Diocor film-coated tablets 160 mg/12.5 mg 30 pieces

Pharmacodynamics. Diocor is an antihypertensive drug that contains 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 various tissues. It has a wide range of physiological effects, including both direct and indirect participation in the regulation of blood pressure. As a potent 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 for oral administration. It acts selectively on the AT1 receptor subtype _, which is responsible for the effects of angiotensin II. Valsartan does not exhibit any partial agonist activity at AT1 receptors _{. The affinity of valsartan for AT1} receptors is approximately 20,000 times higher than for AT2 receptors _.

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

In patients with hypertension, the drug causes a decrease in blood pressure without affecting the pulse 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 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 reduction in blood pressure is achieved.

The point of action of thiazide diuretics is the cortical layer of the distal convoluted 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 the inhibition of the Na ⁺ Cl ^{– pump,} which occurs due to competition for Cl ^{– transport sites.} As a result, the excretion of sodium and chlorine ions increases approximately equally. As a result of the diuretic effect, there is a decrease in the volume of circulating blood plasma, as a result of which renin activity, aldosterone secretion, urinary potassium excretion and, as a result, a decrease in the concentration of potassium in the blood plasma increase. The relationship between renin and aldosterone is mediated by angiotensin II, therefore the use of an angiotensin II receptor antagonist reduces the loss of potassium associated with the use of hydrochlorothiazide.

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

Valsartan. In the range of doses studied, the kinetics of valsartan are linear. With repeated use of the drug, no changes in kinetic parameters were observed. When taking the drug once a day, cumulation is insignificant.

Valsartan is highly bound (94-97%) to plasma proteins, mainly albumin. The equilibrium volume of distribution is low (≈17 l). The excretion of valsartan with feces is 70% (of the administered dose). ≈30% is excreted in the urine, mainly unchanged.

When valsartan is administered with food, the AUC is reduced by 48%, although starting approximately 8 hours after administration, its plasma concentration is the same in both the fasted and fed state. The decrease in AUC is not accompanied by a significant decrease in the therapeutic effect.

Hydrochlorothiazide. After oral administration, the absorption of hydrochlorothiazide is very rapid (t _max – about 2 hours). The pharmacokinetics of the drug in the distribution and elimination phases are generally described by a biexponential descending curve; T _½ of the final phase is 6-15 hours.

In the therapeutic dose range, the mean AUC increases in direct proportion to the increase in dose. The pharmacokinetics of hydrochlorothiazide do not change with repeated administration; with once-daily administration, cumulation is insignificant.

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

When hydrochlorothiazide is taken with food, both an increase and a decrease in its systemic bioavailability have been observed compared with the corresponding figure when taken in the fasted state. The range of these changes is small and clinically insignificant.

Valsartan / hydrochlorothiazide. When co-administered with valsartan, the systemic bioavailability of hydrochlorothiazide is reduced by ≈30%. Co-administration of hydrochlorothiazide does not significantly affect the kinetics of valsartan. This interaction does not affect the efficacy of the combined use of valsartan and hydrochlorothiazide. Controlled clinical trials have shown a clear antihypertensive effect of this combination, which exceeded that of each component separately, as well as the effect of placebo.

Ag in patients in whom monotherapy is ineffective.

The recommended dose of the drug is 1 tablet of 80 mg / 12.5 mg (Diocor 80) 1 time per day. If the blood pressure is not reduced sufficiently after 3-4 weeks of treatment, it is recommended to consider continuing treatment at a dosage of 1 tablet of 160 mg / 12.5 mg (Diocor 160) 1 time per day. The maximum daily dose is 320 mg / 25 mg. The maximum antihypertensive effect is achieved within 2-4 weeks of use. The drug can be taken regardless of meals, washed down with a small amount of water.

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

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

Elderly patients: No dosage adjustment is required for elderly patients.

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

Hypersensitivity to any of the components of the drug and other sulfonamide-derived drugs.

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 pregnancy (see Use during pregnancy and lactation).

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

Adverse reactions are generally mild and transient and are listed below.

Cardiovascular system: tachycardia, hypotension, vasculitis.

From the blood system: neutropenia, thrombocytopenia.

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

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

On the part of the organ of vision: visual impairment.

Respiratory system: nasopharyngitis, cough, nasal congestion, bronchitis, acute bronchitis, chest pain, shortness of breath, pharyngolaryngeal pain, sinusitis, very rarely – pulmonary edema with granulocytic infiltration and IgG deposition in alveolar membranes, associated with the use of hydrochlorothiazide. Noncardiogenic pulmonary edema may be immunologically mediated by an idiosyncratic reaction to hydrochlorothiazide, which occurs rarely.

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

Metabolic disorders: hyperkalemia, dehydration.

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

Skin and subcutaneous tissue disorders: increased sweating, rash, itching.

Immune system disorders: hypersensitivity/allergic reactions, including serum sickness.

Musculoskeletal system: back pain, arthralgia, muscle cramps, muscle strain, neck pain, pain in extremities, sprain, muscle pain, arthritis.

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

Laboratory indicators: hypokalemia, hyponatremia, increased bilirubin, creatinine, and urea nitrogen levels, decreased hemoglobin and hematocrit.

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

Hydrochlorothiazide has been widely used for many years, and doses exceeding those contained in Diocor are often used. When performing monotherapy with thiazide diuretics, including hydrochlorothiazide, some adverse reactions may occur.

Electrolyte and metabolic changes. Hypokalemia has been reported with thiazide diuretics. Thiazide diuretics may cause hypercalcemia, hyponatremia, and hypochloremic alkalosis, which may induce hepatic encephalopathy or hepatic coma. Thiazides cause increased urinary excretion of magnesium, which may lead to hypomagnesemia. Thiazides may increase plasma cholesterol, triglycerides, and uric acid, which may precipitate gout attacks in asymptomatic patients. Impaired glucose tolerance may occur, which may result in the manifestation of latent diabetes mellitus.

Other possible side effects

Cardiovascular system: arrhythmia, heart failure, postural hypotension, the severity of which increases with alcohol consumption, the use of anesthetics or sedatives; nosebleeds.

From the blood system: thrombocytopenia, sometimes with purpura, very rarely – leukopenia, agranulocytosis, bone marrow suppression, hemolytic anemia, aplastic anemia.

Mental disorders: sleep disturbances, depression, confusion, disorientation, mood swings.

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

Respiratory system: respiratory failure, respiratory distress, pneumonitis.

On the part of the digestive system: loss of appetite, moderately pronounced nausea and vomiting, disorders of the gastrointestinal tract, constipation, feeling of thirst, inflammation of the salivary glands, very rarely – pancreatitis.

From the hepatobiliary system: cholestasis or jaundice, cholecystitis.

Skin and subcutaneous tissue disorders: 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.

Changes in electrolyte balance. Caution should be exercised when using Diocor simultaneously with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, as well as with drugs that may cause an increase in potassium levels in the blood (e.g. heparin).

Cases of hypokalemia have been reported during treatment with thiazide diuretics.

Regular monitoring of serum potassium levels is recommended.

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

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

In case of hypotension, the patient should be placed in a horizontal position and, if necessary, an intravenous infusion of saline should be given. 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 may cause oliguria and / or progressive azotemia, 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 excluded that due to 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, special caution should be exercised 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 the artery to a solitary kidney, valsartan may lead to increases in plasma creatinine or blood urea and should not be used in this category of patients.

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

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

Systemic lupus erythematosus: Thiazide diuretics have been reported to cause exacerbation of systemic lupus erythematosus.

Other metabolic disorders: Thiazides may cause changes in glucose tolerance and increases in blood cholesterol, triglycerides, and uric acid. Diabetic patients may require adjustment of insulin or oral hypoglycemic agents.

Thiazides may reduce urinary calcium excretion and cause intermittent and small increases in serum calcium in the absence of known disorders of calcium metabolism. Significant hypercalcemia may indicate latent hyperparathyroidism. Thiazides should be discontinued prior to testing for parathyroid function.

Hepatic impairment. In patients with mild to moderate hepatic impairment without cholestasis, no dose adjustment is required. However, the drug should be used with caution. Liver disease does not significantly alter the pharmacokinetic parameters of hydrochlorothiazide.

Photosensitivity. There have been reports of photosensitivity reactions with thiazides. If a photosensitivity reaction occurs during treatment, treatment with the drug should be discontinued. If it is necessary to re-administer the diuretic, it is recommended to protect the affected areas from the sun or artificial ultraviolet radiation.

General: Special caution should be exercised when administering the drug to patients who have shown hypersensitivity to other angiotensin II receptor antagonists. Allergic reactions to hydrochlorothiazide are most likely to occur in patients with allergies and asthma.

Angioedema. Angioedema (including swelling of the larynx and glottis leading to airway obstruction and/or swelling of the face, lips, pharynx and/or tongue) has been reported in patients treated with valsartan. Some of these patients had a history of angioedema with other drugs, including other angiotensin II receptor antagonists. If angioedema develops, treatment with the drug should be discontinued immediately. Re-administration of the drug is contraindicated.

Acute angle-closure glaucoma. The use of hydrochlorothiazide, a sulfonamide has been associated with the occurrence of an idiosyncratic reaction that can lead to acute transient myopia and acute angle-closure glaucoma. There is a sharp decrease in visual acuity or eye pain. These symptoms usually last for several hours per week during the use of the drug. Untreated glaucoma can lead to irreversible loss of vision. The drug should be discontinued immediately. A risk factor for the development of acute glaucoma is an allergic reaction to the use of sulfonamides or penicillins. Hydrochlorothiazide can reduce the level of protein-bound iodine in the blood plasma.

Hydrochlorothiazide is capable of increasing the concentration of free bilirubin in the blood serum.

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

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

Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.

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

Breastfeeding. It is not known whether valsartan is excreted in human milk. Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses cause diuresis, which may lead to a decrease in breast milk production. Alternative treatments with better established safety profiles for use during breastfeeding are preferable.

If the use of the drug is absolutely necessary, breastfeeding should be discontinued.

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

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

Interactions associated with the combination of valsartan/hydrochlorothiazide

Concomitant use is not recommended.

Lithium. When lithium preparations are used simultaneously with ACE inhibitors and thiazides, including hydrochlorothiazide, a temporary increase in plasma lithium concentrations and toxicity has been reported. There is no experience with the simultaneous use of Dicor and lithium preparations, therefore such a combination is not recommended. If the use of the drug is still necessary, it is recommended to check the concentration of lithium in the blood plasma during their simultaneous use.

Concomitant use requiring special precautions

Other antihypertensive drugs. It is possible to enhance the antihypertensive effect when Diocor is used simultaneously with other antihypertensive drugs (e.g. ACE inhibitors, β-adrenergic blockers, calcium channel blockers).

Pressor amines (e.g. noradrenaline, adrenaline): A decreased response to pressor amines may occur, but not to the extent that their use should be excluded.

NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid 3 g/day and non-selective NSAIDs. The antihypertensive effect of both the angiotensin II antagonist and the thiazide component may be reduced when used simultaneously with non-steroidal anti-inflammatory drugs (e.g. salicylic acid derivatives, indomethacin). The simultaneous use of these drugs may lead to a decrease in renal function and an increase in plasma potassium levels. Therefore, monitoring of renal function during treatment is recommended, as well as monitoring of adequate hydration of the patient.

Interactions related to valsartan

Concomitant use is not recommended.

Dual blockade of the RAAS with angiotensin receptor antagonists (ARBs), ACE inhibitors or aliskiren. Caution should be exercised when concomitantly administering ARBs, including valsartan, with other RAAS-blocking agents, such as ACE inhibitors or aliskiren.

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

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that may increase plasma potassium levels. Caution should be exercised and frequent monitoring of plasma potassium levels should be performed if drugs that affect potassium levels are used in combination with valsartan.

Transporters. In vitro studies have shown that valsartan is a substrate for the hepatic uptake transporter OATP1B1/OATP1B3 and the hepatic efflux transporter MRP2. The clinical significance of these findings is unknown. Concomitant use of inhibitors of the uptake transporter (e.g. rifampicin, cyclosporine) or efflux transporter (e.g. ritonavir) may increase systemic exposure to valsartan. Appropriate precautions should be taken when initiating and terminating concomitant use of these medicinal products.

There are no interactions. No clinically significant interactions have been observed during valsartan monotherapy with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.

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

Interactions related to hydrochlorothiazide

Concomitant use requiring special precautions. The risk of hypokalemia is increased by concomitant use of saluretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G and salicylic acid derivatives. These drugs may enhance the effect of hydrochlorothiazide on blood potassium levels, therefore it is necessary to monitor the potassium content in the blood.

Drugs that can cause torsades de pointes: Class Ia antiarrhythmics (quinidine, disopyramide); Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide); Some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol); Others (e.g. bepridil, cisapride, diphemanil, erythromycin for intravenous administration, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine for intravenous administration).

Due to the risk of hypokalemia, hydrochlorothiazide should be used with caution with the following drugs:

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

Calcium salts and vitamin D. When used simultaneously with vitamin D or calcium salts, potentiation of an increase in calcium levels in the blood plasma is possible.

Antidiabetic agents (oral agents, insulin). Thiazides may cause changes in glucose tolerance. It may be necessary to adjust the dose of insulin or oral hypoglycemic agents in patients with diabetes mellitus. Concomitant use of metformin and hydrochlorothiazide in renal insufficiency may lead to the development of metabolic acidosis.

Beta-blockers and diazoxide: Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta-blockers may increase the risk of hyperglycemia. Thiazides, including hydrochlorothiazide, may enhance the hyperglycemic effect of diazoxide.

Medicines used to treat gout (probenecid, sulfinpyrazone and allopurinol). The dose of uricosuric agents that stimulate the excretion of uric acid may need to be adjusted, as hydrochlorothiazide may increase the level of uric acid in the blood plasma. An increase in the dose of probenecid or sulfinpyrazone may be necessary.

Concomitant use of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergics (e.g. atropine, biperiden). Increased bioavailability of thiazide diuretics has been observed with concomitant use of cholinergic blockers (e.g. atropine, biperiden), possibly due to decreased gastrointestinal motility 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. Cholestyramine slows down the absorption of thiazide diuretics.

Cytotoxic drugs (e.g. cyclophosphamide, methotrexate): Reduced renal excretion of cytotoxic drugs (e.g. cyclophosphamide, methotrexate) may lead to potentiation of their myelosuppressive effects.

Non-depolarizing muscle relaxants (e.g. tubocurarine). Thiazides potentiate the action of curare derivatives.

Cyclosporine: Concomitant use of cyclosporine may increase the risk of hyperuricemia and symptoms resembling gout flares.

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

Methyldopa: Cases of hemolytic anemia have been reported with the concomitant use of hydrochlorothiazide and methyldopa.

Carbamazepine. The risk of hyponatremia may increase. Clinical monitoring of the patient’s condition and laboratory blood monitoring are necessary.

Iodine-containing contrast media: Dehydration caused by diuretics may increase the risk of acute renal failure, especially when high doses of contrast media are administered. Fluid balance should be restored before iodine administration.

There are no data on cases of Diocor overdose.

The main manifestation of overdose may be marked hypotension, which, in turn, may lead to impaired consciousness, heart failure and/or shock.

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

If the drug has been taken recently, vomiting should be induced or gastric lavage should be performed. The primary task is to stabilize the circulatory system. If hypotension occurs, the patient should be placed in the supine position and the body’s salt and fluid levels should be replenished as quickly as possible. Valsartan cannot be removed by hemodialysis due to its high plasma protein binding, although hemodialysis is effective in removing hydrochlorothiazide.

Keep out of the reach of children in the original packaging at a temperature not exceeding 25 °C.