Fosicard (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group PTC ehf. (Iceland)

Manufactured By

Balkanpharma-Dupnitsa, AD (Bulgaria)

ATC Code

C09AA09 (Fosinopril)

Active Substance

Fosinopril (Rec.INN registered by WHO)

Dosage Forms

	Fosicard	Tablets 5 mg: 28 or 30 pcs.
		Tablets 10 mg: 28 or 30 pcs.
		Tablets 20 mg: 28 or 30 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat-cylindrical, marked “FL 5”.

Excipients: lactose monohydrate – 59 mg, sodium croscarmellose – 2 mg, pregelatinized corn starch (starch 1500) – 12 mg, microcrystalline cellulose – 20 mg, glyceryl dibehenate – 2 mg.

7 pcs. – blisters (4) – cardboard packs^×.
10 pcs. – blisters (3) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.

Tablets white or almost white, round, flat-cylindrical, marked “FL 10”.

Excipients: lactose monohydrate – 118 mg, sodium croscarmellose – 4 mg, pregelatinized corn starch (starch 1500) – 24 mg, microcrystalline cellulose – 40 mg, glyceryl dibehenate – 4 mg.

7 pcs. – blisters (4) – cardboard packs^×.
10 pcs. – blisters (3) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.

Tablets white or almost white, round, flat-cylindrical, marked “FL 20”.

Excipients: lactose monohydrate – 108 mg, sodium croscarmellose – 4 mg, pregelatinized corn starch (starch 1500) – 24 mg, microcrystalline cellulose – 40 mg, glyceryl dibehenate – 4 mg.

7 pcs. – blisters (4) – cardboard packs^×.
10 pcs. – blisters (3) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.

^× protective stickers may additionally be applied.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE inhibitor

Pharmacological Action

ACE inhibitor. Fosinopril is a prodrug from which the active metabolite fosinoprilat is formed in the body. The drug has antihypertensive, vasodilating, diuretic and potassium-sparing effects.

Fosinoprilat prevents the conversion of angiotensin I to the vasoconstrictor substance angiotensin II, which leads to vasodilation and reduced aldosterone secretion. Reduces total peripheral resistance and systemic blood pressure. Suppresses aldosterone synthesis, inhibits tissue ACE. The antihypertensive effect is also due to the suppression of bradykinin metabolism, which has a pronounced vasodilating effect.

The decrease in blood pressure is not accompanied by a change in blood volume, cerebral and renal blood flow, blood supply to internal organs, skeletal muscles, skin, or reflex activity of the myocardium.

The antihypertensive effect of the drug persists during long-term treatment, and tolerance to the drug does not develop. After oral administration, the antihypertensive effect develops within 1 hour, reaches a maximum after 2-6 hours and lasts for 24 hours.

Pharmacokinetics

Absorption

After oral administration, absorption from the gastrointestinal tract is about 30-40%. The degree of absorption does not depend on food intake, but the rate of absorption may be slowed. The time to reach C_max in blood plasma is 3 hours and does not depend on the dose taken.

Distribution

Plasma protein binding of fosinoprilat is 95%. Fosinoprilat has a relatively small V_d and binds to a small extent to blood cellular components. Does not penetrate the blood-brain barrier.

Elimination

Fosinopril is eliminated from the body equally through the liver and kidneys. In patients with arterial hypertension with normal renal and hepatic function, the T_1/2 of fosinoprilat is approximately 11.5 hours. In patients with heart failure, the T_1/2 value is 14 hours.

Pharmacokinetics in special patient groups

In patients with impaired renal function (creatinine clearance less than 80 ml/min/1.73 m²), the total clearance of fosinopril from the body is approximately half that of patients with normal renal function, while absorption, bioavailability and plasma protein binding do not change significantly. Reduced renal excretion is compensated by increased hepatic excretion. A moderate increase in plasma AUC values (less than double compared to normal) is observed in patients with varying degrees of renal failure, including end-stage renal failure (creatinine clearance less than 10 ml/min/1.73 m²). The clearance of fosinopril during hemodialysis and peritoneal dialysis averages 2% and 7%, respectively, relative to urea clearance values.

In patients with impaired liver function (with alcoholic or biliary cirrhosis), the rate of hydrolysis of fosinopril may be reduced, but the degree of hydrolysis does not change significantly. The total clearance of fosinopril from the body of such patients is approximately half compared to patients with normal liver function.

Indications

• Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs /in particular, with thiazide diuretics/);
• Chronic heart failure (as part of combination therapy).

ICD codes

Dosage Regimen

The drug is taken orally. The dose should be selected individually.

For arterial hypertension, the recommended initial dose of the drug is 10 mg once a day. The dose of the drug must be selected depending on the dynamics of blood pressure. The maintenance dose is 10-40 mg once a day. If there is insufficient therapeutic effect, additional prescription of diuretics is possible.

If treatment with Fosicard is started against the background of ongoing diuretic therapy, its initial dose should be no more than 10 mg with careful medical monitoring of the patient’s condition.

For chronic heart failure, the recommended initial dose is 5 mg once or twice a day. Depending on the therapeutic effectiveness, the dose can be increased at weekly intervals up to a maximum daily dose of 40 mg once a day.

In case of impaired renal and/or hepatic function, dose adjustment of the drug is not required.

No differences in the effectiveness and safety of treatment with the drug are observed in patients aged 65 years and older and young patients. However, greater susceptibility to the drug in some elderly patients cannot be ruled out, due to possible overdose phenomena due to delayed elimination of the drug.

Adverse Reactions

From the cardiovascular system excessive decrease in blood pressure, orthostatic hypotension, tachycardia, palpitations, arrhythmias, angina pectoris, myocardial infarction, chest pain, facial flushing, hypertensive crisis, cardiac arrest, fainting.

From the digestive system nausea, vomiting, constipation, intestinal obstruction, pancreatitis, hepatitis, stomatitis, glossitis, dyspeptic symptoms, abdominal pain, anorexia, intestinal edema, cholestatic jaundice, dysphagia, flatulence, appetite disturbance, change in body weight, dry oral mucosa.

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

From the urinary system development or worsening of symptoms of chronic renal failure, proteinuria, oliguria.

From the central nervous system stroke, cerebral ischemia, dizziness, headache, weakness; when used in high doses – insomnia, anxiety, depression, confusion, paresthesia, drowsiness.

From the senses: hearing and vision impairment, tinnitus.

Allergic reactions: skin rash, itching, angioedema.

From the hematopoietic organs lymph node inflammation.

From the musculoskeletal system arthritis.

From metabolism exacerbation of gout.

From laboratory parameters hypercreatininemia, increased urea concentration, increased activity of liver transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia; decrease in hemoglobin and hematocrit, neutropenia, leukopenia, eosinophilia, increased ESR.

Effect on the fetus impaired fetal kidney development, decreased blood pressure in the fetus and newborns, impaired renal function, hyperkalemia, skull bone hypoplasia, oligohydramnios, limb contractures, pulmonary hypoplasia.

Contraindications

• Hypersensitivity to fosinopril and other components of the drug;
• Hereditary and/or idiopathic angioedema (including history) after taking other ACE inhibitors;
• Pregnancy;
• Lactation period (breastfeeding);
• Age under 18 years (efficacy and safety have not been established);
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

With caution, the drug should be used in renal failure, hyponatremia (risk of dehydration, arterial hypotension, chronic renal failure), bilateral renal artery stenosis or stenosis of the artery of a single kidney, aortic stenosis, condition after kidney transplantation, during desensitization, systemic connective tissue diseases, including systemic lupus erythematosus, scleroderma (increased risk of developing neutropenia or agranulocytosis), during hemodialysis, cerebrovascular diseases (including cerebral circulatory insufficiency), coronary artery disease, chronic heart failure of functional class III and IV according to the NYHA classification, diabetes mellitus, bone marrow depression, hyperkalemia, when following a diet with limited salt, in conditions accompanied by a decrease in blood volume (including diarrhea, vomiting), in elderly patients.

Use in Pregnancy and Lactation

Fosicard is contraindicated for use during pregnancy. The use of ACE inhibitors in the II and III trimesters of pregnancy causes damage or even death of the developing fetus. Newborns whose mothers took ACE inhibitors during pregnancy are recommended to be closely monitored for the timely detection of arterial hypotension, oliguria and hyperkalemia.

Fosinopril is excreted in breast milk, so it is not recommended to take the drug during lactation. If the use of the drug during this period is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

In case of impaired liver function, dose adjustment of the drug is not required.

Use in Renal Impairment

In case of impaired renal function, dose adjustment of the drug is not required.

The drug should be used with caution in renal failure.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

With caution, the drug should be used in elderly patients.

Special Precautions

Before starting treatment, it is necessary to analyze previous antihypertensive therapy, the degree of blood pressure increase, dietary restrictions on salt and/or fluid and other clinical circumstances.

Patients with severe arterial hypertension or concomitant decompensated chronic heart failure should begin treatment with Fosicard in a hospital setting.

Before and during treatment with the drug, monitoring of blood pressure, renal function, potassium levels, hemoglobin, creatinine, urea, electrolyte concentrations and activity of liver transaminases in the blood is necessary.

Angioedema

Cases of angioedema have been reported in patients using Fosicard. Swelling of the tongue, pharynx, or larynx may cause airway obstruction with possible fatal outcome. If such reactions develop, it is necessary to stop taking the drug, administer a solution of epinephrine (adrenaline) (1:1000) subcutaneously and carry out other emergency therapy measures.

Intestinal mucosal edema

Edema of the intestinal mucosa has rarely been observed during the use of ACE inhibitors. These patients complained of abdominal pain (while nausea and vomiting may be absent), in some cases, intestinal mucosal edema occurred without facial edema, C1-esterase levels were normal. Symptoms disappeared after discontinuation of ACE inhibitors. Intestinal mucosal edema should be included in the differential diagnosis of patients taking ACE inhibitors who complain of abdominal pain.

Anaphylactic reactions during dialysis using high-permeability membranes may develop in patients using ACE inhibitors during hemodialysis with high-permeability membranes, as well as during LDL apheresis with dextran sulfate adsorption. In these cases, the possibility of using a different type of dialysis membrane or another antihypertensive therapy should be considered.

Neutropenia/agranulocytosis

Agranulocytosis and bone marrow suppression may develop during treatment with ACE inhibitors. These cases are more common in patients with impaired renal function, especially in the presence of systemic connective tissue diseases (systemic lupus erythematosus or scleroderma). Before starting therapy with ACE inhibitors and during treatment, the total number of leukocytes and the leukocyte formula are determined (once a month during the first 3-6 months of treatment and in the first year of using the drug in patients at increased risk of neutropenia).

Arterial hypotension

In patients with uncomplicated arterial hypertension, arterial hypotension may develop due to the use of Fosicard.

Symptomatic arterial hypotension when using ACE inhibitors most often develops in patients after intensive treatment with diuretics, a diet limiting salt intake, or during renal dialysis. Transient arterial hypotension is not a contraindication for the use of the drug after measures to restore blood volume.

In patients with chronic heart failure, treatment with ACE inhibitors may cause an excessive antihypertensive effect, which can lead to oliguria or azotemia with a fatal outcome. Therefore, when treating chronic heart failure with Fosicard, patients should be carefully monitored, especially during the first 2 weeks of treatment, as well as with any increase in the dose of Fosicard or the diuretic.

A reduction in the diuretic dose may be required in patients with hyponatremia and patients previously intensively treated with diuretics. Arterial hypotension is not a contraindication for further use of Fosicard. Some reduction in systemic blood pressure is a common and desirable effect at the beginning of drug use in heart failure. The degree of this reduction is greatest in the early stages of treatment and stabilizes within one or two weeks from the start of treatment. Blood pressure usually returns to pre-treatment values without reducing therapeutic effectiveness.

Impaired liver function

If noticeable jaundice and a pronounced increase in liver enzyme activity appear, treatment with Fosicard should be discontinued and appropriate treatment prescribed.

Impaired renal function

In patients with arterial hypertension with bilateral renal artery stenosis or stenosis of the artery of a single kidney, as well as with simultaneous use of diuretics without signs of impaired renal function during treatment with ACE inhibitors, the concentration of blood urea nitrogen and serum creatinine may increase. These effects are usually reversible and disappear after discontinuation of treatment. A reduction in the dose of the diuretic and/or Fosicard may be required.

In patients with severe chronic heart failure, with altered activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors can lead to oliguria, progressive azotemia and, in rare cases, to acute renal failure and possible death.

Surgical interventions/general anesthesia

ACE inhibitors may enhance the antihypertensive effect of agents used for general anesthesia. Before surgery (including dentistry), it is necessary to warn the surgeon/anesthesiologist about the use of ACE inhibitors.

Caution should be exercised when driving vehicles or performing other work that requires increased attention, as dizziness may occur, especially after the initial dose of an ACE inhibitor in patients taking diuretics.

Caution should be exercised during physical exercise or in hot weather due to the risk of dehydration and arterial hypotension due to a decrease in blood volume.

Use in pediatrics

The safety and effectiveness of the use of Fosicard in children have not been established.

Effect on the ability to drive vehicles and mechanisms

Caution should be exercised when driving vehicles and working with mechanisms that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms excessive decrease in blood pressure, bradycardia, shock, disturbance of water-electrolyte balance, acute renal failure, stupor.

Treatment administration of the drug should be discontinued; gastric lavage, intake of sorbents (for example, activated charcoal), vasopressor agents, infusion of 0.9% sodium chloride solution and further symptomatic and supportive treatment are indicated. The use of hemodialysis is ineffective.

Drug Interactions

Concomitant use of antacids (for example, aluminum or magnesium hydroxide, simethicone) may reduce the absorption of Fosicard. Therefore, these agents should be used at an interval of at least 2 hours.

When ACE inhibitors are used concomitantly with lithium salts, the serum lithium concentration and the risk of lithium intoxication may increase; therefore, Fosicard and lithium preparations should be used concomitantly with caution.

NSAIDs may reduce the antihypertensive effect of other ACE inhibitors, especially in patients with arterial hypertension and low plasma renin concentration.

Concomitant use with diuretics, in combination with a strict diet limiting salt intake, or with dialysis, may lead to an excessive decrease in blood pressure, especially during the first hour after taking the initial dose of Fosicard.

Potassium preparations, potassium-sparing diuretics (amiloride, spironolactone, triamterene) increase the risk of hyperkalemia. In patients with heart failure, diabetes mellitus, who are simultaneously taking potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes or other agents causing hyperkalemia (for example, heparin), ACE inhibitors increase the risk of increased serum potassium levels.

Fosinopril enhances the hypoglycemic effect of sulfonylurea derivatives, insulin.

Fosinopril increases the risk of leukopenia when used concomitantly with allopurinol, cytotoxic agents, immunosuppressants, procainamide.

Estrogens weaken the antihypertensive effect of fosinopril due to their ability to retain water.

Antihypertensive drugs, narcotic analgesics, agents for general anesthesia enhance the hypotensive effect of Fosicard.

The bioavailability of the drug when used concomitantly with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline bromide, digoxin, acetylsalicylic acid and warfarin does not change.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

FOSI-RU-00004-DOC-PHARM

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.