Amprilan nl pills 2.5 mg + 12.5 mg №30

Pharmaceutical form

Capsule flat white or almost white pills with a risk on the one hand and marking "12.5" on the other hand.

Clinical data

Therapeutic indications

Arterial hypertension (for patients who are recommended combination therapy).

Dosage and administration

Inside Dose picked individually. The usual dose for adults is 1 pill of Amprilan NL (2.5 mg / 12.5 mg) per day, if necessary, can be increased to 1 pill of Amprilan ND (5.0 mg / 25 mg). In case of impaired renal function of mild or moderate degree (creatinine clearance of more than 30 ml / min., Serum creatinine of approximately 3 mg / dL or 265 mcmol / l), the usual dose of the drug is recommended. With creatinine clearance less than 30 ml / min. the drug is not recommended. The duration of therapy is not limited.

Contraindications

 Ramipril
Hypersensitivity to Ramipril and any other ingredient of the drug or other ACE inhibitors, history of angioedema, including associated with previous therapy, ACE inhibitors, hemodynamically significant bilateral stenosis of the renal arteries, arterial stenosis of the single kidney, condition after kidney transplantation, hemodialysis, renal failure (creatinine clearance less than 30 ml / min.), hemodynamically significant aortic or mitral stenosis (the risk of an excessive decrease in blood pressure, followed by dysfunction kidney)hypertrophic obstructive cardiomyopathy, primary hyper aldosteronism, pregnancy and lactation, age up to 18 years (efficacy and safety have not been established).

Hydrochlorothiazide
Hypersensitivity to the drug or other sulfonamides in history, gout, diabetes mellitus (severe forms), chronic renal failure (creatinine clearance less than 20-30 ml / min, anuria), severe liver failure, refractory hypokalemia, hypercalcemia, hyponatremia, pregnancy, period lactation, age up to 3 years (solid dosage form).

Special instructions and precautionary measures

Ramipril: severe lesions of the coronary and cerebral arteries (risk of reducing blood flow with an excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias, chronic heart failure stage IV, decompensated pulmonary heart, renal and / or hepatic insufficiency, hyperkalemia, hyponatremia (including on the background of diuretics and a diet with restricted salt intake), conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), systemic connective diseases Kani, 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.

Hydrochlorothiazide: hypokalemia, hyponatremia, hypercalcemia, coronary heart disease, hepatic failure, cirrhosis, history of bronchial asthma, advanced age.

Interaction with other drugs

Ramipril
Strengthens the inhibitory effect of ethanol on the central nervous system. Salt intake with food may reduce the hypotensive effect of ramipril. With the simultaneous use of ramipril and other drugs that reduce blood pressure (for example, diuretics, nitrates, tricyclic antidepressants, agents for general anesthesia) leads to an increase in the hypotensive effect of ramipril. The simultaneous appointment of ramipril and potassium or potassium-sparing diuretic drugs can cause hyperkalemia. Vasopressor sympathomimetics (epinephrine, norepinephrine) can reduce the hypotensive effect of ramipril. In this regard, with simultaneous treatment should be carefully monitored blood pressure levels. The simultaneous appointment of ramipril and Allopurinol, immunosuppressants, corticosteroids, procainamide, cytotoxic drugs increases the likelihood of changes in the peripheral blood picture (the risk of 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, blood sugar levels should be carefully monitored, especially at the beginning of the joint use.
The simultaneous use of ramipril and nonsteroidal anti-inflammatory drugs (NSAIDs) (for example, Acetylsalicylic acid and indomethacin) can weaken the hypotensive effect of ramipril. Additionally, simultaneous use may 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 poison 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 increases the likelihood of toxic effects of glycosides (including increased excitability of the ventricles) due to the likely development of hypokalemia and hypomagnesemia. Drugs that bind intensively to proteins (indirect anticoagulants, clofibrate, NSAIDs) enhance 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, reduces the effect of oral hypoglycemic drugs,norepinephrine, epinephrine and arthritic drugs, enhances the cardiotoxic and neurotoxic effects of lithium preparations, the action of peripheral muscle relaxants, reduces quinidine excretion. With the simultaneous use of methyldopa may develop hemolysis. Kolestiramin reduces the absorption of hydrochlorothiazide. Hydrochlorothiazide reduces the effect of oral contraceptives.

Pregnancy and breastfeeding

The drug is contraindicated in pregnancy. When pregnancy occurs, the drug should be immediately discontinued. If necessary, the appointment of the drug in the period of lactation is necessary to stop breastfeeding.

Influence on ability to drive a car and other mechanisms

During the period of treatment, care must be taken when driving vehicles, as well as during classes of potentially hazardous activities that require increased concentration of attention and quickness of psychomotor reactions.

Side effects

Ramipril
Since the cardiovascular system: decrease in blood pressure, orthostatic hypotension, orthostatic collapse, tachycardia, rarely - arrhythmia, heartbeat, palpitations, exacerbation of Raynaud's syndrome. With an excessive decrease in blood pressure, mainly in patients with ischemic heart disease and clinically significant constriction of cerebral vessels, myocardial ischemia (angina pectoris, myocardial infarction) and cerebral ischemia (possibly with a dynamic impairment of cerebral circulation or stroke) can develop.
From the genitourinary system: development or intensification of symptoms of renal failure, proteinuria, oliguria, interstitial nephritis, nephrotic syndrome, decrease in urine volume, gynecomastia, decrease in potency, libido.
From the side of the central nervous system:cerebral ischemia, stroke, dizziness, headache, weakness, drowsiness, peripheral neuropathy (paresthesia), nervous irritability, anxiety, tremor, muscle spasm, mood disorders, apathy, when used in high doses - insomnia, anxiety, depression, ataxia, confusion, fainting.
From the senses: vestibular disorders, taste disorders (for example, metallic taste), smell, hearing and vision, blepharitis, dry conjunctiva, lacrimation, tinnitus.
From the digestive system: nausea, vomiting, diarrhea or constipation, pain in the epigastric region, intestinal obstruction, flatulence, pancreatitis, hepatitis, cholestatic jaundice, cholecystitis (with cholelithiasis), impaired liver function with the development of liver failure, melena, ileus, dry mouth, thirst, loss of appetite, stomatitis, glossitis, inflammation of the salivary glands.
On the part of the respiratory system: “Dry” cough, bronchospasm, shortness of breath, rhinorrhea, rhinitis, sinusitis, pharyngitis, hoarseness, bronchitis, interstitial pneumonia, pulmonary embolism, pulmonary infarction, pulmonary edema.
Allergic reactions: skin rash, pruritus, urticaria, conjunctivitis, photosensitization, angioedema of the face, extremities, lips, tongue, throat and / or larynx, exfoliative dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal nephrosis (inflammatory syndrome) (necrosis)., pemphigus, serositis, onycholysis, vasculitis, myositis, muscle weakness, myalgia, arthralgia, arthritis, eosinophilia.
Other:convulsions, alopecia, herpes zoster, hyperthermia, increased sweating.
Laboratory values: hypercreatininemia, increased urea nitrogen, increased activity of liver enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia, anemia, decreased hemoglobin and hematocrit, neutropenia, thrombocytopenia, agronulocytosis, pancytopenia, hemolytic anemia, anemia, anemia, anemia, the emergence of anemia, anemia, emergence anemia, anemia, anemia, anemia, anemia, anemia, anemia, anemia, anemia
Effect on the fetus: fetal dysfunction, reduction of fetal and newborn blood pressure, renal dysfunction, hyperkalemia, cranial bone hypoplasia, oligohydramnios, limb contracture, cranial bones deformity, pulmonary hypoplasia.

Hydrochlorothiazide
From the side of water-electrolyte and acid-base balance: possible development of hypokalemia and hylochloremic alkalosis (dry mouth, increased thirst, heart rhythm disturbances, changes in mood and psyche, cramps or muscle pain, nausea, vomiting, weakness; with hypochloraemic alkalosis, hepatic encephalopathy or hepatic coma may develop),hyponatremia (confusion, convulsions, apathy, slowing the process of thinking, fatigue, irritability), hypomagnesemia (arrhythmias).
From the hemopoietic system: agranulocytosis, thrombocytopenia, hemolytic and aplastic anemia, leukocytopenia, eosinophilia, neutropenia, pancytopenia.
WITHabout the side of the cardiovascular system: arrhythmia, orthostatic hypotension, tachycardia.
From the digestive system: cholecystitis, pancreatitis, jaundice, diarrhea, sialadenitis, constipation, anorexia, epigastric pain.
Metabolism: hypercholesterolemia, hypertriglyceridemia, hyperglycemia, glycosuria, hyperuricemia, hypercalcemia, exacerbation of the course of gout.
From the side of the central nervous system: depression, sleep disturbance, anxiety, paresthesia, confusion, dizziness.
From the senses: Xantopsia, visual impairment.
From the genitourinary system: impaired renal function, reduced potency,
interstitial nephritis.
Allergic reactions:skin rash, urticaria, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress syndrome (pneumonitis, non-cardiogenic pulmonary edema), toxic epidermal necrolysis, photosensitization; Anaphylactic reactions (up to life threatening anaphylactic shock).
Other: hyperthermia, weakness.

Overdose

Ramipril

Symptoms: a pronounced decrease in blood pressure, bradycardia, shock, impaired water and electrolyte status, acute renal failure, stupor, dry mouth, weakness, drowsiness.
Treatment: give the patient a horizontal position with raised legs, in mild cases of overdose - gastric lavage, the introduction of adsorbents and sodium sulfate (it is desirable to hold events during the first 30 minutes after taking the drug) With a decrease in blood pressure - intravenous catecholamines, angiotensin II; in bradycardia, the use of a pacemaker. The drug is not displayed during hemodialysis.
Hydrochlorothiazide
Symptoms: hypokalemia (adynamia, paralysis, constipation, arrhythmias), drowsiness, lower blood pressure. Treatment: electrolyte infusion; compensation of K + deficiency (prescription of K + and potassium-sparing diuretic drugs).

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Pharmacotherapeutic group: antihypertensive combination agent (ACF inhibitor + diuretic).

Pharmacological properties.

Ramipril Angiotensin-converting enzyme (ACE) inhibitor, prevents the conversion of angiotensin I to angiotensin II without a compensatory increase in heart rate. Reduces the production of aldosterone, total vascular peripheral resistance, pressure in the pulmonary capillaries, resistance in the pulmonary vessels, does not alter the glomerular filtration rate, increases coronary blood flow. With prolonged use of the drug, myocardial hypertrophy is reduced in patients with arterial hypertension, the frequency of arrhythmias during myocardial reperfusion decreases; improves blood circulation ischemic myocardium.Cardioprotective effect due to the effect on the synthesis of prostaglandins, the induction of the formation of nitric oxide in endothelial cells. The drug reduces platelet aggregation. 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. Thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium, chlorine, potassium, Magnesium ions, and water in the distal nephron; delays the excretion of Calcium ions, uric acid. It has antihypertensive properties; hypotensive effect develops due to the expansion of arterioles. Virtually no effect on normal blood pressure (BP). The diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours. The antihypertensive effect occurs after 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect. Ramipril and hydrochlorothiazide have an additive effect. Ramipril reduces the loss of potassium ions caused by taking hydrochlorothiazide.

Pharmacokinetics

 The pharmacokinetics of ramipril and hydrochlorothiazide, when administered concurrently, does not differ from that when administered separately. Ramipril absorption averages 50 - 60%. Eating does not affect the degree of absorption, but reduces its speed, the time to reach the maximum concentration (TCmax- 2-4 hours).After ingestion, the absorption of hydrochlorothiazide is 60-80%. The maximum concentration of hydrochlorothiazide in the blood is achieved within 1-5 hours after ingestion. The connection of ramipril with plasma proteins is 73%, ramiprilat - 56%. Connection with plasma proteins hydrochlorothiazide - 64%. The half-life (T1 / 2) for ramipril is 5.1 h; in the distribution and elimination phase, the decrease in the concentration of ramiprilat in the serum occurs from T1 / 2 - 4-5 days. T1 / 2 increases with renal failure. The volume of distribution Ramipril - 90 liters, ramiprilata - 500 liters. Ramipril metabolism occurs mainly in the liver with the formation of the active metabolite of ramiprilat, which inhibits the angiotensin-converting enzyme (ACE) 6 times more active than ramipril and the inactive metabolite diketopiperazine, which are then glucuronized. The drug is excreted mainly in the form of metabolites, the kidneys, 60%, the intestines - 40%. Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. The half-life is 5-15 hours.

PHARMACEUTICAL DATA

List of excipients

Sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch (starch 1500), sodium fumarate.

Special storage conditions

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.