Fosinap^® (Tablets) Instructions for Use

Marketing Authorization Holder

Canonpharma Production, CJS (Russia)

ATC Code

C09AA09 (Fosinopril)

Active Substance

Fosinopril (Rec.INN registered by WHO)

Dosage Forms

	Fosinap®	Tablets 10 mg: 7, 10, 14, 15, 20, 28 or 30 pcs.
		Tablets 20 mg: 7, 10, 14, 15, 20, 28 or 30 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, flat-cylindrical, with a bevel.

Excipients: colloidal silicon dioxide – 0.7 mg, croscarmellose sodium – 5 mg, lactose monohydrate – 66.8 mg, macrogol (polyethylene glycol 4000) – 0.5 mg, sodium stearyl fumarate – 1 mg, povidone – 7 mg, microcrystalline cellulose – 47.88 mg, calcium stearate – 1.12 mg.

7 pcs. – contour cell packs (1) – cardboard packs.
7 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
15 pcs. – contour cell packs (1) – cardboard packs.
15 pcs. – contour cell packs (2) – cardboard packs.
30 pcs. – contour cell packs (1) – cardboard packs.

Tablets white or almost white, flat-cylindrical, with a bevel.

Excipients: colloidal silicon dioxide – 1 mg, croscarmellose sodium – 5.7 mg, lactose monohydrate – 97.3 mg, macrogol (polyethylene glycol 4000) – 1 mg, sodium stearyl fumarate – 1.5 mg, povidone – 10.5 mg, microcrystalline cellulose – 71.32 mg, calcium saccharate – 1.68 mg.

7 pcs. – contour cell packs (1) – cardboard packs.
7 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
15 pcs. – contour cell packs (1) – cardboard packs.
15 pcs. – contour cell packs (2) – cardboard packs.
30 pcs. – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE blocker

Pharmacological Action

ACE inhibitor. It is a prodrug from which the active metabolite fosinoprilat is formed in the body.

The mechanism of antihypertensive action is believed to be associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II, a potent vasoconstrictor substance.

As a result of the decrease in angiotensin II concentration, a secondary increase in plasma renin activity occurs due to the elimination of the negative feedback during renin release and a direct decrease in aldosterone secretion.

In addition, fosinoprilat appears to affect the kinin-kallikrein system by preventing the breakdown of bradykinin.

Due to its vasodilating action, it reduces total peripheral vascular resistance (afterload), pulmonary capillary wedge pressure (preload) and resistance in pulmonary vessels; increases cardiac output and exercise tolerance.

Pharmacokinetics

When taken orally, it is slowly absorbed from the gastrointestinal tract.

Food intake may reduce the rate, but not the extent of absorption.

It is metabolized in the liver and in the gastrointestinal mucosa by hydrolysis to form fosinoprilat, through the pharmacological activity of which the antihypertensive effect is realized.

The binding of fosinoprilat to plasma proteins is 97-98%.

The T_1/2 of fosinoprilat is 11.5 hours.

It is excreted by the kidneys – 44-50% and through the intestine – 46-50%.

Indications

Arterial hypertension (as monotherapy or as part of combination therapy).

Chronic heart failure (as part of combination therapy).

ICD codes

Dosage Regimen

Administer orally. Individualize the dosage regimen based on blood pressure dynamics and therapy tolerability.

Initiate therapy at a recommended starting dose of 10 mg once daily.

For arterial hypertension, titrate the dose to a usual maintenance dose of 20 mg to 40 mg administered once daily. The maximum daily dose is 40 mg.

For chronic heart failure as part of combination therapy, initiate at 10 mg once daily. If the initial dose is well-tolerated, titrate upwards to a target maintenance dose of 20 mg to 40 mg once daily.

In patients at high risk for symptomatic hypotension, such as those with salt or volume depletion, consider a lower initial dose of 5 mg under close medical supervision.

Discontinue diuretic therapy 2-3 days prior to initiating fosinopril, if possible, to reduce the risk of hypotension.

For patients with renal impairment or those undergoing hemodialysis, no initial dosage adjustment is typically required; titrate dose based on clinical response.

For patients with hepatic impairment, use with caution; dose adjustment is not usually necessary.

Monitor blood pressure, renal function, and serum potassium levels regularly during therapy, especially after initiation and following dosage increases.

Adverse Reactions

Infections and infestations common – upper respiratory tract infections, pharyngitis, rhinitis, viral infections; frequency unknown – pneumonia, laryngitis, sinusitis, tracheobronchitis.

Blood and lymphatic system disorders frequency unknown – eosinophilia, leukopenia, lymphadenitis, neutropenia.

Metabolism and nutrition disorders frequency unknown – exacerbation of gout, appetite disorders, anorexia, changes in body weight, hyperkalemia.

Psychiatric disorders: common – mood changes, sleep disorders; frequency unknown – depression, behavior disorders, confusion, anxiety.

Nervous system disorders: common – dizziness, headache, paresthesia; uncommon – syncope; frequency unknown – ischemic stroke, transient ischemic attack, tremor, impaired balance, memory impairment, somnolence, acute cerebrovascular accident.

Eye and ear disorders: common – vision disorders; frequency unknown – hearing impairment, ear pain and tinnitus, dizziness.

Cardiac and vascular disorders: common – palpitations, arrhythmias, angina pectoris, pronounced decrease in blood pressure, orthostatic hypotension; uncommon – shock; frequency unknown – myocardial infarction, tachycardia, cardiac arrest, conduction disorder, hypertensive crisis, flushing, hemorrhages, arterial hypertension, peripheral vascular diseases.

Respiratory, thoracic and mediastinal disorders common – dry cough, sinus disorder; frequency unknown – dyspnea, bronchospasm, pulmonary congestion, dysphonia, epistaxis, sinusitis, chest pain.

Gastrointestinal disorders common – nausea, vomiting, diarrhea, abdominal pain, dyspepsia, dysgeusia; frequency unknown – pancreatitis, tongue edema, dysphagia, oral cavity disorder, abdominal distension, constipation, flatulence, dry mouth.

Hepatobiliary disorders: frequency unknown – hepatitis.

Skin and subcutaneous tissue disorders: common – skin rash; uncommon – angioedema; frequency unknown – hyperhidrosis, skin hemorrhages (ecchymosis), pruritus, dermatitis, urticaria.

Musculoskeletal and connective tissue disorders: common – musculoskeletal pain, myalgia; frequency unknown – muscle weakness, arthritis.

Renal and urinary disorders common – urination disorder; frequency unknown – development or worsening of symptoms of chronic renal failure.

Reproductive system and breast disorders: common – sexual dysfunction; frequency unknown – prostate disorders.

General disorders and administration site conditions: common – increased fatigue, chest pain, edema, asthenia; frequency unknown – peripheral edema, pain, fever.

Investigations: common – increased activity of hepatic transaminases, hyperbilirubinemia; uncommon – increased urea concentration, hypercreatininemia; rare – hyponatremia, decreased hemoglobin and hematocrit; frequency unknown – increased ESR.

Effects 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 ACE inhibitors (including history); hereditary or idiopathic angioedema, history of angioedema (including after taking other ACE inhibitors); simultaneous use of fosinopril with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m² body surface area); simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy; simultaneous use with neutral endopeptidase inhibitors (e.g., drugs containing sacubitril) due to the high risk of developing angioedema; pregnancy, lactation (breastfeeding); children and adolescents under 18 years of age.

With caution arterial hypotension, bilateral renal artery stenosis or stenosis of the artery of a single kidney; renal failure; condition after kidney transplantation; aortic or mitral stenosis; hypertrophic obstructive cardiomyopathy; chronic heart failure (CHF) III-IV functional class (according to NYHA classification); coronary artery disease; cerebrovascular diseases (including cerebral circulatory insufficiency); systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bone marrow hematopoiesis depression; immunosuppressive therapy, simultaneous use of allopurinol or procainamide, or a combination of these complicating factors (increased risk of neutropenia and agranulocytosis); diabetes mellitus; hyperkalemia; simultaneous use with potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes; simultaneous use with lithium preparations; burdened allergic history or history of angioedema; simultaneous desensitization; simultaneous LDL apheresis using dextran sulfate; simultaneous hemodialysis using high-flux membranes; conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting, previous diuretic treatment, adherence to a salt-restricted diet), hyponatremia (risk of dehydration, arterial hypotension, chronic renal failure); use during major surgical interventions or during general anesthesia; use in patients of the Black race; use in elderly patients.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

Fosinopril is excreted in breast milk. If it is necessary to use fosinopril during lactation, the issue of discontinuing breastfeeding should be decided.

During treatment, women of childbearing age should use reliable methods of contraception.

Use in Hepatic Impairment

Should be used with caution in patients with impaired liver function. Dose adjustment is usually not required.

Use in Renal Impairment

Should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, with renal failure, condition after kidney transplantation, with hemodialysis; with simultaneous use of fosinopril with aliskiren and drugs containing aliskiren in patients with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m² body surface area).

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated.

Geriatric Use

Should be used with caution in elderly patients. No special adjustment of the fosinopril dosage regimen is required in this category of patients.

Special Precautions

2-3 days before starting treatment with fosinopril, previous diuretic therapy is recommended to be discontinued, except for patients with malignant or treatment-resistant arterial hypertension. In such cases, fosinopril therapy should be started immediately, at a reduced dose, with careful medical supervision and cautious dose increase.

Symptomatic arterial hypotension when using ACE inhibitors most often develops in patients after intensive diuretic treatment, a diet restricting salt intake, or during renal dialysis. Transient arterial hypotension is not a contraindication for continuing treatment after measures to restore circulating blood volume.

In patients with chronic heart failure, treatment with ACE inhibitors can cause an excessive antihypertensive effect, which can lead to oliguria or azotemia with a fatal outcome. Therefore, when treating patients with chronic heart failure with fosinopril, careful clinical monitoring is necessary, especially during the first 2 weeks of treatment, as well as with any increase in the dose of fosinopril or the diuretic.

ACE inhibitors rarely cause intestinal mucosa edema. In this case, patients experience abdominal pain (sometimes without nausea and vomiting), facial edema may also be absent, C1-esterase levels are normal. After discontinuation of ACE inhibitors, the symptoms disappear. Intestinal mucosa edema should be considered in the differential diagnosis in patients with abdominal pain while taking ACE inhibitors.

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

Agranulocytosis and bone marrow function suppression may develop during treatment with ACE inhibitors. These cases are noted more often 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 treatment in patients with an increased risk of neutropenia).

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

In arterial hypertension in patients 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 renal impairment 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 fosinopril may be required.

In patients with severe chronic heart failure, with altered RAAS activity, treatment with ACE inhibitors can lead to oliguria, progressive azotemia and, in rare cases, to acute renal failure and possible death.

During therapy with fosinopril, the patient should exercise caution when performing physical exercises or in hot weather due to the risk of dehydration and arterial hypotension due to a decrease in circulating blood volume.

No special adjustment of the fosinopril dosage regimen is required in elderly patients. Before and during treatment with the drug, monitoring of blood pressure, renal function, potassium levels, hemoglobin, creatinine, urea, electrolyte concentrations and activity of hepatic transaminases in the blood is necessary.

Effect on ability to drive vehicles and operate machinery

During the use of fosinopril, patients should exercise caution when driving vehicles and operating machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with antacids, a decrease in the absorption of fosinopril is possible.

With simultaneous use with lithium carbonate, an increase in the concentration of lithium in the blood plasma and an increased risk of intoxication are possible.

With simultaneous use with indomethacin, other NSAIDs (acetylsalicylic acid), a decrease in the effectiveness of ACE inhibitors is possible.

With simultaneous use of fosinopril with diuretics, especially at the beginning of diuretic therapy, as well as in combination with a strict diet limiting salt intake, or with hemodialysis, a pronounced decrease in blood pressure may develop, especially in the first hour after taking the initial dose of fosinopril.

With simultaneous use, potassium preparations, potassium-sparing diuretics, potassium-containing salt substitutes and other drugs that can increase the potassium content in the blood serum (including ARB II, heparin, tacrolimus, cyclosporine; drugs containing co-trimoxazole), increase the risk of hyperkalemia.

With simultaneous use with antihypertensive drugs, an enhancement of the antihypertensive effect is possible.

With simultaneous use with drugs used in anesthesia, analgesics, an enhancement of the antihypertensive effect is possible.

With simultaneous use with acenocoumarol, a case of bleeding has been described.

Fosinopril enhances the hypoglycemic effect of sulfonylurea derivatives and insulin.

Fosinopril increases the risk of developing leukopenia/agranulocytosis with simultaneous use with allopurinol, cytotoxic agents, immunosuppressants, procainamide.

With simultaneous use, estrogens weaken the antihypertensive effect of fosinopril due to the ability to retain water.

In patients taking ACE inhibitors and mTOR inhibitors (temsirolimus, sirolimus, everolimus) simultaneously, an increased frequency of angioedema has been observed.

In patients taking ACE inhibitors and dipeptidyl peptidase-4 inhibitors (gliptins) simultaneously, an increased frequency of angioedema has been observed.

In patients taking estramustine simultaneously, an increased frequency of angioedema has been observed with simultaneous use with ACE inhibitors.

There is evidence of an increased risk of angioedema with simultaneous use of ACE inhibitors and neutral endopeptidase inhibitors (racecadotril).

When ACE inhibitors are used concomitantly with medicinal products containing sacubitril (a neprilysin inhibitor), the risk of angioedema increases, therefore the concomitant use of these drugs is contraindicated.

ACE inhibitors should be administered no earlier than 36 hours after the withdrawal of drugs containing sacubitril.

The administration of drugs containing sacubitril is contraindicated in patients receiving ACE inhibitors, as well as within 36 hours after the withdrawal of ACE inhibitors.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.