Ramipril-SZ, tablets 10 mg 30 pcs

Ramipril-SZ is an 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 reduces 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.

It is known that ramipril significantly reduces 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, increased 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 about 1-2 h, peaks within 3-6 h, and lasts at least 24 h.

Indications

Active ingredient

Composition

Active ingredient:

Ramipril – 10 mg;

Ancillary substances:

Lactose monohydrate 143.5 mg,

Magnesium stearate 1.5 mg.

Magnesium stearate 1.5 mg.

How to take, the dosage

The tablets should be swallowed whole (not chewed), and drunk with a sufficient amount (1/2 cup) of water, regardless of meals (i.e., the tablets can be taken before, during or after meals). The dose is selected depending on the therapeutic effect and tolerability of the drug by the patient. Treatment with Ramipril-SZ is usually prolonged, and its duration in each particular case is determined by the doctor. Unless otherwise prescribed, the following dosing regimens are recommended with normal renal and hepatic function.

In essential hypertension

The usual starting dose is 2.5 mg once daily in the morning. If this dose fails to normalize BP for 3 weeks or more, the dose may be increased to 5 mg of ramipril daily. If the 5 mg dose is not effective enough, it may be doubled further after 2-3 weeks to a maximum recommended daily dose of 10 mg per day. As an alternative to increasing the dose to 10 mg per day, if the daily dose of 5 mg is not sufficiently hypotensive, other hypotensive agents, such as diuretics or slow calcium channel blockers, may be added to the treatment.
In chronic heart failure

The recommended starting dose: 1.25 mg once daily (1/2 tablet of 2.5 mg). The dose may be increased depending on the patient’s response to the therapy. It is recommended that the dose be doubled at 1-2 week intervals. If a daily dose of 2.5 mg or more is required, it may be given either once daily or divided into 2 doses. The maximum recommended daily dose is 10 mg.

In diabetic or nondiabetic nephropathy

The recommended starting dose is 1.25 mg once daily (1/2 tablet 2.5 mg). The dose may be increased to 5 mg once daily. For these conditions, doses above 5 mg once daily in controlled clinical trials have been insufficiently studied.
To reduce the risk of myocardial infarction, stroke, or cardiovascular mortality in patients at high cardiovascular risk

The recommended starting dose is 2.5 mg once daily. Depending on the patient’s tolerance, the dose may be gradually increased. It is recommended that the dose be doubled after 1 week of treatment and increased to the usual maintenance dose of 10 mg once daily for the next 3 weeks of treatment. Doses exceeding 10 mg have not been adequately studied in controlled clinical trials. The use of the drug in patients with IQ less than 0.6 ml/sec has not been studied sufficiently.
In heart failure developed within the first few days (2nd to 9th day) after acute myocardial infarction

The recommended initial dose is 5 mg per day, divided into two single doses of 2.5 mg, which are taken one in the morning and the other in the evening. If the patient cannot tolerate this initial dose (excessive BP reduction is observed), it is recommended that 1.25 mg twice daily (1/2 tablet of 2.5 mg) be given for two days. Then, depending on the patient’s response, the dose may be increased. It is recommended that the dose be doubled at 1-3 day intervals when it is increased. Later, the total daily dose, which was initially divided into two doses, may be given once. The maximum recommended dose is 10 mg.

The current experience of treatment of patients with severe heart failure (functional class III-IV according to NYHA classification) arising immediately after acute myocardial infarction is insufficient. If a decision is made to treat these patients with Ramipril-SZ, it is recommended that treatment should be started with the lowest possible dose of 1.25 mg once daily (1/2 tablet of 2.5 mg) and special care should be taken with each dose increase.

Interaction

Contraindicated combinations
– Use of certain high-flow membranes with a negatively charged surface (e.g. polyacrylonitrile membranes) in hemodialysis or hemofiltration; use of dextran sulfate in low-density lipoprotein apheresis Risk of severe anaphylactic reactions.

Not recommended combinations

– With potassium salts, potassium-saving diuretics (e.g., amiloride, triamterene, spironolactone) More pronounced increases in serum potassium are possible (careful monitoring of serum potassium is required when used simultaneously).

Combinations to be used with caution

– With hypotensive agents (especially diuretics) and other drugs that reduce BP (nitrates, tricyclic antidepressants) Potentiation of hypotensive effect; When combining with diuretics serum sodium content should be monitored.

– With hypnotics, narcotic and non-narcotic analgesics More pronounced BP reduction is possible;
– With vasopressor sympathomimetics (epinephrine) Reduction of the hypotensive effect of ramipril, it is required a careful BP control.

– With allopurinol, procainamide, cytostatics, immunosuppressants, systemic glucocorticosteroids and other agents that may affect hematological parameters Co-use increases the risk of leukopenia.
– With lithium salts Increased serum concentration of lithium and increased cardio- and neurotoxic effects of lithium.

– With hypoglycemic agents for oral administration (sulfonylurea derivatives, biguanides), insulin Due to the reduction of insulin resistance under the influence of ramipril, the hypoglycemic effect of these drugs may increase up to the development of hypoglycemia.Combinations to be taken into consideration

– With nonsteroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid) the effect of ramipril may be weakened, the risk of renal dysfunction and increase of serum potassium may increase.

– With heparin Increased serum potassium may occur.

– With sodium chloride Weakening of the hypotensive effects of ramipril and less effective treatment of symptoms of chronic heart failure.

– With ethanol Increased vasodilation. Ramipril may increase the adverse effects of ethanol on the body.

– With estrogens Weakening of the hypotensive effect of ramipril (fluid retention).

– Desensitization therapy in hypersensitivity to insect venoms ACE inhibitors, including ramipril, increase the likelihood of severe anaphylactic or anaphylactoid reactions to insect venoms. When ACE inhibitors and gold drugs (sodium aurothiomalate) for intravenous administration are used simultaneously, a symptom complex including facial hyperemia, nausea, vomiting, and arterial hypotension has been described.

Special Instructions

The treatment is carried out with regular medical supervision. Prior to treatment (1 week), prior antihypertensive therapy, including diuretics should be cancelled (if diuretics cannot be cancelled, doses should be reduced and water-electrolyte balance should be corrected). In patients with a malignant course of hypertension the dose is increased gradually, every 24 hours, under BP control until the maximum effect is achieved.

While therapy it is necessary to monitor blood pressure, constantly monitor peripheral blood count (before treatment, during the first 3-6 months of therapy and at intervals up to 1 year, especially in patients with increased risk of neutropenia), protein, plasma potassium level, urea nitrogen, creatinine, renal function, body weight and diet compliance. In case a patient develops hyponatremia and dehydration it is necessary to correct the dosage regimen (dose lowering). In case of cholestatic jaundice development and progression of fulminant liver necrosis the treatment is discontinued.

Hemodialysis through high-performance polyacrylonitrile metal metal sulfate membranes (e.g. AN69), hemofiltration or LDL-apheresis should be avoided (anaphylaxis or anaphylactoid reactions may occur). It should be borne in mind that when using ramipril in patients with autoimmune diseases and syndromes, the risk of neutropenia increases.

Hyposensitization therapy may increase the risk of anaphylactic reactions. It is recommended to exclude the use of alcoholic beverages during treatment. Use with caution for drivers of vehicles and people whose profession requires high concentration.

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 pregnancy. Before starting treatment you should make sure that there is no pregnancy. If a patient becomes pregnant during treatment, 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.

Similarities