Amprilan NL, tablets 2, 5+12, 5 mg, 30 pcs.

ACE catalyzes the conversion of angiotensin I to angiotensin II. ACE is identical to kininase, the enzyme that catalyzes the breakdown of bradykinin.

Blockade of ACE leads to a decrease in the concentration of angiotensin II, increased plasma renin activity, increased bradykinin effect and increased secretion of aldosterone, which may cause an increase in serum potassium levels.

The antihypertensive and hemodynamic effects of ramipril in patients with arterial hypertension are the result of vasodilation and reduction of OPPS, which in turn gradually reduces BP. Cardiac rhythm usually does not change. With long-term therapy, left ventricular hypertrophy decreases without adverse effects on cardiac function.

The antihypertensive effect after a single oral dose of the drug is seen in 1-2 hours, reaches a maximum after 3-6 hours and lasts for 24 hours.

Ramipril is effective in the treatment of CHF. In patients with signs of CHF after myocardial infarction, ramipril reduces risk of sudden death, progression of heart failure and decreases number of hospitalizations for exacerbation of CHF.

In both patients with and without diabetes mellitus, the drug significantly reduces the existing microalbuminuria and the risk of nephropathy. These effects are noted in patients with both elevated and normal BP.

Indications

Active ingredient

Composition

Active substance:

Ramipril – 2.5 mg,

Hydrochlorothiazide 12.5.

Auxiliary substances:

Sodium bicarbonate – 2.5 mg;

Lactose monohydrate – 155 mg;

croscarmellose sodium – 4 mg

; Pregelatinized starch – 30 mg;

Sodium stearyl fumarate – 2 mg,

PB 22886 Yellow dye mixture (lactose monohydrate, iron oxide yellow dye (E172) – 4 mg.

How to take, the dosage

Overly, whole, without chewing, regardless of meals, with plenty of fluid.

The dose is adjusted according to the therapeutic effect and patient tolerance.

The treatment with Amprilan® is long; its duration is determined by the physician in each individual case.

Hypertension: The recommended starting dose of Amprilan® is 2.5 mg once daily. Depending on the patient’s response, the dose may be doubled at 1-2 week intervals. Usually the maintenance dose is 2.5-5 mg/day, the maximum daily dose is 10 mg. Patients taking diuretics should discontinue or decrease their dose at least 3 days before starting Amprilan®.

CRC: The recommended starting dose of Amprilan® is 1.25 mg once daily. Depending on the therapeutic effect, the dose may be doubled at intervals of 1-2 weeks.

The maximum daily dose is 10 mg.

In patients receiving high doses of diuretics, the dose of diuretics should be reduced before starting therapy with Amprilan®.

Heart failure that developed within a few days (days 2 to 9 days) after acute myocardial infarction: the recommended starting dose is 5 mg/day divided into 2 single doses of 2.5 mg (1 tablet), one taken in the morning and one in the evening. If the patient cannot tolerate the initial dose (excessive BP reduction is observed), it should be reduced to 1.25 mg 2 times a day. Then, depending on the patient’s response, the dose may be doubled again (2.5 mg) at 1-3 day intervals. Later, the daily dose, which was first divided into two, may be given once. The maximum daily dose is 10 mg. If the patient does not tolerate the dose increase to 2.5 mg 2 times a day, then treatment with the drug should be discontinued.

Diabetic nephropathy and nephropathy with a background of chronic diffuse renal disease: The recommended starting dose of Amprilan® is 1.25 mg once daily. Depending on patient tolerance to ramipril, the dose can be subsequently increased: It is recommended that the dose be doubled every 2 weeks to a maintenance dose of 5 mg once daily.

Limiting the risk of myocardial infarction, stroke, and cardiovascular death: The recommended starting dose of Amprilan® is 2.5 mg once daily and this dose is increased gradually thereafter based on tolerance to the drug: we recommend doubling the dose after 1 week of therapy and again after 2-3 weeks until the maintenance dose of 10 mg once daily is targeted.

Particular patient groups.

Renal dysfunction: In patients with a creatinine Cl greater than 30 ml/min, no dose adjustment is required. For patients with creatinine Cl less than 30 ml/min, the initial daily dose is 1.25 mg and the maximum daily dose is 5 mg. Liver function disorders. Initial dose is 1.25 mg once daily. The maximum dose is 2.5 mg once daily.

Elderly patients: Close monitoring of elderly patients (over 65 years) taking diuretics is necessary. The dose of Amprilan® should be adjusted according to the level of blood pressure.

Interaction

Vasopressor sympathomimetics (epinephrine, norepinephrine) may decrease the hypotensive effect of ramipril. BP levels should be carefully monitored when these drugs are used concomitantly.

ACE inhibitors increase the CNS depressant effect of ethanol.

Lithium drugs: Concomitant use of lithium drugs and ACE inhibitors has reported cases of reversible increase in lithium concentration in blood serum. Concomitant use with thiazide diuretics may increase the concentration of lithium and the risk of its toxic effects against the ACE inhibitor.

NSAIDs: Combination of ACE inhibitors with NSAIDs (non-selective COX-1 and COX-2 inhibitors from the group of NSAIDs, such as acetylsalicylic acid in doses that have anti-inflammatory effects): decreases the hypotensive effect of ACE inhibitors; increases the risk of renal dysfunction, up to the development of acute renal failure; increases serum potassium in patients with pre-existing renal dysfunction.

Tricyclic antidepressants, antipsychotics (neuroleptics): increase the hypotensive effect and increase the risk of orthostatic hypotension (additive effect).

GCS, tetracosactide: decrease hypotensive effect (fluid retention).

Potassium-saving diuretics (spironolactone, triamterene, amiloride, eplerenone) and potassium preparations: Combined use of ramipril and potassium-saving diuretics as well as potassium preparations and potassium containing food salt substitutes is not recommended.

Perhaps caution should be exercised and plasma potassium and ECG parameters should be monitored regularly.

Hypoglycemic oral agents (sulfonylurea derivatives) and insulin: use of ACE inhibitors may increase the hypoglycemic effect of oral hypoglycemic agents and insulin in patients with diabetes; their combined use may increase glucose tolerance, which may require adjustment of doses of oral hypoglycemic agents and insulin.

Allopurinol, cytostatic drugs, immunosuppressants, GCS (when used systemically) and procainamide: Concomitant use of these drugs with ACE inhibitors may increase the risk of leukopenia.

General anesthetic agents: ACE inhibitors may increase the hypotensive effect of some general anesthetic agents.

Gold preparations: Nitrate-like reactions (nausea, vomiting, marked BP reduction, facial hyperemia) have been noted when ACE inhibitors, including ramipril, are administered to patients receiving gold preparations (sodium aurothiomalate) by IV.

Special Instructions

Renal function should be assessed at the start of treatment. Renal function should be carefully monitored in patients with impaired renal function, heart failure, bilateral renal artery stenosis or artery stenosis of the single kidney, as well as in patients after renal transplantation.

Hepatic failure

In rare cases with ACE inhibitors cholestatic jaundice occurs with progression of which fulminant liver necrosis develops, sometimes with fatal outcome. If jaundice or significant increase in liver transaminase activity occurs with ACE inhibitors, the use of Amprilan® should be discontinued.

In patients with uncomplicated arterial hypertension after the first dose of the drug, symptomatic arterial hypotension is rare. The risk of developing arterial hypotension is increased in the following patients:

Aortic/mitral stenosis/GCMP

ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and with aortic and/or mitral stenosis.

Neutropenia/agranulocytosis

In patients taking ACE inhibitors there may be cases of neutropenia/agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function in the absence of other complications neutropenia is rare and resolves on its own after ACE inhibitors withdrawal.

Ramipril should be used with great caution in patients with connective tissue disease concomitantly receiving immunosuppressive therapy, allopurinol or procainamide, especially in existing renal impairment. Such patients may develop severe infections that do not respond to intensive antibiotic therapy. If ramipril is used, it is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that in case of any signs of infectious disease (sore throat, fever) it is necessary to immediately consult a physician.

Hyperkalemia

May develop during treatment with ACE inhibitors, including ramipril. Risk factors of hyperkalemia include renal insufficiency, elderly age, diabetes mellitus, some concomitant conditions (decreased BOD, decompensated acute heart failure, metabolic acidosis), concomitant use of potassium-saving diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing salt substitutes, and other drugs that increase plasma potassium content (e.g. heparin). Hyperkalemia can lead to serious cardiac rhythm disturbances, sometimes fatal.

Potassium-saving diuretics and potassium preparations

The combined use of Amprilan® and potassium-saving diuretics as well as potassium preparations and potassium-containing salt substitutes is not recommended.

Surgical interventions/general anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may result in a significant decrease in BP, especially with the use of general anesthetics with hypotensive effect.

The use of ACE inhibitors, including ramipril, should be discontinued 12 hours before surgery and the anesthesiologist should be informed about the use of ACE inhibitors.

Cough

Dry cough may occur with ACE inhibitor therapy, which disappears after discontinuation of the drugs of this group. If you have a dry cough, you should be aware of the possible association of this symptom with ACE inhibitor therapy.

Anaphylactoid reactions during desensitization procedures

There have been isolated reports of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy with venom of hymenopteran insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Administration of ACE inhibitor should be avoided in patients receiving immunotherapy with venom of hymenopterous insects. However, the development of anaphylactoid reactions can be avoided by temporarily withdrawing the ACE inhibitor at least 24 hours before the desensitization procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis with dextran sulfate. To prevent anaphylactoid reactions, therapy with an ACE inhibitor should be discontinued before each LDL apheresis procedure using high-flow membranes.

Hemodialysis

In patients receiving ACE inhibitors, anaphylactoid reactions have been noted during hemodialysis using high-flow membranes (e.g., AN69®). Therefore, it is advisable to use a different type of membrane or to use a hypotensive drug from a different pharmacotherapeutic group.

Impact on ability to drive or perform work requiring increased speed of physical and mental reactions

At the time of treatment, caution must be exercised during potentially hazardous activities requiring increased concentration and rapid psychomotor reactions, as dizziness, drowsiness, confusion and other side effects are possible.

Contraindications

With caution: Severe coronary and cerebral artery lesions (risk of reduced blood flow with excessive BP reduction); malignant arterial hypertension; unstable angina pectoris; aortic and/or mitral stenosis; severe ventricular rhythm disorders; chronic heart failure (NYHA functional class IV); decompensated pulmonary heart; renal and/or liver failure; hyperkalemia; hyponatremia (includingincluding against the background of diuretics and diet with restriction of table salt intake); conditions accompanied by the decrease of the blood circulation volume, including diarrhea, vomiting; systemic connective tissue diseases; diabetes mellitus; inhibition of medullary hematopoiesis; elderly age; hemodialysis with high-flow polyacrylonitrile membranes – risk of anaphylactoid reactions; before LDL apheresis procedure; simultaneous desensitizing therapy with allergens (for example, Hymenoptera venom).

Side effects

Prevalence of side effects (WHO):

CCS side: often – marked decrease in BP (at the beginning of therapy, when increasing the dose or joining diuretic therapy), orthostatic hypotension, syncopal states; rarely – peripheral edema, palpitations, angina, arrhythmia; very rarely – myocardial ischemia, myocardial infarction, increased circulatory disorders against stenotic vascular lesions, Raynaud’s syndrome, vasculitis, tachycardia, blood flushes to the face.

Nervous system disorders: frequently – headache, weakness; rarely – fatigue, nervousness, depression, tremor, loss of balance, confusion, anxiety, dizziness, motor anxiety, sleep disturbance; very rarely – paresthesia, smell perception disorders (parosmia), transient ischemic attacks, ischemic stroke, cerebral ischemia, concentration disorders.

Urogenital system disorders: rare – transient impotence, decreased libido, renal dysfunction up to acute renal failure, increased urine output, increased pre-existing proteinuria, increased concentration of urea and creatinine; very rare – gynecomastia.

Respiratory system: often – dry non-productive cough, increasing at night and in the supine position, more often occurring in women and non-smoking patients, sinusitis, bronchitis, shortness of breath; rarely – nasal congestion, pharyngitis, bronchospasm, including aggravation of bronchial asthma.

Skin disorders: often – maculopapular skin rash; rarely – skin itching, increased sweating (against a background of decreased BP); very rarely – maculopapularular exanthema and erythema, vesicular rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, worsening of psoriasis, psoriasiform, pemphigoid and lichenoid skin and mucosa lesions, alopecia; very rarely – urticaria, onycholisis, exfoliative dermatitis, photosensitization.

Digestive system disorders: often – inflammation of the mucous membrane of the gastrointestinal tract, digestive disorders, abdominal discomfort, dyspepsia, nausea, diarrhea, vomiting; rarely – increased liver enzymes activity, increased bilirubin concentration, cholestatic jaundice, acute liver failure, cholestatic hepatitis, hepatocellular lesions, dry oral mucosa, abdominal pain, gastritis, constipation, pancreatitis, including.including lethal (cases of pancreatitis with lethal outcome while taking ACE inhibitors were extremely rarely observed), intestinal angioneurotic edema, decreased appetite, anorexia; very rarely – glossitis; aphthous stomatitis.

Musculoskeletal system: often – myalgia, muscle cramps; rarely – arthralgia.

Senses: rare – visual disorders, including blurred vision, conjunctivitis, hearing impairment, disorders of smell and taste (e.g., metallic taste, partial or temporary loss of taste sensation).

Allergic reactions: very rare – angioedema syndrome with involvement of the mucosa of the lips, eyes, tongue, throat and pharynx, anaphylactic or anaphylactoid reactions (insect venoms), increased concentration of antinuclear bodies.

Laboratory parameters: rarely, hyperkalemia, moderate (sometimes pronounced) hypohemoglobinemia or neutropenia, erythropenia and thrombocytopenia, increased pancreatic enzyme activity; very rarely, hyponatremia, proteinuria (although usually ACE inhibitors reduce prior proteinuria) or increased diuresis (combined with worsening heart function), agranulocytosis, pancytopenia, bone marrow depression, hemolytic anemia.

Others: rarely – hyperthermia; very rarely – fever.

Overdose

Symptoms: marked BP decrease, bradycardia, shock, impaired water-electrolyte balance, acute renal failure, stupor.

Treatment: in mild cases of overdose – gastric lavage, prescription of adsorbents and sodium picosulfate (preferably within 30 minutes after ingestion). In case of marked BP decrease – intravenous injection of catecholamines, alpha 1-adrenergic agonists (norepinephrine, dopamine), angiotensin II (angiotensinamide), the patient should be laid on his back on the surface with low headboard, the blood pressure can be increased by infusion of 0.9% sodium chloride solution, a temporary artificial pacemaker may be used if necessary. BP, renal function and serum potassium should be monitored carefully. The effectiveness of hemodialysis has not been established.

Pregnancy use

Amprilan® is contraindicated during pregnancy as it may have adverse effects on the fetus (including renal dysfunction, hyperkalemia, skull bone hypoplasia, pulmonary hypoplasia).

Pregnancy should therefore be excluded before starting the use of Amprilan® in women of childbearing age.

If pregnancy is diagnosed, the use of Amprilan® should be stopped as soon as possible.

Breastfeeding should be discontinued if it is necessary to use Amprilan® during lactation.

Similarities