Valsartan, Hydrochlorothiazide

Pharmacological properties

Diocor is an antihypertensive drug, which includes an angiotensin II receptor antagonist and a thiazide diuretic.

The active hormone of the renin-angiotensin-aldosterone system is angiotensin II, which is formed from angiotensin I with the participation of ACE. Angiotensin II binds to specific receptors located on cell membranes in different tissues. It has a wide range of physiological effects, including both direct and indirect participation in the regulation of blood pressure. As a powerful vasoconstrictor, angiotensin II causes a direct vasopressor effect. In addition, it stimulates the secretion of aldosterone and promotes sodium retention.

Valsartan is an active and specific angiotensin II receptor antagonist intended for oral administration. It acts selectively on AT subtype receptors₁responsible for the effects of angiotensin II. Any partial agonistic activity against receptors of the subtype AT_{1 in}Alsartan does not show. Valsartan affinity for AT subtype receptors_{1 p} approximately 20,000 times higher than for AT subtype receptors₂.

Valsartan does not inhibit ACE (kininase II), which converts angiotensin I to angiotensin II and destroys bradykinin. No side effects due to bradykinin are noted. In clinical trials that compared valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower in patients using valsartan than in patients using an ACE inhibitor. Valsartan does not interact and does not block receptors of other hormones or ion channels, which play an important role in the regulation of the function of the cardiovascular system.

In patients with hypertension, the drug causes a decrease in blood pressure, without affecting heart rate.

In most patients, after taking a single dose of the drug, the onset of antihypertensive activity is noted within 2 hours, and the maximum decrease in blood pressure is achieved after 4-6 hours. The antihypertensive effect persists for more than 24 hours after taking a single dose of Diocor. With the regular use of the drug, the maximum therapeutic effect is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. When combined with hydrochlorothiazide, a more effective decrease in blood pressure is achieved.

The point of application of the action of thiazide diuretics is the cortical layer of the distal sinuous renal tubules, where receptors are located that are highly sensitive to the action of diuretics, and the transport of sodium and chlorine ions is inhibited. The mechanism of action of thiazides is associated with inhibition of the Na pump⁺Cl^–what happens due to competition for transport places Cl^–. As a result, the excretion of sodium and chlorine ions increases approximately equally. Due to the diuretic action, a decrease in the volume of circulating blood plasma is noted, resulting in increased renin activity, aldosterone secretion, excretion of potassium in urine, and as a result, a decrease in the concentration of potassium in blood plasma. The relationship between renin and aldosterone is mediated by angiotensin II, therefore, the use of the angiotensin II receptor antagonist reduces the potassium loss associated with the use of a thiazide diuretic.

Pharmacokinetics After oral administration, absorption of valsartan and hydrochlorothiazide occurs rapidly, but the degree of absorption varies widely. The average absolute bioavailability of Diocor is 23%.

Valsartan. In the range of doses studied, the kinetics of valsartan is linear. With repeated use of the drug, no changes in kinetic parameters were noted. When taking the drug 1 time per day, cumulation is negligible.

Valsartan to a large extent (94–97%) binds to plasma proteins, mainly with albumin. The equilibrium distribution volume is low (≈17 L). Excretion of valsartan with feces is 70% (of the oral dose). ≈30% is excreted in the urine, mainly unchanged.

When using valsartan with food, AUC decreases by 48%, although, starting from about 8 hours after taking the drug, its concentration in blood plasma both during fasting and during meals is the same. The decrease in AUC is not accompanied by a significant decrease in the therapeutic effect.

Hydrochlorothiazide. After oral administration, the absorption of hydrochlorothiazide occurs very quickly (t_max - about 2 hours). The pharmacokinetics of the drug in the phases of distribution and excretion is described as a whole by a biexponential downward curve; T_½ final phase - 6-15 hours

In the therapeutic dose range, the average AUC increases in direct proportion to the dose increase. With repeated use, the pharmacokinetics of hydrochlorothiazide does not change; when applied once a day, cumulation is negligible.

When administered, the bioavailability of hydrochlorothiazide is 60–80%. Excreted in urine: 95% of the dose unchanged and ≈4% in the form of a hydrolyzate of 2-amino-4-chloro-m-benzenedisulfonamide.

With the simultaneous administration of hydrochlorothiazide with food, both an increase and a decrease in its systemic bioavailability were noted compared with the corresponding indicator when taken on an empty stomach. The range of these changes is small and clinically insignificant.

Valsartan / hydrochlorothiazide. With simultaneous administration with valsartan, the systemic bioavailability of hydrochlorothiazide decreases by ≈30%. The simultaneous use of hydrochlorothiazide does not significantly affect the kinetics of valsartan. The specified interaction does not affect the effectiveness of the combined use of valsartan and hydrochlorothiazide. In controlled clinical trials, a clear antihypertensive effect of this combination was revealed, which exceeded that of each of the components separately, as well as the placebo effect.

Indications

Ag in patients in whom monotherapy is ineffective.

Application

The recommended dose of the drug is 1 tablet 80 mg / 12.5 mg (Diocor 80) 1 time per day. with an insufficient decrease in hell after 3-4 weeks of treatment, it is recommended to consider the possibility of continuing treatment at a dosage of 1 tablet 160 mg / 12, 5 mg (Diocor 160) 1 time per day. the maximum daily dose is 320 mg / 25 mg. maximum antihypertensive effect is achieved within 2-4 weeks of use. the drug can be taken regardless of food intake, washed down with a small amount of water.

In case of impaired renal function. For patients with mild to moderate impaired renal function (creatinine clearance 30 ml / min), dose adjustment is not required.

With impaired liver function. For patients with minor and moderate hepatic insufficiency of non-biliary origin and without cholestasis, the dose of valsartan should not exceed 80 mg, the drug should be prescribed with caution.

Elderly patients. For elderly patients, dose adjustment is not required.

The duration of the drug is determined by the doctor individually.

Contraindications

Hypersensitivity to any of the components of the drug and other drugs that are derivatives of sulfonamide.

Severe liver dysfunction, biliary cirrhosis and cholestasis.

Severe renal impairment (creatinine clearance 30 ml / min), anuria.

Refractory hypokalemia, hyponatremia, hypercalcemia, symptomatic hyperuricemia. Pregnant women and women planning a pregnancy (see Use during pregnancy and lactation).

The simultaneous use of angiotensin receptor antagonists, including valsartan, or angiotensin-converting enzyme inhibitors with aliskiren in patients with diabetes mellitus or impaired renal function (glomerular filtration rate of 60 ml / min / 1.73 m²).

Side effects

Adverse reactions are generally mild and transient in nature and are given below.

From the cardiovascular system: tachycardia, arterial hypotension, vasculitis.

From the blood system: neutropenia, thrombocytopenia.

From the nervous system: headache, dizziness, hypesthesia, paresthesia, syncope, insomnia, drowsiness.

On the part of the organ of hearing: noise / ringing in the ears, vertigo, otitis media.

From the side of the organ of vision: visual impairment.

From the respiratory system: nasopharyngitis, cough, nasal congestion, bronchitis, acute bronchitis, chest pain, shortness of breath, pharyngolaryngeal pain, sinusitis, very rarely - pulmonary edema with granulocyte infiltration and deposition of IgG in the alveolar membranes associated with the use of hydrochlorothiazide. Non-cardiogenic pulmonary edema can be immunologically mediated by an idiosyncratic reaction to hydrochlorothiazide, which is rare.

From the digestive system: diarrhea, abdominal pain, dyspepsia, dry mouth, gastroenteritis, nausea, isolated cases of increased liver function.

Metabolic disorders: hyperkalemia, dehydration.

From the genitourinary system: pollakiuria, very rarely - impaired renal function, acute renal failure, urinary tract infection, decreased libido.

On the part of the skin and subcutaneous tissue: increased sweating, rash, itching.

From the immune system: hypersensitivity reactions / allergies, including serum sickness.

From the musculoskeletal system: back pain, arthralgia, muscle cramps, muscle strain, neck pain, limb pain, sprain, myalgia, arthritis.

Common disorders: fatigue, nervousness, asthenia, fever, viral infections, edema, peripheral edema, angioedema.

Laboratory indicators: hypokalemia, hyponatremia, an increase in the level of bilirubin, creatinine and urea nitrogen, a decrease in hemoglobin and hematocrit.

Other adverse reactions characteristic of hydrochlorothiazide may also be potential for Diocore, even if they were not observed with the use of the combined drug (valsartan / hydrochlorothiazide).

Hydrochlorothiazide is widely used for many years, and more often it is used in a dose exceeding that of Diocor. During monotherapy with thiazide diuretics, including hydrochlorothiazide, some adverse reactions may occur.

Changes in electrolytes and metabolism. The development of hypokalemia in the treatment of thiazide diuretics has been reported. When thiazide diuretics are used, hypercalcemia, hyponatremia and hypochloremic alkalosis can develop, which can induce hepatic encephalopathy or hepatic coma. Thiazides cause increased urinary excretion of magnesium, which can lead to hypomagnesemia. Thiazide diuretics can cause an increase in the concentration of cholesterol, triglycerides and uric acid in the blood plasma, which can provoke gout attacks in patients with asymptomatic disease. A decrease in glucose tolerance is possible, which can cause a manifestation of latent diabetes mellitus.

Other possible adverse reactions

From the cardiovascular system: arrhythmia, heart failure, postural hypotension, the severity of which increases with alcohol, the use of drugs for anesthesia or sedatives; nosebleeds.

From the blood system: thrombocytopenia, sometimes with purpura, very rarely - leukopenia, agranulocytosis, inhibition of bone marrow function, hemolytic anemia, aplastic anemia.

From the psyche: sleep disturbance, depression, confusion, disorientation, mood changes.

From the side of the organ of vision: xanthopsia, acute angle-closure glaucoma.

From the respiratory system: respiratory failure, respiratory distress, pneumonitis.

From the digestive system: loss of appetite, mild nausea and vomiting, gastrointestinal disorders, constipation, thirst, inflammation of the salivary glands, very rarely pancreatitis.

From the hepatobiliary system: cholestasis or jaundice, cholecystitis.

On the part of the skin and subcutaneous tissue: urticaria and other types of rash, eczema, purpura, photosensitivity; very rarely - necrotizing vasculitis and toxic epidermal necrolysis, skin reactions resembling systemic lupus erythematosus, exacerbation of skin manifestations of systemic lupus erythematosus, erythema multiforme.

From the urinary system: interstitial nephritis.

From the reproductive system: impotence.

General disorders: anaphylactic reactions, shock.

special instructions

Changes in the balance of electrolytes. caution should be exercised while using diocor with potassium-sparing diuretics, potassium supplements, potassium-containing substitutes for edible salt, as well as with drugs that can cause an increase in the level of potassium in the blood (for example, heparin).

During treatment with thiazide diuretics, cases of hypokalemia have been reported.

Regular monitoring of serum potassium levels is recommended.

As with any patient receiving diuretic treatment, serum electrolyte levels should be periodically determined at appropriate intervals.

Patients with a deficiency in the body of sodium and / or bcc. In patients with a pronounced deficiency in the body of sodium and / or BCC, for example, those taking diuretics in high doses, occasionally arterial hypotension with clinical manifestations may occur at the beginning of treatment with the drug. Therefore, before starting treatment with Diocor®, it is recommended to correct the content of sodium and / or bcc in the body.

In the case of the development of hypotension, the patient should be moved to a horizontal position and, if necessary, carry out IV infusion of a physiological solution. After stabilization of blood pressure, treatment with Diocor® can be continued.

Patients with severe heart failure or other cases of activation of the renin-angiotensin-aldosterone system. In patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system (for example, in patients with acute coronary insufficiency), treatment with ACE inhibitors can cause oliguria and / or progressive azotemia, and in some cases lead to the development of acute renal failure. The use of the drug in patients with severe chronic heart failure is not justified, since it cannot be ruled out that, due to the suppression of the renin-angiotensin-aldosterone system, the use of valsartan may also be associated with impaired renal function.

Primary hyperaldosteronism. The drug should not be used in patients with primary hyperaldosteronism, since their renin-angiotensin system is not activated.

Aortic and mitral stenosis, obstructive hypertrophic cardiomyopathy. As with other vasodilators, you should be especially careful when using the drug in patients with aortic and mitral stenosis or obstructive hypertrophic cardiomyopathy.

Renal artery stenosis. In patients with unilateral or bilateral renal artery stenosis, or stenosis of a single kidney artery, valsartan can lead to an increase in plasma creatinine or blood urea, therefore, this category of patients should not be used.

Impaired renal function. When prescribing the drug to patients with mild or moderate impaired renal function (creatinine clearance ≥30 ml / min), dose adjustment is not required, however, periodic monitoring of the potassium content in blood plasma, creatinine and uric acid is recommended. Thiazide diuretics can provoke azotemia in patients with chronic renal impairment. They are ineffective as monotherapy for severe renal failure (creatinine clearance 30 ml / min), but they can be used with proper care in combination with loop diuretics even in patients with creatinine clearance 30 ml / min.

The simultaneous use of angiotensin receptor antagonists, including valsartan, or angiotensin converting enzyme inhibitors with aliskiren in patients with impaired renal function (glomerular filtration rate of 60 ml / min / 1.73 m²) is contraindicated. Kidney transplantation.There is no data on the safety of valsartan in patients with recent kidney transplantation.

Systemic lupus erythematosus. There are reports that thiazide diuretics can exacerbate systemic lupus erythematosus.

Other metabolic disorders. Thiazide diuretics can cause a change in glucose tolerance, as well as an increase in the concentration of cholesterol, triglycerides and uric acid in the blood. Diabetic patients may need a dose adjustment of insulin or oral hypoglycemic agents.

Thiazides can reduce urinary calcium excretion and lead to intermittent and a slight increase in serum calcium levels in the absence of known impaired calcium metabolism. Significant hypercalcemia may indicate latent hyperparathyroidism. The use of thiazides should be discontinued before the parathyroid function test.

Impaired liver function. In patients with mild to moderate hepatic impairment without cholestasis, dose adjustment is not required. However, the drug should be taken with caution. Liver diseases do not significantly change the pharmacokinetic parameters of hydrochlorothiazide.

Photosensitivity. There have been reports of photosensitization with thiazide diuretics. If a photosensitivity reaction occurs during treatment, discontinue treatment with the drug. If there is a need for repeated administration of a diuretic, it is recommended to protect vulnerable areas from the sun or artificial ultraviolet radiation.

Are common. You should be especially careful when using the drug in patients who have been hypersensitive to other angiotensin II receptor antagonists. Allergic reactions to hydrochlorothiazide are most likely to occur in patients with allergies and AD.

Angioneurotic edema. The occurrence of Quincke edema (including swelling of the larynx and glottis, which leads to airway obstruction, and / or swelling of the face, lips, pharynx, and / or tongue) has been reported in patients receiving valsartan. Some of them had a history of Quincke edema when using other drugs, including other angiotensin II receptor antagonists. With the development of Quinckes edema, treatment with the drug should be stopped immediately. Repeated use of the drug is contraindicated.

Acute angle-closure glaucoma. The use of hydrochlorothiazide, sulfonamide was associated with the occurrence of an idiosyncratic reaction, which can lead to acute transient myopia and acute angle-closure glaucoma. A sharp decrease in visual acuity or pain in the eyes is noted. This symptomatology usually lasts for several hours a week with the use of the drug. Untreated glaucoma can lead to irreversible loss of vision. Stop using the drug immediately. A risk factor for the development of acute angle-closure glaucoma is an allergic reaction to the use of sulfonamide or penicillin. Hydrochlorothiazide may decrease plasma protein bound iodine levels.

Hydrochlorothiazide is able to increase the concentration of free bilirubin in the blood serum.

Use during pregnancy and lactation. Pregnancy. Valsartan. The use of angiotensin II receptor antagonists is contraindicated in pregnant women and women planning a pregnancy. Women planning a pregnancy should be prescribed alternative antihypertensive therapy with an established safety profile regarding use during pregnancy. If pregnancy is detected during the treatment with Diocor, the drug should be immediately discontinued and, if necessary, replaced with another drug approved for use in pregnant women.

Given the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus cannot be ruled out when Diocor is used in the first trimester. It is known that the use of angiotensin II receptor antagonists during the II and III trimester can induce fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia).

If angiotensin II receptor antagonists have been used since the second trimester of pregnancy, ultrasound monitoring of kidney and skull function is recommended. Infants whose mothers have taken angiotensin II receptor antagonists need careful observation regarding hypotension.

Hydrochlorothiazide. Hydrochlorothiazide crosses the placental barrier. Based on the pharmacological mechanisms of action of hydrochlorothiazide, its use in the II and III trimester of pregnancy can lead to impaired fetoplacental circulation and cause effects in the fetus and newborn, such as jaundice, electrolyte imbalance and thrombocytopenia.

The period of breastfeeding. It is not known whether valsartan passes into breast milk. Hydrochlorothiazide passes into breast milk in an insignificant amount. Thiazides in high doses cause diuresis, which can lead to a decrease in the production of breast milk. During breastfeeding, alternative treatment methods with a more studied safety profile regarding use during breastfeeding should be preferred.

If the use of the drug is absolutely necessary, breast-feeding should be discontinued.

Children. The safety and effectiveness of Diocor in children have not been established, therefore, the drug should not be used in pediatric practice.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. At the beginning of drug therapy (1-2 days), one should refrain from driving vehicles or working with other mechanisms. In the future, it must be borne in mind that the reaction rate can be reduced in the presence of symptoms such as dizziness, headache, fatigue, or nausea.

Interactions

Interactions associated with the combination of valsartan / hydrochlorothiazide

Concomitant use is not recommended.

Lithium. With the simultaneous use of lithium preparations with ACE inhibitors or thiazide diuretics, including hydrochlorothiazide, a reversible increase in plasma lithium concentration and toxicity was noted. There is no experience with the simultaneous use of Wild and lithium preparations, so this combination is not recommended. If the use of the drug is still necessary, it is recommended that the concentration of lithium in the blood plasma be monitored with their simultaneous use.

Concomitant use requiring special care

Other antihypertensive drugs. It is possible to enhance the antihypertensive effect with the combined use of Diocor with other antihypertensive drugs (for example, ACE inhibitors, β-adrenergic receptor blockers, calcium channel blockers).

Pressor amines (e.g. norepinephrine, epinephrine). A decrease in response to pressor amines may be noted, but not so much as to preclude use.

NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid 3 g / day and non-selective NSAIDs. It is possible to reduce the antihypertensive effect of both an angiotensin II antagonist and a thiazide component while using it with NSAIDs (for example, salicylic acid derivatives, indomethacin). The simultaneous use of these drugs can lead to a decrease in kidney function and an increase in the level of potassium in the blood plasma.Therefore, it is recommended to monitor renal function during treatment, as well as control the adequate hydration of the patient.

Valsartan-related interactions

Concomitant use is not recommended.

Double blockade of RAAS by drugs of angiotensin receptor antagonist groups (ARA), ACE inhibitors or aliskiren. Caution should be exercised while using ARA drugs, including valsartan, with other drugs that block RAAS, such as drugs from the ACE inhibitor group or aliskiren.

The simultaneous use of angiotensin receptor antagonists, including valsartan, or ACE inhibitors with aliskiren in patients with diabetes mellitus or in patients with impaired renal function (glomerular filtration rate (GFS) 60 ml / min / 1.73 m²) is contraindicated.

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that can increase the level of potassium in the blood plasma. Caution should be exercised and often control the potassium content in blood plasma if necessary, the use of drugs that affect the level of potassium in combination with valsartan.

Conveyors. According to the results of in vitro studies, valsartan is a substrate for the liver transporter of capture OATP1B1 / OATP1B3 and the liver conveyor excretion MRP2. The clinical significance of these data is unknown. The simultaneous use of capture transporter inhibitors (e.g. rifampicin, cyclosporin) or excretion transporters (e.g. ritonavir) can increase the systemic exposure of valsartan. Appropriate measures should be taken at the beginning and at the end of the concomitant use of these medicines.

No interactions. No clinically significant interactions were observed during monotherapy with valsartan when using such drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.

Digoxin and indomethacin can interact with hydrochlorothiazide in the combination of valsartan / hydrochlorothiazide.

Interactions associated with hydrochlorothiazide

Concomitant use requiring special care. The risk of developing hypokalemia increases with the simultaneous use of saluretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G and salicylic acid derivatives. These drugs can enhance the effect of hydrochlorothiazide on the level of potassium in the blood, so it is necessary to control the content of potassium in the blood.

Medicines that can cause ventricular tachycardia of the pirouette type: antiarrhythmic drugs of class Ia (quinidine, disopyramide); class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide); certain antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazin, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol); others (for example, bepridil, cisapride, difemanil, erythromycin for iv administration, halofantrine, ketanserin, misolastine, pentamidine, sparfloxacin, terfenadine, vincamine for iv administration).

Because of the risk of hypokalemia, hydrochlorothiazide should be used with caution with the indicated drugs.

Cardiac glycosides. Thiazide diuretics can cause side effects such as hypokalemia or hypomagnesemia, which, in turn, increase the risk of arrhythmias with glycoside intoxication.

Calcium salts and vitamin D. When used simultaneously with vitamin D or calcium salts, potentiation of increased plasma levels of calcium is possible.

Antidiabetic agents (oral medications, insulin).Thiazide diuretics can cause a change in glucose tolerance. A dose adjustment of insulin or oral hypoglycemic drugs in patients with diabetes may be required. The simultaneous use of metformin and hydrochlorothiazide with functional renal failure may lead to the development of metabolic acidosis.

Β-adrenergic blockers and diazoxide. The simultaneous use of thiazide diuretics, including hydrochlorothiazide, with β-adrenergic blockers can increase the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may increase the hyperglycemic effect of diazoxide.

Medicines used to treat gout (probenecid, sulfinpyrazone and allopurinol). A dose adjustment of uricosuric agents that stimulate the excretion of uric acid may be required, since hydrochlorothiazide can increase the level of uric acid in blood plasma. An increase in the dose of probenecid or sulfinpyrazone may be required.

The simultaneous use of thiazide diuretics can increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergics (e.g. atropine, biperiden). An increase in the bioavailability of a thiazide diuretic is observed with the simultaneous use of cholinergic receptor blockers (for example, atropine, biperidene), which is possibly associated with a decrease in the motor activity of the digestive tract and delayed gastric emptying.

Amantadine. Thiazides, including hydrochlorothiazide, may increase the risk of side effects of amantadine.

Cholestyramine and cholesterol. The absorption of hydrochlorothiazide is impaired in the presence of anion exchange resins. Colestyramine slows down the absorption of thiazide diuretics.

Cytotoxic drugs (e.g. cyclophosphamide, methotrexate). Decreased renal excretion of cytotoxic drugs (e.g. cyclophosphamide, methotrexate) can lead to potentiation of their myelosuppressive effect.

Non-depolarizing muscle relaxants (e.g. tubocurarine). Thiazides potentiate the effect of curariform muscle relaxants.

Cyclosporin. The simultaneous use of cyclosporine may increase the risk of developing hyperuricemia and the appearance of symptoms resembling exacerbation of gout.

Alcohol, anesthetics and sedatives. May increase the severity of orthostatic hypotension.

Methyldopa. Cases of the development of hemolytic anemia with the simultaneous use of a thiazide diuretic and methyldopa have been reported.

Carbamazepine. The risk of hyponatremia may increase. We need clinical monitoring of the patients condition and laboratory blood control.

Contrast agents containing iodine. With dehydration caused by diuretics, the risk of acute renal failure may increase, especially with the introduction of a contrast agent in high doses. Before the introduction of iodine, it is necessary to restore the water balance.

Overdose

There are no data on cases of overdose of diocore.

The main manifestation of an overdose can be severe arterial hypotension, which, in turn, can lead to impaired consciousness, heart failure and / or shock.

In case of an overdose of hydrochlorothiazide, the following signs and symptoms may occur: nausea, drowsiness, hypovolemia, electrolyte disturbances associated with arrhythmia and muscle cramps. Characteristic signs of an overdose are also tachycardia, weakness, confusion, dizziness, paresthesia, exhaustion, vomiting, thirst, polyuria, oliguria, anuria, alkalosis, elevated levels of urea nitrogen in the blood (mainly renal failure).

If the drug has been taken recently, you should induce vomiting or gastric lavage. The primary concern is the stabilization of blood circulation.If arterial hypotension occurs, the patient should be given a supine position and as soon as possible to replenish the content of salts and fluids in the body. Valsartan cannot be excreted by hemodialysis due to significant binding to plasma proteins, although hemodialysis is effective for removing hydrochlorothiazide from the body.

Storage conditions

Out of the reach of children in the original packaging at a temperature of no higher than 25 ° C.

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