Zokora-HCTZ 20/12.5 Davipharm treatment for hypertension (3 blisters x 10 tablets)

Pharmacological group: Hematoplasty drugs. ATC code: C09CA08.

hydrochlorothiazid:

Pharmacological group: Thizazid diuretics. ATC code: C03AA03.

Zokora-HCTZ 20/12.5 is a fixed form of olmesartan medoxomil, Angiotensin II receptor antagonist and hydrochlorothiazide, thiazid diuretics. This combination increases the effect of anti -hypertension, lower blood pressure than using two individual drugs.

1 time/day of the tablet combines effectively within 24 hours.

olmesartan medoxomil is an oral, selective antagonistic Angiotensin II receptor (AT1). Angiotensin II is the vasodilic hormone of the renin-analiotensin-aldosteron system and plays an important role in the pathophysiology of hypertension. The impact of angiotensin II includes vascular contractions, synthesis stimulation and release of aldosteron, heart stimulation and nodia reabsorption at the kidneys.

olmesartan inhibits vascular shrinkage and aldosteron secretion of Angiotensin II by inhibiting it attached to the AT1 receptor in the tissue including blood vessel and adrenal glands. The effect of olmesartan is not related to the source or the synthesis of angiotensin II. The selective antagonistic effect Angiotensin II (AT1) by olmesartan increases the level of plasma renin and angiotensin I and angiotensin II levels, and reduces plasma aldosteron levels.

In hypertension, Olmesartan Medoxomil causes prolonged dosage blood pressure lowering.

There is no evidence that causes hypotension in the first dose, fast heart reflection when long -term treatment, or hypertension overcurrence after stopping treatment.

Olmesartan medoxomil dose 1 time/ day has the effect of lowering blood pressure within 24 hours. 1 time/ day for hypotension effect similar to the dose twice a day with a total daily dose equivalent.

When treated continuously, the effect of lowering blood pressure reaches maximum after 8 weeks after the beginning of treatment, although most of the hypotension effect is achieved after 2 weeks of treatment.

hydrochlorothiazid is a thiazid diuretic. The anti -hypertension mechanism of thiazid diuretics is still unknown. Thiazid acts on electrolyte reabsorption mechanism in the renal tubules, increasing directly sodium and chloride elimination with equivalent amounts. The diuretic effect of hydrochlorothiazid reduces plasma volume, increases plasma renin activity and increases aldosteron secretion, thereby increasing the loss of potassium and bicarbonate in urine, and decreased serum potassium. Renin-Anotensin is related to Angiotensin II and therefore the use of simultaneous use of Angiotensin II receptor counterfeiting compensates for potassium loss due to thiazid diuretics. With hydrochlorothiazid, diuretic effects appear after 2 hours of medication and maximum effect after 4 hours, while diuretic effect lasts about 6 - 12 hours.

pharmacokinetics

absorption and distribution

olmesartan medoxomil

olmesartan medoxomil is a pharmacy. It is rapidly converted into active metabolites of olmesartan by the esterase enzyme in the intestine and the vein of the door during the intestinal absorption. Olmesartan Medoxomil or Medoxomil is not found in the intact in plasma or excretory substances. Olmesartan's absolute bioavailability when using the tablet form is 25.6%.

Olmesartan's peaked plasma concentration is reached within 2 hours after taking a dose of olmesartan medoxomil and plasma Olmesartan concentration increases almost to the maximum dose of 80 mg.

Food has a very small impact on the bioavailability of olmesartan, so it can be taken Olmesartan Medoxomil with or not with food.

Olmesartan is highly connected to plasma proteins (99.7%), but the likelihood of competitive interaction with plasma proteins between Olmesartan and other drugs with many other low -blood plasma proteins clinically. Olmesartan's cohesion with blood cells is negligible. The volume of distribution after use of low intravenous injection (16 - 29L).

hydrochlorothiazide

After oral, combined with olmesartan medoxomil and hydrochlorothiazid, the average time reaches the plasma peak concentration of hydrochlorothiazide is 1.5 - 2 hours.

hydrochlorothiazid connects 68% plasma proteins and distribution integral is 0.83 - 1.14 l/kg.

metabolism and elimination

olmesartan medoxomil

The total plasma clearance of olmesartan is 1.3 l/ hour and is relatively slower than the blood rate in the liver (90 l/ h). After taking a dose of Olmesartan Medoxomil marking the isotopes 14C, 10 - 16% of the drug marks the excretion of the urine (most in the first 24 hours) and the rest is eliminated through feces. Based on the body's bioavailability of 25.6%, the absorption olmesartan can be calculated by the kidneys are 40%and the liver is 60%. All the isotopes mark are Olmesartan. No other metabolites are found. Olmesartan's liver cycle is low. Because most of the olmesartan is eliminated by biliary tract, contraindicated olmesartan for patients with biliary clogging.

The total selling time of olmesartan varies from 10 to 15 hours after the use of repeated oral doses. Stable state is achieved after a few doses and no accumulation in 14 days after the dose is repeated. The clearance of the kidney is about 0.5 - 0.7 l/ hour and does not depend on the dose.

hydrochlorothiazide

Hydroclorothiazid is not metabolized in humans and excreted almost completely in the form of constant activity in urine. About 60% of oral doses are eliminated in a constant form within 48 hours. The renal clearance is about 250 - 300 ml/ min. The total selling time of hydrochlorothiazid is 10 - 15 hours.

The whole body's body bioavaila is reduced by about 20% when used with olmesartan medoxomil, but this reduction is not clinically significant. Olmesartan pharmacokinetics are not affected when used with hydrochlorothiazide.

pharmacokinetics in special subjects

Elderly (≥ 65 years)

In patients with hypertension, Olmesartan's AUC in a stable state increased by about 35% in the elderly (65 - 75 years old) and about 44% in people ≥ 75 years older than the youth group.

Clinical data is limited, showing the whole body clearance of hydrochlorothiazid in a healthy elderly group or hypertension than a healthy young volunteer.

kidney failure

In patients with renal failure, Olmesartan's AUC in a stable state increases by 62%, 82% and 179% in patients with mild, medium and severe renal failure compared to healthy evidence group. Hydrochlorothiazid's waste time is longer in patients with renal failure.

Hepatic failure

After taking the only dose, the AUC value of Olmesartan is 6% higher in mild liver failure and 65% in people with liver failure compared to a healthy evidence group. After using the repeated dose in medium liver failure patients, AUC Olmesartan is about 65% higher than the healthy evidence group. Olmesartan's CMAX value is the same between a healthy and liver failure patient. Olmesartan Medoxomil has not been assessed in patients with severe liver failure. Hepatic failure does not significantly affect the pharmacy of hydrochlorothiazid.

Very common, ADR ≤ 1/10

Common, 1/100 ≤ ADR

The drug can cause other unwanted effects. It is necessary to closely monitor and recommend the patient to notify the doctor with unwanted effects when using the drug.

Caution when using

Reducing internal blood volume

Symptomic hypotension, especially after the first dose, may occur in patients with a decrease in blood volume and/ or hypoglycet hematoma due to diuretics, diets that are low in salt, diarrhea or vomiting. This situation must be overcome before the patient uses a combination tablet.

Other conditions irritate the renin-analiotensin-aldosteron system.

In patients with blood vessel tone and renal function dependent mainly on the activity of the renin-angiotensin-aldosteron system (for example, patients with congestive heart failure or kidney failure, including kidney artery stenosis), treated with drugs that affect this system can lead to acute blood pressure, hyper nitrogen nitrogen, urinary minimum or rarely acute renal insufficiency.

kidney hypertension

Increased risk of severe hypotension and renal failure when patients with narrowed kidney stenosis or artery stenosis in the renal artery also work to use drugs that affect the renin-angiotensin-aldosteron system.

kidney failure and kidney transplant

Contraindicated Zokora-HCTZ 20/12.5 in patients with severe renal failure (CLCR

Contraindicated for patients with renal failure at all stages.

There is no experience in treating patients with kidney transplant.

Double Renin-Anotensin-Aldosteron System

Double-Renin-Anotensin-Aldosteron-sealed closing system is used by simultaneous use of angiotensin transfer enzyme inhibitors, Angiotensin II or Aliskiren receptor antagonists that increase the risk of lowering blood pressure, hyperkalemia and reducing kidney function (including acute renal failure). Not recommended to use simultaneously.

If needed to be used, only under the supervision of experts, monitoring kidney function, electrolytes and regular blood pressure. Should not use the enzyme inhibitors Angiotensin and Angiotensin II receptor antagonist in patients with diabetes.

Hepatic failure

Mild liver failure: Precautions when using Zokora 20/12.5.

Moderate and severe liver failure: Inexperienced in using Olmesartan Medoxomil in patients with severe liver failure. In medium liver failure patients, the maximum dose of olmesartan medoxomil is 20 mg. In addition, the minor change of water and electrolyte balance during thiazid treatment can cause liver coma in patients with liver failure or progressive liver disease.

contraindicated tablets combined in medium and severe liver failure, bile stasis and biliary obstruction.

Aortic valve stenosis and mitral valve, hypertrophic heart muscle

Like other vasodilators, cautious when prescribed patients with aortic stenosis or mitral valve, or hypertrophic cardiomyopathy.

Cuong Aldosteron Tien Phat

Patient Aldosteron primary generals generally will not respond to antihypertensive drugs action through the inhibition of the Renin-Anotensin system. Therefore, it is not recommended to use the combined tablet in these patients.

Impact on metabolism and endocrine

Thiazid treatment may reduce glucose tolerance. In patients with diabetes, insulin dose and oral hypoglycemic drugs may be adjusted. Potential diabetes can manifest during treatment with thiazid.

Other undesirable effects related to thiazid treatment are increased cholesterol and triglyceride levels.

Hypertension or gout can be predicted in patients treated with thiazid.

Electrolyte balance

For any patient treated with diuretics, it is necessary to periodically monitor the concentration of electrolytes.

thiazid, including hydrochlorothiazid, can cause water and electrolyte imbalance (including hypotension, hypoglyc sodium and alkaline infection due to chloride reduction). Warning signs of water and electrolyte imbalance are dry mouth, thirst, weakness, sleep, drowsiness, restlessness, pain or cramps, muscle fatigue, hypotension, urinary discharge, fast heartbeat, digestive disorders such as nausea or vomiting.

The highest risk of hypokalemia is in cirrhosis patients, in urinary patients, patients who are taking unreasonable oral supplements and patients are being treated simultaneously with corticosteroids or ACTH.

In contrast, due to the antagonistic effect at the Angiotensin II receptor of olmesartan medoxomil, hyperkalemia may occur, especially when kidney failure and/ or heart failure, and diabetes. Closely monitor serum potassium concentration in patients at risk. Potassium diuretics, potassium supplements or salt -replacement substitutes containing potassium and other drugs can increase serum potassium levels (for example, heparin) should be cautious when used with combined tablets.

There is no evidence that Olmesartan Medoxomils reduce or prevent hematuria due to diuretics. Reduce normal chlorine mild and no need to be treated.

Thiazid may reduce calcium secretion in urine and lead to slightly and non -continuous increase in serum calcium concentration in the absence of attached calcium metabolic disorders. Hypercalcemia may be a symptom of hyperthyroidism. Thiazid should be stopped before testing the adjacent function.

Thiazid is known to increase the magnesium exhaust in the urine, which can lead to hypoglycemia.

Hypoglyc sodium due to increased volume may occur in edematous patients when hot weather.

lithium

As with other Angiotensin II receptor antagonists, it is not recommended for simultaneous use in combination with lithium.

Similar chronic diarrhea Sprue

In serious rare cases, chronic diarrhea accompanied by a lot of weight loss has been reported in patients using Olmesartan for several months to several years, possibly due to slow -slow hypersensitivity.

Patient biopsy often shows intestinal atrophy. If the patient has these symptoms during treatment with Olmesartan, eliminating other causes of the disease. Consider stopping Olmesartan Medoxomil in the event of no other cause of disease.

In the case of symptoms that disappear and intestinal diseases similar to Sprue is determined by biopsy, should not be treated with olmesartan medoxomil.

racial difference

Like other preparations containing Angiotensin II receptor counterfeit substances, the hypotension effect of the tablet combines less in black patients than other skin -colored patients, maybe because of the high rate of black skin hypertension with low renin.

Doping resistance test

hydrochlorothiazid in preparations can give positive results in doping resistance tests.

Other

Like other anti -hypertension agents, excessive hypotension in patients with ischemia or ischemia can lead to myocardial infarction or cardioma.

Hypersensitivity reaction to hydrochlorothiazid may occur in patients with or without a history of asthma, but more often in patients with a history.

Systemic erythematosus lupus may appear or more serious has been reported when using thiazid diuretics.

Warning and caution related to excipients

Preparations contain lactose. Patients with rare genetic diseases with galactose tolerance, lapp lactase deficiency or glucose-galactose absorption disorders should not be used.

Preparations containing Polysorbat 80 can cause allergies, castor oil can cause abdominal pain, diarrhea.

To be out of reach of children.

The effect of the drug on the ability to drive and operate machinery

combined tablets have little and medium impact on the ability to drive and operate machinery. Dizziness and fatigue can sometimes occur in patients using anti -hypertension, which can affect reflexes.

Use drugs for women during pregnancy and lactation

pregnancy:

Due to the effects of olmesartan medoxomil and hydrochlorothiazide on pregnancy, it is not recommended to use the combination of tablets during the first 3 months of pregnancy. Contraindicated tablet combined in the three months and the last three months of pregnancy.

olmesartan medoxomil

Using Angiotensin II receptor antagonists does not recommend in the first three months of pregnancy and contraindicated in the middle and the last three months of pregnancy.

Epidemiological evidence related to the risk of teratogenicity when using Acei in the first three months of pregnancy has not been concluded, but it is not possible to eliminate the possibility of slightly increasing risk. While there is no data on epidemiological controlled epidemiology about the risk of Angiotensin II antagonist, the same risk may occur in this group of drugs. Unless it is necessary to continue using Angiotensin receptor inhibitors, patients are intended to be pregnant, so they should be transferred to other antihypertensive drugs that have been identified as safe to use during pregnancy. When detecting pregnancy, stopping treatment with Angiotensin II receptor counterclicking and if possible, it is possible to start treating with other drugs.

Using Angiotensin II receptor counterclose in the three months and the last three months of pregnancy has determined to harm the fetus (kidney failure, hypotension, hyperkalemia). If using Angiotensin II receptor antagonists in the middle of the middle of pregnancy, the ultrasound recommends test kidney function and the fetal skull.

Babies born with mothers use Angiotensin II receptor counterclose should be monitored with hypotension.

hydrochlorothiazide

Clinical data of hydrochlorothiazid for pregnancy is very limited, especially in the first three months of pregnancy. Inadequate animal research data.

hydrochlorothiazid through the placenta. Based on the pharmacological mechanism of hydrochlorothiazid, using hydrochlorothiazid in the middle and the last three months of pregnancy can affect the perfusion of the placenta and cause jaundice, water and electrolyte balance disorders and platelet deficiency in the fetus and infants.

hydrochlorothiazid should not be used for pregnancy, pregnancy hypertension or pre -eclampsia due to the risk of decreased plasma volume and reducing nutrition through the placenta, without beneficial effects on the disease.

hydrochlorothiazid should not be used to treat primary hypertension in pregnant women except for rare cases without any other treatment.

breastfeeding period:

olmesartan medoxomil

Because there is no information related to the use of a combination of nursing women, it is not recommended for use for nursing women and should use drugs that have been proven to be safe when breastfeeding, especially during newborns.

hydrochlorothiazide

hydrochlorothiazid excreted small amounts in breast milk. High -dose thiazid causes a lot of urination and can reduce milk secretion. It is not recommended to use combined tablets during breastfeeding. If using a combination tablet during breastfeeding, use the lowest dose possible.

Drug interaction

The ability to interact related to Zokora-HCTZ coordination 20/12.5

Not recommended to use simultaneously

Lithi:

Inchogively increased serum and toxic lithium concentration that has been reported when used simultaneously with lithium with angiotensin transfer enzyme inhibitors, rarely occurs with Angiotensin II receptor resistant. In addition, thiazid reduces lithium clearance and can increase the toxicity of lithium. Therefore, it is not recommended to use lithium and combined tablets. If it is necessary to use together, lithium concentration must be monitored.

Be cautious when using simultaneously

baclofen: The hypersensitivity reaction may occur.

Non -steroid anti -inflammatory (NSAIDs):

NSAIDS (for example, acetylsalicylic> 3 g/ day, non-selective COX-2 and NSAIDs inhibitors) can reduce the anti-hypertension effect of thiazid and Angiotensin II receptor antagonist.

In some patients with impaired renal function (for example, patients with dehydration or elderly people with impaired renal function) The combination of Angiotensin II receptor resistant with cycloxygenase inhibitors can damage more kidney, including acute renal failure, and often recover. Therefore, be careful when coordinating, especially in the elderly. Patients should drink water properly and monitor kidney function after starting to use simultaneously drugs and periodic checks later.

The simultaneous use has been recorded

Amifostin:

There may be hypersensitivity reactions.

Interactive ability related to Olmesartan Medoxomil

Do not recommend general use

Angiotensin transfer enzyme inhibitors (Acei), Angiotensin II receptor inhibitors or Aliskiren:

Clinical data shows the double blockade of the Renin-Anotensin-Aldosteron (RAAS) system when using a combination of ACEI, Angiotensin II or Aliskiren receptor inhibitors, increasing unwanted frequency of blood pressure, hyperkemia and reducing kidney function (including acute renal failure) compared to the use of retail drugs on RAAS.

Potassium concentration:

Based on the experience of using drugs that act on the renin-angiotensin-aldosteron system, use with diuretics to keep potassium, potassium supplements, potassium-containing salt or other drugs that can increase blood potassium concentration (eg heparin, acei) can lead to increased serum potassium concentration. If the drug affects the potassium concentration is indicated to be used with combined tablets, monitoring plasma potassium levels.

Isolate colesvelam bile acid:

Simultaneous use of colesvelam hydrochloride acid isolation reduces blood drug concentration and peak concentration of olmesartan, reduces news. Use Olmesartan Medoxomil for at least 4 hours before using ColesVEVEVELAM Hydrochorid to reduce drug interaction.

Other information

After treatment with antacid (aluminum/ Magnesi Hydroxyd), there is a significant reduction in bioavailability of olmesartan.

Olmesartan Medoxomil does not affect the pharmacokinetics and pharmacokinetics of warfarin and pharmacokinetics of digoxin.

Shared use of Olmesartan and Pravastatin clinically does not affect the pharmacokinetics of both drugs in healthy people.

, Olmesartan does not have the effect of inhibiting the cytochrom P450 1A1/2, 2A6, 2C8, 2C19, 2C19, 2D6, 2E1 and 3A4 in vitro, and does not have the lowest touch effect on the Cytochrom P450 system in the mouse. There is no clinical interaction between Olmesartan and metabolic drugs by Cytochrom P450 system.

Interactive ability related to hydrochlorothiazide

Not recommended to use simultaneously

Potassium concentration:

Hydroclorothiazid's potassium reduction effect may occur when used with drugs that reduce potassium or hypokalemia (for example, other potassium diuretics, laxatives, corticosteroids, acthers, amphotericin, carbenoxolon, penicillin G sodium or Salicylic acid derivatives).

Be cautious when using simultaneously

Calcium salt:

thiazid diuretics may increase serum calcium concentration due to reduction. If you have to prescribe calcium supplements, monitor plasma calcium concentrations and adjust the corresponding calcium dose.

cholestyramin and colestipol resin:

When there is anion exchange, the absorption of hydrochlorothiazid decreases.

digitalis glycosid:

Hypotension or hypoglycemia of thiazid can cause Digitalis touch arrhythmia.

Medications influenced by serum potassium concentration:

Monitoring serum and ECG concentration is often recommended when using tablets in combination with drugs affected by serum potassium concentration (e.g. digitalis glycosides and anti -arrhythmia) and with torsion -causing drugs (including several anti -arrhythmic drugs), hypotension is one of the factors that can cause tip.

IA anti -arrhythmia (quinidin, hydroquinidin, disopyramid).

Anti -arrhythmia Group III (Amiodaron, Sotalol, Dofetilid, Ibutilid).

Some anti -psychotic drugs (Thioridazin, Clopromazin, levopromazin, trifloperaazin, cyanmemazin, sulpid, amisulprid, rayprid, pimozid, haloperidol, mizolastin, droperidol).

Non -polar muscle relaxants (eg tuboCurarin):

hydrochlorothiazid may increase the effect of non -polarized muscle relaxants.

Sympathoma (e.g. atropin, biperiden):

Increases the bioavailability of thiazid diuretics due to reducing the gastrointestinal motility and reducing the speed of stomach empty.

Anti -diabetic drugs (oral or insulin):

Treatment with thiazid affects the ability to tolerate glucose. May need to adjust the dose of anti -diabetic drugs.

metformin:

Be cautious when using metformin due to the risk of lactic acid increased due to impaired renal function may occur related to hydrochlorothiazid.

Beta and diazoxid blockers:

Thiazid may increase the effect of hyperglycemia of beta and diazoxid blockers.

AMIN affects blood pressure (for example: Adrenalin):

can reduce the effects of amines that affect blood pressure.

Gout treatment (e.g. Probenecid, sulfinpyrazol and allopurinol):

Need to adjust the dose of drugs that excrete urine in urine because hydrochlorothiazid may increase serum uric acid levels. Probenecid or sulfinpyrazol may be needed.

Used with a thiazid can increase the frequency of hypersensitivity reactions to allopurinol.

Amantadin:

Thiazid may increase the risk of unwanted effects due to Amantadin.

cytotoxic toxin (eg cyclophosphamide, methotrexate):

Thiazid can reduce the elimination of the kidneys of cytotoxic drugs and have the ability to inhibit the marrow.

salicylat:

In case of high doses of salicylate, hydrochlorothiazid may increase the toxicity of salicylate on the central nervous system.

methyldopa:

There has been a hemolytic anemia report when using simultaneously hydrochlorothiazid and methyldopa.

cyclosporin:

Used with cyclosporin may increase the risk of hyperuricemia and complication gout.

tetracyclin:

Using tetracycline and hydrochlorothiazid increases the risk of increased urea due to tetracyclin. This interaction may not happen to doxycycline.