during the first two weeks of treatment. It may be necessary to reduce the dose.

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 strengthen oliguria or azotemia, and in rare cases lead to death. Therefore, in such patients, the use of Fozikard N should start with minimum therapeutic doses and under the strict control of blood pressure, especially during the first two weeks of treatment.

Hydrochlorothiazide can cause hypokalemia, hyponatremia and hypochloremic alkalosis. In the presence of fosinopril, the risk of hypokalemia decreases.

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. It is necessary to periodically monitor the concentration of electrolytes in the blood serum.

The concentration of uric acid in the blood may increase, and some patients taking thiazide diuretics may develop an acute attack of gout.

In patients with diabetes, the need for insulin may change, latent forms of diabetes may acquire a manifest form against the background of the use of thiazide diuretics. Increasing the concentration of triglycerides and cholesterol is associated with the treatment of thiazide diuretics.

Cough caused by ACE inhibitors, including fosinopril, is usually unproductive and persistent, and passes after discontinuation of drugs. Cough caused by ACE inhibitors 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 lightning necrosis of hepatocytes.

Use in Pediatrics

Safety and efficacy of the drug Fozikard N in children and adolescents under the age of 18 years have not been established.

Overdose:

Symptoms: expressed lower AD, aetiology, shock, violation vodno-elektrolitnogo balance, acute renal failure, stupor.

Treatment: give the patient a lying position with raised legs. In mild cases, gastric lavage, artificial vomiting, the introduction of adsorbents and sodium sulfate for 30 minutes after taking the drug are indicated. By reducing HELL - in/in the introduction of catecholamines, angiotensin II, when bradycardia - use of pejjsmeker. The drug is not excreted in hemodialysis and peritoneal dialysis.

Drug interaction:

With the simultaneous use of drugs potassium, potassium-spiking diuretics (spironolactone, amiloride, triamteren) increases the risk of hyperkalemia. It is necessary to control the level of potassium in the blood serum (1 every 2-3 weeks).

Used with other antihypertensive drugs, diuretics, opioid analgesics, funds for General anesthesia increase gipotenzivne Fozikard N.

Fosicard N with simultaneous use enhances the hypoglycemic effect of sulfonylurea derivatives, insulin.

While the use of Fozikard N with allopourinolom, cytostatics, immunosuppressants, procainamide increases risk of leukopenia.

NSAIDs reduce the severity of antigipertenzivnogo effect Fozikard N.

At the same time taking the Nosicard H with lithium salts may increase the concentration of lithium in the blood serum and the risk of lithium toxicity.

While the use of Fostermom N may require higher doses probenecida or sulfinpirazon, used to treat gout, as hydrochlorothiazide may increase the concentration of uric acid in the blood.

Antacids (aluminium or magnesium hydroxide), simethicone can reduce the absorption Fozikard N. Take these drugs should be at intervals of not less than 2 h

Colestyramine resin and colestipol can decrease the absorption of hydrochlorothiazide. Fozikard N should be taken at least 1 hour before or 4-6 hours after administration of these funds.

Hydrochlorothiazide can increase the concentration of calcium ions in the blood serum by reducing its excretion from the body. While the use of Fostermom N may require a dose reduction of calcium.

Bioavailability of the drug while the use of chlorthalidone, nifedipine, propranolol, cimetidine, metoclopramide, propanthelin bromide, digoxin, acetylsalicylic acid and warfarin does not change.

Absorption of hydrochlorothiazide is enhanced when administered simultaneously with drugs that reduce the motility of the gastrointestinal tract.

Terms and conditions of storage:

The drug should be stored out of reach of children at temperature not exceeding 25°C. shelf Life - 2 years.