On AMPRILAN
Active material: Gidroxlorotiazid, Ramipril
When ATH: C09BA05
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.03
Manufacturer: KRKA d.d. (Slovenia)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Pills white or nearly white, flat, kapsulovidnye, scored on one side and marking “25” on the other hand.
| 1 tab. | |
| ramipril | 5 mg |
| gidroxlorotiazid | 25 mg |
Excipients: natriya carbonate, lactose monohydrate, Croscarmellose sodium, pre-gelatinized starch (starch 1500), sodium fumarate.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.
7 PC. – blisters (8) – packs cardboard.
7 PC. – blisters (12) – packs cardboard.
7 PC. – blisters (14) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.
Pharmacological action
Combined antihypertensive drug.
Ramipril – ACE inhibitor, lets turn angiotenzina I angiotenzin II without a compensatory increase in HEART RATE.
Reduces the production of aldosterone, PR, the pressure in the pulmonary capillaries, resistance in the pulmonary vessels, does not change the speed clubockova filtering, increases coronary blood flow. With long-term use the drug decreases myocardial hypertrophy in patients with hypertension, decreases the frequency of arrhythmias during myocardial reperfusion injury; išemizirovannogo improves blood circulation infarction.
Cardioprotective effect due to the influence of the synthesis of prostaglandins, induction of nitric oxide formation in èndoteliocitah. The drug reduces agregatia platelets. Start action hypotensive – through 1.5 hours after ingestion, maximum effect – through 5-9 no, duration – 24 no. The drug had no withdrawal symptoms.
Gidroxlorotiazid – tiazidnый diuretic, diuretic effect which involves a violation of the reabsorption of sodium ions, Chlorine, Potassium, Magnesium, water in the distal nephron.
Delays excretion of calcium ions, Uric acid. Has provides antihypertensive effect, developing by widening arteriol. Almost no effect on normal blood pressure. The antihypertensive effect occurs within 3-4 day, but in order to achieve optimum therapeutic effect may require 3-4 of the week. The diuretic effect after 1-2 no, reaches through 4 h and lasts for 6-12 no.
Ramipril and hydrochlorothiazide have additive effect. Ramipril reduces loss of potassium ions, caused gidrohlorotiazida reception.
Pharmacokinetics
Pharmacokinetics ramiprila and gidrohlorotiazida while receiving no different from that in their separate application.
Absorption
After intake suction ramiprila averages 50-60%. Eating does not affect the degree of suction, but reduces its speed. Tmax is 2-4 no.
After intake of absorption of hydrochlorothiazide is 60-80%, Cmax hydrochlorothiazide in the blood is achieved through 1-5 no
Distribution
Linking ramiprila with blood plasma proteins is 73%, ramiprilata – 56%. Vd ramiprila – 90 l, ramiprilata – 500 l.
Plasma protein binding of hydrochlorothiazide is 64%.
Metabolism
Ramiprila metabolism occurs mainly in the liver with the formation of the active metabolita ramiprilata, which ingibiruet enzyme in 6 times more active, than ramipril and inactive metabolite diketopiperazina, who will then glukuroniziruyutza.
Hydrochlorothiazide is not metabolized.
Deduction
T1/2 ramiprila – 5.1 no; in the phase of distribution and elimination of reduction of ramiprilata concentration in the serum comes with T1/2 – 4-5 days. Ramipril is excreted primarily as metabolites: urine – 60 %, with feces – 40%. Hydrochlorothiazide in unmodified form to quickly return with urine. T1/2 is 5-15 no.
Pharmacokinetics in special clinical situations
T1/2 ramiprila and its metabolites is increased in renal failure.
Testimony
- Arterial hypertension (patients, which shows the combination therapy).
Dosage regimen
The drug is taken orally. Dose picked individually.
Daily intake for adults – 1 tab. / day.
At violation of the kidney mild or moderate degree (CC>30 ml / min, serum creatinine is approximately 3 mg / dL or 265 mmol / l) the usual recommended dose. At CC<30 ml / min, drug use is not recommended.
Duration of therapy is not limited.
Side effect
Ramipril
Cardio-vascular system: decrease in blood pressure, orthostatic hypotension, Orthostatic hypotension, tachycardia; rarely – arrhythmia, palpitations, exacerbation of Raynaud's syndrome. If excessive decline in ad, mainly in patients with ischemic heart disease and clinically significant narrowing of blood vessels in the brain, may develop myocardial ischaemia (angina, myocardial infarction) and brain ischemia (Perhaps with dynamic violation of cerebral circulation or stroke).
From the digestive system: nausea, vomiting, diarrhea or constipation, epigastric pain, ileus, flatulence, pancreatitis, hepatitis, cholestatic jaundice, cholecystitis (in the presence of cholelithiasis), violation of the liver with the development of liver failure, ground, ileus, dry mouth, thirst, decreased appetite, stomatitis, glossitis, inflammation of the salivary glands.
From the central and peripheral nervous system: dizziness, headache, weakness, drowsiness, perifericheskaya neuropathy (paresthesia), nervous anxiety, anxiety, tremor, muscle spasm, mood disorders, apathy; When used in high doses-insomnia, anxiety, depression, ataxia, confusion, fainting.
The respiratory system: dry cough, bronchospasm, breathlessness, rhinorrhea, rhinitis, sinusitis, pharyngitis, hoarseness, bronchitis, interstitial pneumonia, pulmonary embolism, pulmonary infarction, pulmonary edema.
From the urinary system: development or increased symptoms of kidney failure, proteinuria, oligurija, interstitial nephritis, nephrotic syndrome, decrease in urine.
Reproductive system: gynecomastia, reduced potency, libido.
From the senses: vestibular disorders, taste disturbances (eg, metallic taste), olfactory, hearing and vision, blepharitis, dryness of the conjunctiva, lacrimation, noise in ears.
From the hematopoietic system: anemia, reduction of the concentration of hemoglobin and hematocrit, neutropenia, thrombocytopenia, agranulocytosis, pancytopenia, gemoliticheskaya anemia, the appearance of antinuclear antibodies, eozinofilija.
Metabolism: giperkreatininemiя, increased BUN, increase in liver enzymes, giperʙiliruʙinemija, hyperkalemia, giponatriemiya.
Allergic reactions: skin rash, itch, hives, conjunctivitis, photosensitivity, angioneurotic edema of the face, limbs, lips, language, pharynx and / or larynx, exfoliative dermatitis, erythema multiforme exudative (incl. Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), pemphigus, serositis, onixolizis, vasculitis, myositis, muscular weakness, myalgia, arthralgia, arthritis.
Other: convulsions, alopecia, shingles, hyperthermia, increased perspiration.
Effect on the fetus: the functions of the fetus, reducing ad fetal/neonatal, impairment of renal function, hyperkalemia, hypoplasia of the skull bones, oligogidramnion, contracture of limbs, deformation of the skull bones, pulmonary hypoplasia.
Gidroxlorotiazid
Cardio-vascular system: arrhythmia, orthostatic hypotension, tachycardia.
From the digestive system: cholecystitis, pancreatitis, jaundice, diarrhea, sialadenitis, constipation, anorexia, epigastric pain.
From the central and peripheral nervous system: depression, sleep disturbance, anxiety, paresthesia, confusion, dizziness.
From the urinary system: impairment of renal function, interstitial nephritis.
From the senses: Xanthopsia, visual impairment.
From the hematopoietic system: agranulocytosis, thrombocytopenia, gemoliticheskaya anemia, aplasticheskaya anemia, leukopenia, eozinofilija, neutropenia, pancytopenia.
Metabolism: the development of hypokalemia and gipohloremičeskogo alkalosis (dry mouth, increased thirst, heart rhythm disturbances, change of mood and psyche, cramping or aching muscles, nausea, vomiting, weakness; When gipohloremičeskom alkaloze to the development of hepatic encephalopathy or hepatic coma), giponatriemii (confusion, convulsions, apathy, slowing the process of thinking, fatigue, irritability), gipomagniemii (Arrhythmia), hypercholesterolemia, hypertriglyceridemia, giperglikemiâ, glycosuria, hyperuricemia, hypercalcemia, worsening of gout.
Allergic reactions: skin rash, hives, purpura, Necrotizing Vasculitis, Stevens-Johnson syndrome, acute respiratory distress syndrome (pneumonitis, nekardiogennyj Lung edema), toxic epidermal necrolysis, photosensitivity, anaphylactic reactions (until life threatening anaphylactic shock).
Other: hyperthermia, weakness, reduced potency.
Contraindications
Ramipril
- A history of angioedema (incl. associated with previous therapy, ACE inhibitors);
-hemodynamically significant stenoses bilateral renal artery;
is stenosis of artery only kidneys;
-condition after kidney transplantation;
-hemodialysis;
- Renal failure (CC<30 ml / min);
-hemodynamically significant aortic or mitral stenosis (the risk of excessive loss AD with consequent impairment of renal function);
- Gipertroficheskaya obstruktivnaya cardiomyopathy;
- Primary hyperaldosteronism;
- Pregnancy;
- Lactation;
- Childhood and adolescence up 18 years (efficacy and safety have not been established);
-hypersensitivity to ACE inhibitors;
-hypersensitivity to ramiprilu and/or preparation components.
FROM caution the drug should be taken with heavy defeats of the coronary and cerebral arteries (the danger of reducing blood flow when excessive decline in ad), unstable angina, severe ventricular rhythm, stage IV chronic heart failure, декомпенсированном pulmonary heart, kidney and / or liver failure, hyperkalemia, giponatriemii (incl. against the backdrop of diuretics and diet with restriction of salt intake), states, accompanied by a decrease in the bcc (incl. diarrhea, vomiting), systemic connective tissue diseases (incl. Scleroderma and SLE), diseases, requiring the appointment of SCS and immunosuppressants (the lack of clinical experience), diabetes, suppression of bone marrow hematopoiesis, in elderly patients.
Gidroxlorotiazid
- Gout;
- Diabetes (severe);
- Chronic renal failure (CC<20-30 ml / min, anurija);
- Severe hepatic impairment;
- Refractory hypokalaemia;
- Hypercalcemia;
- Giponatriemiya;
- Pregnancy;
- Lactation;
- Children under 3 years;
-hypersensitivity to sulfonamidam history;
- Hypersensitivity to the drug.
FROM caution the drug should be taken with hypokalemia, giponatriemii, hypercalcemia, CHD, hepatic insufficiency, cirrhosis, bronchial asthma in history, in elderly patients.
Pregnancy and lactation
The drug is contraindicated in pregnancy. If pregnancy should immediately stop taking the drug.
If necessary, use during lactation should decide the issue of termination of breastfeeding.
Cautions
Ramipril
At the beginning of treatment should be to evaluate kidney function. There is a need to closely monitor renal function during treatment with ramipril especially in patients with compromised renal function, with the defeat of the renal vessels (eg, clinically insignificant stenosis of the renal arteries or hemodynamically significant stenosis of the artery only kidneys); Heart Failure.
The risk of hypersensitivity and allergopodobnyh (anaphylactoidnykh) reactions is increased in patients, at the same time receiving ACE inhibitors and undergoing hemodialysis procedure using dialysis membranes AN 69. Similar reactions were detected by afereze ENGINEERS using dextran sulfate, Therefore, in the treatment of ACE inhibitors, you should avoid using this method.
During treatment with ramipril in patients with impaired renal function, especially while treatment dioretikami, may increase levels of urea and creatinine in the serum. In this case treatment should continue lower doses ramiprila or cancel product. In patients with impaired renal function, increased risk of giperkaliemii.
In patients with compromised liver function due to lower liver enzymes can be slowed metabolism ramiprila and education metabolita active. In this regard, the treatment of such patients should start only under strict medical supervision.
Use caution when assigning ramiprila patients, We are on a salt-free diet or malosolevoy (increased risk of arterial hypotension). In patients with reduced BCC (as a result of diuretic therapy), When performing dialysis, If you have diarrhea and vomiting may develop symptomatic hypotension.
Transient hypotension is not a contraindication to continuing treatment after stabilization AD. In case of recurrence of arterial expressed hypotension should reduce the dose or stop the drug.
Patients, subjected to extensive surgical procedures or other cause hypertension hypotension means during general anesthesia, ramipril may cause blockade education angiotenzina II due to compensatory Renin release. If the physician Associates development arterial hypotension with the above-mentioned mechanism, hypotension can be adjusted for increases in the volume of blood plasma.
In rare cases during treatment ACE inhibitors are observed agranulocytosis, erythropenia, thrombocytopenia, gemoglobinemiâ or oppression bone marrow. At the beginning of and during treatment, it is necessary to control the amount of white blood cells to detect possible neutropenia/agranulocytosis. More frequent monitoring is recommended at
patients with renal insufficiency, with connective tissue diseases (incl. SLE or Scleroderma) and patients, at the same time taking medicines, affecting the blood. The uniform of the blood count should be implemented also in the occurrence of clinical signs of neutropenia, agranulocytosis and increased bleeding.
In patients with arterial hypertension during treatment of ramipril rarely increase the level of potassium in the blood serum. Risk giperkaliemii increases in chronic heart failure, While kalisberegatmi dioretikami treatment (incl. spironolactone, amilorid, triamterene) and the appointment of drugs potassium.
When using ACE inhibitors during desensibiliziruûŝej therapy for osinomu or bee venom may arise anaphylactoidnye reaction (incl. hypotension, breathlessness, vomiting, skin rash), which can be life threatening. Hypersensitivity reactions may occur when insect bites (incl. Bees, OS). When it is necessary to carry out treatment of desensibilization bee osinym or poison you must cancel the ACE inhibitors and continue treatment suitable drugs from other groups.
Gidroxlorotiazid
For prevention of deficiency of potassium and magnesium is prescribed a diet with a high content of these salts, potassium-sparing diuretics, salts of potassium and magnesium. Requires regular monitoring of plasma potassium, Glucose, Uric acid, lipids and creatinine.
Use in Pediatrics
The drug is contraindicated in patients childhood and adolescence till 18 years.
Effects on ability to drive vehicles and management mechanisms
During treatment, it is necessary to be careful when driving vehicles, as well as during classes potentially hazardous activities, require high concentration and speed of psychomotor reactions.
Overdose
Ramipril
Symptoms: marked reduction in blood pressure, bradycardia, shock, violation vodno-elektrolitnogo balance, acute renal failure, stupor, dry mouth, weakness, drowsiness.
Treatment: give the patient a horizontal position with pripodnatami feet, in mild cases of overdose – gastric lavage, introduction of adsorbents and sodium sulfate (It is advisable to carry out activities during the first 30 minutes after administration). By reducing blood pressure – in/in the introduction of Catecholamines, angiotensin II; When bradycardia – use Pejsmekera. The drug does not appear in the kidney.
Gidroxlorotiazid
Symptoms: kaliopenia (adinamija, paralysis, constipation, Arrhythmia), drowsiness, decrease in blood pressure.
Treatment: infusion of electrolyte solutions, compensation deficiency of potassium (prescribing potassium kalisberegath dioretikov).
Drug Interactions
Ramipril
Together with the use of ramipril do dampening effect of ethanol on the central nervous system.
Salt intake with food can reduce gipotenzivny effect ramiprila.
If you use ramiprila and other means, lowering blood pressure, (incl. Diuretic, nitrates, tricyclic antidepressants, funds for general anesthesia) amplified gipotenzivny effect ramiprila.
While appointing ramiprila and drugs/potassium kalisberegath dioretikov can develop hyperkalemia.
In connection with the possible decrease gipotenzivnogo effect ramiprila should carefully monitor the level of HELL while applying Amprilana® LP vazopressornymi simpatomimetikami (epinephrine, norepinephrine).
While applying ramiprila with allopourinolom, immunosuppressants, GCS, prokaynamydom, zitostatikami, increasing the likelihood of changes in peripheral blood picture (the risk of leukopenia).
Due to the reduced excretion of lithium and the risk of toxic effects should be monitored lithium concentration in the blood serum while applying ramiprila with lithium.
Together with the use of ACE inhibitors may increase effect gipoglikemicakih funds (incl. insulin or sulfonylurea derivatives), that, in some cases, can cause hypoglycemia. Should carefully monitor the blood sugar levels, especially at the beginning of combination therapy.
While applying ramiprila with NSAIDS (incl. acetylsalicylic acid, Indomethacin) perhaps weakening gipotenzivnogo effect ramiprila, as well as giperkaliemii development and increased risk of kidney function.
While applying ramiprila with estrogens may weakening gipotenzivnogo effect.
Together with the use of heparin and ramiprila may giperkaliemii development.
During treatment with ACE inhibitors anaphylacticskie and anaphylactoidnye reaction to poison stinging insects (may and other allergens) more pronounced.
Gidroxlorotiazid
Together with the use of a thiazide diuretic with glycosides naperstanki increased probability of manifestations of the toxic effects of glycosides (incl. anxiety of the ventricles) because of the likely development of hypokalemia and gipomagniemii.
If you are applying to reinforce gipotenzivny effect of hydrochlorothiazide: vasodilators, beta-blockers, barbiturates, fenotiazinы, tricyclic antidepressants, ethanol, as well as medicines, rapidly bind to blood proteins (indirect anticoagulants, clofibrate, NSAIDs).
While applying hydrochlorothiazide increases the neurotoxicity of salicylates, cardiotoksicescoe and neurotoxic effect drugs lithium, effects of peripheral muscle relaxants.
While applying hydrochlorothiazide ters of oral contraceptives, oral hypoglycemic agents, norepinephrine, epinephrine and protivopodagricakih drugs, reduces the excretion of quinidine.
If you are applying with hydrochlorothiazide metildopoj may develop hemolysis.
If you are applying with kolestiraminom decreases absorption of hydrochlorothiazide hydrochlorothiazide.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 2 year.
