Composition, form of production and packaging
Tablets, film-coated 1 tab.
hydrochlorothiazide 12.5 mg
losartan 50 mg
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
7 pcs. - blisters (12) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.
10 pieces. - blisters (9) - packs of cardboard.
10 pieces. - blisters (28) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (6) - packs of cardboard.
Tablets, film-coated 1 tab.
hydrochlorothiazide 25 mg
losartan 100 mg
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
7 pcs. - blisters (12) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.
10 pieces. - blisters (9) - packs of cardboard.
10 pieces. - blisters (28) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (6) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Losartan / Hydrochlorothiazide-Teva is a combined antihypertensive drug with fixed doses of active components.
The active substances of the combination losartan / hydrochlorothiazide have an additive antihypertensive effect, reducing blood pressure (BP) more than each of the components individually. Due to the diuretic effect, hydrochlorothiazide increases the activity of blood renin (ARP), stimulates the secretion of aldosterone, increases the concentration of angiotensin II and reduces the serum potassium content. The administration of losartan blocks all the physiological effects of angiotensin II and, as a result of suppression of aldosterone, contributes to a decrease in potassium loss caused by the intake of a diuretic.
Losartan has a moderate and transient uricosuric effect. Hydrochlorothiazide causes a slight increase in the concentration of uric acid in the blood; The combination of losartan and hydrochlorothiazide helps reduce the severity of hyperuricemia caused by a diuretic.
Losartan is an antagonist of angiotensin II receptors (APA). Losartan and its pharmacologically active metabolite (E 3174) both in vitro and in vivo block all the physiological effects of angiotensin II, regardless of the source or route of synthesis. Losartan selectively binds to AT 1 -receptors and does not bind or block receptors of other hormones and ion channels, which play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit ACE-kinase II, and, accordingly, does not interfere with the destruction of bradykinin, therefore side effects mediated by bradykinin (eg, angioedema) are rare.
When using losartan, the absence of negative feedback influence on renin secretion leads to an increase in ARP. Increased ARP leads to an increase in angiotensin II in blood plasma. However, antihypertensive activity and a decrease in plasma aldosterone concentration are preserved, which indicates an effective blockade of angiotensin II receptors. Losartan and its active metabolite have a greater affinity for angiotensin I receptors than for angiotensin II receptors. The active metabolite is 10-40 times more active than losartan. After a single oral intake, the antihypertensive effect (a decrease in systolic and diastolic blood pressure) peaks at 6 hours, then gradually decreases within 24 hours. The maximum antihypertensive effect develops in 3-6 weeks after the start of the drug.
The concentration of losartan and its active metabolite in the blood plasma, as well as the antihypertensive effect of losartan increase with increasing dose of the drug.Since losartan and its active metabolite are angiotensin II receptor antagonists, they both contribute to the antihypertensive effect.
Losartan does not affect vegetative reflexes and does not have a lasting effect on the concentration of noradrenaline in the blood plasma.
In patients with hypertension and left ventricular hypertrophy, losartan, often in combination with hydrochlorothiazide, reduces the risk of cardiovascular morbidity and mortality.
Hydrochlorothiazide. The mechanism of hypotensive action of thiazide diuretics is unknown. Thiazide diuretics do not affect normal BP.
Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the reabsorption of electrolytes in the distal tubules of the kidneys. Hydrochlorothiazide approximately equally increases the excretion of sodium and chloride. Excretion of sodium can be accompanied by a small loss of potassium ions, bicarbonates and a delay in calcium ions in the body.
When administered, the diuretic effect begins after 2 hours, reaches a maximum on average 4 hours and lasts from 6 to 12 hours.
PHARMACOKINETICS
The pharmacokinetics of losartan and hydrochlorothiazide with simultaneous administration does not differ from that in their separate application.
Suction
Losartan. When ingested, losartan is well absorbed from the digestive tract, metabolized by "primary passage" through the liver, resulting in an active carboxylated metabolite and inactive metabolites. Systemic bioavailability of losartan in the form of tablets is about 33%. Cmax in the blood plasma of losartan and its active metabolite are achieved after 1 h and 3-4 h, respectively. When losartan was taken during a meal, there was no clinically significant effect on the profile of losartan concentration in the blood plasma.
Hydrochlorothiazide. After ingestion, it is incomplete, but rather quickly absorbed from the digestive tract. 60-80% of the dose is absorbed from the digestive tract.The time to reach C max in blood plasma is -1.5-3 h.
Distribution
Losartan. The binding of losartan and its active metabolite to blood plasma proteins (mainly albumin) is more than 99%. V d - 34 liters. Studies in rats have shown that losartan practically does not penetrate the BBB.
Hydrochlorothiazide. It penetrates the hematoplacental barrier, it is excreted into breast milk. Does not penetrate the BBB.
Metabolism
Losartan. After ingestion and / or administration of losartan labeled with 14 C isotope, the radioactivity of the circulating blood plasma is associated with the presence of losartan and its active metabolite in it.
In addition to the active metabolite, biologically inactive are formed, incl. two major metabolites formed as a result of the hydroxylation of the butyl side chain, and one secondary metabolite is N-2-tetrazole-glucuronide.
Hydrochlorothiazide. It is slightly metabolized in the liver. At least 61% of the ingested dose is excreted unchanged for 24 hours.
Excretion
Losartan. The plasma clearance of losartan and its active metabolite is about 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml / min and 26 ml / min, respectively. After ingestion, losartan is excreted by the kidneys - about 4% unchanged and about 6% of the dose in the form of an active metabolite.
After oral administration, the concentration of losartan and its active metabolite in the blood plasma decreases polyexponentially with a finite T 1/2 of about 2 hours and 6-9 hours, respectively. With a single admission of the drug at a dose of 100 mg, neither losartan nor its active metabolite significantly accumulate in the blood plasma.
The excretion of losartan and its metabolites occurs through the intestine with bile and kidneys. In healthy volunteers, after ingestion of losartan labeled with isotope14 C, about 35% of the radioactive label is found in urine and 58% in feces.
Hydrochlorothiazide. Quickly excreted by the kidneys. T 1/2 varied from 5.6 to 14.8 hours. At least 61% of the dose taken orally was excreted unchanged for 24 hours.
Pharmacokinetics in special clinical cases
The concentrations of losartan and its active metabolite in blood plasma and the rate of absorption of hydrochlorothiazide in elderly patients with hypertension do not differ significantly from these indices in young patients with arterial hypertension.
In patients with mild and moderate alcoholic cirrhosis of the liver, when taking the drug inside the concentration of losartan and its active metabolite in the blood plasma were respectively 5 and 1.7 times higher than in young male volunteers. Concentrations of losartan in blood plasma were 2 times higher in women with arterial hypertension compared with men with arterial hypertension. This apparent pharmacokinetic difference is not clinically significant. The concentrations of active metabolite in men and women did not differ.
With a creatinine clearance (CK) of more than 10 ml / min, the concentration of losartan in the blood plasma does not differ from that with normal kidney function. In patients on hemodialysis, the area under the concentration-time curve (AUC) of losartan is approximately 2 times greater than in patients with normal renal function.The plasma concentrations of the active metabolite of losartan do not change in patients with impaired renal function or patients on hemodialysis. Lozartan and its active metabolite can not be removed by hemodialysis.
INDICATIONS
- Arterial hypertension (in patients who are shown combined therapy).
DOSING MODE
Inside, regardless of food intake, with enough water.
The initial and maintenance dose is 1 tablet of 12.5 mg + 50 mg once a day.
For patients who can not achieve adequate control of blood pressure, the dose can be increased - 1 tablet of 25 mg + 100 mg once a day.
The maximum dose is 1 tablet of 25 mg + 100 mg once a day.
The maximum antihypertensive effect in most cases is achieved within 3-4 weeks from the start of treatment.
In elderly patients, correction of the initial dose of the drug Losartan / Hydrochlorothiazide-Teva is not required.
Lozartan / Hydrochlorothiazide-Teva is not recommended for use in patients under 18 years of age due to lack of efficacy and safety data for this age group.
Patients with moderate renal insufficiency (KK 30-50 ml / min) correction of the initial dose is not required.
SIDE EFFECT
In clinical studies with losartan / hydrochlorothiazide, no adverse events specific to this combination drug have been observed.
Undesirable effects were limited to those reported earlier with losartan and / or hydrochlorothiazide alone.
The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%, often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - 0.01%, including single messages.
Losartan
On the part of the blood and lymphatic system: rarely - reduction of hemoglobin, reduction of hematocrit, very rarely - suppression of bone marrow function, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia, lymphadenopathy, eosinophilia.
From the endocrine system: rarely - the syndrome of inadequate secretion of antidiuretic hormone.
From the nervous system: often - headache, dizziness, fainting; infrequently - insomnia, anxiety, anxiety, confusion, depression, sleep disorder, drowsiness; rarely - memory impairment, paresthesia, peripheral neuropathy, tremor, migraine.
From the side of the organ of vision: rarely - visual impairment, conjunctivitis, decreased visual acuity, a feeling of dryness and burning sensation in the eyes.
From the side of the organ of hearing and labyrinthine disturbances: infrequently - vertigo, noise in the ears.
From the side of the cardiovascular system: often - a marked decrease in blood pressure, orthostatic hypotension; infrequent pain in the chest, stenocardia, AV blockade of the 2nd degree, cerebrovascular accident, myocardial infarction, palpitation, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular fibrillation).
From the respiratory system, chest and mediastinum: often - cough; infrequently - a rhinitis, zalozhennost a nose; very rarely - sinusitis, pharyngitis, laryngitis, dyspnea, bronchitis.
From the digestive system: often - nausea, diarrhea; infrequently - abdominal pain, constipation; rarely - dryness of the oral mucosa, toothache, flatulence, vomiting, gastritis; very rarely - pancreatitis.
From the liver and bile ducts: infrequently - increased activity of liver transaminases, increased bilirubin concentration; very rarely - hepatitis.
From the skin and subcutaneous tissues: rarely - alopecia, psoriasis, dermatitis, dry skin; very rarely - pseudolymphoma.
Allergic reactions: infrequent - skin rash, itchy skin; rarely - angioedema, swelling of the face, extremities, lips, tongue, vocal cords and / or larynx, dysphonia, urticaria; very rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, photosensitization.
From the musculoskeletal and connective tissue: often - muscle spasm, back pain, leg pain, myalgia; infrequently - pain in the hands, arthralgia, musculoskeletal pain, stiffness and swelling of the joints.
From the urinary system: often - a violation of kidney function; rarely uremia, acute renal failure; very rarely - oliguria, anuria.
On the part of the reproductive system: infrequently - impotence; rarely - gynecomastia.
Other: often - asthenia, fatigue, hyperkalemia; infrequently - increased body temperature, a slight increase in urea and creatinine, hyperkalemia; rarely - hyponatremia;very rarely - hyperglycemia, epistaxis, vasculitis.
Hydrochlorothiazide
From the blood and lymphatic system: rarely - neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, oppression of bone marrow function.
From the side of metabolism and nutrition: infrequently - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, increased concentration of cholesterol and triglycerides, gout.
From the nervous system: often - depression, sleep disturbance; infrequently - insomnia, paresthesia, dizziness.
From the side of the organ of vision: rarely - transient focalization, xanthopsia.
From the side of the organ of hearing: rarely - vertigo.
From the cardiovascular system: rarely - orthostatic hypotension.
On the part of the respiratory system, chest and mediastinal organs: infrequently - respiratory distress syndrome, pneumonitis, pulmonary edema.
On the part of the digestive system: rarely - sialadenitis, constipation, diarrhea, irritation of the gastrointestinal mucosa; very rarely - pancreatitis.
From the liver and biliary tract: infrequently - jaundice (intrahepatic cholestasis).
Allergic reactions: rarely - photosensitivity; very rarely - hives, toxic epidermal necrolysis, Lyell's syndrome.
From the musculoskeletal and connective tissue: infrequently - muscle spasm.
From the urinary system: infrequently - glycosuria, interstitial nephritis, renal failure.
Other: infrequently - fever, hyperkalemia, vasculitis.
CONTRAINDICATIONS
- Hypersensitivity to any of the components of the drug (as well as increased sensitivity to other drugs that are derivatives of the sulfonamide);
- Pregnancy;
- the period of breastfeeding;
- Anuria, severe renal dysfunction (CK less than 30 ml / min), patients on hemodialysis;
- severe violations of the liver (more than 9 points on the scale Child-Pugh);
- cholestasis;
- refractory hypokalemia;
- a symptomatic increase in the concentration of uric acid in the blood plasma;
- dehydration;
- children's age till 18 years;
- primary hyperaldosteronism;
- simultaneous use with potassium preparations, potassium-sparing diuretics;
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
Carefully
Violations of the water-electrolyte balance (VEB) (decrease in the volume of circulating blood (bcc), hyponatremia, hypochloraemic alkalosis, hypomagnesemia, gnopokalemia) that can develop against intercurrent diarrhea or vomiting; impaired renal function (QC more than 30 ml / min); violations of the liver (less than 9 points on the scale Child-Pugh); cardiac ischemia; cerebrovascular diseases; aortic stenosis; mitral stenosis; hypertrophic obstructive cardiomyopathy (GOKMP);bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; diabetes; hypercalcemia, hyperuricemia and / or gout; weighed allergic anamnesis (in some patients, angioedema has developed earlier with other medications, including ACE inhibitors); bronchial asthma; systemic connective tissue diseases, incl.systemic lupus erythematosus (SLE); hypovolaemia, incl. against a background of high doses of diuretics; and also with simultaneous administration with non-steroidal anti-inflammatory drugs (NSAIDs), incl. with inhibitors of cyclooxygenase-2 (COX-2).
PREGNANCY AND LACTATION
The use of the drug Losartan / Hydrochlorothiazide-Teva during pregnancy is contraindicated. It is known that drugs acting directly on the renin-angiotensin-aldosterone system (RAAS), when used in the II and III trimesters of pregnancy, can cause developmental defects or even the death of the developing fetus. Therefore, when diagnosing a pregnancy, the drug Lozartan / Hydrochlorothiazide-Teva should be discontinued as soon as possible.
Women of reproductive age in the planning of pregnancy recommended the use of antihypertensive drugs with an established safety profile.
Due to the fact that thiazide diuretics penetrate the hematoplacental barrier, their use in pregnant women is not recommended, as the risk of development of such adverse effects in the mother and fetus as embryonic jaundice, thrombocytopenia, VEB violations increases.
Diuretics do not prevent the development of toxicosis of pregnancy, while there is no convincing evidence that they have a positive effect on the course of toxicosis.
It is not known whether losartan is excreted in breast milk. Hydrochlorothiazide is excreted in breast milk. The drug Losartan / Hydrochlorothiazide-Teva is contraindicated for use during breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution in the violation of kidney function (QC more than 30 ml / min).
Contraindicated in severe violations of kidney function (QC less than 30 ml / min), in patients on hemodialysis.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution for violations of the liver (less than 9 points on the scale Child-Pugh).
Is contraindicated in severe hepatic dysfunction (more than 9 points on the Child-Pugh).
APPLICATION FOR CHILDREN
The drug losartan / hydrochlorothiazide-Teva is not recommended for use in patients under 18 years of age due to a lack of data on efficacy and safety for this age group.
APPLICATION IN ELDERLY PATIENTS
Elderly patients correction of the initial dose losartan / hydrochlorothiazide-Teva is not required.
SPECIAL INSTRUCTIONS
Patients with a history of angioneurotic edema (general and further at the background of ACE inhibitors and ARA) require careful monitoring.
There are reports that in some patients taking the drug Losartan / Hydrochlorothiazide Teva, in connection with the suppression of RAAS function observed change in kidney function, including kidney failure; These changes were reversible and disappeared after discontinuation of therapy.
As with other agents acting on the RAAS, use of the drug losartan / hydrochlorothiazide-Teva in patients with bilateral renal artery stenosis and stenosis of the artery to a solitary kidney may lead to increased concentrations of urea and creatinine in serum. These changes in renal function was reversible and disappeared after discontinuation.
During treatment with losartan / hydrochlorothiazide-Teva, as with any antihypertensive therapy, possibly marked reduction in blood pressure. Patients should be examined in order to detect clinical signs of EBV reduction bcc and disorders, including hyponatremia, hypochloremic alkalosis, hypokalemia or hypomagnesemia, which may occur due to diarrhea or vomiting episodes, as a result of diuretic therapy, while limiting the consumption of salt. These patients should be monitored in serum electrolytes.
The simultaneous use of potassium preparations, potassium-sparing diuretics are not recommended (see. The section "Interaction with other drugs").
In patients with impaired hepatic function (less than 9 points on a scale Child-Pugh) drug Losartan / Hydrochlorothiazide Teva, should be used with caution, because even minor violations EBV can cause the development of hepatic coma.
Patients with primary hyperaldosteronism use of antihypertensive drugs acting on the RAAS, including drug Losartan / Hydrochlorothiazide Teva-ineffective.
The sharp decline in blood pressure during therapy with Losartan / Hydrochlorothiazide-Teva, as in the treatment of other antihypertensive drugs in patients with ischemic cardiovascular and cerebrovascular diseases can lead to myocardial infarction or stroke.
In patients with heart failure as a failure of kidney function, and without it, the use of the drug Losartan / Hydrochlorothiazide Teva-how and other means of acting on the RAAS, increases the risk of a sharp decline in blood pressure and the development of acute renal failure.
Caution must be exercised when using the drug Losartan / Hydrochlorothiazide-Teva in patients with aortic stenosis, mitral stenosis and GOKMP.
Therapy with Losartan / Hydrochlorothiazide-Teva can lead to impaired glucose tolerance. In some cases, it may require a dosage adjustment hypoglycemic agents (including insulin).
Use of the drug Losartan / Hydrochlorothiazide-Teva can decrease calcium excretion by the kidneys and cause occasional and insignificant increase of calcium in blood serum. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. The drug Losartan / Hydrochlorothiazide Teva, should be discontinued prior to the study of functions of the parathyroid glands.
Increasing the concentration of cholesterol and triglycerides in the blood plasma it can also be associated with the drug Losartan / Hydrochlorothiazide-Teva.
Some patients taking the drug Losartan / Hydrochlorothiazide Teva, may lead to hyperuricemia and / or exacerbation of gout. Because losartan decreases the concentration of uric acid, its combination with hydrochlorothiazide reduces the severity of hyperuricemia caused a diuretic.
Patients receiving the drug losartan / hydrochlorothiazide-Teva, hypersensitivity reactions may occur even if there is no indication of the presence of allergy or bronchial asthma in history. There are reports of acute development or progression of SLE in patients receiving thiazide diuretics.
Note that angiotensin II receptor antagonists, including losartan, are less effective for the treatment of hypertension when applied at blacks patients than in the other patients.
Before the drug Losartan / Hydrochlorothiazide-Teva is possible to obtain a positive result in doping control, since it includes hydrochlorothiazide.
Effects on ability to transport management and work with technology
In applying the drug Losartan / Hydrochlorothiazide Teva-caution when driving and operating techniques that require attention and psychomotor speed reactions, due to the fact that the possible development of undesired side effects in the nervous system (dizziness, somnolence).
OVERDOSE
Information about specific treatment of overdose combination of losartan / hydrochlorothiazide no.
In the event of an overdose of the drug losartan / hydrochlorothiazide-Teva should be stopped, patient monitor closely indicators of functions of vital organs, symptomatic therapy - induction of emesis if the drug recently adopted, as well as the elimination of dehydration, electrolyte imbalance, hepatic coma and blood pressure reduction standard methods.
Losartan
information on overdose of losartan in humans is limited.
The most likely overdose symptoms are a marked reduction in blood pressure and tachycardia; bradycardia may be due to parasympathetic (vagal) stimulation.
Treatment:In case of a reduction in blood pressure is a supportive therapy. Losartan and its active metabolite are output via hemodialysis.
Hydrochlorothiazide
The most frequent symptoms of hydrochlorothiazide overdose are due to electrolyte deficiency (hypokalemia, chloropenia, hyponatremia) and dehydration due to excessive diuresis. When simultaneous administration of cardiac glycosides may exacerbate hypokalemia arrhythmias. Not assigned to what extent hydrochlorothiazide can be removed from the body by hemodialysis.
DRUG INTERACTION
Losartan
In clinical pharmacokinetic studies showed no clinically significant interaction of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.
Reportedly, rifampicin and fluconazole reduce the concentration of the active metabolite, the clinical significance of this interaction is not known.
The combination of losartan, like other means of blocking angiotensin II or its effects, potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium-containing additives or potassium salts, can lead to an increase in the potassium content in the blood serum.
When applied simultaneously with losartan drugs lithium caution due to a possible reduction in excretion of lithium.
NSAIDs, including selective inhibitors of COX-2 may reduce the effects of diuretics and other hypotensive drugs therefore the antihypertensive effect of angiotensin II receptor antagonists may be attenuated while the use of NSAIDs (including COX-2 inhibitors).
In some patients with impaired renal function (e.g., elderly patients or patients with reduced BCC, including receiving diuretics), treated with NSAIDs (including COX-2 inhibitors), treatment antagonists of angiotensin II receptors or ACE inhibitors can cause further deterioration in renal function including acute renal failure (ARF), which is usually reversible.
Cases of dual blockade of the RAAS (e.g., while the use of an ACE inhibitor and receptor antagonist angiotensin II) in patients diagnosed with atherosclerosis, heart failure, diabetes more often accompanied by a pronounced decrease in BP faintness, hyperkalemia, and renal dysfunction (including OPN) of compared with the use of one of the drugs acting on RAAS.
While the use of tricyclic antidepressaitami, galoperidopom, klopromazinom, sulpiride baclofen, amifostivom increased risk of abrupt reduction in blood pressure /
Hydrochlorothiazide
With simultaneous use of thiazide diuretics with barbiturates, narcotic analgesics, ethanol may increase the risk of orthostatic hypotension.
With simultaneous application may require a dosage adjustment gnpoglikemicheskih means (for ingestion, and insulin). In view of the risk of lactic acidosis due to the possibility of renal impairment in the application of hydrochlorothiazide, metformin should be used with caution.
In the application of hydrochlorothiazide with other antihypertensive agents observed an additive effect.
In the presence of the anion exchange resin is disturbed absorption of hydrochlorothiazide. Colestyramine or colestipol in single doses bind hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by 85% and 43%, respectively.
Glucocorticosteroids, adrenocorticotropic hormone leads to a marked decrease in the content of electrolytes, in particular, can cause hypokalemia.
May reduce the severity of the response to administration of pressor amines (e.g., epinephrine).
Possible potentiation of non-depolarizing muscle relaxant action type (e.g., tubocurarine chloride).
Diuretics reduce renal clearance of lithium and increase the risk of its toxic action; the combined use of diuretics and drugs lithium is not recommended.
In some cases, NSAID (including COX-2) may reduce the diuretic, natriuretic and antihypertensive effects of diuretics.
Due to the influence of thiazide diuretics, calcium metabolism, taking them can distort the results of the research function of the parathyroid glands.
While the use of atropine, biperidenom thiazide diuretics increases bioavailability due to decreased GI motility and gastric emptying rate.
With simultaneous use of thiazide diuretics reduce renal excretion methotrexate, cyclophosphamide and enhance their myelosuppressive effects.
Thiazide diuretics may exacerbate the toxic effects of salicylate on the central nervous system when used in high doses.
Reported some cases of hemolytic anemia, while the use of thiazide diuretics and methyldopa.
At simultaneous application with cyclosporine increases the likelihood of developing hyperuricemia and gout.
Hypokalemia as giponatriemnya caused by the use of thiazide diuretics, increase the risk of arrhythmias during concomitant use with cardiac glycosides.
The simultaneous use of thiazide diuretics with antiarrhythmic drugs (quinidine, gidrohinid, disopyramide, amiodarone, sotalol, ibutilide), some antipsychotics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, tsiamemazin, amisulpride, sultopride, sulpiride, tiapride, pimozide, haloperidol, droperidol) and other drugs (bepridil, tsizaprnd, difemanil, erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, vincamine) may be accompanied by the development of hypokalemia, which in turn can become a pr Ichin development of arrhythmias such as "pirouette".
While the use of calcium supplementation there is a possibility of hypercalcemia, so it is necessary to monitor serum calcium levels.
In an application with carbamazepine are at risk of hyponatremia.
With the development of dehydration during treatment with thiazide diuretics, there is a possibility of acute renal failure, especially with simultaneous use of iodine preparations.
TERMS OF RELEASE FROM PHARMACY
On prescription.
TERMS AND CONDITIONS OF STORAGE
Store at a temperature not exceeding 25 В° C. Keep out of the reach of children. Shelf life - 2 years. Do not use after the expiration date printed on the package.
