Amprilan NL - instructions for use, doses, side effects, contraindications

Ramipril. The angiotensin-converting enzyme (ACE) inhibitor, prevents the conversion of angiotensin I into angiotensin II without a compensatory increase in the heart rate. Reduces the production of aldosterone, general vascular peripheral resistance, pressure in the pulmonary capillaries, resistance in pulmonary vessels, does not change the rate of glomerular filtration, enhances coronary blood flow. With prolonged use of the drug, myocardial hypertrophy decreases in patients with arterial hypertension, the incidence of arrhythmias decreases with myocardial reperfusion; improves circulation of the ischemic myocardium. Cardioprotective effect is due to the effect on the synthesis of prostaglandins, induction of the formation of nitric oxide in endotheliocytes. The drug reduces the aggregation of platelets. The onset of hypotensive action is 1.5 hours after ingestion, the maximum effect is 5-9 hours, the duration of action is 24 hours. The drug has no withdrawal syndrome.

Hydrochlorothiazide. A thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties; the hypotensive effect develops due to the expansion of arterioles. Virtually no effect on normal blood pressure (BP). Diuretic effect occurs in 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours. Antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect. Ramipril and hydrochlorothiazide have additive effect. Ramipril reduces the loss of potassium ions caused by the intake of hydrochlorothiazide.

Pharmacokinetics:

The pharmacokinetics of ramipril and hydrochlorothiazide with simultaneous administration does not differ from that in their separate administration

The absorption of ramipril averages 50 - 60%. Eating does not affect the degree of absorption, but decreases its speed, the time to reach the maximum concentration (TCmax) - 2-4 hours.

After oral intake of hydrochlorothiazide is 60-80%. The maximum concentration of hydrochlorothiazide in the blood is reached 1-5 hours after ingestion. The connection of ramipril with plasma proteins is 73%, ramiprilata - 56%. Linkage with proteins of plasma of blood hydrochlorothiazide - 64%. The half-life (T1 / 2) for ramipril is 5.1 hours; in the phase of distribution and elimination, a decrease in the concentration of ramiprilate in the serum takes place from T1 / 2 to 4-5 days. T1 / 2 increases with renal insufficiency. The volume of distribution of Ramipril - 90 liters, ramiprilata - 500 liters.

Metabolism of ramipril occurs mainly in the liver with the formation of an active metabolite of ramiprilata, which inhibits the angiotensin-converting enzyme (ACE) 6 times more actively than ramipril and an inactive metabolite of diketopiperazine, which are then glucuronized.

The drug is excreted mainly in the form of metabolites, kidneys - 60%, intestines - 40%. Hydrochlorothiazide It is not metabolized and is quickly excreted through the kidneys. The half-life is 5-15 hours.

Indications:

Arterial hypertension (patients who are shown combined therapy).

Contraindications:

Ramipril

Hypersensitivity to ramipril and any other ingredient of the drug or other ACE inhibitors, angioneurotic edema history, including associated with prior treatment with ACE inhibitors, hemodynamically significant bilateral renal artery stenosis, stenosis of arteries solitary kidney, post-renal transplant, hemodialysis, renal failure (creatinine clearance less than 30 mL / min.), hemodynamically significant aortic or mitral stenosis (reduction in the risk of excessive blood pressure with subsequent disturbance function tion kidney), hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, pregnancy and lactation, age 18 years (effectiveness and safety are installed).

Hydrochlorothiazide

Increased sensitivity to the drug or other sulfonamides history, gout, diabetes (severe) chronic renal failure (creatinine clearance of less than 20-30 ml / min, anuria), severe hepatic failure, refractory hypokalemia, hypercalcemia, hyponatremia, pregnancy, lactation, age up to 3 years (solid dosage form).

Carefully:Ramipril

Severe lesions of coronary and cerebral arteries (risk of blood flow decrease with excessive decrease of blood pressure), unstable angina, severe ventricular arrhythmias, chronic heart failure of stage IV, decompensated pulmonary heart, renal and / or hepatic insufficiency, hyperkalemia, hyponatremia (including against a background of diuretics and a diet with a restriction of salt intake), conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), systemic connective diseases Ani, including scleroderma, and systemic lupus erythematosus, a disease requiring the appointment of corticosteroids (glucocorticoids) and immunosuppressants (no clinical experience), diabetes, inhibition of bone marrow hematopoiesis, old age.

Hydrochlorothyrazide

Hypokalemia, hyponatremia, hypercalcemia, ischemic heart disease, hepatic insufficiency, cirrhosis, history of bronchial asthma, elderly age.

Pregnancy and lactation:

The drug is contraindicated in pregnancy. At the onset of pregnancy, the drug should be stopped immediately.If it is necessary to prescribe the drug during lactation it is necessary to stop breastfeeding.

Dosing and Administration:

Inside. The dose is selected individually. Usual dose for adults -1 Amprilan NL tablet (2.5 mg / 12.5 mg) per day, if necessary, can be increased to 1 tablet Amprilana ND (5.0 mg / 25 mg).

If the kidney function is mild or moderate (creatinine clearance more than 30 ml / min, serum creatinine about 3 mg / dL or 265 μmol / l), the usual dose of the drug is recommended. When creatinine clearance is less than 30 ml / min. the drug is not recommended.

The duration of therapy is not limited.

Side effects:

Ramipril

From the cardiovascular system: reduction of blood pressure, orthostatic hypotension, orthostatic collapse, tachycardia, rarely - arrhythmia, palpitations, palpitations, exacerbation of Raynaud's syndrome. In case of excessive decrease in blood pressure, mainly in patients with coronary heart disease and clinically significant narrowing of the cerebral vessels, myocardial ischemia (angina pectoris) and cerebral ischemia (possibly with dynamic cerebral blood flow disorder or stroke) may develop.

From the genitourinary system: development or strengthening of symptoms of renal failure, proteinuria, oliguria, interstitial nephritis, nephrotic syndrome, decrease in urine volume, gynecomastia, decreased potency, libido.

From the central nervous system: cerebral ischemia, stroke, dizziness, headache, weakness, drowsiness, peripheral neuropathy (paresthesia), nervous excitability, anxiety, tremor, muscle spasm, mood disorders, apathy, when used in high doses - insomnia, anxiety, depression, ataxia, confusion, fainting.

From the sense organs: vestibular disorders, taste disorders (eg, metallic taste), smell, hearing and vision, blepharitis, dry conjunctiva, lacrimation, tinnitus.

From the digestive system: nausea, vomiting, diarrhea or constipation, epigastric pain, intestinal obstruction, flatulence, pancreatitis, hepatitis, cholestatic jaundice, cholecystitis (with cholelithiasis), liver dysfunction with hepatic insufficiency, melena, ileus, dry mouth, thirst, loss of appetite, stomatitis, glossitis, inflammation of the salivary glands.

From the respiratory system: "dry" cough, bronchospasm, dyspnea, rhinorrhea, rhinitis, sinusitis, pharyngitis, hoarseness, bronchitis, interstitial pneumonia, pulmonary embolism, pulmonary infarction, pulmonary edema.

Allergic reactions: skin rash, pruritus, urticaria, conjunctivitis, photosensitivity, angioneurotic edema of face and extremities, lips, tongue, pharynx and / or larynx, exfoliative dermatitis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome) , pemphigus, serositis, onycholysis, vasculitis, myositis, muscle weakness, myalgia, arthralgia, arthritis, eosinophilia.

Other: cramps, alopecia, shingles, hyperthermia, increased sweating.

Laboratory indicators: hypercreatininemia, increased levels of urea nitrogen, elevated "liver" enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia, anemia, decrease in hemoglobin concentration or hematocrit, neutropenia, thrombocytopenia, agronulotsitoz, pancytopenia, hemolytic anemia, occurrence of antinuclear antibodies.

Influence on the fetus: impaired fetal function, decreased fetal and newborn infants, impaired renal function, hyperkalemia, skull bones hypoplasia, oligohydramnia, limb contracture, skull bones deformation, lung hypoplasia.

Hydrochlorothiazide

From the side of water-electrolyte and acid-base balance: hypokalemia and hypochloremic alkalosis may develop (dry mouth, thirst, heart rhythm, mood and psyche, convulsions or pain in the muscles, nausea, vomiting, weakness, hypochloremic alkalosis may develop hepatic encephalopathy or hepatic coma), hyponatremia ( confusion, convulsions, apathy, slowing down the process of thinking, fatigue, irritability), hypomagnesemia (arrhythmias).

On the part of the hematopoiesis system: agranulocytosis, thrombocytopenia, hemolytic and aplastic anemia, leukocytopenia, eosinophilia, neutropenia, pancytopenia.

From the cardiovascular system: arrhythmia, orthostatic hypotension, tachycardia.

From the digestive system: cholecystitis, pancreatitis, jaundice, diarrhea, sialadenitis, constipation, anorexia, epigastric pain.

From the side of metabolism: hypercholesterolemia, hypertriglyceridemia, hyperglycemia, glucosuria, hyperuricemia, hypercalcemia, exacerbation of gout.

From the central nervous system: depression, sleep disturbance, anxiety, paresthesia, confusion, dizziness.

From the sense organs: xantopsy, visual impairment.

From the genitourinary system: impaired renal function, decreased potency, interstitial nephritis.

Allergic reactions: skin rash, hives, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress syndrome (pneumonitis, noncardiogenic pulmonary edema), toxic epidermal necrolysis, photosensitivity; anaphylactic reactions (up to the life threatening anaphylactic shock).

Other: hyperthermia, weakness.

Overdose:

Ramipril

Symptoms: marked decrease in blood pressure, bradycardia, shock, disturbance of the water-electrolyte state, acute renal failure, stupor, dry mouth, weakness, drowsiness.

Treatment: patient to give a horizontal position with raised legs, in mild cases of overdosage - gastric lavage,the introduction of adsorbents and sodium sulfate (it is advisable to conduct activities during the first 30 minutes after taking the drug). With a decrease in blood pressure - intravenous injection of catecholamines, angiotensin II; with bradycardia - the application of pacemaker. The drug is not excreted during hemodialysis.

Hydrochlorothiazide

Symptoms: hypokalemia (adynamia, paralysis, constipation, arrhythmias), drowsiness, lowering blood pressure.

Treatment: infusion of electrolyte solutions; compensation of K + deficiency (appointment of K + and potassium-sparing diuretics).

Interaction:

Ramipril

Increases the inhibitory effect of ethanol on the central nervous system. Taking salt with food can reduce the hypotensive effect of ramipril.

With the simultaneous use of ramipril and other agents that reduce blood pressure (eg, diuretics, nitrates, tricyclic antidepressants, agents for general anesthesia) leads to an increase in the hypotensive effect of ramipril.

The simultaneous administration of ramipril and potassium or potassium-sparing diuretics may cause hyperkalemia.

Vasopressornye sympathomimetics (epinephrine, norepinephrine) can reduce the hypotensive effect of ramipril.In this regard, with simultaneous treatment should carefully monitor blood pressure.

Simultaneous administration of ramipril and allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics increases the likelihood of changes in the peripheral blood picture (the risk of developing leukopenia).

Simultaneous administration of ramipril and lithium preparations leads to a decrease in lithium excretion, it is necessary to control the concentration of lithium in the blood serum - the risk of toxic effects.

ACE inhibitors can enhance the effect of hypoglycemic agents (eg, insulin or sulfonylurea derivatives), which in some cases can cause hypoglycemia. In this regard, the level of sugar in the blood should be carefully monitored, especially at the beginning of the joint application.

The simultaneous use of ramipril and non-steroidal anti-inflammatory drugs (NSAIDs) (eg, acetylsalicylic acid and indomethacin) can reduce the hypotensive effect of ramipril. In addition, simultaneous use can cause hyperkalemia and increase the risk of impaired renal function.

The simultaneous use of ramipril with estrogen can weaken the hypotensive effect.

The simultaneous use of heparin and ramipril can cause hyperkalemia. Anaphylactic and anaphylactoid reactions to the venom of stinging insects (and possibly other allergens) are more pronounced during treatment with ACE inhibitors.

Hydrochlorothiazide

With simultaneous use of digitalis glycosides with thiazide diuretics, the likelihood of toxic effects of glycosides (including increased excitability of the ventricles) increases due to the likely development of hypokalemia and hypomagnesemia.

Medicines that bind intensely to proteins (indirect anticoagulants, clofibrate, NSAIDs) increase the diuretic effect of hydrochlorothiazide.

The hypotensive effect of hydrochlorothiazide is enhanced by vasodilators, beta-blockers, barbiturates, phenothiazines, tricyclic antidepressants, ethanol. Hydrochlorothiazide enhances the neurotoxicity of salicylates, weakens the effect of oral hypoglycemic drugs, norepinephrine, epinephrine and antidotal drugs,enhances the cardiotoxic and neurotoxic effect of lithium preparations, the action of peripheral muscle relaxants, reduces the excretion of quinidine. With the simultaneous administration of methyldopa, the development of hemolysis is possible. Kolestyramine reduces the absorption of hydrochlorothiazide.

Hydrochlorothiazide reduces the effect of oral contraceptives.

Special instructions:

Ramipril

At the beginning of treatment, it is necessary to evaluate the kidney function. Kidney function should be carefully monitored during treatment with ramipril, especially in patients with weakened renal function, with renal vessels (for example, clinically insignificant stenosis of the renal arteries or hemodynamically significant stenosis of the artery of a single kidney); heart failure.

The risk of hypersensitivity and allergic-like (anaphylactoid) reactions is increased in patients who simultaneously take ACE inhibitors and undergo hemodialysis procedures using dialysis membranes AN69. Similar reactions were revealed in the apheresis of low-density lipoproteins using dextran sulfate, therefore, when treating with ACE inhibitors, the use of this method should be avoided.

During treatment with ramipril in patients with impaired renal function, especially with simultaneous treatment with diuretics, the level of urea and creatinine in the serum can increase. In this case, treatment should be continued with lower doses of ramipril or discontinue the drug. In patients with impaired renal function, the risk of hyperkalemia increases.

In patients with impaired hepatic function, the metabolism of ramipril and the formation of an active metabolite may be slowed by a decrease in the activity of "liver" enzymes. In this regard, the treatment of such patients should be started only under strict medical supervision.

Caution should be exercised when prescribing ramipril to patients on a low-salt or salt-free diet (increased risk of developing hypotension). In patients with reduced circulating blood volume (as a result of diuretic therapy), during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop.

Transient arterial hypotension is not a contraindication for continuing treatment after stabilizing blood pressure.In the case of repeated occurrence of severe arterial hypotension, the dose should be reduced or the drug should be withdrawn.

In patients undergoing extensive surgical interventions or receiving other means that cause arterial hypotension, during general anesthesia, ramipril can cause blockade of the formation of angiotensin II due to compensatory release of renin. If the doctor connects the development of arterial hypotension with the mechanism mentioned above, arterial hypotension can be corrected by an increase in the volume of blood plasma.

In rare cases, during treatment with ACE inhibitors, agranulocytosis, erythrocytopenia, thrombocytopenia, hemoglobinemia or bone marrow suppression are observed. At the beginning and during treatment it is necessary to control the number of white blood cells to detect possible neutropenia / agranulocytosis. More frequent monitoring is recommended in patients with renal insufficiency, with connective tissue diseases (eg, systemic lupus erythematosus or scleroderma) and in patients taking concomitant medications that affect hemopoiesis.Interactions with other drugs). Counting blood cells should also be carried out when there are clinical signs neutropenia / agranulocytosis and increased bleeding.

In patients with hypertension in the treatment of ramipril, there is rarely an increase in the serum potassium level. The risk of hyperkalemia increases with chronic heart failure, simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and the administration of potassium preparations.

When ACE inhibitors are used during desensitizing therapy, anaphylactoid reactions (for example, arterial hypotension, dyspnoea, vomiting, skin rash) can occur to aspen or bee venom, which can be life threatening. Hypersensitivity reactions can occur with insect bites (eg, bees or wasps). If it is necessary to conduct desensitizing treatment with bee or aspen poison, it is necessary to abolish ACE inhibitors and continue treatment with suitable drugs from other groups.

Hydrochlorothiazide

To prevent deficiency of K + and Mg2 + prescribe a diet with a high content of these salts, potassium-sparing diuretics, K + salts and Mg2 +. Regular monitoring of the potassium, glucose, uric acid, lipid and creatinine levels is necessary.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles, as well as during occupations, with potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 2.5 mg of ramipril and 12.5 mg of hydrochlorothiazide.

Packaging:

For 7 or 10 tablets in a blister pack.

Blister by 7 tablets: 2,4, 8, 12 or 14 blisters in a cardboard box together with instructions for use.

Blister for 10 tablets: 3, 6 or 9 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001110/08

Date of registration:27.02.2008

Expiration Date:Unlimited

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, dd, Novo mesto, AO Slovenia

Information update date: & nbsp24.08.2017

Illustrated instructions

Instructions

Amprilan® NL (Amprilan® HL)