Instructions Valsakor HD 320 film-coated tablets 320 mg + 25 mg blister No. 28
Composition
active ingredients: 1 film-coated tablet contains 320 mg of valsartan and 25 mg of hydrochlorothiazide;
excipients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, croscarmellose sodium, povidone, colloidal anhydrous silica; hypromellose, titanium dioxide (E 171), macrogol 4000, red iron oxide (E 172) – only in Valsakor H 320.
Dosage form
Film-coated tablets.
Main physicochemical properties:
Valsakor HD 320: oval biconvex tablets, film-coated, light yellow in color, with a notch on one side.
Pharmacotherapeutic group
Angiotensin II antagonists and diuretics. ATX code C09D A03.
Pharmacological properties
Pharmacodynamics
Valsartan/hydrochlorothiazide
The positive effect of valsartan in combination with hydrochlorothiazide on cardiovascular mortality and morbidity is still unknown.
Epidemiological studies have shown that long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular mortality and morbidity.
Valsartan
Valsartan is an active, potent and specific angiotensin II receptor antagonist (ARA II) for oral administration. It acts selectively on the AT1 receptor subtype, which is responsible for the known actions of angiotensin II. When the concentration of angiotensin II in the blood plasma increases after blockade of AT1 receptors, stimulation of unblocked AT2 receptors occurs, which regulate the action of AT1 receptors. Valsartan does not exhibit any agonist activity towards AT1 receptors and has a much higher affinity (approximately 20,000 times) for AT1 receptors than for AT2 receptors. It is not known whether valsartan binds to or blocks other hormone receptors or ion channels that are important in cardiovascular regulation.
Valsartan does not inhibit the activity of angiotensin-converting enzyme (ACE), also known as kininase II, which converts angiotensin I to angiotensin II and catalyzes the breakdown of bradykinin. Since there is no effect on ACE and no increase in bradykinin or substance P levels, it is unlikely that angiotensin II antagonists would be associated with cough.
Administration of valsartan to patients with hypertension results in a reduction in blood pressure without a change in heart rate. In most patients, the onset of antihypertensive action occurs within 2 hours after a single oral dose, and the maximum reduction in blood pressure is achieved within 4-6 hours. The antihypertensive effect lasts for more than 24 hours after dosing. With repeated dosing, the maximum effect is achieved within 2-4 weeks and is maintained during long-term therapy. In combination with hydrochlorothiazide, an additional reduction in blood pressure is achieved.
Abrupt discontinuation of valsartan did not result in the appearance of arterial hypertension or other adverse clinical events.
Hydrochlorothiazide
The point of action of thiazide diuretics is the cortical part of the distal convoluted renal tubules, where receptors are located that are highly sensitive to the action of thiazide diuretics, and where the transport of Na and Cl ions into the distal convoluted tubules is inhibited. The mechanism of action of thiazides is associated with the inhibition of the Na+Cl- pump, which, apparently, occurs due to competition for Cl- transport sites. As a result, the mechanisms of electrolyte reabsorption change: the excretion of sodium and chloride increases to approximately the same extent; as a result of the diuretic effect, a decrease in the volume of circulating plasma is observed with a subsequent increase in renin activity, aldosterone secretion and urinary potassium excretion and, consequently, a decrease in the concentration of potassium in the blood serum. The relationship between renin and aldosterone is mediated by angiotensin II, therefore, concomitant treatment with valsartan, possibly through blockade of the renin-angiotensin-aldosterone system (RAAS), reduces hydrochlorothiazide-induced potassium excretion compared with hydrochlorothiazide monotherapy.
Pharmacokinetics
Valsartan/hydrochlorothiazide
The systemic availability of hydrochlorothiazide is reduced by approximately 30% when co-administered with valsartan. The kinetics of valsartan are not significantly affected by co-administration with hydrochlorothiazide. This apparent interaction does not affect the combined use of valsartan and hydrochlorothiazide, since the clear hypotensive effect of the combination exceeds that achieved with monotherapy with either active substance.
Valsartan
Absorption
After oral administration of valsartan, peak plasma concentrations of valsartan (Cmax) are reached after 2-4 hours. The mean absolute bioavailability is 23%. Food intake reduces the exposure (measured by AUC) of valsartan by approximately 40% and Cmax by approximately 50%, although from approximately 8 hours after administration, plasma concentrations of valsartan are similar in fed and fasted patients. However, this decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect. Therefore, valsartan can be taken regardless of food intake.
The steady-state volume of distribution of valsartan after intravenous administration is approximately 17 liters, indicating that valsartan is not actively distributed into tissues. Valsartan is actively bound to serum proteins (94-97%), particularly albumin.
Biotransformation
Valsartan is biotransformed to a negligible extent, as only 20% of the dose is recovered as metabolites. The hydroxyl metabolite has been detected in plasma at low concentrations (less than 10% of the AUC for valsartan). This metabolite is pharmacologically inactive.
Breeding
Valsartan exhibits multiexponential decay kinetics (t½α <1 hour and t½ß approximately 9 hours). Valsartan is excreted primarily in the feces (approximately 83% of the dose) and urine (approximately 13% of the dose), mainly unchanged. After intravenous administration, the plasma clearance of valsartan is approximately 2 l/h and the renal clearance is 0.62 l/h (approximately 30% of the total clearance). The elimination half-life of valsartan is 6 hours.
Hydrochlorothiazide
Absorption
Absorption of hydrochlorothiazide after oral administration is rapid (tmax approximately 2 hours), with similar absorption profiles for the suspension and tablet formulations. The absolute bioavailability of hydrochlorothiazide is 60-80% after oral administration. Concomitant administration with food has been reported to result in both an increase and a decrease in the systemic bioavailability of hydrochlorothiazide compared with the fasting state. The frequency of these effects is small and of minimal clinical significance. The increase in mean AUC is linear and dose-proportional over the therapeutic dose range. There is no change in the kinetics of hydrochlorothiazide with repeated dosing, and accumulation is minimal with once-daily dosing.
Distribution
The kinetics of distribution and elimination are generally described by a biexponential decline curve. The apparent volume of distribution is 4-8 l/kg. Hydrochlorothiazide in the general circulation binds to serum proteins (40-70%), mainly serum albumin.
Hydrochlorothiazide also accumulates in erythrocytes, approximately 1.8 times higher than plasma levels.
Breeding
More than 95% of the absorbed dose of hydrochlorothiazide is excreted unchanged in the urine. Renal excretion consists of passive filtration and active secretion in the renal tubules. The terminal half-life is 6-15 hours.
Special patient groups
Elderly people
Slightly higher systemic exposure to valsartan was observed in some elderly subjects than in young subjects; however, this has not been shown to have any clinical significance.
Limited data indicate that the systemic clearance of hydrochlorothiazide is reduced in both healthy elderly subjects and elderly subjects with hypertension compared to healthy young volunteers.
Kidney dysfunction
At the recommended dose of valsartan/hydrochlorothiazide, no dose adjustment is required for patients with creatinine clearance 30-70 ml/min.
There are no data for valsartan/hydrochlorothiazide in patients with severe renal impairment (creatinine clearance < 30 ml/min) and patients undergoing dialysis. Valsartan is highly bound to plasma proteins and is not dialysable, whereas hydrochlorothiazide is cleared by dialysis.
Renal clearance of hydrochlorothiazide consists of passive filtration and active tubular secretion. As expected for a substance that is almost entirely excreted by the kidneys, renal function has a marked effect on the kinetics of hydrochlorothiazide.
Liver dysfunction
There are no data on the use of valsartan in patients with severe hepatic impairment. Liver disease does not significantly affect the pharmacokinetics of hydrochlorothiazide.
Indication
Arterial hypertension in patients whose blood pressure is not adequately controlled by monotherapy.
Contraindication
Hypersensitivity to any of the components of the drug; hypersensitivity to sulfonamide derivatives; severe hepatic impairment, cirrhosis and cholestasis; anuria, severe renal impairment (creatinine clearance < 30 ml/min); refractory hypokalemia, hyponatremia, hypercalcemia or symptomatic hyperuricemia; concomitant use of angiotensin receptor antagonists, including valsartan, or ACE inhibitors with aliskiren in patients with diabetes mellitus or renal insufficiency (glomerular filtration rate (GFR) < 60 ml/min/1.73 m2); pregnant women or women planning to become pregnant (see section "Use during pregnancy and lactation").
Interaction with other medicinal products and other types of interactions
Interactions with the combination of valsartan and hydrochlorothiazide
Concomitant use is not recommended.
Lithium
Transient increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors and/or thiazides, including hydrochlorothiazide. Due to insufficient experience with the concomitant use of valsartan and lithium, this combination is not recommended. If the combination proves necessary, monitoring of serum lithium levels is recommended.
Other antihypertensive drugs
The drug may enhance the effect of other antihypertensive drugs (e.g. ACE inhibitors, beta-blockers, calcium channel blockers).
Pressor amines (e.g., noradrenaline, adrenaline)
A reduced response to pressor amines is possible, but this is not sufficient to stop taking them.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day), and nonselective NSAIDs
Concomitant use of angiotensin II receptor blockers (ARBs) with NSAIDs may result in a weakening of the antihypertensive effect. Concomitant use of Valsacor H 320 and Valsacor HD 320 and NSAIDs may increase the risk of worsening renal function and lead to an increase in serum potassium.
Therefore, monitoring of renal function at the beginning of treatment is recommended, as well as adequate fluid intake.
Interactions related to valsartan
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ARA drugs, ACE inhibitors, or aliskiren
When ARBs, including valsartan, are used concomitantly with other RAAS-blocking agents such as ACE inhibitors or aliskiren, the incidence of hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) is increased compared with monotherapy. Dual blockade of the RAAS with ACE inhibitors, ARBs, or aliskiren is not recommended. If dual RAAS blockade is considered absolutely necessary, it should be used only under specialist supervision and with close monitoring of renal function, electrolytes, and blood pressure.
The concomitant use of angiotensin receptor antagonists, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see section 4.3).
Concomitant use is not recommended.
Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, and other substances that may increase potassium levels
Caution should be exercised when concomitantly taking drugs that affect potassium levels. Serum potassium levels should be monitored frequently.
Conveyors
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 or discontinuing concomitant use of these medicinal products.
Lack of interactions
In studies with valsartan, no clinically significant interactions were observed when valsartan was administered with any of the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide. Digoxin and indomethacin may interact with hydrochlorothiazide in Valsacor HD 320 (see Interactions with Hydrochlorothiazide).
Interactions related to hydrochlorothiazide
Concomitant use requiring special precautions
Drugs associated with increased potassium loss and hypokalemia (e.g., kaliuretic diuretics, corticosteroids, laxatives, adrenocorticotropic hormones, amphotericin, carenoxolone, penicillin G, salicylic acid and derivatives).
If these drugs must be prescribed together with the combination of valsartan/hydrochlorothiazide, monitoring of plasma potassium levels is recommended. These drugs may potentiate the effect of hydrochlorothiazide on serum potassium levels.
Drugs capable of inducing ventricular tachycardia "torsades de pointes"
Due to the risk of hypokalemia, hydrochlorothiazide should be used with caution with medicinal products that may induce torsades de pointes, in particular class Ia and III antiarrhythmics and some antipsychotics.
Drugs that affect serum sodium levels
The hyponatremic effect of diuretics may be enhanced by concomitant administration of such drugs as antidepressants, antipsychotics, antiepileptic drugs, etc. Caution is recommended in the long-term use of these drugs.
Drugs that can cause ventricular tachycardia "torsades de pointes":
Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide); Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide); Some neuroleptics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol); Others (e.g. bepridil, cisapride, diphemanil, erythromycin intravenously, halofantrine, mizolastine, pentamidine, terfenadine, vincamine intravenously).
Due to the risk of hypokalemia, hydrochlorothiazide should be administered with caution with drugs that can induce ventricular tachycardia "torsades de pointes".
Cardiac glycosides
Calcium salts and vitamin D
Thiazide diuretics, including hydrochlorothiazide, in combination with vitamin D or calcium salts may cause an increase in serum calcium levels. Concomitant use of thiazide diuretics with calcium salts may cause hypercalcemia in patients predisposed to hypercalcemia (e.g., patients with hyperparathyroidism, malignancy, or conditions associated with vitamin D deficiency) by increasing tubular calcium reabsorption.
Antidiabetic medications (oral agents and insulin)
Thiazides may alter glucose tolerance. Dosage adjustment of antidiabetic agents may be required.
Metformin should be used with caution due to the risk of lactic acidosis caused by probable functional renal failure associated with hydrochlorothiazide.
Beta-blockers and diazoxide
Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta-blockers may increase the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may potentiate the hyperglycemic effect of diazoxide.
Medicines used in the treatment of gout (probenecid, sulfinpyrazone and allopurinol)
There is a need for dose adjustment of antigout drugs, as hydrochlorothiazide may increase serum uric acid levels. If necessary, the dose of probenecid or sulfinpyrazone should be increased. Concomitant administration of thiazide diuretics may increase the frequency of hypersensitivity reactions to allopurinol.
Anticholinergic drugs (e.g., atropine, biperiden)
The bioavailability of thiazide diuretics may be increased by anticholinergic drugs (e.g. atropine, biperiden), in particular due to a decrease in gastric motility and gastric emptying rate. It is also expected that prokinetic drugs, e.g. cisapride, may reduce the bioavailability of thiazide diuretics.
Amantadine
Thiazide diuretics increase the risk of side effects caused by amantadine.
Ion exchange resins
The absorption of thiazide diuretics, including hydrochlorothiazide, is impaired by concomitant administration of cholestyramine or colestipol.
Cytotoxic drugs (e.g., cyclophosphamide, methotrexate)
Thiazides may reduce the renal excretion of cytotoxic drugs and potentiate their myelosuppressive effects.
Nondepolarizing skeletal muscle relaxants (e.g., tubocurarine)
Thiazides, including hydrochlorothiazide, enhance the effect of curare derivatives.
Cyclosporine
Concomitant use with cyclosporine may increase the risk of hyperuricemia and the appearance of symptoms resembling an exacerbation of gout.
Alcohol, barbiturates, or narcotics
Concomitant use of thiazide diuretics with substances that also contribute to lowering blood pressure (e.g. by reducing sympathetic nervous system activity or vasodilating action) may potentiate orthostatic hypotension.
Methyldopa
Cases of hemolytic anemia have been reported with concomitant use of hydrochlorothiazide and methyldopa.
Carbamazepine
Hyponatremia may develop in patients receiving hydrochlorothiazide concomitantly with carbamazepine. Such patients should be informed of the possibility of a hyponatremic reaction and monitored appropriately.
Iodine contrast medium
In case of dehydration due to diuretics, there is an increased risk of acute renal failure, especially with high doses of iodine preparations. Patients should be rehydrated before administration.
Application features
Serum electrolyte imbalance
Valsartan
Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may increase potassium levels (e.g. heparin) is not recommended. Potassium levels should be monitored if necessary.
Hydrochlorothiazide
Hypokalemia has been reported during treatment with thiazide diuretics, including hydrochlorothiazide. Frequent monitoring of serum potassium is recommended.
Treatment with thiazide diuretics, including hydrochlorothiazide, has been associated with hyponatremia and hypochloraemic alkalosis. Thiazides, including hydrochlorothiazide, increase urinary magnesium excretion, which may lead to hypomagnesemia. Thiazide diuretics decrease calcium excretion. This may lead to hypercalcemia.
Periodic serum electrolyte analysis should be performed at appropriate intervals for every patient receiving diuretic therapy.
Patients with sodium and/or volume imbalance
Patients taking thiazide diuretics should be monitored for clinical signs of fluid or electrolyte imbalance.
In case of hypotension, the patient should be placed in the supine position and, if necessary, an intravenous infusion of saline should be given. Treatment may be continued as soon as blood pressure has stabilized.
Patients with severe congestive heart failure or other conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose renal function depends mainly on the activity of the RAAS (e.g. patients with severe congestive heart failure), treatment with agents that act on the RAAS may cause oliguria and/or progressive azotemia, in rare cases with acute renal failure. The safety of Valsacor HD 320 in patients with severe congestive heart failure has not been established.
Therefore, it should not be excluded that renal failure may develop due to inhibition of the RAAS when using Valsakor HD 320.
Valsakor HD 320 should not be used in such patients.
Renal artery stenosis
Valsacor HD 320 should not be used to treat hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, as blood urea and serum creatinine levels may increase in such patients.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism should not use Valsakor HD 320, as their RAAS is not activated.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, special caution should be exercised in patients suffering from aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy.
Kidney dysfunction
No dose adjustment is required for patients with mild to moderate renal impairment and creatinine clearance ≥ 30 ml/min. Valsacor HD 320 should be used with caution in severe renal impairment (creatinine clearance <30 ml/min). Thiazide diuretics may cause azotemia in patients with chronic renal impairment. They are ineffective as monotherapy in severe renal impairment (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.
Kidney transplantation
There is no experience with the safe use of Valsacor HD 320 in patients with a recent kidney transplant.
Liver dysfunction
In patients with mild to moderate hepatic impairment without cholestasis, no dose adjustment is required. However, Valsacor HD 320 should be used with caution. Liver disease does not significantly alter the pharmacokinetic parameters of hydrochlorothiazide.
Angioedema
Angioedema (including laryngeal and glottis swelling resulting in airway obstruction and/or swelling of the face, lips, pharynx and/or tongue) has been reported in patients treated with valsartan, some of whom had a history of angioedema with other drugs, including other ARBs. If angioedema develops, ARB treatment should be discontinued immediately. Re-administration is contraindicated.
Systemic lupus erythematosus
Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics, including hydrochlorothiazide.
Other metabolic disorders
Thiazide diuretics, including hydrochlorothiazide, may impair glucose tolerance and increase serum cholesterol, triglycerides, and uric acid. Dosage adjustment of antidiabetic agents, including insulin, may be required in diabetic patients.
Thiazides may reduce urinary calcium excretion and cause a concomitant and minor increase in serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be a manifestation of latent hyperaldosteronism. Thiazides should be discontinued before testing parathyroid function.
Photosensitivity
Photosensitivity reactions have been reported with thiazide diuretics. If photosensitivity reactions occur during treatment, it is recommended to discontinue treatment. If re-administration of the diuretic is necessary, it is recommended to protect areas that may be exposed to the sun or artificial ultraviolet light.
Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment should be stopped immediately, and, if appropriate, alternative therapy should be started.
General
Caution should be exercised in patients with hypersensitivity to other ARBs. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients with allergies and asthma.
Hydrochlorothiazide has been associated with idiosyncratic reactions resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute decrease in visual acuity or eye pain, usually occurring within hours to 1 week after administration. Untreated acute angle-closure glaucoma may lead to permanent loss of vision.
Hydrochlorothiazide treatment should be discontinued as soon as possible. Urgent medical or surgical attention may be required if intraocular pressure remains uncontrolled. Risk factors for the development of acute angle-closure glaucoma may include a history of allergy to sulfonamides or penicillins.
Dual blockade of RAAS
Hypotension, syncope, stroke, hyperkalemia and changes in renal function, including acute renal failure, have been observed in susceptible individuals, especially with the combination of drugs that affect this system. Due to dual blockade of the RAAS, the concomitant use of aliskiren and ARA II or ACE inhibitors is not recommended.
Special information about some of the excipients
Valsakor HD 320 contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
No dose adjustment is required for elderly patients.
Hydrochlorothiazide may reduce the level of protein-bound iodine in the blood plasma. Hydrochlorothiazide may increase the concentration of free bilirubin in the blood serum.
Ability to influence reaction speed when driving vehicles or other mechanisms
At the beginning of the use of the drug (the period is determined by the doctor), it is forbidden to drive vehicles and work with other mechanisms. Later, the degree of prohibition is determined by the doctor.
Use during pregnancy or breastfeeding
Pregnancy
Like other drugs that directly act on the RAAS, Valsakor HD 320 is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is detected during therapy, the drug should be discontinued immediately and, if necessary, replaced with another drug approved for use in pregnant women.
Ang II antagonists may cause fetal damage similar to that caused by ACE inhibitors.
It is known that the use of ACE inhibitors during the second and third trimesters of pregnancy can cause fetal damage and death. Hydrochlorothiazide crosses the placenta. Intrauterine exposure to thiazide diuretics may lead to thrombocytopenia in the fetus or newborn and may be associated with other adverse reactions that occur in adults.
Breastfeeding period
If use of the drug is clearly necessary, breast-feeding should be discontinued. Alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant. There is no information regarding the use of valsartan during breast-feeding. Hydrochlorothiazide is excreted in human milk in small quantities. Thiazides in high doses cause diuresis, which may suppress milk production.
Method of administration and doses
Dosage
The recommended dose of Valsacor HD 320 is 1 tablet per day. Titration of the individual components is recommended. In each case, the increase to the next dose by titration of the individual components should be monitored to reduce the risk of arterial hypotension and other side effects.
When clinically appropriate, direct transfer from monotherapy to the fixed combination may be considered for patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy, respectively, provided that the recommended dose titration sequence for the individual components is followed.
The clinical response to Valsacor H 320 should be assessed after initiation of therapy. If adequate blood pressure reduction is not achieved, patients should be switched to Valsacor HD 320.
The maximum daily dose is 320 mg/25 mg.
The antihypertensive effect is mainly observed in the first 2 weeks of treatment.
In most patients, the maximum effect is observed within 4 weeks. However, some patients may require 4-8 weeks of treatment. This should be taken into account when titrating the dose.
If no relevant additional effect is observed after 8 weeks of taking Valsacor HD 320, a decision should be made to treat with an additional or alternative antihypertensive drug.
Application method
Valsakor HD 320 can be taken regardless of meals, washing down the tablets with water.
No dose adjustment is required for patients with mild to moderate renal impairment (GFR ≥ 30 ml/min). Due to the hydrochlorothiazide content, the drug is contraindicated in patients with severe renal impairment (GFR < 30 ml/min) and anuria (see sections 4.3, 4.5 and 5.2). Concomitant use with aliskiren is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m2) (see section 4.3).
Liver dysfunction
In patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg (see section 4.4). No dose adjustment of hydrochlorothiazide is required in patients with mild to moderate hepatic impairment. Due to the valsartan content, the drug is contraindicated in patients with severe hepatic impairment or biliary cirrhosis and cholestasis (see sections 4.4, 4.4 and 5.2).
Diabetes mellitus
The concomitant use of valsartan and aliskiren is contraindicated in patients with diabetes mellitus (see section "Contraindications").
Elderly patients
No dose adjustment is required for elderly patients.
Children
Valsakor HD 320 is not recommended for use in children due to lack of data on safety and efficacy.
Overdose
Symptoms
Overdose with valsartan may lead to marked hypotension, which may lead to depression of consciousness, circulatory collapse and/or shock. The following signs and symptoms may also occur due to overdose with hydrochlorothiazide: nausea, drowsiness, hypovolemia and electrolyte imbalance, which are accompanied by cardiac arrhythmias and muscle spasms. The most characteristic signs and symptoms of overdose are also tachycardia, hypotension, shock, weakness, confusion, dizziness, muscle spasms, paresthesia, exhaustion, impaired consciousness, vomiting, thirst, polyuria, oliguria, anuria, alkalosis, increased blood urea nitrogen (mainly renal failure).
Treatment
Therapeutic measures depend on the time of administration and the type and severity of symptoms; the most important thing is to stabilize the circulatory status.
If hypotension occurs, the patient should be placed in the supine position and blood volume and salt balance should be corrected.
Valsartan cannot be removed by hemodialysis due to its strong binding to plasma proteins, while hydrochlorothiazide can be removed by dialysis.
Adverse reactions
Adverse reactions that occurred more frequently with valsartan and hydrochlorothiazide than with placebo, as reported in clinical trials and laboratory observations, as well as isolated postmarketing reports, are presented below by organ system. Adverse reactions that occurred with each component alone but were not observed in clinical trials may occur during treatment with valsartan and hydrochlorothiazide.
Adverse reactions are classified according to frequency of occurrence: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); unknown (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Frequency of adverse reactions when taking valsartan/hydrochlorothiazide
Infections
Uncommon: viral infections, fever.
Metabolism and nutrition
Uncommon: dehydration.
Not known: hypokalemia, hyponatremia.
From the nervous system
Very common: headache, fatigue.
Uncommon: asthenia, dizziness, insomnia, anxiety, paresthesia.
Rare: depression.
Not known: loss of consciousness (syncope).
From the organs of vision
Uncommon: blurred vision
