Universal reference book for medicines
Product name: Teveten ® PLUS (TEVETEN ® PLUS)

Active substance: eprosartan, hydrochlorothiazide

Type: Antihypertensive drug

Manufacturer: ABBOTT PRODUCTS (Germany) manufactured by ABBOTT HEALTHCARE (France)
Composition, form of production and packaging
The tablets covered with a film membrane of
yellow-brown color, oval in shape, biconvex, with engraving "5147" on one side;
on a break of a tablet of white color.
1 tab.

eprosartan mesylate 735.8 mg,

which corresponds to the content of eprosartan 600 mg

hydrochlorothiazide 12.5 mg

[PRING] microcrystalline cellulose - 43.3 mg, lactose monohydrate 43.3 mg, corn pregelatinized corn starch 43.3 mg, crospovidone 38.5 mg, magnesium stearate 7.2 mg, purified water 50.9 mg.

The composition of the film shell: Opadry II Butterscotch 85F27320 - 39 mg (polyvinyl alcohol - 15.60 mg, macrogol 3350 - 7.88 mg, talc - 5.77 mg, titanium dioxide (E171) - 9.41 mg, iron oxide yellow (E172) - 0.33 mg, iron oxide black (E172) - 0.004 mg).

14 pcs.
- blisters (1) - packs of cardboard.
14 pcs.
- blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

Combined antihypertensive agent (angiotensin II receptor antagonist + diuretic).

Eprosartan

The angiotensin II receptor antagonist, selectively acting on AT 1 -receptors located in the vessels, heart, kidneys and adrenal cortex, forms a strong bond with them, followed by a slow dissociation.

Prevents the development or weakening of the effects of angiotensin II, inhibits the activity of RAAS.
Has vasodilating, hypotensive and mediated diuretic effect.
Reduces arterial vasoconstriction, OPSS, pressure in a small circle of circulation, reabsorption of water and sodium in the proximal segment of the renal tubules, and secretion of aldosterone.
With prolonged use suppresses the proliferative effect of angiotensin II on smooth muscle cells of blood vessels and myocardium.
Antihypertensive effect after taking a single dose of oral develops within 24 hours, and a stable therapeutic effect develops with regular intake within 2-3 weeks without affecting the heart rate.

Does not cause the development of orthostatic hypotension in response to taking the first dose of the drug.

Increases renal blood flow and glomerular filtration rate, reduces the excretion of albumins (nephroprotective effect), while maintaining renal self-regulation, regardless of the degree of renal failure.

Has no effect on lipid, carbohydrate and purine metabolism.

At the termination of treatment does not cause withdrawal syndrome.

Less often than ACE inhibitors, it causes the appearance of effects associated with bradykinin activity (including dry persistent cough).

Two large, randomized, controlled trials of ONTARGET (a study continuing until the end result, to study the effects of telmisartan alone and in conjunction with ramipril) and VA NEPHRON-D (a study of diabetic nephropathy conducted by the Ministry of Veterans Affairs) an ACE inhibitor with an angiotensin II receptor antagonist.

The ONTARGET study was conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus with signs of damage to target organs.
The VA NEPHRON-D study was performed in patients with type 2 diabetes and diabetic nephropathy. These studies showed no significant beneficial effects on kidney and / or cardiovascular function and mortality, while at the same time there was an increased risk of hyperkalemia, acute renal damage, and / or hypotension compared with monotherapy. Taking into account similar pharmacodynamic characteristics, these results are also relevant for other ACE inhibitors and angiotensin II receptor antagonists.
In this regard, the combined use of ACE inhibitors and angiotensin II receptor antagonists in patients with diabetic nephropathy is not recommended.

In addition, ALTITUDE (a study of the action of aliskiren in patients with type 2 diabetes mellitus, where cardiovascular and renal function changes were taken as end points) was conducted, which tested the benefits of adding aliskiren to standard therapy (an ACE inhibitor or a receptor antagonist angiotensin II) in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both.
The study was prematurely terminated because of the increased risk of adverse outcomes.The lethal outcome of cardiovascular diseases and stroke were much more frequent in the treatment group with the addition of aliskiren than in the placebo group, in addition, undesirable events and serious adverse events (hyperkalaemia, hypotension and renal dysfunction) were more common in the aliskiren group than in the group placebo.
The combined use of aliskiren with an ACE inhibitor or angiotensin II receptor blocker is contraindicated in patients with type 2 diabetes or renal insufficiency (CC less than 60 ml / min).

Hydrochlorothiazide

Is a thiazide diuretic.
Thiazides affect the mechanisms of reabsorption of electrolytes in the renal tubule, increasing the volume of release of liquid, sodium and chlorine.
Due to the diuretic action of hydrochlorothiazide, the volume of plasma decreases, the renin activity in the blood plasma increases, the secretion of aldosterone increases, which causes an increased excretion of potassium and hydrocarbonates in the urine and a decrease in the potassium concentration in the blood serum.
The mechanism of hypotensive action of hydrochlorothiazide is a combined diuretic and vasodilating effect.
Teveten ® plus

In patients with elevated systolic blood pressure, eprosartan provides a statistically significant reduction.
Addition to a single daily dose (600 mg or 1200 mg) of eprosartan 12.5 mg of hydrochlorothiazide provides an additional statistically significant reduction in systolic blood pressure compared with the daily intake of only eprosartan.
The combined administration of eprosartan with hydrochlorothiazide reduces the loss of potassium associated with the diuretic effect of hydrochlorothiazide.
The diuretic effect of the drug Teveten ® plus develops within the first 2 hours, and reaches a maximum - 4 hours after ingestion.
Stable antihypertensive effect develops, usually after 2-3 weeks of treatment.

PHARMACOKINETICS

Eprosartan

Suction

When administered, the absolute bioavailability is about 13%.
C max Eprosartan is determined 1-2 hours after ingestion.
Distribution

The binding of eprosartan to plasma proteins is high (98%) and remains constant after reaching a therapeutic concentration in the blood plasma.

V d of eprosartan is 13 liters.
Eprosartan is practically not cumulative.
Excretion

T 1/2 is usually 5-9 hours. The total clearance of eprosartan is 130 ml / min.
When ingestion is withdrawn mainly unchanged through the intestine (90%), kidney (7%).A small part (less than 2%) is excreted by the kidneys in the form of glucuronides.
Pharmacokinetics in special clinical cases

The degree of binding of eprosartan to blood plasma proteins does not depend on sex, age, liver function and does not change with mild or moderate renal insufficiency, but can decrease with severe renal failure.

In elderly patients, the values ​​of C max and AUC increase, on average, by a factor of 2, which, however, does not require correction of the dosing regimen.

With liver failure, the AUC values ​​increase by an average of almost 40%, which does not require correction of the dosing regimen.

When Eprosartan is used in patients with moderate CRF (30 to 59 ml / min KK), the values ​​of AUC and C max are higher by 30%, and those with severe CRF (5 to 29 ml / min) increase by 50% healthy volunteers.

The pharmacokinetics of eprosartan does not differ in male and female patients.

Hydrochlorothiazide

Hydrochlorothiazide does not penetrate the BBB, but it penetrates the placental barrier, is excreted in breast milk.

It is not metabolized.
Quickly excreted by the kidneys. After ingestion, at least 61% of the dose is excreted unchanged for 24 hours.
Teveten ® plus

The simultaneous administration of eprosartan
and hydrochlorothiazide, and from the clinical point of view does not have a significant effect on the pharmacokinetics of both components.
Eating does not affect the bioavailability of eprosartan and hydrochlorothiazide, but delays their absorption.
C max in blood plasma are reached 4 hours after taking eprosartan and 3 hours after taking hydrochlorothiazide inside.
INDICATIONS

- arterial hypertension (in monotherapy or in combination with other antihypertensive drugs).

DOSING MODE

The drug is taken orally 1 tablet / day in the morning, regardless of food intake.

Dose correction of Teveten ® plus in elderly patients , patients with mild and moderate impairment of liver function , as well as in patients with impaired renal function (CK> 30 ml / min) is not required.

SIDE EFFECT

Most often, patients receiving treatment with the combination of eprosartan + hydrochlorothiazide experienced such undesirable drug reactions as headache and non-specific gastrointestinal disorders, which occurred in approximately 11% and 8% of patients (compared with 14% and 8% of those receiving placebo), respectively.

Depending on the frequency of occurrence, the following groups of side effects are distinguished: very often (? 1/10);
often (? 1/100, <1/10); infrequently (? 1/1000, <1/100); rarely (? 1/10 000, <1/1000); very rarely (<1/10 000); frequency is unknown (can not be calculated from available data).
Undesirable drug reactions that occur during placebo-controlled clinical trials or described in the scientific literature are presented below.
Adverse reactions in each frequency category are listed for eprosartan, a combination of eprosartan + hydrochlorothiazide, and hydrochlorothiazide used in monotherapy.
From the blood and lymphatic system: infrequently - leukopenia;
very rarely - hemolytic anemia *; frequency unknown - agranulocytosis, thrombocytopenia, aplastic anemia.
From the immune system: infrequently - hypersensitivity reactions;
frequency unknown - anaphylactic reactions.
From the side of metabolism and nutrition: often - hyperglycemia;
infrequently - hyperuricemia, exacerbation of gout, hyponatremia, hypokalemia, hypochloraemia, hypercholesterolemia; frequency unknown - hypercalcemia, hypomagnesemia, hypertriglyceridemia, anorexia.
From the side of the psyche: infrequently - depression, anxiety, insomnia, nervousness, libido disorders;
frequency unknown - worry.
From the nervous system: very often - headache **, often - dizziness, paresthesia.

From the side of the organ of vision: the frequency is unknown - acute myopia, secondary closed-angle glaucoma *.

From the side of the hearing organ and labyrinthine disturbances: infrequently - vertigo **.

From the side of the cardiovascular system: often - a marked decrease in blood pressure, orthostatic hypotension;
frequency unknown - necrotizing angiitis.
From the respiratory system: often - rhinitis;
rarely - respiratory distress syndrome (including pneumonitis and non-cardiogenic pulmonary edema).
From the digestive system: often - nonspecific abnormalities from the digestive tract (nausea, vomiting, diarrhea);
infrequently - constipation **; rarely - pancreatitis *.
From the side of the liver and biliary tract: the frequency is unknown - jaundice, incl.
intrahepatic cholestatic jaundice.
From the skin and subcutaneous tissues: often - allergic skin reactions (skin rash, itching);
infrequently - angioedema; frequency unknown - toxic epidermal necrolysis, photosensitivity reactions.
From the osteomuscular and connective tissue: infrequently - muscle spasms **;
frequency unknown - systemic lupus erythematosus.
From the side of the kidneys and urinary tract: the frequency is unknown - interstitial nephritis, renal failure, renal dysfunction in patients at risk (stenosis of the renal arteries), glucosuria.

On the part of the genitals: infrequently - sexual dysfunction.

General disorders: often - asthenia;
infrequently - hyperthermia.
* - frequency of occurrence, taking into account data from the scientific literature on hydrochlorothiazide

** - frequency comparable to placebo.

CONTRAINDICATIONS

- severe renal failure (CK <30 ml / min);

- severe hepatic insufficiency (more than 9 points on the Child-Pugh scale);

- cholestasis and obstruction of the biliary tract;

- hemodynamically significant bilateral stenosis of the renal arteries or severe arterial stenosis of a single functioning kidney;

- resistant to treatment hypokalemia or hypercalcemia;

- refractory hyponatremia;

- symptomatic hyperuricemia or gout;

- simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or renal dysfunction (CC less than 60 ml / min);

- rare hereditary intolerance of galactose, lactase deficiency or glucose-galactose insufficiency insufficiency syndrome (because the drug contains lactose);

- Pregnancy;

- the period of breastfeeding;

- age under 18 years (effectiveness and safety not established);

- hypersensitivity to eprosartan, hydrochlorothiazide, other sulfanilamide derivatives and other components of the drug.

Caution should be used for severe chronic heart failure (NYHA functional class IV), bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, lowering of bcc, violation of water-electrolyte balance of blood (due to taking large doses of diuretics, repeated vomiting, prolonged diarrhea , salt-free diets), mild or moderate hepatic insufficiency (less than 9 on the Child-Pugh scale without the history of cholestasis), diabetes mellitus, stenosis of the aortic and mitral
of valves or hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, CHD (application experience limited), acute myopathy, secondary angle-closure glaucoma, systemic lupus erythematosus.
PREGNANCY AND LACTATION

Pregnancy

Teveten ® plus is contraindicated in pregnancy.

Eprosartan

The results of epidemiological studies on the risk of developing teratogenic effects with the use of ACE inhibitors during the first trimester of pregnancy do not allow for unambiguous conclusions, but a slight increase in risk can not be excluded.
While data from controlled epidemiological studies on the risk of angiotensin II receptor antagonists are not available, a similar risk may exist for this class of drugs. Unless continued therapy with angiotensin II receptor antagonists is considered necessary, patients planning a pregnancy should switch to taking approved hypotensive drugs that have established safety characteristics for use in pregnancy.Eprosartan therapy should be discontinued immediately after the diagnosis of pregnancy, and if necessary, alternative therapy should be initiated.
It is known that therapy with angiotensin II receptor antagonists in the II and III trimesters of pregnancy is toxic to the fetus (impaired renal function, low blood pressure, ossification of the skull bones) and newborn (renal failure, arterial hypotension, hyperkalemia).

If treatment with eprosartan is necessary in the second trimester of pregnancy, ultrasound monitoring of kidney function and monitoring of the skull in the fetus is recommended.

Newborns whose mothers have taken eprosartan should be carefully monitored for arterial hypotension.

Hydrochlorothiazide

The experience with the use of hydrochlorothiazide in pregnancy, particularly in the first trimester, is limited.

Hydrochlorothiazide penetrates the placental barrier.
Taking into account the mechanism of action of hydrochlorothiazide, the use of this drug in the II and III trimesters of pregnancy can lead to a violation of fetoplacental perfusion and the development of pathological effects in the newborn and fetus, such as jaundice, electrolyte disorders and thrombocytopenia. Do not use hydrochlorothiazide for gestational edema, arterial hypertension in pregnant women or preeclampsia, due to the risk of a decrease in the volume of plasma and the development of hypoperfusion of the placenta and the absence of any positive effects on the course of the disease.
Hydrochlorothiazide should not be used with essential hypertension in pregnant women, except in rare situations when there are no therapeutic alternatives.

Breastfeeding period

Eprosartan

Due to the lack of information regarding the use during the period of breastfeeding, the use of Teveten ® plus is not recommended, and the appointment of antihypertensive drugs with a well established safety profile is preferred, especially when feeding newborns or prematurely born children.

Hydrochlorothiazide

Hydrochlorothiazide is excreted in breast milk in small amounts.
In high doses, thiazides increase diuresis, which can reduce the production of breast milk. The use of the drug Teveten ® plus during breastfeeding is contraindicated.
Fertility

There are no clinical data on the effect on reproductive function.
Pre-clinical studies of eprosartan do not confirm any effects on the fertility of males and females.There are no preclinical studies on the possible effects of hydrochlorothiazide on fertility.
APPLICATION FOR FUNCTIONS OF THE LIVER

Contraindicated in renal failure (QC less than 30 ml / min).

In patients with impaired renal function (QC more than 30 ml / min), no special selection of Teveten Plus is required.

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Teveten Plus is not required for patients with mild or moderate liver function disorders.

Use with caution in patients with moderate or severe impairment of liver function.
At present, there is no clinical experience with the use of Teveten Plus in patients with severe liver damage.
APPLICATION FOR CHILDREN

Contraindicated in children and adolescents under 18 years.

APPLICATION IN ELDERLY PATIENTS

Dose correction of Teveten ® plus in elderly patients is not required.

SPECIAL INSTRUCTIONS

Patients with a risk of impaired renal function

In patients whose kidney function is dependent on the activity of the RAAS (e.g., severe chronic heart failure IV NYHA functional class classification) during treatment with ACE inhibitors may develop oliguria and / or progressive azotemia, and, in rare cases, acute renal failure. These phenomena are most likely to occur in patients taking concomitant diuretics. Due to lack of experience of application of angiotensin II receptor antagonists in patients with severe chronic heart failure IV NYHA functional class classification can not be excluded impaired renal function during treatment with the drug Teveten ®Plus, due to the suppression of RAAS activity. Due to the increased risk of severe hypotension and renal insufficiency in these patients, renal function should be closely monitored.
Patients with impaired renal function
Before assigning Teveten preparation ® plus patients with renal failure and periodically during treatment should monitor renal function and potassium content of uric acid in serum. If during this period there is deterioration of renal function, treatment with Teveten ® Plus should be discontinued.
Patients with impaired renal function may occur Hydrochlorothiazide-associated azotemia.
The experience of the drug in patients undergoing kidney transplantation, is absent.
Patients with impaired liver function
Eprosartan should be used with caution in patients with mild to moderate hepatic insufficiency due to limited clinical experience with the drug in these patients.
Due to the possibility of intrahepatic cholestasis, hydrochlorothiazide should be used with caution in the treatment of mild to moderate hepatic impairment.
Changes in fluid and electrolyte balance may precipitate hepatic coma.
Metabolic and endocrine disorders
Hydrochlorothiazide may reduce glucose tolerance that may require correction of the dose of hypoglycemic drugs and insulin. Latentnoprotekayuschy diabetes can manifest in the course of treatment with Teveten ® plus. At a dose of 12.5 mg of hydrochlorothiazide contained in the preparation Teveten ® plus hitherto observed only mild metabolic and endocrine undesirable effects (increase in the concentration of cholesterol and triglycerides in the serum).
Disturbances of water and electrolyte balance
Application hydrochlorothiazide can lead to disruption of water-electrolyte balance of the blood (hypokalemia, hyponatremia, hypercalcemia, hypomagnesemia and hypochloraemic alkalosis).
All patients receiving treatment with diuretics, including hydrochlorothiazide, should periodically monitor the content of electrolytes in the blood serum.
Potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium, should be used together with the drug Teveten ® Plus with caution.
Symptomatic arterial hypotension

In severe hyponatremia or reducing bcc (e.g., during treatment with large doses of diuretics, repeated vomiting, prolonged diarrhea and malosolevoy salt-free diet), the drug Teveten ® Plus may cause a sharp decrease in blood pressure. Hyponatremia need correction and / or BCC and, if possible, prior to the cancellation of a diuretic drug treatment Teveten ® plus.
Acute myopia and secondary glaucoma zakrytougolnaya
Hydrochlorothiazide, as the sulfonamide may cause idiosyncratic response, expressed in acute transient myopia and fit acute angle-closure glaucoma. Symptoms include a sharp decrease in visual acuity or pain in the eye, usually develop over a period of several hours to several weeks after the start of the drug. The lack of treatment of acute angle-closure glaucoma can lead to irreversible vision loss. The primary treatment is to as quickly as possible the abolition of hydrochlorothiazide. You may need urgent medical or surgical treatment if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma attack may be the presence of allergic reactions to sulfanilamide or penicillin in history.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism use of antihypertensive drugs that inhibit the RAAS, usually ineffective. In this regard, the use of the drug Teveten ® plus this group of patients is not recommended.
Stenosis of the aortic and mitral valves, hypertrophic obstructive cardiomyopathy
As with other vasodilators, when administering the drug to patients with stenosis of aortic or mitral valve or with hypertrophic obstructive cardiomyopathy requires caution.
Other warnings and precautions
Hypersensitivity reactions to hydrochlorothiazide is most likely to occur in patients with a history of allergies, including hypersensitive to derivatives of sulfanilamide.
There are reports of the development of exacerbation or activation of systemic lupus erythematosus in patients receiving thiazide diuretics.
Hydrochlorothiazide may produce a positive result when testing for drug testing.
Dual blockade of the RAAS
The combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) as compared with the individual application means acting on the RAAS. In connection with this dual blockade of the RAAS by combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended.
If dual blockade is necessary, it should be carried out strictly under the supervision of a specialist and a constant monitoring of renal function, maintenance of electrolytes and blood pressure.
The combined use of ACE inhibitors and angiotensin II receptor antagonists is not recommended for patients with diabetic nephropathy.
Impact on the ability to drive vehicles and manage mechanisms

During treatment with Teveten ® Plus should be careful when driving and other lesson potentially dangerous activities which require high concentration and psychomotor speed reactions, due to the possibility of dizziness and weakness.
OVERDOSE

Data on overdose in humans is limited. During post-marketing studies were isolated reports of receiving doses of eprosartan up to 12,000 mg. Despite the fact that the majority of patients did not have symptoms, it should be noted that in one patient after administration of eprosartan in a dose of 12 000 mg originated vascular collapse. The patient fully recovered. For combination eprosartan + hydrochlorothiazide adopted maximum dose was 3600 mg of Eprosartan / 75 mg hydrochlorothiazide. In this case, the reception has been carried out for the purpose of suicide.
An overdose is likely to cause a marked reduction in blood pressure. Other symptoms may be associated with a reduction in BCC and loss of electrolytes (hypokalemia, hypochloremia, hyponatremia), and most likely manifest as nausea and drowsiness.
Treatmentshould be symptomatic and supportive. Depending on the time of taking the drug inside is required provocation emesis, gastric lavage and / or activated carbon. In marked decrease in blood pressure, the patient must be put on the back, lift legs and arrange for the restoration of the BCC.
Eprosartan is not removed with hemodialysis. The degree of hydrochlorothiazide excretion via hemodialysis is not installed.
DRUG INTERACTION

Hydrochlorothiazide + Eprosartan
lithium Formulations
reversible increase lithium content in the serum and an increase in toxicity was observed in the combined use of drugs with lithium ACE inhibitors and, in rare cases, angiotensin II receptor antagonists. Furthermore, thiazides reduce renal clearance of lithium and hence may increase the risk of its toxic action. In this connection, the combined use of the drug Teveten ® Plus with lithium therapy is not recommended. If necessary, the intent of the combination requires regular monitoring of lithium in blood serum.
Baclofen
Intensifying antihypertensive action.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
As with ACE inhibitors, angiotensin II combined use of receptor antagonists and NSAIDs may increase the risk of renal function, including the possibility of acute renal failure and increase in the potassium content in blood serum, especially in patients with existing reduced kidney function.
Such combinations should be used with caution, especially in elderly patients. Patients should consume enough fluids and to monitor renal function after initiation and periodically after combination therapy.
The combined use of losartan with indomethacin (NSAID) resulted in a decrease in efficiency of an angiotensin II receptor, the presence of class specific effect can not be ruled out.
Amifostine
Intensifying antihypertensive action.
Other antihypertensive agents
antihypertensive effect of the drug Teveten ® plus can be amplified while the use of other antihypertensives.
Ethanol, barbiturates, tools for anesthesia, or antidepressants
may experience orthostatic hypotension.
eprosartan
Eprosartan is not inhibited isozymes CYP1A, 2A6, 2C9 / 8, 2C19, 2D6, 2E and 3A cytochrome P450 vitro in .
Drugs affecting potassium
Based on experience with other drugs affecting renin-angiotensin system, combined use of potassium-sparing diuretics, potassium preparations salt substitute containing potassium, and other medications that increase in serum potassium content (e.g., heparin, ACE inhibitors) may cause an increase in serum potassium. If drugs affecting the potassium content are assigned in combination with the drug, to regularly monitor the content of potassium in serum.
Dual blockade of the RAAS
These clinical studies have shown that dual blockade of the RAAS by combined use of ACE inhibitors, receptor antagonists of angiotensin II or aliskiren is associated with increased incidence of adverse effects, such as hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) as compared with the individual application means, acting on the RAAS.
Hydrochlorothiazide
Drugs affecting potassium
Hypokalemic effect of hydrochlorothiazide can be amplified with concomitant administration of other drugs, resulting in potassium excretion and hypokalemia (e.g., other kaliynesberegayuschie diuretics, laxatives, corticosteroids, glycyrrhizic acid (contained in licorice root), adrenocorticotropic hormone, amphotericin B (for on / in the ), carbenoxolone, penicillin G (sodium salt) or salicylic acid derivatives). In this regard, the use of this combination is not recommended.
Calcium salts and vitamin D
Thiazide diuretics may increase serum calcium levels due to the reduction of its excretion. If necessary, use of calcium preparations or kaltsiysberegayuschih drugs (e.g., vitamin D), necessary to control serum calcium levels and adjust the dose.
Cholestyramine and colestipol resins
Absorption of hydrochlorothiazide is reduced while the use of anion exchange resins, e.g., cholestyramine or colestipol.
Separate reception of hydrochlorothiazide and resin can minimize their drug interaction, i.e., hydrochlorothiazide is recommended to take at least 4 hours or up to 4-6 h after administration resins.
cardiac glycosides
Hypokalemia or hypomagnesemia caused by thiazide diuretics, promotes the development of arrhythmias.
Medications dependent change of potassium content
is recommended to periodically monitor the content of potassium in blood serum and electrocardiogram in the case of simultaneous application of the drug to the drugs, the effectiveness of which is influenced by the potassium content abnormalities in serum (e.g., cardiac glycosides and antiarrhythmic drugs), and with following drugs (including antiarrhythmic drugs), causing polymorphic ventricular tachycardia type "pirouette" (ventricular tachycardia); while hypokalemia is a risk factor predisposing to the development of polymorphic ventricular tachycardia type "pirouette" (ventricular tachycardia):
- Class IA antiarrhythmic drugs (e.g., quinidine, gidrohinidin, disopyramide);
- class III antiarrhythmics (e.g., amiodarone, dofetilide, ibutilide) and sotalol;
- some neuroleptics (e.g., thioridazine, chlorpromazine, levomepromazine, trifluoperazine, tsiamemazin, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);
- other drugs (e.g., bepridil, cisapride, difemanil, erythromycin w / w, halofantrine, mizolastine, pentamidine, terfenadine, vincamine w / w).
Non-depolarizing muscle relaxants (e.g., tubocurarine)
hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants.
Anticholinergics (e.g., atropine, biperiden)
Increasing the bioavailability of thiazide diuretics by decreasing gastrointestinal motility and gastric emptying rate.
Preparations for the treatment of diabetes mellitus (hypoglycemic drugs and insulin)
Application thiazide may affect glucose tolerance that may require correction dose hypoglycemic agents.
Metformin
Metformin should be used with caution because of the risk of lactic acidosis due to possible functional renal failure under the action of hydrochlorothiazide.
Beta-blockers and diazoxide
Thiazides may enhance the hyperglycaemic effect of beta-blockers and diazoxide.
Pressor amines (e.g., norepinephrine)
Possible reduced pressor effect amines.
Anti-gout drugs (probenecid, sulfinpyrazone and allopurinol)
needed correction doses protivopodagricakih preparations as hydrochlorothiazide can increase the concentration of uric acid in
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