Ramazid N
Latin name: Ramazid N
ATX code: C09BA05
Active ingredient: hydrochlorothiazide (Hydrochlorothiazide) + ramipril (Ramipril)
Manufacturer: Actavis Ltd. (Actavis Ltd.) (Malta); Actavis GROUP AO (Actavis GROUP hf.) (Iceland)
Description and photo updated: 2019-27-02
Prices in pharmacies: from 129 rubles.
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Ramazid N is a combined antihypertensive drug.
Release form and composition
Ramazid N dosage form:
- 2.5 mg + 12.5 mg tablets: from almost white to white, flat, oval, marked "12.5" and a notch on one side (7, 10 or 14 pcs. in blisters; in cardboard a pack of 2 or 4 blisters of 7 pcs., 1 or 3 blisters of 10 pcs., 1 or 2 blisters of 14 pcs.);
- tablets 5 mg + 25 mg: from almost white to white, flat, oval, marked "25" and a notch on one side (7, 10 or 14 pieces in blisters; in a cardboard box 2 or 4 blisters each 7 pcs., 1 or 3 blisters of 10 pcs., 1 or 2 blisters of 14 pcs.);
- tablets 5 mg + 12.5 mg: pink, inclusions are allowed, flat, oblong, with lateral risks, marking "R2" and a notch are applied on one side (10 pcs. in blisters; in a cardboard box 3 or 10 blisters).
Each pack also contains instructions for the use of Ramazid N.
Composition for 1 tablet at a dosage of 2.5 mg + 12.5 mg (5 mg + 25 mg):
- active substances: ramipril + hydrochlorothiazide - 2.5 mg + 12.5 mg (5 mg + 25 mg);
- excipients: pregelatinized corn starch, sodium carbonate, croscarmellose sodium, lactose monohydrate, sodium stearyl fumarate.
Composition for 1 tablet at a dosage of 5 + 12.5 mg:
- active substances: ramipril + hydrochlorothiazide - 5 mg + 12.5 mg;
- excipients: sodium bicarbonate, sodium stearyl fumarate, calcium sulfate dihydrate, pregelatinized corn starch, reddish brown dye PB24823.
Pharmacological properties
Pharmacodynamics
The active substances of Ramazid N - ramipril and hydrochlorothiazide, have an additive effect. Ramipril reduces the loss of potassium ions caused by the intake of hydrochlorothiazide.
Ramipril
Ramipril is one of the ACE inhibitors (angiotensin-converting enzyme). Its action is aimed at counteracting the process of transformation of angiotensin I into angiotensin II, while a compensatory increase in heart rate (heart rate) is not observed. The substance helps to reduce the production of aldosterone, OPSS (total peripheral vascular resistance), pressure in the pulmonary capillaries, resistance in the pulmonary vessels. During therapy, there is an increase in coronary blood flow, the glomerular filtration rate does not change.
During a long course in patients with arterial hypertension, myocardial hypertrophy decreases, there is a decrease in the frequency of arrhythmias during myocardial reperfusion, and an improvement in the blood circulation of the ischeminized myocardium. The cardioprotective effect is due to the effect of ramipril on the biosynthesis of prostaglandins, the induction of the formation of nitric oxide in endotheliocytes. Ramipril reduces platelet aggregation. The beginning of the development of the hypotensive effect is observed 1.5 hours after ingestion of the substance, the maximum effect develops after 5-9 hours, the duration of the effect is 24 hours. There is no withdrawal syndrome with ramipril.
Hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic, its effect is associated with impaired reabsorption of magnesium, chlorine, sodium, potassium, water ions in the distal nephron. The substance delays the excretion of uric acid and calcium ions. Hydrochlorothiazide has antihypertensive properties. Normal blood pressure (blood pressure) is practically not affected.
The antihypertensive effect of the substance develops due to the following effects: change in the reactivity of the vascular wall; decrease in BCC (circulating blood volume); strengthening of the depressor effect on the ganglia; decrease in pressor influence.
The development of the diuretic effect is observed after 1–2 hours, it reaches its maximum value after 4 hours, its duration is 6–12 hours. The antihypertensive effect is observed after 3-4 days of therapy; 3-4 weeks may pass before the optimal therapeutic effect is achieved.
Pharmacokinetics
The pharmacokinetic processes of the active substance of Ramazid N when taken simultaneously from those when used separately do not differ.
Ramipril
The average absorption of ramipril is 50-60%. The intake of food does not affect the degree of absorption, while its speed decreases. T max (time to reach maximum concentration) ranges from 2 to 4 hours.
The metabolism of ramipril occurs mainly in the liver, with the formation of an active metabolite, ramiprilat. It inhibits ACE more actively than ramipril, 6 times. Diketopiperazine (an inactive metabolite) is also formed. Subsequently, the metabolites of ramipril are glucuronized.
Communication with blood plasma proteins: ramipril - 73%, ramiprilat - 56%.
T 1/2 (half-life) of ramipril is 5.1 hours; a decrease in the serum concentration of ramiprilat in the blood in the phase of distribution and elimination occurs with T 1/2 from 4 to 5 days. With renal failure, T 1/2 increases.
V d (volume of distribution): ramipril - 90 l, ramiprilat - 500 l.
The excretion of the drug is carried out mainly in the form of metabolites by the kidneys and through the intestines (60 and 40%, respectively).
Hydrochlorothiazide
After oral administration, hydrochlorothiazide is absorbed at a level of 60-80%. C max (maximum concentration) in the blood is reached in 1–5 hours.
The connection with plasma proteins is 64%.
Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. T 1/2 ranges from 5 to 15 hours.
Indications for use
Ramazid N is prescribed for the treatment of hypertension in patients who are indicated for combination therapy.
Contraindications
Ramipril
Absolute:
- renal failure (in patients with creatinine clearance less than 20 ml / min.);
- primary hyperaldosteronism;
- hypertrophic obstructive cardiomyopathy;
- burdened history of angioedema, including those associated with previous therapy with ACE inhibitors;
- hemodialysis;
- stenosis of an artery of a single kidney;
- hemodynamically significant bilateral renal artery stenosis;
- condition after kidney transplantation;
- hemodynamically significant aortic / mitral stenosis (associated with the risk of an excessive decrease in blood pressure, which can cause impaired renal function);
- pregnancy and lactation;
- age up to 18 years;
- individual intolerance to the components of the drug and other ACE inhibitors.
Relative (Ramazid N is prescribed under medical supervision):
- renal / hepatic impairment;
- severe lesions of the coronary / cerebral arteries (associated with the danger of a decrease in blood flow with an excessive decrease in blood pressure);
- unstable angina;
- chronic heart failure stage IV;
- severe ventricular rhythm disturbances;
- decompensated cor pulmonale;
- hyponatremia (including those arising from a diet with limited salt intake and the use of diuretics);
- hyperkalemia;
- systemic connective tissue diseases;
- conditions that are accompanied by a decrease in BCC (including vomiting, diarrhea);
- oppression of bone marrow circulation;
- diabetes;
- elderly age.
Hydrochlorothiazide
Absolute:
- chronic renal failure (in patients with creatinine clearance less than 20-30 ml / min and / or anuria);
- gout;
- diabetes mellitus in severe forms;
- refractory hypokalemia;
- hypercalcemia;
- hyponatremia;
- I trimester of pregnancy and lactation;
- individual intolerance to the components of the drug.
Relative (Ramazid N tablets are prescribed under medical supervision):
- cirrhosis of the liver;
- hypokalemia;
- hypercalcemia;
- hyponatremia;
- cardiac ischemia;
- elderly age.
Ramazid N, instructions for use: method and dosage
Ramazid N tablets are taken orally every day, once a day in the morning.
The drug should be used only after individual selection of the dose of each of the active components.
Usual starting and maintenance dose: ramipril 2.5 mg + hydrochlorothiazide 12.5 mg. If necessary, the dose is increased at intervals of at least three weeks. Maximum dose: ramipril 5 mg + hydrochlorothiazide 25 mg.
For patients with impaired renal function of mild to moderate degree (with creatinine clearance more than 30 ml / min, serum creatinine value of about 3 mg / dL or 265 μmol / L), dose adjustment is not required. It is not recommended to take Ramazid N for patients with creatinine clearance less than 30 ml / min.
Side effects
Ramipril
- sense organs: vestibular disturbances, tinnitus, taste disturbances (in particular, metallic taste in the mouth), smell, vision and hearing;
- cardiovascular system: orthostatic hypotension, decreased blood pressure, tachycardia, orthostatic collapse; rarely - arrhythmia, myocardial infarction, angina pectoris;
- central nervous system: anxiety, cerebral ischemia, dizziness, stroke, muscle spasm, weakness, drowsiness, paresthesia, headache, nervous irritability, tremors, mood disorders; when taking high doses - fainting, insomnia, anxiety, confusion, depression;
- genitourinary system: the onset / intensification of symptoms of renal failure, decreased libido, decreased urine volume, proteinuria;
- respiratory system: bronchospasm, rhinorrhea, shortness of breath, rhinitis, bronchitis, dry cough, sinusitis;
- digestive system: impaired hepatic function with the development of liver failure, thirst, dry mouth, stomatitis, decreased appetite, glossitis, intestinal obstruction, nausea, constipation or diarrhea, vomiting, epigastric pain, pancreatitis, hepatitis, cholestatic jaundice;
- allergic reactions: skin rash, itching, conjunctivitis, urticaria, photosensitivity, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), exudative erythema multiforme (including Stevens-Johnson syndrome), pemphigus, onycholysis, myositis, myalgia arthralgia, vasculitis, eosinophilia, inflammation of the serous membrane (eg, pericardium, peritoneum, pleura), angioedema of the extremities, face, tongue, lips, larynx and / or pharynx;
- effect on the fetus: oligohydramnios, limb contracture, lung hypoplasia, hyperkalemia, fetal dysfunction, decreased blood pressure of the fetus and newborns, hypoplasia of the skull bones, renal dysfunction, deformation of the skull bones;
- laboratory parameters: the appearance of antinuclear antibodies, an increase in the level of urea nitrogen, hypercreatininemia, an increase in the activity of hepatic transaminases, hyperkalemia, hyperbilirubinemia, hyponatremia;
- others: increased sweating, convulsions, pyrexia, alopecia.
Hydrochlorothiazide
- hematopoietic system: leukocytopenia, thrombocytopenia, agranulocytosis, aplastic / hemolytic anemia;
- water-electrolyte / acid-base balance: hypokalemia and hypochloremic alkalosis (in the form of increased thirst, xerostomia, cardiac arrhythmias, changes in the psyche and mood, cramps or muscle pain, nausea, vomiting, weakness; development of hepatic coma or hepatic encephalopathy is possible), hypomagnesemia (in the form of arrhythmias), hyponatremia (in the form of confusion, seizures, apathy, slowing down of the thinking process, fatigue, irritability);
- digestive system: diarrhea, constipation, sialoadenitis, anorexia, epigastric pain, cholecystitis, jaundice, pancreatitis;
- cardiovascular system: orthostatic hypotension, arrhythmia, tachycardia;
- allergic reactions: skin rash, photosensitivity, necrotizing vasculitis, purpura, Stevens-Johnson syndrome, respiratory distress (in the form of pneumonitis, noncardiogenic pulmonary edema), anaphylactic reactions (possibly up to life-threatening anaphylactic shock);
- metabolism: hyperuricemia, hyperglycemia, exacerbation of gout, glucosuria.
Overdose
- the main symptoms of an overdose of Ramazid N: stupor, xerostomia, drowsiness, weakness, shock, bradycardia, a marked decrease in blood pressure, imbalance in water and electrolyte balance, acute renal failure;
- therapy: the patient should take a horizontal position with raised legs. In case of a mild overdose, gastric lavage, the use of adsorbents and sodium sulfate are indicated (it is desirable that these measures be carried out within the first 30 minutes after taking the drug). In the case of a decrease in blood pressure, catecholamines, angiotensin II are administered intravenously. The development of bradycardia may require the use of a pacemaker (pacemaker). During hemodialysis, the drug is not excreted.
special instructions
Ramipril
Renal function should be assessed before starting therapy. During treatment, careful monitoring of renal function is required, especially in patients with renal vascular damage, impaired renal function, heart failure.
In patients undergoing hemodialysis procedures using dialysis membranes AN69, during the use of ACE inhibitors, the likelihood of hypersensitivity and anaphylactoid (allergic) reactions increases. Similar reactions have been reported in low-density lipoprotein apheresis with dextran sulfate, so this method should be avoided when treating with ramipril.
During the period of application of Ramazid N in patients with impaired renal function, especially against the background of simultaneous treatment with diuretics, an increase in serum levels of urea and creatinine in the blood is possible. In such cases, a dose reduction or complete withdrawal of therapy is indicated. With impaired renal function, the risk of developing hyperkalemia increases.
In patients with impaired liver function, the metabolism of ramipril and the formation of an active metabolite may be slowed down, which is associated with a decrease in the activity of hepatic enzymes. It is necessary to begin treatment of patients with such a disorder only under strict medical supervision.
If patients follow a low-salt or salt-free diet, caution is required when prescribing ramipril, since in this case there is an increased likelihood of arterial hypotension. With a reduced BCC (due to diuretic therapy), dialysis, vomiting and diarrhea, symptomatic hypotension may develop.
Transient arterial hypotension is not a contraindication for continuing treatment after BP stabilization has been achieved. If severe arterial hypotension develops again, it is necessary to reduce the dose or cancel Ramazid N.
In patients who undergo major surgical interventions or receive other drugs that cause arterial hypotension during general anesthesia, the use of ramipril can lead to a blockade of angiotensin II formation due to compensatory renin release. If the doctor associates the development of arterial hypotension with the above-mentioned mechanism, it can be corrected by increasing the volume of blood plasma.
During treatment with ACE inhibitors, in rare cases, hemoglobinemia, agranulocytosis, thrombocytopenia, erythrocytopenia, or bone marrow suppression are noted. At the beginning of the course and during the period of further therapy, it is necessary to monitor the number of white blood cells in order to identify possible agranulocytosis / neutropenia. More frequent monitoring is recommended for patients with renal impairment, connective tissue diseases (including systemic lupus erythematosus or scleroderma), and patients taking drugs that affect blood formation. The counting of blood cells is also necessary in the case of the development of clinical signs of agranulocytosis / neutropenia and increased bleeding.
When treating with ramipril in patients with arterial hypertension, an increase in serum potassium levels in the blood is rarely observed. The risk of hyperkalemia increases with the following diseases / conditions: chronic heart failure, simultaneous use with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and potassium preparations.
During desensitizing therapy to wasp or bee venom while taking ramipril, anaphylactoid reactions (manifested in the form of arterial hypotension, shortness of breath, vomiting, skin rash) may develop, which can be life-threatening. With insect bites (wasps or bees), hypersensitivity reactions may occur. In patients requiring desensitizing therapy with wasp or bee venom, ramipril should be discontinued and replaced with an antihypertensive drug from another group.
Hydrochlorothiazide
In order to prevent K + and Mg 2+ deficiency, potassium-sparing diuretics, magnesium and potassium salts are prescribed. Requires regular monitoring of plasma glucose, potassium, uric acid, creatinine and lipids.
Hydrochlorothiazide during anti-doping control can give a positive reaction.
Influence on the ability to drive vehicles and complex mechanisms
During the period of therapy with Ramazid N, caution should be exercised when driving vehicles, since there is a possibility of dizziness. This is especially possible after taking the initial dose of an ACE inhibitor in patients taking drugs with a diuretic effect. Until the response to treatment is clarified, it is recommended to refrain from driving.
Application during pregnancy and lactation
Ramazid N is not prescribed during pregnancy / lactation.
Pediatric use
The safety / efficacy of Ramazid N in pediatric patients under 18 years of age has not been established, and therefore, the drug is not prescribed for this age group of patients.
With impaired renal function
In renal failure, Ramazid N should be used with caution.
Prescribing the drug to patients with creatinine clearance less than 20 ml / min is contraindicated.
For violations of liver function
In liver failure, Ramazid N should be used with caution.
Use in the elderly
Ramazid N is prescribed for elderly patients under medical supervision.
Drug interactions
Ramipril
- drugs that lower blood pressure (anesthetics, nitrates, diuretics, tricyclic antidepressants): there is an increase in the antihypertensive effect of ramipril;
- norepinephrine, adrenaline (vasopressor sympathomimetics): the hypotensive effect of ramipril may decrease; in the case of simultaneous use, it is necessary to carefully monitor the blood pressure level;
- potassium preparations, potassium-sparing diuretics: hyperkalemia may develop;
- lithium preparations: against the background of combined use, there is a decrease in lithium excretion; monitoring of the concentration of lithium in the blood serum is required, which is associated with the risk of developing toxic effects;
- allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics: the likelihood of changes in the peripheral blood picture increases;
- acetylsalicylic acid, indomethacin and other non-steroidal anti-inflammatory drugs: the hypotensive effect of ramipril may be weakened, while the risk of impaired renal function increases, hyperkalemia may develop;
- insulin, sulfonylurea derivatives and other hypoglycemic agents: their effect may be enhanced, in some patients this may cause hypoglycemia; if necessary, the simultaneous use of blood sugar levels should be carefully monitored, especially at the beginning of combination therapy;
- heparin: against the background of combined use, the development of hyperkalemia is possible;
- ethanol: its depressing effect on the nervous system is enhanced;
- salt (with food): The hypotensive effect of ramipril may be reduced.
During the period of use of ramipril, anaphylactoid and anaphylactic reactions to the venom of stinging insects (probably to other allergens) are more pronounced.
Hydrochlorothiazide
- clofibrate, indirect anticoagulants, non-steroidal anti-inflammatory drugs (drugs that intensively bind to proteins): against the background of combined use, the diuretic effect of hydrochlorothiazide is enhanced;
- digitalis glycosides: the likelihood of their toxic effects, including increased excitability of the ventricles, increases (associated with an increased risk of hypomagnesemia and hypokalemia);
- phenothiazines, ethanol, vasodilators, barbiturates, beta-blockers, tricyclic antidepressants: the antihypertensive effect of hydrochlorothiazide is enhanced;
- salicylates: their neurotoxicity increases against the background of combined use;
- lithium preparations: their neurotoxic and cardiotoxic effect on hydrochlorothiazide increases;
- oral hypoglycemic drugs, epinephrine, norepinephrine, anti-gout drugs: their effect is weakened;
- peripheral muscle relaxants: there is an increase in their effect;
- quinidine: its excretion is reduced;
- methyldopa: against the background of combined use, hemolysis may develop;
- cholestyramine: absorption of hydrochlorothiazide decreases;
- oral contraceptives: there is a decrease in their effectiveness.
Analogs
Ramazid N analogs are Amprilan ND, Konsilar-D24, Vasolong N, Tritace plus, Dilaprel Plus, Hartil-D, etc.
Terms and conditions of storage
Store at temperatures up to 25 ° C. Keep out of the reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Ramazid N
Mostly there are positive reviews about Ramazid N, in which patients note the rapid development of a therapeutic effect that lasts for 24 hours. The advantages also include a convenient dosing regimen. Side effects are infrequent, but they can be pronounced.
The price of Ramazid N in pharmacies
Approximate price for Ramazid N per package 30 pcs. can be:
- tablets 2.5 mg + 12.5 mg - 259 rubles;
- tablets 5 mg + 25 mg - 309 rubles.
Ramazid N: prices in online pharmacies
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Drug name Price Pharmacy |
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Ramazid N 5 mg + 25 mg tablets 30 pcs. 129 RUB Buy |
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Ramazid N 5mg + 12.5mg tablets 30 pcs. 188 r Buy |
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Ramazid N 2.5 mg + 12.5 mg tablets 30 pcs. 219 r Buy |
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Ramazid N 5mg + 12.5mg tablets 100 pcs. RUB 635 Buy |
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Ramazid N 5 mg + 25 mg tablets 100 pcs. RUB 690 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
