Амприлан® NL

General characteristics. Structure:

Active ingredients: 2,5 mg of a ramipril, 12, 5 mg of a hydrochlorothiazide.

Excipients: Natrii hydrocarbonas, lactoses monohydrate, croscarmellose sodium, starch prezhelatinizirovanny (starch 1500), the sodium stearylfumarating.

The hypotensive combined drug.

Pharmacological properties:

Pharmacodynamics. Ramipril. Inhibitor of the angiotensin-converting enzyme (ACE), interferes with transformation of angiotensin I into angiotensin II without compensatory increase in heart rate. Reduces products of Aldosteronum, the general vascular peripheric resistance, pressure in pulmonary capillaries, resistance in pulmonary vessels, does not change a glomerular filtration rate, strengthens a coronary blood stream. At prolonged use of drug the myocardium hypertrophy at patients with arterial hypertension decreases, the frequency of arrhythmias at myocardium reperfusion decreases; blood circulation of an isheminizirovanny myocardium improves. Cardiotyre-tread action is caused by influence on synthesis of prostaglandins, induction of formation of nitrogen oxide in endotheliocytes. Drug reduces aggregation of thrombocytes. The beginning of hypotensive action - in 1,5 hours after intake, the maximum effect - in 5-9 hours, action duration - 24 hours. Drug has no withdrawal.

Hydrochlorothiazide. Thiazide diuretic which diuretic effect is connected with disturbance of a reabsorption of ions of sodium, chlorine, potassium, magnesium, water in distal department of nephron; removal of calcium ions, uric acid detains. Has anti-hypertensive properties; hypotensive action develops due to expansion of arterioles. Practically does not exert impact on the normal arterial pressure (AP). The diuretic effect occurs in 1-2 hours, reaches a maximum in 4 hours and 6-12 hours proceed. Anti-hypertensive action comes in 3-4 days, but for achievement of optimum therapeutic effect 3-4 weeks can be required. Ramipril and a hydrochlorothiazide possess the additive action. Ramipril reduces the loss of potassium ions caused by reception of a hydrochlorothiazide.

Pharmacokinetics. The pharmacokinetics ramiprit and the hydrochlorothiazide at a concomitant use does not differ from that at their separate appointment. Absorption of a ramipril averages 50 - 60%. Meal does not influence extent of absorption, but reduces its speed, time of achievement of the maximum concentration (Tsmax-2-4 hours). After intake absorption of a hydrochlorothiazide makes 60-80%. The maximum concentration of a hydrochlorothiazide in blood is reached in 1-5 hours after intake. Communication of a ramipril   with proteins of a blood plasma makes 73%, a ramiprilat - 56%. Communication with proteins of a blood plasma of a hydrochlorothiazide - 64%. An elimination half-life (T1/2) for a ramipril - 5,1 h; in a phase of distribution and elimination decrease in concentration of a ramiprilat in blood serum happens to T1/2 - 4-5 days. T1/2 increases at a renal failure. The volume of distribution of Ramipril - 90 l, a ramiprilat - 500 l. Metabolism of a ramipril happens generally in a liver to formation of an active metabolite of a ramiprilat which inhibits the angiotensin-converting enzyme (ACE) 6 times more active, than ramiprit also an inactive metabolite of diketopiperazine which then and glyukuronizirutsya. Drug is removed preferential in the form of metabolites, kidneys - 60%, by intestines - 40%. The hydrochlorothiazide is not metabolized and quickly removed through kidneys. The elimination half-life makes 5-15 hours.

Indications to use:

Arterial hypertension (patients to whom the combination therapy is shown).

Route of administration and doses:

Inside. The dose is selected individually. The usual dose for adults-1 tablet of Amprilan of NL (2,5 mg / 12,5 mg) in days, if necessary can be increased to 1 tablet of Amprilan of ND (5,0 mg / 25 by mg). At a renal failure of easy or moderate degree (clearance of creatinine more than 30 ml/min., creatinine of serum about 3 mg/dl or 265 µmol/l) the usual dose of drug is recommended. At clearance of creatinine less than 30 ml/min. it is not recommended to use drug. Duration of therapy is not limited.

Features of use:

Ramipril: severe damages of coronary and cerebral arteries (danger of decrease in a blood-groove at excessive decrease in the ABP), unstable stenocardia, heavy ventricular disturbances of a rhythm, chronic heart failure of the IV stage, dekompensirovanny "pulmonary heart", a renal and/or liver failure, a hyperpotassemia, a hyponatremia (including against the background of diuretics and a diet with salt consumption restriction), the states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting), general diseases of connecting fabric, including a scleroderma and a system lupus erythematosus, the diseases demanding purpose of GKS (glucocorticosteroids) and immunodepressants (lack of clinical experience), a diabetes mellitus, oppression of a marrowy hemopoiesis, advanced age.

Hydrochlorthiazidum: a hypopotassemia, a hyponatremia, a hypercalcemia, coronary heart disease, a liver failure, cirrhosis, bronchial asthma in the anamnesis, advanced age.

Drug is contraindicated at pregnancy. At pregnancy approach administration of drug has to be immediately stopped. In need of purpose of drug in the period of a lactation it is necessary to stop breastfeeding.

During treatment it is necessary to be careful when driving motor transport, and also during the occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Ramipril.
From cardiovascular system: decrease in the ABP, orthostatic hypotension, an orthostatic collapse, tachycardia, is rare - arrhythmia, heartbeat, heartbeat, an aggravation of a syndrome of Reynaud. At excessive decrease in the ABP, generally at patients with coronary heart disease and clinically significant vasoconstriction of a brain, myocardium ischemia (stenocardia, a myocardial infarction) and brain ischemia can develop (it is possible with dynamic disturbance of cerebral circulation or a stroke).

From urinogenital system: development or strengthening of symptoms of a renal failure, proteinuria, oliguria, intersticial nephrite, nephrotic syndrome, reduction of volume of urine, gynecomastia, decrease in a potentiality, libido.

From central nervous a brain sistemy:ishemiya, a stroke, dizziness, a headache, weakness, drowsiness, peripheral neuropathy (paresthesias), nervous irritability, concern, a tremor, a muscular spasm, disturbances of mood, apathy, at use in high doses - sleeplessness, uneasiness, a depression, an ataxy, confusion of consciousness, a syncope.

From sense bodys: vestibular disturbances, taste disturbances (for example, metal taste), sense of smell, hearing and sight, blepharites, dryness of a conjunctiva, dacryagogue, sonitus.

From the alimentary system: nausea, vomiting, diarrhea or a lock, pain in epigastric area, intestinal impassability, a meteorism, pancreatitis, hepatitis, cholestatic jaundice, cholecystitis (in the presence of a cholelithiasis), an abnormal liver function with development of a liver failure, a melena, Ilheus, dryness in a mouth, thirst, a loss of appetite, stomatitis, a glossitis, an inflammation of sialadens.

From respiratory system: Sukhoi cough, bronchospasm, asthma, rhinorrhea, rhinitis, sinusitis, pharyngitis, hoarseness, bronchitis, intersticial pneumonia, embolism of a pulmonary artery, lung heart attack, fluid lungs.

Allergic reactions: skin rash, itch, small tortoiseshell, conjunctivitis, photosensitization, Quincke's disease of the person, extremities, lips, language, throat and/or throat, exfoliative dermatitis, multiformny exudative erythema (including Stephens-Johnson's syndrome), toxic epidermal necrolysis (Lyell's disease), pemphigus, serositis, онихолизис, vasculitis, miositis, muscular weakness, mialgiya, arthralgia, arthritis, eosinophilia.

Prochiye:sudorog, alopecia, shingles, hyperthermia, the increased sweating.

Laboratory indicators: giperkreatininemiya, increase in level of an urea nitrogen, increase in activity of "hepatic" enzymes, hyperbilirubinemia, hyperpotassemia, hyponatremia, anemia, decrease in concentration of hemoglobin and hematocrit, neutropenia, thrombocytopenia, agranulocytosis, pancytopenia, hemolitic anemia, emergence of antinuclear antibodies.

Influence on a fruit: dysfunction of a fruit, decrease in the ABP of a fruit and newborns, renal failure, hyperpotassemia, hypoplasia of bones of a skull, олигогидрамнион, contracture of extremities, deformation of bones of a skull, hypoplasia of lungs.

Hydrochlorothiazide.
From water and electrolytic and acid-base balance: development of a hypopotassemia and gilokhloremichesky alkalosis is possible (dryness in a mouth, strengthening of thirst, disturbance of a heart rhythm, change of mood and mentality, a spasm or muscle pain, nausea, vomiting, weakness; at a gipokhloremichesky alkalosis development of hepatic encephalopathy or a hepatic coma), hyponatremias (confusion of consciousness, a spasm, apathy, delay of process of thinking, fatigue, irritability), hypomagnesiemia (arrhythmia) is possible.

From system of a hemopoiesis: agranulocytosis, thrombocytopenia, hemolitic and aplastic anemia, leykotsitopeniya, eosinophilia, neutropenia, pancytopenia.

From cardiovascular system: arrhythmia, orthostatic hypotension, tachycardia.

From the alimentary system: cholecystitis, pancreatitis, jaundice, diarrhea, a sialadenitis, a lock, anorexia, pains in epigastriums.

From a metabolism: hypercholesterolemia, gipertriglitseridemiya, hyperglycemia, glucosuria, hyperuricemia, hypercalcemia, aggravation of a course of gout.

From the central nervous system: depression, sleep disorder, concern, paresthesias, confusion of consciousness, dizziness.

From sense bodys: xanthopsia, vision disorders.

From urinogenital system: renal failure, decrease in a potentiality, intersticial nephrite.

Allergic reaktsii:kozhny rash, small tortoiseshell, purpura, necrotic vasculitis, Stephens-Johnson's syndrome, respiratory distress syndrome (pneumonitis, not cardiogenic hypostasis of a lung), toxic epidermal necrolysis, photosensitization; anaphylactic reactions (up to a life-threatening acute anaphylaxis).

Others: hyperthermia, weakness.

Interaction with other medicines:

Ramipril.
Strengthens the oppressing effect of ethanol on the central nervous system. Reception of salt with food can reduce hypotensive effect of a ramipril. At simultaneous use of a ramipril and other means, the reducing ABP (for example, diuretics, nitrates, tricyclic antidepressants, means for the general anesthesia) leads to strengthening of hypotensive effect of a ramipril. Co-administration of a ramipril and drugs of potassium or kaliysberegayushchy diuretics can become the hyperpotassemia reason. Angiotonic sympathomimetics (Epinephrinum, Norepinephrinum) can snizhatgipotenzivny effect of a ramipril. In this regard at simultaneous treatment it is necessary to control the ABP level carefully.

Co-administration of a ramipril and Allopyrinolum, immunodepressants, corticosteroids, procaineamide, tsitostatik increases probability of changes of a peripheral picture of blood (risk of development of a leukopenia). Co-administration of a ramipril and drugs of lithium leads to decrease in excretion of lithium, it is necessary to control concentration of lithium in blood serum - risk of emergence of toxic effects. APF inhibitors can strengthen effect of hypoglycemic means (for example, insulin or derivatives of sulphonylurea) that in some cases can become the hypoglycemia reason. In this regard sugar level in blood has to be controlled carefully, especially at the beginning of combined use.

Simultaneous use of a ramipril and non-steroidal anti-inflammatory drugs (NPVP) (for example, acetylsalicylic acid and indometacin) can weaken hypotensive effect of a ramipril. In addition simultaneous use can cause a hyperpotassemia and increase risk of a renal failure. Simultaneous use of a ramipril with estrogen can weaken hypotensive effect. Simultaneous use of heparin and a ramipril can become the hyperpotassemia reason. Anaphylactic and anaphylactoid reactions to poison of stinging insects (it is possible also to other allergens) are more expressed during treatment by APF inhibitors.

Hydrochlorothiazide. At simultaneous use of glycosides of a foxglove with thiazide diuretics the probability of manifestation of toxic effects of glycosides (including a hyperexcitability of ventricles) because of probable development of a hypopotassemia and a hypomagnesiemia increases. The medicines which are intensively contacting proteins (indirect anticoagulants, Clofibratum, NPVP), strengthen diuretic effect of a hydrochlorothiazide.

The hypotensive effect of a hydrochlorothiazide is strengthened by vazodilatator, beta adrenoblockers, barbiturates, fenotiazina, tricyclic antidepressants, ethanol. The hydrochlorothiazide strengthens a neurotoxicity of salicylates, weakens effect of peroral hypoglycemic medicines, Norepinephrinum, Epinephrinum and antigouty drugs, strengthens cardiotoxic and neurotoxic effect of drugs of lithium, action of peripheral muscle relaxants, reduces quinidine removal. At a concomitant use Methyldopums hemolysis development is possible. Colestyraminum reduces absorption of a hydrochlorothiazide. The hydrochlorothiazide reduces effect of oral contraceptives.

Contraindications:

Ramipril.
Hypersensitivity to a ramipril and any other ingredient of drug or other APF inhibitors, the Quincke's disease in the anamnesis including connected with the previous therapy by APF inhibitors, hemodynamically significant bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney, a state after transplantation of kidneys, a hemodialysis, a renal failure (clearance of creatinine less than 30 ml/min.), hemodynamically significant aortal or mitral stenosis (risk of excessive decrease in the ABP with the subsequent renal failure), a hypertrophic subaortic stenosis, primary hyper aldosteronism, pregnancy and the period of a lactation, age up to 18 years (efficiency and safety are not established).

Hydrochlorothiazide.
Hypersensitivity to drug or other sulfonamides in the anamnesis, gout, a diabetes mellitus (severe forms), a chronic renal failure (clearance of creatinine less than 20-30 ml/min., an anury), a heavy liver failure, a refractory hypopotassemia, a hypercalcemia, a hyponatremia, pregnancy, the lactation period, age up to 3 years (a firm dosage form).

Overdose:

Ramipril. Symptoms: the expressed decrease in the ABP, bradycardia, shock, disturbance of a water and electrolytic state, an acute renal failure, a stupor, dryness in a mouth, weakness, drowsiness.
Treatment: to give to the patient horizontal position with the raised legs, in mild cases of overdose - a gastric lavage, administration of adsorbents and sodium of sulfate (it is desirable to hold events within the first 30 min. after administration of drug). At decrease in the ABP - intravenous administration of catecholamines, angiotensin P; at bradycardia - use of the Pacemaker. Drug is not removed when carrying out a hemodialysis.

Hydrochlorothiazide. Symptoms: hypopotassemia (adynamia, paralysis, lock, arrhythmias), drowsiness, decrease in the ABP. Treatment: infusion of electrolytic solutions; compensation of deficit of K+ (purpose of drugs K+ and kaliysberegayushchy diuretics).

Storage conditions:

To store at a temperature no more than 25 °C. To store in the place, unavailable to children

Issue conditions:

According to the recipe

Packaging:

Tablets on 2,5 mg of a ramipril and 12,5 mg of Hydrochlorthiazidum. The blister on 7 tablets: 2,4, 8,12 or 14 blisters in a cardboard pack together with the application instruction. The blister on 10 tablets: 3 blisters in a cardboard pack together with the application instruction