Ramipril-SZ, tablets 5 mg 30 pcs

A ACE inhibitor. It is a prodrug from which the active metabolite ramiprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I into angiotensin II, which is a powerful vasoconstrictor. The decrease in angiotensin II concentration results in a secondary increase in plasma renin activity by eliminating the negative feedback of renin release and directly reducing aldosterone secretion. Due to its vasodilator effect, it decreases RPO (post-load), congestion pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; it increases cardiac minute volume and exercise tolerance.

In patients with signs of chronic heart failure after myocardial infarction, ramipril reduces the risk of sudden death, progression of heart failure to severe/resistant failure, and reduces hospitalizations for heart failure.

Ramipril is known to significantly reduce the incidence of myocardial infarction, stroke and cardiovascular death in patients with increased cardiovascular risk due to vascular disease (CHD, previous stroke or peripheral vascular disease) or diabetes with at least one additional risk factor (microalbuminuria, arterial hypertension, high total cholesterol, low HDL, smoking). Reduces overall mortality and the need for revascularization procedures, slows the onset and progression of chronic heart failure. Both in patients with and without diabetes mellitus, ramipril significantly reduces the existing microalbuminuria and the risk of nephropathy. These effects are noted in patients with both elevated and normal BP.

The hypotensive effect of ramipril develops in approximately 1-2 h, peaks within 3-6 h, and lasts at least 24 h.

Pharmacokinetics

In oral administration, absorption is 50-60%; food does not affect the degree of absorption but slows absorption. Cmax is reached after 2-4 hours. It is metabolized in the liver with the formation of the active metabolite ramiprilat (6 times more active ACE inhibitor than ramipril), inactive diketopiperazine and glucuronidized.

All formed metabolites, except for ramiprilat, have no pharmacological activity. Binding to plasma proteins for ramipril is 73%, for ramiprilat – 56%. Bioavailability after oral administration of 2.5-5 mg of ramipril is 15-28%; for ramiprilat it is 45%. After daily administration of ramipril at a dose of 5 mg/day, steady plasma concentration of ramiprilat is reached by day 4.

The T1/2 for ramipril is 5.1 h; in the distribution and elimination phase, serum ramiprilat concentrations fall with a T1/2 of 3 h, followed by a transient phase with a T1/2 of 15 h, and a prolonged end phase with very low plasma ramiprilat concentrations and T1/2 of 4-5 days. T1/2 is increased in chronic renal failure.

The Vd of ramipril is 90 L, of ramiprilat is 500 L. The kidneys excreted 60%, through the intestine – 40% (mainly as metabolites). In renal dysfunction excretion of ramipril and its metabolites slows down in proportion to the decrease of CK; in liver dysfunction conversion to ramiprilat slows down; in heart failure concentration of ramiprilat is 1.5-1.8 times higher.

Indications

Active ingredient

Composition

Active ingredient:

Ramipril – 5 mg;

Ancillary substances:

lactose monohydrate 143.5 mg,

magnesium stearate 1.5 mg.

How to take, the dosage

It is taken orally. The initial dose is 1.25-2.5 mg 1-2 times a day.

If necessary, the dose can be gradually increased.

The maintenance dose is adjusted individually, depending on the indication for use and effectiveness of the treatment.

Interaction

Concomitant use of potassium-saving diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and food supplements containing potassium may cause hyperkalemia (especially in patients with renal impairment) because ACE inhibitors decrease aldosterone content, which leads to potassium retention in the body against limiting potassium excretion or its additional intake into the body.

Concomitant use with NSAIDs may decrease the hypotensive effect of ramipril and impair renal function.

In concomitant use with loop or thiazide diuretics the antihypertensive effect is increased. Severe arterial hypotension, especially after the first dose of the diuretic appears to be due to hypovolemia, which leads to transient enhancement of hypotensive effect of ramipril. There is a risk of hypokalemia development. There is an increased risk of impaired renal function.

Concomitant use with agents with hypotensive effect may increase the hypotensive effect.

Concomitant use with immunosuppressants, cystostatics, allopurinol, procainamide may increase the risk of leukopenia.

Concomitant use with insulin, hypoglycemic agents with sulfonylurea derivatives, metformin may lead to hypoglycemia.

Concomitant use with allopurinol, cystostatics, immunosuppressants, procainamide may increase the risk of leukopenia.

Concomitant use with lithium carbonate may increase the concentration of lithium in the blood serum.

Special Instructions

In patients with concomitant renal dysfunction, doses are adjusted individually according to CK values. All patients should undergo renal function tests before initiation of treatment.

When treating with ramipril the renal function, electrolyte composition of blood, level of liver enzymes in blood, as well as peripheral blood count are regularly monitored (especially in patients with diffuse connective tissue diseases, in patients receiving immunosuppressants, allopurinol).

Patients with fluid and/or sodium deficiency should have correction of water-electrolyte disorders before starting treatment. During treatment with ramipril hemodialysis using polyacrylonitrile membranes should not be performed (increased risk of anaphylactic reactions).

Contraindications

Side effects

Cardiovascular system and blood (hematopoiesis, hemostasis): hypotension (10.7%), including postural (2.2%), angina (2.9%), syncope (2.1%), heart failure (2%), myocardial infarction (1.7%), vertigo (1.5%), chest pain (1.1%), in less than 1% – arrhythmia, palpitation, hemolytic anemia, myelodepression, pancytopenia, thrombocytopenia, eosinophilia, agranulocytosis; vasculitis.

Gastrointestinal organs: nausea (2.2%), vomiting (1.6%), diarrhea (1.1%), in less than 1% – dry mouth or increased salivation, anorexia, dyspepsia, dysphagia, constipation, abdominal pain, gastroenteritis, pancreatitis, hepatitis, liver dysfunction (cholestatic jaundice, fulminant necrosis of liver with fatal outcome), changes in transaminase levels.

Nervous system and sensory organs: dizziness (4.1%), headache (1.2%), asthenia (0.3%), in less than 1% – cerebrovascular disorders, amnesia, somnolence, seizures, depression, sleep disorders, neuralgia, neuropathy, paresthesia, tremor, hearing loss, vision disorders.

Respiratory system: non-productive cough (7.6%), upper respiratory tract infections, in less than 1% – dyspnea, pharyngitis, sinusitis, rhinitis, tracheobronchitis, laryngitis, bronchospasm.

Urogenital system: renal dysfunction (1.2%), less than 1% – proteinuria, oliguria, edema; impotence.

Skin disorders: urticaria, prurigo, rash, erythema multiforme, photosensitization.

Other: in less than 1% – weight loss, anaphylactoid reactions, increased levels of urea nitrogen and creatinine, angioedema (0.3%), arthralgia/arthritis, myalgia, fever, increased antinuclear antibody titer, hyperkalemia, changes in enzyme activity, concentration of bilirubin, uric acid, glucose.

Overdose

Symptoms: excessive peripheral vasodilation with development of marked BP decrease, shock; bradycardia, water-electrolyte disorders, acute renal failure, stupor.

The treatment: gastric lavage, administration of adsorbents, sodium sulfate (if possible during the first 30 minutes). In case of marked BP decrease, administration of alpha1-adrenergic agonists (norepinephrine, dopamine) may be added to therapy for replenishment of circulating blood volume and restoration of electrolyte balance. If bradycardia is refractory to drug treatment, a temporary artificial pacemaker may be required. In case of overdose it is necessary to monitor serum concentrations of creatinine and electrolytes.

Pregnancy use

It is contraindicated in children under 18 years of age.

It is contraindicated in pregnancy. Before starting treatment, make sure that there is no pregnancy. If the patient becomes pregnant during the treatment period, the drug therapy with ramipril should be replaced with another therapy as soon as possible. Otherwise, there is a risk of fetal damage, especially in the first trimester of pregnancy.

Fetal effects: impaired fetal renal development, decreased fetal and neonatal BP, impaired renal function, hyperkalemia, skull hypoplasia, oligohydramnios, limb contracture, skull deformity, lung hypoplasia.

The FDA fetal category of action is D.

Breastfeeding should be stopped during treatment.

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