Instructions for Ramizes Com tablets 5 mg + 25 mg blister No. 30
Composition
active ingredients: ramipril, hydrochlorothiazide;
1 tablet contains ramipril 5 mg and hydrochlorothiazide 25 mg or ramipril 2.5 mg and hydrochlorothiazide 12.5 mg;
Excipients: lactose monohydrate, microcrystalline cellulose 102, crospovidone, hypromellose, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
5 mg/25 mg tablets: white or almost white, round tablets with a flat surface with a score and a bevel;
2.5 mg/12.5 mg tablets: white or almost white, round tablets with a biconvex surface with a score or white or almost white, round tablets with a flat surface with a score and a bevel
Pharmacotherapeutic group
Combination drugs of angiotensin-converting enzyme (ACE) inhibitors.
ATX code C09B A05.
Pharmacological properties
Mechanism of action.
Ramipril. Ramiprilat, the active metabolite of the prodrug ramipril, is an inhibitor of the enzyme dipeptidylcarboxypeptidase I (also known as angiotensin-converting enzyme, or kinase II). In plasma and tissues, this enzyme catalyzes the conversion of angiotensin I to angiotensin II, an active vasoconstrictor, and the cleavage of bradykinin, an active vasodilator. Reduced formation of angiotensin II and inhibition of bradykinin cleavage result in vasodilation.
Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a decrease in aldosterone secretion. In black (Afro-Caribbean) hypertensive patients (a population usually characterized by low renin activity), the response to monotherapy with ACE inhibitors was on average less pronounced than in patients of other races.
Hydrochlorothiazide. Hydrochlorothiazide is a thiazide diuretic. As for thiazide diuretics, the mechanism of their antihypertensive action is not yet fully understood. They inhibit the reabsorption of sodium and chloride ions in the distal tubules. Increased renal excretion of these ions is accompanied by increased diuresis (due to osmotic binding of water). The excretion of potassium and magnesium is also increased, while the excretion of uric acid is reduced. Possible mechanisms of the hypotensive action of hydrochlorothiazide are changes in sodium balance, a decrease in extracellular fluid and plasma volume, changes in renal vascular resistance, or a decrease in the responses to noradrenaline and angiotensin II.
Pharmacodynamics.
Ramipril. The use of ramipril leads to a significant decrease in peripheral arterial resistance. As a rule, there are no significant changes in renal plasma flow or glomerular filtration rate. In patients with arterial hypertension, the appointment of ramipril leads to a decrease in blood pressure in both the horizontal and vertical positions, which is not accompanied by a compensatory increase in heart rate.
In most patients, the antihypertensive effect occurs approximately 1-2 hours after a single oral dose of the drug. The maximum effect after a single oral dose usually occurs after 3-6 hours. The antihypertensive effect after a single dose is usually maintained for 24 hours.
With long-term treatment with ramipril, the maximum antihypertensive effect develops after 3-4 weeks. It has been proven that with long-term therapy, the antihypertensive effect persists for 2 years.
Abrupt discontinuation of ramipril does not cause a rapid and excessive increase in blood pressure (rebound phenomenon).
Hydrochlorothiazide: For hydrochlorothiazide, the onset of the diuretic effect occurs after approximately 2 hours and lasts for 6-12 hours, with a maximum effect occurring after 4 hours. The antihypertensive effect occurs after 3-4 days of treatment and may persist for 1 week after the end of treatment.
The antihypertensive effect is accompanied by a slight increase in glomerular filtration rate, renal vascular resistance, and plasma renin activity.
Concomitant use of ramipril and hydrochlorothiazide. The use of this combination leads to a greater reduction in blood pressure than the use of either active substance alone. Concomitant use of ramipril and hydrochlorothiazide reduces the potassium loss that accompanies the diuretic effect, presumably due to inhibition of the activity of the renin-angiotensin-aldosterone system. The combination of an ACE inhibitor with a thiazide diuretic has a synergistic effect and also reduces the risk of hypokalemia caused by the use of the diuretic itself.
Pharmacokinetics.
Ramipril.
Peak plasma concentrations of ramiprilat, the only active metabolite of ramipril, are reached 2-4 hours after administration of ramipril. After the use of usual doses of ramipril once daily, steady-state plasma concentrations of ramiprilat are reached after approximately 4 days of treatment.
Distribution: Plasma protein binding is approximately 73% for ramipril and 56% for ramiprilat.
Metabolism: Ramipril is almost completely metabolized to ramiprilat and to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat.
Elimination. Metabolites are eliminated primarily by the kidneys. The decline in plasma ramiprilat concentrations is multiphasic. Due to the strong cumulative binding to ACE and the slow dissociation from the enzyme, ramiprilat has a prolonged terminal elimination phase at very low plasma concentrations. The effective half-life of ramipril after repeated doses of 5-10 mg ramipril once daily is 13-17 hours and is longer at low doses (1.25-2.5 mg). The difference is due to the saturable capacity of the enzyme to bind ramiprilat. After a single oral dose of ramipril, neither ramipril nor its metabolite were detected in breast milk. However, the effect of repeated doses is unknown.
Patients with renal impairment (see section 4.2). In patients with renal impairment, renal excretion of ramiprilat is reduced and renal clearance of ramiprilat is proportional to creatinine clearance. This results in increased plasma concentrations of ramiprilat, which decrease more slowly than in subjects with normal renal function.
Patients with impaired hepatic function (see section "Dosage and administration"). In patients with impaired hepatic function, the conversion of ramipril to ramiprilat occurs more slowly due to reduced hepatic esterase activity. In such patients, increased plasma levels of ramipril are observed. However, the maximum plasma concentrations of ramiprilat in these patients did not differ from those in subjects with normal hepatic function.
Hydrochlorothiazide.
Absorption: After oral administration, 70% of hydrochlorothiazide is absorbed from the gastrointestinal tract. Peak plasma concentrations of hydrochlorothiazide are reached within 1.5-5 hours.
Distribution: For hydrochlorothiazide, plasma protein binding is approximately 40%.
Metabolism: Hydrochlorothiazide is metabolized in the liver to very small extent.
Excretion: Hydrochlorothiazide is excreted by the kidneys almost completely (> 95%) unchanged; 50-70% of a single dose is excreted within 24 hours. The half-life is 5-6 hours.
Patients with renal impairment (see section 4.2). In patients with renal impairment, renal excretion of hydrochlorothiazide is reduced and renal clearance of hydrochlorothiazide is proportional to creatinine clearance. This results in increased plasma concentrations of hydrochlorothiazide, which decline more slowly than in subjects with normal kidneys.
Patients with hepatic impairment (see section 4.2). The pharmacokinetics of hydrochlorothiazide were not significantly altered in patients with hepatic cirrhosis.
No pharmacokinetic studies of hydrochlorothiazide have been conducted in patients with heart failure.
Ramipril and hydrochlorothiazide. Concomitant administration of ramipril and hydrochlorothiazide did not affect their bioavailability. The combination product can be considered a bioequivalent product containing the individual active substances.
Indication
Treatment of essential hypertension in patients for whom combination therapy (ramipril and hydrochlorothiazide) is recommended.
Contraindication
Hypersensitivity to ramipril or to other ACE inhibitors, hydrochlorothiazide, other thiazide diuretics, sulfonamides or to any of the excipients included in the preparation.
History of angioedema (hereditary, idiopathic or previously experienced while taking ACE inhibitors or angiotensin II receptor antagonists).
Patients with hypotension or hemodynamically unstable conditions.
The concomitant use of ACE inhibitors and extracorporeal treatments that result in contact of blood with negatively charged surfaces should be avoided, as such use may lead to severe anaphylactoid reactions. Such extracorporeal treatments include dialysis or haemofiltration using certain membranes with high hydraulic permeability (e.g. polyacrylonitrile) and low-density lipoprotein apheresis using dextran sulphate (see section 4.5).
Bilateral renal artery stenosis or unilateral renal artery stenosis in the presence of a single functioning kidney.
Severe renal impairment (creatinine clearance <30 ml/min) in patients not undergoing hemodialysis, anuria.
Clinically significant electrolyte imbalances, the course of which may worsen during treatment with the drug (see section "Special instructions").
Treatment-resistant hypokalemia or hypercalcemia.
Symptomatic hyperuricemia (gout).
Severe liver dysfunction, hepatic encephalopathy.
Pregnant women or women planning to become pregnant (see “Use during pregnancy or breastfeeding”).
Breastfeeding (see section "Use during pregnancy or breastfeeding").
Concomitant use with aliskiren-containing drugs in patients with diabetes or in patients with moderate or severe renal impairment (creatinine clearance < 60 ml/min).
Concomitant use with angiotensin II receptor antagonists in patients with diabetic nephropathy.
Interaction with other medicinal products and other types of interactions
Food: Concomitant food intake has no significant effect on the absorption of ramipril.
Contraindicated combinations.
Extracorporeal therapy methods that result in contact of blood with negatively charged surfaces, such as dialysis or hemofiltration using certain high flux membranes (e.g. polyacrylonitrile membranes) and low density lipoprotein apheresis using dextran sulfate - due to an increased risk of severe anaphylactoid reactions (see section "Contraindications"). If such treatment is necessary, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.
Concomitant use with aliskiren-containing products is contraindicated in patients with diabetes or moderate or severe renal impairment (creatinine clearance <60 ml/min) and is not recommended for use in all other patients.
Concomitant use with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended for use in all other patients.
Combinations requiring special caution.
Potassium salts, heparin, potassium-sparing diuretics and other active substances that increase plasma potassium levels (including angiotensin II antagonists, trimethoprim, tacrolimus, ciclosporin). Hyperkalaemia may occur, therefore careful monitoring of plasma potassium levels is necessary.
Antihypertensive drugs (e.g. diuretics) and other active substances that may lower blood pressure (e.g. nitrates, tricyclic antidepressants, anaesthetics, alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). The risk of arterial hypotension may be increased (see section "Method of administration and dosage" for diuretics).
Vasopressor sympathomimetics and other active substances (e.g. epinephrine) which may reduce the antihypertensive effect of ramipril. Regular monitoring of blood pressure is recommended.
Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may cause changes in the blood picture. Increased likelihood of hematological reactions (see section "Special instructions").
Lithium salts. Since ACE inhibitors can reduce the excretion of lithium, this may lead to increased lithium toxicity. Regular monitoring of plasma lithium levels is necessary. The risk of lithium toxicity may be increased with concomitant use of thiazide diuretics and the already increased risk of lithium toxicity caused by ACE inhibitors may be increased. Therefore, the concomitant use of ramipril/hydrochlorothiazide and lithium is not recommended.
Antidiabetic agents, including insulin. Hypoglycemic reactions may occur. Hydrochlorothiazide may weaken the effect of antidiabetic agents. Therefore, blood glucose levels should be monitored particularly closely at the beginning of concomitant use of these agents. Metformin should be used with caution, taking into account the risk of lactic acidosis due to possible hydrochlorothiazide-induced functional renal failure.
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid. The antihypertensive effect of Ramizes® Com is expected to be reduced. Furthermore, the concomitant use of ACE inhibitors and NSAIDs may be associated with an increased risk of renal impairment and an increase in blood potassium levels.
Oral anticoagulants: When used simultaneously with hydrochlorothiazide, the anticoagulant effect may be weakened.
Corticosteroids, ACTH, amphotericin B, carbenoxolone, large amounts of licorice, laxatives (with prolonged use) and other kaliuretic drugs or active substances that reduce the amount of potassium in the blood plasma. Increased risk of hypokalemia.
Digitalis preparations, active substances that can increase the duration of the QT interval, antiarrhythmic agents. In the presence of electrolyte imbalance (e.g. hypokalemia, hypomagnesemia), proarrhythmic effects may be enhanced and antiarrhythmic effects may be attenuated.
Periodic monitoring of serum potassium and ECG is recommended if hydrochlorothiazide is taken concomitantly with drugs that affect serum potassium levels (e.g. digitalis glycosides and antiarrhythmic drugs) and the following drugs that induce torsades de pointes (including some antiarrhythmic drugs), as hypokalemia is a contributing factor to the development of torsades de pointes:
class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide);
class III antiarrhythmics (amiodarone, sotalol, dofetilide, ibutilide);
some neuroleptics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoroperazine, cyamemazine, sulpiride, sultopride, amisulpiride, tiapride, pimozide, haloperidol, droperidol);
other medicines (e.g. bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, intravenous vincamine).
Methyldopa: Isolated cases of hemolytic anemia have been reported with concomitant use of hydrochlorothiazide and methyldopa.
Cholestyramine or other ion exchange resins administered orally. Impaired absorption of hydrochlorothiazide. Sulfonamide diuretics should be taken at least 1 hour before or 4-6 hours after taking these drugs.
Curare-like muscle relaxants. Possible enhancement and prolongation of the action of muscle relaxants.
Calcium salts and drugs that increase the level of calcium in the blood plasma. When used simultaneously with hydrochlorothiazide, an increase in calcium concentrations in the blood plasma can be expected, therefore it is necessary to carefully monitor the level of calcium in the blood plasma.
Carbamazepine: There is a risk of hyponatremia due to an increase in the effect of hydrochlorothiazide.
Iodinated contrast media: In case of dehydration caused by the use of diuretics, including hydrochlorothiazide, there is an increased risk of developing acute renal failure, especially when large doses of iodinated contrast media are administered.
Penicillin. Excretion of hydrochlorothiazide occurs in the distal tubules of the nephron, which reduces the excretion of penicillin.
Quinine: Hydrochlorothiazide reduces the excretion of quinine.
Vildagliptin: An increased incidence of angioedema has been observed in patients receiving concomitant ACE inhibitors and vildagliptin.
mTOR inhibitors (e.g. temsirolimus): An increased incidence of angioedema has been observed in patients receiving concomitant ACE inhibitors and mTOR (mammalian target of rapamycin) inhibitors.
Heparin: Possible increase in serum potassium concentrations.
Salicylates: When used in high doses of salicylates, hydrochlorothiazide may enhance their toxic effects on the central nervous system.
Cyclosporine. Concomitant use of cyclosporine may increase hyperuricemia and increase the risk of complications such as gout.
Alcohol: Ramipril may cause increased vasodilation and thus enhance the effects of alcohol.
Alcohol, barbiturates, narcotics, or antidepressants. May increase orthostatic hypotension.
Salt. The antihypertensive effect of the drug may be weakened with increased salt intake in the diet.
Beta-blockers and diaxozide. Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta-blockers may increase the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may potentiate the hyperglycemic effect of diaxozide.
Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of side effects of amantadine.
Pressor amines (e.g. adrenaline): The effect of pressor amines may be reduced, but not to the extent that would preclude their use.
Antigout agents (probenecid, sulfinpyrazone and allopurinol). Dose adjustment of uricosuric agents may be required as hydrochlorothiazide may increase serum uric acid levels. Dose increase of probenecid or sulfinpyrazone may be required. Concomitant use of thiazides may increase the incidence of hypersensitivity reactions to allopurinol.
Anticholinergics (e.g., atropine, biperiden): Bioavailability of thiazide-type diuretics increases due to decreased gastrointestinal motility and decreased gastric emptying rate.
The effect of drugs on laboratory test results.
Due to their effect on calcium metabolism, thiazides may interfere with the results of parathyroid function tests (see section 4.4).
Specific hyposensitization. ACE inhibition increases the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom. It is believed that this effect may also be observed for other allergens.
The drug contains lactose, so it should not be prescribed to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Application features
Pregnancy: Treatment with ACE inhibitors or angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued ACE inhibitor/angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.8).
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with aliskiren-containing medicinal products.
Dual blockade of the renin-angiotensin-aldosterone system by the combined use of Ramizes® Com and aliskiren is not recommended, as there is an increased risk of developing arterial hypotension, hyperkalemia and changes in renal function.
The combined use of Ramizes® Com and aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min) (see section "Contraindications").
Patients at high risk of hypotension.
Patients with an overactive renin-angiotensin-aldosterone system. Patients with an overactive renin-angiotensin-aldosterone system are at risk of a sudden significant fall in blood pressure and deterioration of renal function due to ACE inhibition. This is particularly true when an ACE inhibitor or concomitant diuretic is given for the first time or when the dose is increased for the first time. An increased activity of the renin-angiotensin-aldosterone system, which requires medical supervision, including regular monitoring of blood pressure, can be expected, for example, in patients:
with severe arterial hypertension;
with decompensated heart failure;
with hemodynamically significant obstruction of the inflow or outflow tracts of blood from the left ventricle (for example, aortic or mitral valve stenosis);
with unilateral renal artery stenosis in the presence of another functioning kidney;
with pronounced or latent fluid or electrolyte depletion (including those patients receiving diuretics);
with liver cirrhosis and/or ascites;
who are undergoing major surgical procedures or during anesthesia with drugs that can cause arterial hypotension.
In patients with impaired liver function, the response to treatment with Ramizes® Com may be either enhanced or reduced. In addition, in patients with severe cirrhosis of the liver, accompanied by edema and/or ascites, the activity of the renin-angiotensin system may be significantly increased; therefore, special caution should be exercised when treating these patients.
Correction of dehydration, hypovolemia, or electrolyte depletion is generally recommended before initiating treatment (however, in patients with heart failure, such corrective measures should be carefully weighed against the risk of volume overload).
Surgery: If possible, treatment with ACE inhibitors such as ramipril should be discontinued 1 day before surgery.
Patients at risk of cardiac or cerebral ischemia in the event of acute hypotension. In the initial phase of treatment, the patient requires close medical supervision.
Primary hyperaldosteronism. The combination of ramipril + hydrochlorothiazide is not the drug of choice in the treatment of primary hyperaldosteronism. However, if ramipril + hydrochlorothiazide is used in a patient with primary hyperaldosteronism, careful monitoring of plasma potassium levels is necessary.
Elderly patients: See section "Method of administration and dosage".
Patients with liver disease: In patients with liver disease, electrolyte imbalances resulting from treatment with diuretics such as hydrochlorothiazide may lead to the development of hepatic encephalopathy. If hepatic encephalopathy occurs, treatment should be discontinued immediately.
In hepatic disorders and in patients suffering from progressive liver disease, thiazides should be used with caution, since these drugs can cause intrahepatic cholestasis, and minimal changes in water-salt balance can provoke the development of hepatic coma. Hypothiazide is contraindicated in patients with severe hepatic insufficiency (see section "Contraindications").
Patients with renal impairment. In patients with renal disease, thiazides may precipitate sudden uremia. In patients with renal impairment, cumulative effects of the active substances may occur. If progressive renal dysfunction becomes evident, as indicated by an increase in residual nitrogen, the decision to continue treatment should be carefully considered. Discontinuation of diuretic therapy should be considered (see Contraindications).
Electrolyte imbalance: As in all patients treated with diuretics, plasma electrolytes should be monitored at appropriate intervals. Thiazides, including hydrochlorothiazide, may cause electrolyte imbalance (hypokalemia, hyponatremia, and hypochloraemic alkalosis).
Although hypokalemia may develop with thiazide diuretics, concomitant use of ramipril may reduce diuretic-induced hypokalemia. The risk of hypokalemia is highest in patients with cirrhosis of the liver, in patients with increased diuresis, in patients receiving insufficient electrolytes, and in patients receiving concomitant treatment with corticosteroids and ACTH (see section "Interaction with other medicinal products and other forms of interaction"). During the first week of treatment, baseline plasma potassium levels should be determined. If low potassium levels are detected, correction should be made.
Dilutional hyponatremia may occur. Low sodium levels may be asymptomatic at first, so regular testing is important. In elderly patients and patients with cirrhosis, such tests should be performed more frequently.
Thiazides have been shown to increase urinary magnesium excretion, which may lead to hypomagnesemia.
Hyperkalaemia. Hyperkalaemia has been observed in some patients treated with ACE inhibitors. Patients at risk for hyperkalaemia include patients with renal insufficiency, the elderly (aged 70 years and over), patients with untreated or poorly controlled diabetes mellitus, or those taking potassium salts, potassium-sparing diuretics or other active substances that increase plasma potassium levels, or patients with conditions such as dehydration, acute cardiac decompensation or metabolic acidosis. If concomitant use of the above-mentioned drugs is indicated, regular monitoring of plasma potassium levels is recommended (see section 4.5).
Hepatic encephalopathy: In patients with liver disease, electrolyte imbalances resulting from treatment with diuretics, including hydrochlorothiazide, may lead to the development of hepatic encephalopathy. In the event of hepatic encephalopathy, treatment should be discontinued immediately.
Hypercalcemia: Hydrochlorothiazide stimulates the reabsorption of calcium in the kidneys, which can lead to hypercalcemia. This may distort the results of tests performed to examine the function of the parathyroid glands.
Angioedema. Angioedema has been reported in patients treated with ACE inhibitors such as ramipril (see section 4.8). If angioedema occurs, treatment with Ramizes® Com should be discontinued immediately and emergency treatment initiated. The patient should be kept under medical supervision for at least 12-24 hours and may be discharged only after complete resolution of symptoms.
Cases of intestinal angioedema have been reported in patients treated with ACE inhibitors such as Ramizex (see section 4.8). These patients presented with abdominal pain (with or without nausea/vomiting).
Anaphylactic reactions during desensitization. When using ACE inhibitors, the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens increases. Before conducting desensitization, Ramizes® Com should be temporarily discontinued.
Neutropenia/agranulocytosis. Cases of neutropenia/agranulocytosis have been reported rarely. Bone marrow depression has also been reported. Monitoring of the white blood cell count is recommended to detect possible leukopenia. More frequent monitoring is advisable at the beginning of treatment and in patients with impaired renal function, in patients with concomitant collagen disease (e.g. systemic lupus erythematosus or scleroderma) and in those taking concomitant medications that may cause changes in the blood picture (see sections “Interaction with other medicinal products and other forms of interaction” and “Adverse reactions”).
Ethnic differences. ACE inhibitors cause angioedema more frequently in black patients than in non-blacks. As with other ACE inhibitors, the antihypertensive effect of ramipril may be less pronounced in black patients than in non-blacks. This may be because black hypertensive patients tend to have low-renin states.
Metabolic and endocrine effects. Thiazide therapy may cause impaired glucose tolerance. In some cases, patients with diabetes mellitus may require adjustment of insulin and oral hypoglycemic agents. Latent diabetes mellitus may become manifest during thiazide therapy.
Thiazide diuretic therapy may be associated with increases in cholesterol and triglyceride levels. In some patients, thiazide diuretics may precipitate hyperuricemia or acute gout attacks.
Cough: Cough has been reported with ACE inhibitors. This cough is usually non-productive, persistent and resolves after discontinuation of treatment. The possibility of ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
Acute myopia and secondary acute angle-closure glaucoma. Hydrochlorothiazide is a sulfonamide drug. Sulfonamides and sulfonamide derivatives may cause idiosyncratic reactions resulting in transient myopia and acute angle-closure glaucoma. Symptoms include acute onset, decreased visual acuity or eye pain and usually occur within hours to weeks after starting the drug.
Untreated acute glaucoma can lead to permanent vision loss. The primary treatment for this condition is to discontinue the drug as soon as possible. Urgent medical or surgical attention may be required if intraocular pressure remains uncontrolled. Risk factors for the development of acute angle-closure glaucoma may include a history of allergy to sulfonamides or penicillin.
Acute respiratory toxicity. Very rare cases of severe acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported following the administration of hydrochlorothiazide. Pulmonary oedema usually develops within minutes to hours of taking hydrochlorothiazide. Early symptoms include dyspnoea, fever, worsening of pulmonary function and hypotension. If ARDS is suspected, hydrochlorothiazide should be discontinued and appropriate treatment initiated. Hydrochlorothiazide should not be given to patients who have previously experienced ARDS after taking hydrochlorothiazide.
Others: Patients with or without a history of allergy or bronchial asthma may experience hypersensitivity reactions. Exacerbation or activation of systemic lupus erythematosus has been reported.
Syncope: If a patient experiences syncope, treatment should be discontinued and a physician consulted.
The drug may affect the results of the following laboratory tests:
the drug may reduce the level of protein-bound iodine in blood plasma;
Treatment with the drug should be discontinued before laboratory testing to assess parathyroid function;
The drug is capable of increasing the concentration of free bilirubin in the blood serum.
Use during pregnancy or breastfeeding
Pregnancy.
Ramizes® Com is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this drug, its use should be discontinued immediately and replaced with another drug approved for use in pregnant women.
ACE inhibitors can cause fetal and neonatal morbidity and mortality when administered to pregnant women.
Children with a history of in utero exposure to ACE inhibitors should be closely monitored for hypotension, oliguria, and hyperkalemia. If oliguria develops, blood pressure and renal perfusion should be closely monitored. Exchange transfusion or dialysis may be necessary to reduce hypotension and/or restore renal function. However, the limited experience with these procedures has not been associated with significant clinical benefit. It is unknown whether ramipril and ramiprilat can be removed from the body by hemodialysis.
Since the use of the drug Ramizes®
