Universal reference book for medicines
Product name: CARDOSAL В® PLUS (CARDOSAL В® PLUS)

Active substance: hydrochlorothiazide, olmesartan medoxomil

Type: Angiotensin II receptor antagonist in combination with a diuretic

Manufacturer: BERLIN PHARMA (Russia) manufactured by DAIICHI SANKYO EUROPE (Germany) packed with BERLIN-CHEMIE (Germany)
Composition, form of production and packaging
Tablets, film-coated
1 tab.

hydrochlorothiazide 12.5 mg

olmesartan medoxomil 20 mg

14 pcs.
- packings of cellular contour (1) - packs cardboard.
14 pcs.
- packings cellular planimetric (2) - packs cardboard.
14 pcs.
- packings cellular planimetric (4) - packs cardboard.
14 pcs.
- packings cellular planimetric (7) - packs cardboard.
Tablets, film-coated 1 tab.

hydrochlorothiazide 25 mg

olmesartan medoxomil 20 mg

14 pcs.
- packings of cellular contour (1) - packs cardboard.
14 pcs.
- packings cellular planimetric (2) - packs cardboard.
14 pcs.
- packings cellular planimetric (4) - packs cardboard.
14 pcs.
- packings cellular planimetric (7) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2010.

PHARMACHOLOGIC EFFECT

Cardosal В® plus is a combined preparation that contains an angiotensin II receptor antagonist (olmesartan medoxomil) and a thiazide diuretic (hydrochlorothiazide).The combination of the two active substances has a combined antihypergenic effect, resulting in a decrease in blood pressure to a greater extent than with each of them individually.
When taking the drug once a day, an effective and uniform decrease in blood pressure is achieved within 24 hours.
Olmesartan medoxomil is a specific antagonist of angiotensin II receptors (type AT 1 ).
Angiotensin II is the primary vasoactive component of the renin-angiotensin-aldosterone system (RAAS) and plays a significant role in the pathophysiology of hypertension by affecting AT 1 -receptors. It is suggested that olmesartan medoxomil blocks all effects of angiotensin II mediated by AT 1 -receptors regardless of the source and route of synthesis of angiotensin II.
In the arterial hypertension of olmesartan, medoxomil causes a dose-dependent prolonged decrease in blood pressure.
There is no data on the development of arterial hypotension after taking the first dose of the drug and on the development of the "withdrawal" syndrome (a sharp increase in BP after drug withdrawal).
The use of olmesartan medoxomil once a day provides an effective and gentle decrease in blood pressure during 24 hours. The hypotensive effect of olmesartan medoxomil occurs, as a rule, after 2 weeks, and the maximum effect develops after about 8 weeks.
after the start of therapy.
Hydrochlorothiazide - thiazide diuretic - disrupts the reabsorption of sodium, chlorine and water ions in the renal tubules.
Increases the excretion of ions of potassium, magnesium, hydrocarbonates, delays the body of calcium ions. Diuretic effect occurs 2 hours after taking hydrochlorothiazide inwards, reaches a maximum after 4 hours and lasts up to 12 hours. It helps to decrease high blood pressure. When combined with the administration of olmesartan medoxomil and hydrochlorothiazide, there is a decrease in the loss of potassium ions caused by the action of the diuretic. The result of combined therapy with olmesartan medoxomil and hydrochlorothiazide is potentiation of the hypotensive effect, which depends on the dose of each component of the drug. Combination therapy is well tolerated by patients. With long-term treatment, the effectiveness of combination therapy (olmesartan medoxomil / hydrochlorothiazide) persists, the development of the "withdrawal" syndrome is not observed.
PHARMACOKINETICS

Absorption and distribution

Olmesartan medoxomil is a prodrug.
It quickly turns into pharmacologically active metabolite olmesartan under the action of enzymes in the intestinal mucosa and in the peripheral blood during absorption from the gastrointestinal tract and circulates in the blood as a metabolite (olmesartan). The bioavailability of olmesartan is 25.6% on average.
C max of olmesartan in blood plasma is achieved on average 2 hours after ingestion and increases approximately linearly with a single dose increase to 80 mg.

Eating no significant effect on the bioavailability of olmesartan medoxomil, therefore, olmesartan medoxomil can be taken regardless of food intake.

Clinically significant differences in pharmacokinetic parameters of olmesargan medoxomil were not found depending on sex.

Olmesargan has a high degree of binding to plasma proteins (99.7%).
With the simultaneous use of olmesartan medoxomil with other drugs characterized by a high degree of binding to blood plasma proteins, there is no significant change in this value (which is confirmed by the absence of a clinically significant interaction between olmesartan medoxomil and warfarin). The association of olmesartan with blood cells is negligible.
After oral administration of olmesartan medoxomil in combination with hydrochlorothiazide, the average time to achieve Cmax hydrochlorothiazide is 1.5-2 h.

Hydrochlorothiazide binds to plasma proteins by 68%.
Systemic bioavailability of hydrochlorothiazide with simultaneous use with olmesartanom medoxomil decreases by about 20%, but this small decrease in clinical terms is not significant. Simultaneous administration of hydrochlorothiazide, for its part, does not significantly affect the kinetics of olmesartan medoxomil. In controlled clinical trials, the pronounced antihypertensive effect of this combination was found, which exceeded the effect of each of the components separately, as well as the placebo effect.
Metabolism and excretion

The total plasma clearance of olmesartan is usually 1.3 l / h (the coefficient of variation is 19%) and is relatively low in comparison with the hepatic blood flow (about 90 l / h).
The renal excretion of olmesartan is approximately 40%, with bile through the intestine - about 60%; extrahepatic circulation - minimal. Since most of the olmesartan medoxomil is metabolized in the liver, its use in patients with bile duct obstruction is contraindicated.
The half-life of olmesartan is 10-15 hours. A steady effect of therapy is achieved during the first 14 days of daily administration of olmesartan medoxomil.
Kidney clearance is approximately 0.5-0.7 l / h and is not dose-dependent.
Hydrochlorothiazide in the body is not metabolized and almost completely unchanged is excreted by the kidneys.
After oral intake, about 60% of the dose of hydrochlorothiazide is unchanged in 48 hours. The renal clearance of hydrochlorothiazide is about 250-300 ml / min .; T 1/2 of the final phase is 10-15 h.
Pharmacokinetics in different patient categories

In patients aged 65-75 years with arterial spurtensia, the area under the concentration-time curve (AUC) for olmesartan in the saturation stage is increased by approximately 35% in comparison with the group of patients under the age of 65, in patients over 75 years - by approximately 44 %.
The available data allow us to conclude that the systemic clearance of hydrochlorothiazide in both healthy elderly volunteers and in elderly patients with hypertension is reduced in comparison with volunteers of a younger age. In patients with impaired renal function (CK = 30-60 ml / min.), The AUC for olmesartan in the saturation stage increases by approximately 62%, 82% and 179% in the case of mild, moderate and severe renal dysfunction, respectively, compared to healthy volunteers . For this category of patients, an increase in T 1/2 hydrochlorothiazide is possible.
In patients with impaired liver function of mild and moderate severity after a single oral intake, the values ​​of AUC for olmesartan were 6 and 65% higher, respectively, compared with healthy volunteers.
The unbound fraction of olmesartan 2 hours after taking the dose of the drug in healthy volunteers, in patients with mild and moderate degrees of impaired liver function was 0.26; 0.34 and 0.41% respectively. The effect of liver function abnormalities on the pharmacokinetics of hydrochlorothiazide is negligible.
In patients with severe impairment of liver function (more than 9 on the Child-Pugh scale), there is no data on the pharmacokinetics of olmesartan medoxomil.

INDICATIONS

- Essential arterial hypertension (with inefficiency of olmesartan monotherapy with medoxomil).

DOSING MODE

Cardosal В® plus tablets are taken orally regardless of food intake.
Prior to the appointment of the combined drug Cardosal В® plus, it is recommended that the dose of each of the active substances be separately selected (ie, olmesartan medoxomil and hydrochlorothiazide).
Recommended dose:

Every day, 1 tablet of Cardosal plus, containing 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide, in the absence of adequate blood pressure control against olmesartan monosomal medoxomil at a dose of 20 mg;

In the absence of adequate control of blood pressure against the background of taking Cardosal В® plus, containing 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide, Cardosal plus, containing 20 mg of olmesartan medoxomil and 25 mg hydrochlorothiazide daily for 1 tablet is possible.

The maximum dose of Cardosal plus is 20 mg of olmesartan medoxomil and 25 mg hydrochlorothiazide once a day.

Elderly patients (over 65 years of age) with normal renal function (KC more than 90 ml / min) and patients with impaired renal function (CK = 30-60 ml / min.) Dose adjustment is not required.

SIDE EFFECT

Possible side effects are given below on the descending incidence frequency: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely (<1/10000), including individual messages.

The combination of olmesartan medoxomil and hydrochlorothiazide

From the side of the central nervous system

Often: dizziness.

Not often: syncope.

From the side of the cardiovascular system

Infrequent: palpitation, marked decrease in blood pressure, orthostatic hypotension.

From the skin

Infrequent: skin rash, eczema.

From the side of metabolism

Infrequent: hyper- or hypokalemia, hypercalcemia, hypertriglyceridemia, hyperuricemia, increased lipid concentration in the blood.

From the laboratory indicators

Very rarely: a slight increase in the concentration of creatinine, uric acid and urea nitrogen in the serum, a slight decrease in the concentration of hemoglobin and hematocrit.

Olmesartana Medoxomil (monotherapy)

On the part of the hematopoiesis system

Very rarely: thrombocytopenia.

From the side of the central nervous system

Very rarely: dizziness, headache.

From the side of the cardiovascular system

Rarely: marked decrease in blood pressure.

Infrequently: angina.

From the respiratory system

Often: bronchitis, pharyngitis, rhinitis.

Very rarely: cough.

From the side of the digestive tract

Often: diarrhea, indigestion, gastroenteritis.

Very rarely: pain in the abdomen, nausea, vomiting.

From the urinary system

Often: hematuria, urinary tract infection.

Very rarely: acute renal failure.

From the side of the musculoskeletal system

Often: arthritis, back pain.

Very rarely: muscle cramps, myalgia.

From the skin

Very rarely: itchy skin, exanthema, angioedema, allergic dermatitis, urticaria.

From the side of metabolism

Often: increased activity of creatine phosphokinase, hypertriglyceridemia, hyperuricemia.

Rarely: hyperkalemia.

From the laboratory indicators

Very rarely: an increase in the concentration of creatinine and urea in the blood serum.

Often: increased activity of "liver" transaminases.

Other violations

Often: chest pain, flu-like symptoms, peripheral edema.

Very rarely: weakness, fatigue, drowsiness, malaise.

Hydrochlorothiazide (monotherapy)

On the part of the hematopoiesis system

Rarely: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, and plastic anemia, hemolytic anemia, oppression of bone marrow hematopoiesis.

From the central and peripheral nervous system

Often: dizziness, weakness, headache, increased fatigue.

Rarely: anxiety, sleep disturbance, confusion, apathy, depression, obnubilation, paresthesia, seizures.

From the side of the organ of vision

Rarely: xantopsy, transient disruption of accommodation, reducing the formation of tear fluid.

From the side of the cardiovascular system

Infrequent: orthostatic hypotension.

Rarely: arrhythmias, thrombosis, embolism.

From the respiratory system

Rarely: dyspnea (including interstitial pneumonia and pulmonary edema).

From the side of the digestive tract

Infrequent: anorexia, abdominal pain, nausea, vomiting, diarrhea, constipation, flatulence, inflammation of the salivary glands.

Rarely: pancreatitis, acute cholecystitis, intrahepatic cholestatic jaundice.

Very rarely: paralytic intestinal obstruction.

From the genitourinary system

Rarely: a violation of kidney function, interstitial nephritis, acute renal failure, a violation of potency.

From the side of the musculoskeletal system

Rarely: muscle cramp, muscle weakness, paresis.

From the skin

Infrequent: photosensitization, skin rash, hives.

Rarely: development of lupus-like syndrome (fever, arthralgia, myalgia, serositis, vasculitis, increased erythrocyte sedimentation rate (ESR), leukocytosis, eosinophilia), activation of cutaneous systemic lupus erythematosus, anaphylactic reactions, toxic epidermal necrolysis.

From the laboratory indicators

Often: hyperglycemia, glucosuria, hyperuricemia, increased serum creatinine concentration, violation of water-electrolyte balance (including hyponatremia, hypomagnesemia, hypochloraemia, hypokalemia and hypercalcemia), increased cholesterol and triglyceride levels in the blood.

Other violations

Rarely: fever.

CONTRAINDICATIONS

- hereditary lactose intolerance, lack of lactase in the body or glucose and lactose malabsorption syndrome;

- severe violations of the liver (more than 9 points on the scale Child-Pugh) (risk of developing hepatic coma), bile duct obstruction and cholestasis;

- severe renal dysfunction (CC less than 30 ml / min.);

- refractory hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia;

- Pregnancy;

- lactation period;

- age to 18 years (efficacy and safety of the drug not studied);

- hypersensitivity to olmesartan medoxomil, hydrochlorothiazide or other derivatives of sulfonamides or to any of the excipients that make up the drug (see Composition section).

Carefully:

- bronchial asthma;

- Ischemic heart disease (CHD);

- chronic heart failure in the stage of decompensation;

- severe cerebrovascular disorders;

- Stenosis of the aortic or mitral valve;

- hypertrophic obstructive cardiomyopathy;

- a malfunction of the liver of mild and moderate degree (less than 9 on the Child-Pugh scale);

- impaired renal function (QC more than 30 ml / min, but less than 60 ml / min.);

- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;

- a condition after a recent kidney transplantation (no experience with the drug);

- primary aldosteronism;

- diabetes mellitus, gout;

- Violations of the water-electrolyte balance, dehydration;

- connective tissue diseases, including systemic lupus erythematosus;

- patients who follow a diet with salt restriction or who are on hemodialysis;

- with oppression of bone marrow hematopoiesis;

- conditions accompanied by a decrease in the volume of circulating blood;

- (bcc) incl.
diarrhea, vomiting, or previous therapy with diuretics.
PREGNANCY AND LACTATION

The experience of using olmesartan medoxomil in pregnant women is absent.
However, in view of the available reports of severe teratogenic effects of drugs acting on RAAS, like any drug of this class, CardosalВ® plus is contraindicated in pregnancy. In the case of planning or the onset of pregnancy during therapy with CardosalВ® plus, the drug should be discontinued as soon as possible. It is not known whether olmesartan medoxomil is excreted in breast milk, but thiazides are excreted in breast milk and can suppress lactation, so if you need Cardosal plus plus during lactation, breastfeeding for the period of its intake should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER

Contraindicated in severe renal dysfunction (KK less than 30 ml / min.).

Carefully:

- impaired renal function (QC more than 30 ml / min, but less than 60 ml / min.);

- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;

- a condition after a recent kidney transplantation (no experience with the drug).

Patients with impaired renal function (CK = 30-60 ml / min.) Dose adjustment is not required.

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Contraindicated in severe violations of the liver (more than 9 points on the scale Child-Pugh) (risk of hepatic coma), with obstruction of the biliary tract and cholestasis.

APPLICATION FOR CHILDREN

Contraindicated in children under 18 years.

APPLICATION IN ELDERLY PATIENTS

Elderly patients (over 65 years of age) with normal renal function (CC greater than 90 ml / min) do not need dose adjustment.

SPECIAL INSTRUCTIONS

Symptomatic arterial hypotension, especially after taking the first dose of the drug, can occur in patients with reduced BCC and / or reduced sodium concentration due to intensive therapy with diuretics, dietary restriction of dietary intake, and also due to diarrhea or vomiting.
Corresponding factors should be eliminated before using Cardosal В® plus.
Thiazide diuretics, including hydrochlorothiazide, can cause a violation of bcc or water-electrolyte balance of blood serum (including hypokalemia, hyponatremia and hypochloraemic alkalosis).
Symptoms-precursors are: dryness of the oral mucosa, thirst, weakness, drowsiness, anxiety, myalgia or cramps, muscle weakness, arterial hypotension, oliguria, tachycardia, nausea and vomiting (see Side effect).
Highest risk of hypokalemia exists in patients with liver cirrhosis patients during forced diuresis and in those patients who simultaneously receive AKTT or glucocorticosteroids (see. Section Interaction with other drugs). Conversely, due to antagonism contained in the preparation Kardosal В® plus olmesartan medoxomil shown by angiotensin II receptor (AT 1), Hyperkalemia may occur - particularly in patients with reduced kidney function and / or congestive heart failure, as well as patients with diabetes. Patients with risk factors is recommended that regular monitoring of the concentration of potassium in the blood serum. Information about whether olmesartan medoxomil reduce hyponatremia caused by diuretics or hinder its development, no. In hot weather in patients with symptoms of edema can occur dilutional hyponatremia. Decrease in chloride concentrations generally expressed insignificantly, and treatment is usually not required.
Thiazides may decrease the kidney excretion of calcium ions and also lead to a transient slight increase in calcium concentration in the serum in the absence of a history of its metabolism disorders. Giperkalygiemiya may indicate a hidden hyperparathyroidism. Before examining the function of the parathyroid glands thiazides should be abolished.
It is proved that the thiazide diuretics increase renal excretion of magnesium ions, which can lead to hypomagnesemia.
In patients whose vascular tone and renal function depends to a large extent on the activity of the RAAS (e.g., in patients with severe chronic heart failure or impaired renal function, including renal artery stenosis), treatment with other agents affecting the RAAS, due to the possibility of acute hypotension, azotemia, oliguria or, rarely, acute renal failure. The ability of similar action can not be ruled out when using angiotensin receptor antagonists P.
There is an increased risk of severe arterial hypotension and renal failure if a patient with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney receives therapy with drugs that affect RAAS.
In applying the drug Kardosal В® plus in patients with impaired renal function recommended periodic monitoring of potassium ion concentration, creatinine and uric acid in serum. Experience of olmesartan medoxomil in patients with newly drawn or kidney transplantation in patents with end-stage renal dysfunction offline.
In patients with limited renal function receiving thiazide diuretics may be associated with azotemia. Given the obvious progression of renal failure need to review treatment and decide on the cancellation of diuretics.
As with any antihypertensive agent, excessive lowering of blood pressure in patients with coronary artery disease or cerebrovascular insufficiency may lead to myocardial infarction or stroke.
Thiazide diuretics may cause impaired glucose tolerance, as well as increase the concentration of cholesterol, triglycerides and uric acid in serum. In patients with diabetes may be necessary to dose adjustment of insulin or hypoglycemic agents for oral administration (see. Section Interaction with other drugs). In the treatment of thiazide diuretics flowing latent diabetes mellitus may manifest.
It has been reported that thiazide diuretics may contribute to the development of a gout attack and cause exacerbation of systemic lupus erythematosus. Hypersensitivity reactions to hydrochlorothiazide may occur more likely in patients with allergic history or bronchial asthma (history).
Impact on the ability to drive vehicles and manage mechanisms

The influence of the drug Kardosal В® plus the ability to drive vehicles and management mechanisms are not specifically been studied, so the period of treatment Kardosal В® plus should be careful when driving vehicles and activities potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE

Symptoms: an overdose of olmesartan medoxomil is most likely marked reduction in blood pressure and tachycardia, bradycardia, nausea, drowsiness; an overdose of hydrochlorothiazide - symptoms of electrolyte deficiency (hypokalemia, chloropenia, hyponatremia) and dehydration due to excessive diuresis.
Treatment: recommended gastric lavage and / or reception of activated carbon; therapy aimed at correcting dehydration and disorders of fluid and electrolyte balance. In marked decrease in blood pressure it is recommended to put the patient in a horizontal position, lifting the feet, and spend therapy aimed at filling the BCC.Hemodialysis is not effective.

DRUG INTERACTION

Olmesartan medoxomil
is not recommended since the combined use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs capable increase in serum potassium concentration (e.g., heparin) - may increase the concentration of potassium in blood serum.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin doses of more than 3 g / day, and the cyclooxygenase-2 (COX-2), and angiotensin II receptor antagonists may act synergistically to decrease glomerular filtration.
With the simultaneous use of NSAIDs and angiotensin II receptor antagonists, there may be a risk of developing acute renal failure, so it is recommended that kidney function be monitored at the beginning of treatment and that a sufficient amount of fluid is taken regularly. However, simultaneous treatment can reduce the antihypertensive effect of angiotensin II receptor antagonists, resulting in a partial loss of therapeutic effectiveness. When applied simultaneously with antacids (magnesium and aluminum hydroxides) may moderate decrease in bioavailability of olmesartan medoxomil. There are reports of increasing reversible lithium concentrations in serum and manifestation of toxicity during the simultaneous application of lithium drugs with inhibitors of angiotensin converting enzyme (ACE) and angiotensin II receptor antagonist, olmesartan medoxomil therefore application in combination with lithium therapy is not recommended. If necessary, applying appropriate combination therapy recommended regular monitoring of lithium concentrations in serum.In rare cases, ACE inhibitors can enhance the hypoglycemic effect of insulin and hypoglycemic agents for oral administration (e.g., sulfonylureas) diabetic patients. In these cases, the simultaneous use of ACE inhibitors may require dose reduction hypoglycemic agents for oral and insulin.
Hydrochlorothiazide
Glucocorticosteroids, adrenocorticotropic hormone (ACTH), amphotericin B (parenteral), carbenoxolone, penicillin G sodium salt, salicylic acid derivatives: while receiving their hydrochlorothiazide may occur increasing loss of electrolytes, in particular, the development of hypokalemia.
Simultaneous treatment with ion exchange agents (kolesteramin, kolestepol) reduces the absorption of hydrochlorothiazide.
With simultaneous application of hydrochlorothiazide with calcium salts may increase calcium concentration in serum, due to the reduction of its excretion. If desired destination calcium supplementation in the blood serum concentration should monitor and adjust the dose.
When applied simultaneously with cardiac glycosides hydrochlorothiazide may cause arrhythmias.
Drugs that can cause arrhythmia type "pirouetteВ» ( В«torsades des pointesВ») (a special form of polymorphic ventricular tachycardia wave, or screw-spindle configuration ventricular complexes in combination with an increase or decrease in the QRS complex amplitude of teeth, which can lead to fibrillation or ventricular asystole): due to the risk of hypokalemia of caution is required, while the use of hydrochlorothiazide with some antiarrhythmics (quinidine, gidrohinidin, disopyramide, amiodarone, with AlOl, dofetilide, ibutilide), neuroleptics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, tsiamemazin, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol), and others (bepridal, cisapride, difemanila methylsulfate, erythromycin intravenous, halofantrine,mizolastine, nentamidin, sparfloxacin, terfenadine, vincamine for intravenous administration), which are known that can cause "pirouette" arrhythmia type.
In a joint application with hydrochlorothiazide non-depolarizing muscle relaxants (including tubocurarine chloride) - increased muscle relaxant actions.
Thiazides may increase the risk of side effects of amantadine. Treatment of thiazide diuretics can impair glucose tolerance. With simultaneous use of M-cholinergic antagonists (atropine) and thiazides, due to reduced motility of the gastrointestinal tract bioavailability of thiazide diuretics may increase.
May require dose reduction hypoglycemic agents for oral and insulin.
Protivopodagricakih means (probenecid, sulfinpyrazone, allopurinol) may be necessary to dose adjustment gipourikemicheskogo means (or increase in dose of probenecid sulfinpirazona) as hydrochlorothiazide can increase the concentration of uric acid in serum. The simultaneous use of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol. Sympathomimetic effect while taking thiazide diuretics may be attenuated.
Thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
When receiving high doses of salicylates hydrochlorothiazide may enhance their toxic effect on the central nervous system.
There are reports of rare cases of hemolytic anemia while taking methyldopa with hydrochlorothiazide.
Concomitant use of cyclosporine with hydrochlorothiazide may increase the risk of hyperuricemia and gout exacerbation.
The simultaneous use of tetracyclines with thiazide diuretic increased the risk of increasing the concentration of urea caused by tetracyclines. This interaction does not apply to doxycycline.
Olmesartan medoxomil / hydrochlorothiazide combination in the
simultaneous use of drugs lithium with thiazide diuretics may increase the already increased risk of lithium intoxication caused by ACE inhibitors, so joint use drug Kardosal В®plus lithium and the drugs are not recommended. If such a combination is necessary, it also requires careful control of the concentration of lithium in blood serum.
With the simultaneous use of the drug Kardosal * plus with baclofen and amifostine may increase antihypertensive action.
With simultaneous use of other antihypertensives hypotensive effect of the drug Kardosal В® plus may increase. Ethanol, barbiturates, narcotic analgesics or antidepressants in the application of a preparation Kardosal В® plus can lead to aggravation of orthostatic hypotension.
TERMS OF RELEASE FROM PHARMACY

On prescription.

TERMS AND CONDITIONS OF STORAGE

Store at a temperature not higher than 30 В° C. Drug store out of reach of children!
Shelf life - 3 years.
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