Instructions for Ramimed combi tablets 5 mg + 25 mg No. 30
Composition
active ingredients: 1 tablet contains 2.5 mg ramipril/12.5 mg hydrochlorothiazide or 5 mg ramipril/25 mg hydrochlorothiazide;
Excipients: pregelatinized starch; sodium stearyl fumarate; sodium bicarbonate; lactose monohydrate; croscarmellose sodium.
Dosage form
Pills.
Main physicochemical properties:
5 mg/25 mg tablets – white or almost white capsule-shaped, uncoated, flat tablets with beveled edges, with a score on one side and on the lateral surfaces, dimensions approximately 5.0 x 10.0 mm. Marked 25.
Pharmacotherapeutic group
Combination drugs of angiotensin-converting enzyme (ACE) inhibitors. Ramipril and diuretics. ATC code C09B A05.
Pharmacological properties
Pharmacodynamics
Mechanism of action.
Ramipril. Ramiprilat, the active metabolite of the prodrug ramipril, is an inhibitor of dipeptidylcarboxypeptidase I (also known as ACE 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, reduction of extracellular fluid and plasma volume, changes in renal vascular resistance, or reduced responses to noradrenaline and angiotensin II.
Pharmacodynamics.
Ramipril. The use of ramipril leads to a significant decrease in peripheral arterial resistance. Usually, there are no significant changes in renal plasma flow or glomerular filtration rate (GFR). In patients with arterial hypertension, the use 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 oral administration of a single dose of the drug. The maximum effect after oral administration of a single dose usually occurs after 3-6 hours. The antihypertensive effect after a single dose is 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 achieved after 4 hours. The antihypertensive effect is achieved 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 GFR, 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 (RAAS). The combination of an ACE inhibitor with a thiazide diuretic shows a synergistic effect and also reduces the risk of hypokalemia caused by the use of the diuretic itself.
Pharmacokinetics
Ramipril.
Absorption. After oral administration, ramipril is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations of ramipril are reached within 1 hour. Based on the amount of substance recovered in the urine, absorption is at least 56% and is not significantly affected by the presence of food in the gastrointestinal tract. The bioavailability of the active metabolite ramiprilat after oral administration of 2.5 mg and 5 mg is 45%.
The maximum plasma concentration of ramiprilat, the only active metabolite of ramipril, is reached 2-4 hours after administration of ramipril. After the use of usual doses of ramipril once a day, the equilibrium plasma concentration of ramiprilat is 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 diketopiperazine ester, diketopiperazine acid and glucuronides of ramipril and ramiprilat.
Elimination. Elimination of metabolites occurs primarily by renal excretion. The decline in plasma ramiprilat concentrations is multiphasic. Due to the strong saturable 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 lower doses (1.25-2.5 mg). The difference is due to the saturable binding capacity of the enzyme to 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 decline 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 is slower due to reduced activity of hepatic esterases. In such patients, an increase in plasma levels of ramipril is 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 patients with normal kidneys.
Patients with impaired liver function (see section "Method of administration and dosage"). In patients with cirrhosis of the liver, the pharmacokinetics of hydrochlorothiazide are not significantly altered. No studies have been conducted to study the pharmacokinetics of hydrochlorothiazide in patients with heart failure.
Ramipril and hydrochlorothiazide. Concomitant administration of ramipril and hydrochlorothiazide did not affect their bioavailability. The combined product can be considered bioequivalent to the products containing the individual active substances.
Indication
Treatment of hypertension. This fixed combination is indicated in patients whose blood pressure is not adequately controlled with ramipril or hydrochlorothiazide monotherapy.
Contraindication
Hypersensitivity to the active substance ramipril or to other ACE inhibitors, hydrochlorothiazide, other thiazide diuretics, sulfonamides or to any of the excipients listed in section 6.1. Ramipril should not be used in patients with hypotension or hemodynamically unstable conditions. History of angioedema (hereditary, idiopathic or previously treated with ACE inhibitors or angiotensin II receptor antagonists). Anuria, treatment-resistant hypokalemia or hypercalcemia, refractory hyponatremia, symptomatic hyperuricemia (gout).
The use of extracorporeal therapy methods, resulting in contact of blood with negatively charged surfaces (see section "Interaction with other medicinal products and other types of interactions").
Significant bilateral renal artery stenosis or unilateral renal artery stenosis in a single functioning kidney. Severe renal impairment (creatinine clearance < 30 ml/min) in patients not undergoing hemodialysis.
Clinically significant electrolyte imbalances, the course of which may worsen during use of the drug (see section "Special instructions").
Severe liver dysfunction, hepatic encephalopathy. Pregnant women or women planning to become pregnant (see section "Use during pregnancy or breastfeeding"). Breastfeeding (see section "Use during pregnancy or breastfeeding").
Concomitant use of Ramipril/Amlodipine with aliskiren-containing drugs in patients with diabetes mellitus or renal dysfunction (GFR < 60 ml/min/1.73 m2) (see sections “Pharmacodynamics” and “Interaction with other medicinal products and other types of interactions”).
Concomitant use during treatment with sacubitril/valsartan (see sections “Interaction with other medicinal products and other types of interactions” and “Special precautions for use”).
Concomitant use with angiotensin II receptor antagonists in patients with diabetic nephropathy.
Interaction with other medicinal products and other types of interactions
Clinical studies have shown that dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is associated with an increased incidence of adverse events such as hypotension, hyperkalemia and deterioration of renal function (including the development of acute renal failure) compared with the use of a single agent affecting the RAAS (see sections "Pharmacodynamics", "Contraindications" and "Special Instructions for Use").
Food: Concomitant food intake has no significant effect on the absorption of ramipril.
Contraindicated combinations. Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated as it increases the risk of angioedema (see sections "Contraindications" and "Special warnings and precautions for use"). Ramipril treatment should be initiated no earlier than 36 hours after the last dose of sacubitril/valsartan. Sacubitril/valsartan should be initiated no earlier than 36 hours after the last dose of RAMIMED COMBI.
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 the 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 and patients with 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 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 and its fixed combinations with sulfamethoxazole, 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).
There may be an increased risk of arterial hypotension (see section "Dosage and administration" for diuretics).
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 caused by ACE inhibitors may increase with concomitant use of thiazide diuretics, therefore the concomitant use of ramipril/hydrochlorothiazide and lithium is not recommended.
Antidiabetic agents (oral hypoglycemic agents and 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.
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid. A decrease in the antihypertensive effect of RAMIMED COMBI is expected. Also, the simultaneous use of ACE inhibitors and NSAIDs may be accompanied by an increased risk of impaired renal function and an increase in blood potassium levels.
Oral anticoagulants: When used simultaneously with hydrochlorothiazide, the anticoagulant effect may be weakened.
Corticosteroids, adrenocorticotropic hormone, 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.
Medicinal products affected by changes in serum potassium levels: Periodic monitoring of serum potassium levels and ECG monitoring is recommended when hydrochlorothiazide is administered concomitantly with medicinal products affected by serum potassium levels (e.g. digitalis glycosides and antiarrhythmic medicinal products) and medicinal products known to induce torsades de pointes (including some antiarrhythmic medicinal products), as hypokalaemia is a predisposing factor to torsades de pointes:
Class Ia antiarrhythmics (e.g. quinidine, hydroquinidyl, disopyramide); Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide); Some neuroleptics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpiride, tiapride, pimozide, haloperidol, droperidol); Other drugs (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 for oral use. 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 the concentration of calcium 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 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.
mTOR inhibitors or DPP-4 inhibitors: There is an increased risk of angioedema in patients taking concomitant medicinal products such as mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus) or DPP-4 inhibitors (vildagliptin and possibly saxagliptin or linagliptin). Caution should be exercised when initiating such therapy (see section 4.4).
Cyclosporine: Concomitant use of cyclosporine may exacerbate hyperuricemia and increase the risk of complications such as gout.
Alcohol: Ramipril may lead to increased vasodilation and thus potentiate 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 diazoxide: 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 diazoxide.
Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of side effects caused by 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 necessary, as hydrochlorothiazide may increase serum uric acid levels. Dose increase of probenecid or sulfinpyrazone may be necessary. 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.
Effects of medicinal products 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).
Patients require rehydration before administration of iodine-containing drugs.
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 with respect to other allergens.
Application features
Special patient groups
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 RAAS. There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and deterioration of renal function (including the development of acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections 5.1 and 5.5).
If such dual blockade therapy is considered absolutely necessary, it should only be used under specialist supervision and with frequent and careful monitoring of renal function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
Patients at high risk of hypotension.
Patients with increased RAAS activity. Patients with increased RAAS activity are at risk of a sudden significant decrease in blood pressure and deterioration of renal function due to ACE inhibition. This is particularly true when an ACE inhibitor or concomitant diuretic is first prescribed or the dose is first increased. Increased RAAS activity, which requires medical supervision, including constant monitoring of blood pressure, can be expected in patients:
with severe arterial hypertension; with decompensated congestive heart failure; with hemodynamically significant obstruction of the inflow or outflow tracts of blood from the left ventricle
(e.g. aortic or mitral valve stenosis); with unilateral renal artery stenosis in the presence of a second functioning kidney; with pronounced or latent fluid or electrolyte depletion (including those patients receiving diuretics); with cirrhosis of the liver and/or ascites; who are undergoing major surgery or during anesthesia with drugs that can cause arterial hypotension.
In patients with impaired liver function, the response to treatment with RAMIMED COMBI may be either enhanced or reduced. In addition, in patients with severe cirrhosis of the liver, accompanied by edema and/or ascites, RAAS activity may be significantly increased, so special caution should be exercised when treating these patients.
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 arterial 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.
In patients with impaired liver function, the response to treatment with the drug may be either enhanced or reduced. In addition, in patients with severe cirrhosis of the liver, accompanied by edema and/or ascites, RAAS activity may be significantly increased, so special caution should be exercised when treating these patients.
Thiazides should be used with caution in hepatic impairment and in patients with progressive liver disease, as these drugs can cause intrahepatic cholestasis, and even minimal changes in water-salt balance can precipitate hepatic coma. Hydrochlorothiazide is contraindicated in patients with severe hepatic impairment (see section 4.3).
Monitoring of renal function. Renal function should be monitored before and during treatment and the dose adjusted accordingly, especially in the first weeks of treatment. Patients with impaired renal function (see section "Method of administration and dosage") require particularly careful monitoring. There is a risk of impaired renal function, especially in patients with congestive heart failure or after kidney transplantation, with damage to the renal vessels, including patients with hemodynamically significant unilateral renal artery stenosis.
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 disturbances. As in all patients treated with diuretics, plasma electrolytes should be measured at appropriate intervals. Thiazides, including hydrochlorothiazide, may cause disturbances of water and electrolyte balance (hypokalaemia, hyponatraemia and hypochloraemic alkalosis). Although hypokalaemia may develop with thiazide diuretics, concomitant use of ramipril may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia 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 or adrenocorticotropic hormone (see section 4.5). Initial plasma potassium levels should be determined during the first week of treatment. If a low potassium level is detected, correction is necessary.
Dilutional hyponatremia may occur. Low sodium levels may be asymptomatic at first, so it is important to have regular sodium testing. 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.
Electrolyte monitoring: Hyponatremia. In some patients treated with ramipril, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) with subsequent hyponatremia has been observed. It is recommended that serum sodium levels be monitored regularly in the elderly and in other patients at risk of hyponatremia.
Hepatic encephalopathy: In patients with liver disease, electrolyte imbalance resulting from treatment with diuretics, including hydrochlorothiazide, may lead to the development of hepatic encephalopathy. If hepatic encephalopathy occurs, treatment should be discontinued immediately.
Hypercalcemia: Hydrochlorothiazide stimulates renal calcium reabsorption, which may lead to hypercalcemia. This may distort the results of tests performed to examine parathyroid function.
Angioedema: Angioedema has been reported in patients treated with ACE inhibitors such as ramipril (see section 4.8). This risk may be higher in patients receiving concomitant medicinal products known to cause angioedema, such as mTOR (mammalian target of rapamycin) inhibitors (e.g. temsirolimus, everolimus, sirolimus) or DPP-4 (dipeptidyl peptidase-4) inhibitors (vildagliptin and possibly saxagliptin or linagliptin) or neprilysin (NEP) inhibitors such as racecadotril. The combination of ramipril and sacubitril/valsartan is contraindicated due to the risk of angioedema (see sections 4.3 and 4.5).
In the event of angioedema, treatment with RAMIMED COMBI 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 Ramipril/Amlodipine (see section 4.8). These patients presented with abdominal pain (with or without nausea/vomiting). Symptoms of intestinal angioedema resolved after discontinuation of the ACE inhibitor.
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, the drug RAMIMED COMBI should be temporarily discontinued.
Neutropenia/agranulocytosis. Cases of neutropenia/agranulocytosis have been observed rarely. Bone marrow suppression has also been reported. Monitoring of the white blood cell count is recommended to detect possible leukopenia. More frequent monitoring is advisable in patients at the beginning of treatment and in patients with impaired renal function, 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”).
Acute myopia and secondary acute angle-closure glaucoma. Hydrochlorothiazide, which belongs to the sulfonamides, can cause idiosyncratic reactions leading to acute transient myopia and acute angle-closure glaucoma. Symptoms are characterized by an acute onset of decreased visual acuity or eye pain and typically develop within a few hours to a few weeks of starting the drug. Untreated acute angle-closure glaucoma can lead to irreversible vision loss. Initial treatment involves discontinuation of hydrochlorothiazide as soon as possible. In the event of
