Instructions Valsakor HD 160 film-coated tablets 160 mg + 25 mg blister No. 84
Composition
active ingredients: valsartan; hydrochlorothiazide;
1 film-coated tablet contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide or 160 mg of valsartan and 12.5 mg of hydrochlorothiazide, or 160 mg of valsartan and 25 mg of hydrochlorothiazide;
Excipients: tablet core – microcrystalline cellulose, lactose monohydrate, magnesium stearate, croscarmellose sodium, povidone, colloidal anhydrous silicon dioxide.
Film coating: hypromellose, titanium dioxide (E 171), macrogol 4000, red iron oxide (E 172), yellow iron oxide (E 172) – only in Valsakor® H 80 and Valsakor® HD 160.
Dosage form
Film-coated tablets.
Main physicochemical properties:
Valsakor® H 80: oval biconvex tablets, film-coated, pink in color;
Valsakor® H 160: oval biconvex tablets, film-coated, red-brown in color;
Valsakor® HD 160: oval biconvex tablets, film-coated, light brown in color.
Pharmacotherapeutic group
Angiotensin II antagonists and diuretics. Valsartan and diuretics. ATC code C09D A03.
Pharmacological properties
Pharmacodynamics.
Valsartan
Valsartan is a specific angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT1 receptor subtype, which is responsible for the known effects of angiotensin II (Ang II). Increased plasma Ang II levels after AT1 receptor blockade by valsartan may stimulate the unblocked AT2 receptor, which balances the effect of the AT1 receptor. Valsartan does not exhibit any partial agonist activity at the AT1 receptor and has a much higher (approximately 20,000-fold) affinity for the AT1 receptor than for the AT2 receptor. It is not known whether valsartan binds to or blocks other hormone receptors or ion channels important in cardiovascular regulation.
Valsartan does not inhibit angiotensin-converting enzyme (ACE), also known as kininase II, which converts Ang I to Ang II and leads to the breakdown of bradykinin. Since there is no effect on ACE and there is no potentiation of bradykinin or substance P, it is unlikely that Ang II antagonists cause cough. The incidence of dry cough is significantly lower in patients receiving valsartan compared with patients receiving ACE inhibitors.
The use of valsartan in patients with arterial hypertension leads to a decrease in blood pressure without affecting the pulse rate. In most patients, after a single oral dose, the onset of the hypotensive effect occurs within 2 hours, and the peak reduction in blood pressure is achieved within 4-6 hours. The hypotensive effect lasts for 24 hours after administration. With repeated administration, the maximum reduction in blood pressure with any dose of the drug is usually achieved within 2-4 weeks and is maintained with long-term use. In combination with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.
Abrupt discontinuation of valsartan does not cause rebound hypertension or other adverse effects.
Hydrochlorothiazide
The site of action of thiazide diuretics is primarily the distal convoluted tubule. A high-affinity receptor is present in the renal cortex, which is the major binding site for thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mechanism of action of thiazides is via inhibition of the Na+Cl- symporter, probably by competition for the Cl- site, which affects the mechanisms of electrolyte reabsorption: a direct increase in sodium levels and chloride excretion to approximately equal extent, and an indirect effect of this diuretic, which lowers plasma levels with subsequent increases in plasma renin activity, aldosterone secretion and a decrease in urinary potassium, as well as a decrease in serum potassium. The relationship between renin and aldosterone is mediated by Ang II, therefore, with concomitant administration of valsartan, the decrease in serum potassium is less pronounced than that observed with hydrochlorothiazide monotherapy.
Non-melanoma skin cancer
Available epidemiological data suggest a cumulative dose-dependent association between hydrochlorothiazide exposure and the development of NMSC. One study included a population consisting of 71,533 BCC cases and 8,629 CVD cases, corresponding to 1,430,833 and 172,462 controls, respectively. High levels of hydrochlorothiazide use (cumulative ≥ 50,000 mg) were associated with an adjusted OR of 1.29 (95% CI: 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for CVD. A clear cumulative dose-response relationship was observed for both BCC and RCC. Another study showed a possible association between lip cancer (LC) and hydrochlorothiazide exposure: 633 cases of lip cancer were matched to 63,067 controls using a population-based sampling strategy. A cumulative dose-adjusted OR of 2.1 (95% CI: 1.7-2.6) was demonstrated, increasing to an OR of 3.9 (3.0-4.9) for high use (25,000 mg) and an OR of 7.7 (5.7-10.5) for the highest cumulative dose (100,000 mg) (see Precautions).
Pharmacokinetics.
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.
Distribution
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, plasma clearance of valsartan is approximately 2 l/h and renal clearance is 0.62 l/h (approximately 30% of total clearance). The elimination half-life of valsartan is 6 hours.
Hydrochlorothiazide
Absorption
Hydrochlorothiazide is rapidly absorbed after oral administration (tmax approximately 2 hours). The increase in mean AUC is linear and dose-proportional within the therapeutic range.
The effect of food on the absorption of hydrochlorothiazide is clinically insignificant. The absolute bioavailability of hydrochlorothiazide is 70% after oral administration.
Distribution
The apparent volume of distribution is 4-8 l/kg.
Circulating hydrochlorothiazide is bound to plasma proteins (40-70%), mainly to serum albumin. Hydrochlorothiazide also accumulates in erythrocytes in amounts approximately three times higher than plasma levels.
Breeding
Hydrochlorothiazide is excreted primarily as unchanged drug. Hydrochlorothiazide is eliminated from plasma with a terminal elimination half-life of 6 to 15 hours. There is no change in the kinetics of hydrochlorothiazide with repeated dosing, and accumulation is minimal with once-daily dosing. More than 95% of the absorbed dose is excreted unchanged in the urine. Renal clearance consists of passive filtration and active tubular secretion.
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.
Concomitant use requiring special precautions
Other antihypertensive drugs
The drug may enhance the hypotensive effect of other antihypertensive drugs (e.g. ACE inhibitors, beta-blockers, calcium channel blockers).
Pressor amines (e.g., noradrenaline, adrenaline)
Possible decreased response to pressor amines. The clinical significance of this effect is not known and is not sufficient to warrant discontinuation of their use.
NSAIDs may attenuate the hypotensive effect of both Ang II antagonists and hydrochlorothiazide when used concomitantly. In addition, concomitant use of valsartan/hydrochlorothiazide and NSAIDs may lead to deterioration of renal function and an increase in serum potassium. Therefore, it is recommended to monitor renal function at the beginning of treatment and to ensure that the patient is adequately hydrated.
Interactions related to valsartan
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ARA drugs, ACE inhibitors, or aliskiren
Caution should be exercised when concomitantly using ARBs, including valsartan, with other drugs that block the RAAS, such as ACE inhibitors or aliskiren (see section "Special warnings and precautions for use").
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 taken 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® H 80, Valsacor® H 160 and Valsacor® HD 160 (see interactions with hydrochlorothiazide).
Interactions related to hydrochlorothiazide
Concomitant use requiring special precautions
Drugs that affect serum potassium levels
The hypokalemic effect of hydrochlorothiazide may be enhanced by concomitant use of kaliuretic diuretics, corticosteroids, laxatives, adrenocorticotropic hormones (ACTH), amphotericin, carbenoxolone, penicillin G, salicylic acid and its derivatives.
If the above-mentioned medicinal products are prescribed in combination with hydrochlorothiazide/valsartan, monitoring of serum potassium levels is recommended (see section 4.4).
Drugs that may cause torsades de pointes tachycardia
Class Ia antiarrhythmic drugs (e.g. quinidine, hydroquinidine, disopyramide).
Class III antiarrhythmic drugs (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 IV, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine IV).
Due to the risk of hypokalemia, hydrochlorothiazide should be used with caution simultaneously with drugs that can cause torsades de pointes tachycardia.
Drugs that affect serum sodium levels
The hyponatraemic effect of diuretics may be enhanced by concomitant use of such drugs as antidepressants, antipsychotics and antiepileptics. Long-term use of such drugs should be carried out with special caution.
Cardiac glycosides
In the presence of digitalis-induced cardiac arrhythmias while taking thiazides, hypokalemia or hypomagnesemia may occur (see section "Special warnings and precautions for use").
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.
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
Kidney failure and kidney transplantation
Patients with kidney transplant should not take the drug due to the lack of experience with the safe use of valsartan/hydrochlorothiazide. No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance ≥30 ml/min). Periodic monitoring of serum potassium, creatinine and uric acid levels is recommended.
Thiazide diuretics may provoke azotemia in patients with chronic renal impairment.
Renal artery stenosis
Since serum urea and creatinine levels may increase, patients with unilateral or bilateral renal artery stenosis or stenosis of a solitary kidney are not recommended to take the drug.
Primary hyperaldosteronism
The drug is not recommended for use in patients with primary hyperaldosteronism, as their RAAS is not activated.
Patients with severe chronic heart failure with congestive heart failure or other conditions with RAAS stimulation
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, rarely with acute renal failure. The safety of the drug 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® H 80, Valsakor® H 160, Valsakor® HD 160. Such patients should not take the drug.
Changes in serum electrolyte balance
Caution should be exercised when concomitantly taking potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may increase blood potassium concentrations (heparin).
Hypokalemia has been reported during treatment with thiazide diuretics. Frequent monitoring of serum potassium levels is recommended.
Hydrochlorothiazide
Hypokalemia has been reported during treatment with thiazide diuretics, including hydrochlorothiazide. Regular monitoring of serum potassium is recommended.
Patients receiving diuretic therapy should have periodic evaluation of serum electrolytes at appropriate frequency.
Patients with sodium and/or circulating blood volume (CV) deficiency in the body
Patients taking thiazide diuretics should be observed for clinical signs of fluid or electrolyte imbalance. Danger signs of fluid or electrolyte imbalance include dry mouth, thirst, asthenia (fatigue, weakness), drowsiness, lethargy, agitation (dysphoria), muscle cramps or pain, rapid muscle fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances (nausea and vomiting).
In patients with severe sodium and/or volume depletion, such as those receiving high doses of diuretics, symptomatic hypotension may occasionally occur after initiation of therapy with the drug. Correction of sodium and/or volume depletion should be performed before initiation of therapy.
In case of hypotension, the patient should be placed in a horizontal position and, if necessary, intravenous isotonic saline solution should be administered. Treatment can be continued as soon as blood pressure has stabilized.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
Particular caution should be exercised in patients with aortic or mitral valve stenosis, or with obstructive hypertrophic cardiomyopathy.
Liver dysfunction
The drug should be used with caution in patients with mild to moderate hepatic impairment without cholestasis (see sections 5.1 and 5.2). Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor changes in fluid or electrolyte balance may precipitate hepatic coma.
Systemic lupus erythematosus
Thiazide diuretics, including hydrochlorothiazide, exacerbate or activate systemic lupus erythematosus.
Other metabolic disorders
Thiazide diuretics may affect glucose tolerance and increase serum cholesterol, triglycerides, and uric acid levels. Diabetics may require adjustment of insulin or oral hypoglycemic agents.
Thiazides may reduce urinary calcium excretion and cause intermittent and minor increases in serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may indicate the presence of hyperparathyroidism. Thiazides should be discontinued before parathyroid function tests are performed.
Photosensitivity
Photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If a photosensitivity reaction occurs during treatment with the drug, it is recommended to discontinue treatment. If the diuretic is to be restarted, it is recommended to protect the affected areas from the sun or artificial UV radiation.
Choroidal effusion, acute myopia, and secondary acute angle-closure glaucoma
Sulfonamides and sulfonamide derivatives may cause idiosyncratic reactions resulting in choroidal effusion with visual field defect, acute transient myopia, and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain, usually occurring within hours to weeks of starting the drug. Untreated acute angle-closure glaucoma may result in permanent vision loss.
Treatment with the drug 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.
General disorders
Caution should be exercised when using the drug in patients with hypersensitivity to other Ang II receptor antagonists. Patients with a history of allergy and asthma are more likely to develop allergic reactions.
Non-melanoma skin cancer
An increased risk of non-melanoma skin cancer (NMSC) (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) with increasing cumulative exposure to hydrochlorothiazide (HCTZ) was observed in two epidemiological studies based on the Danish National Cancer Registry. The photosensitizing effects of hydrochlorothiazide may act as a possible mechanism for NMSC.
Patients taking hydrochlorothiazide should be informed of the risk of developing NMSC and advised to regularly examine their skin for new lesions and to report suspicious skin lesions immediately. Patients should be advised of possible preventive measures, such as limited exposure to sunlight and ultraviolet light and, if exposed, appropriate protection, to minimise the risk of skin cancer. Suspicious skin lesions should be investigated promptly, potentially including histological examination of biopsies. The use of hydrochlorothiazide may also need to be reconsidered in patients with a history of NMSC (see Adverse Reactions).
Very rare cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported following the administration of hydrochlorothiazide. Pulmonary oedema usually develops within minutes to hours of taking hydrochlorothiazide. Initial symptoms include dyspnoea, fever, worsening pulmonary function and hypotension. If ARDS is suspected, valsartan/hydrochlorothiazide should be discontinued and appropriate treatment should be initiated. Hydrochlorothiazide should not be given to patients who have previously experienced ARDS after taking 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 these patients had a history of angioedema with other drugs, including other Ang II receptor antagonists. If angioedema develops, treatment with Ang II receptor antagonists should be discontinued immediately. Re-administration is contraindicated.
Dual blockade of RAAS
Hypotension, syncope, stroke, hyperkalemia and changes in renal function, including acute renal failure, have been reported in susceptible patients, especially with the combination of drugs that affect this system. Due to dual blockade of the RAAS, the concomitant use of aliskiren and Ang II receptor antagonists or ACE inhibitors is not recommended.
Hydrochlorothiazide may 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.
Elderly patients do not require dose adjustment.
Important information about some ingredients
Valsakor® H 80, Valsakor® H 160 and Valsakor® HD 160 contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
Pregnancy
Like other drugs that directly act on the RAAS, Valsakor® H 80, Valsakor® H 160 and Valsakor® HD 160 are 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.
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.
Method of administration and doses
The recommended dose is 1 tablet of Valsakor® H 80 (80 mg/12.5 mg) per day. In case of insufficient blood pressure reduction after 3-4 weeks of treatment, it is recommended to consider increasing the dose to 1 tablet of Valsakor® H 160 (160 mg/12.5 mg) once a day. Valsakor® HD 160 (160 mg/25 mg) should be prescribed to patients who do not achieve sufficient blood pressure reduction with Valsakor® H 160.
In case of insufficient blood pressure reduction when taking Valsacor® HD 160, treatment should be started with valsartan/hydrochlorothiazide tablets 320 mg/12.5 mg (Valsacor® H 320). Valsartan/hydrochlorothiazide tablets 320 mg/25 mg (Valsacor® HD 320) should be used in patients whose blood pressure control is insufficient when taking valsartan/hydrochlorothiazide tablets 320 mg/12.5 mg.
The maximum daily dose is 320 mg/25 mg.
The antihypertensive effect is mainly observed in the first 2 weeks. 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.
Valsakor® H 80, Valsakor® H 160 and Valsakor® HD 160 can be taken regardless of meals, with water.
Additional information about special patient categories
Elderly patients
No dose adjustment is required for elderly patients.
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 4.2, 4.3 and 4.5). Concomitant use with aliskiren is contraindicated in patients with renal impairment (GFR <60 ml/min/1.73 m2) (see section 4.3).
Diabetes mellitus
The concomitant use of valsartan and aliskiren is contraindicated in patients with diabetes mellitus (see section "Contraindications").
Liver failure.
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 4.2, 4.3 and 4.4).
Children.
The safety and efficacy of the drug in children have not been established, therefore it is not recommended to use the drug in this category of patients.
Overdose
Symptoms
Overdose with valsartan can lead to severe hypotension, which in turn can lead to depression of consciousness, development of vascular insufficiency and/or shock. The following signs and symptoms may occur as a result of an overdose with hydrochlorothiazide: nausea, drowsiness, hypovolemia, electrolyte imbalance and, as a result, arrhythmia and muscle spasms. The most characteristic signs and symptoms of overdose are also tachycardia, hypotension, shock, weakness, confusion, dizziness, muscle spasms, paresthesia, exhaustion, disorders of consciousness, vomiting, thirst, polyuria, oliguria, anuria, alkalosis, increased blood urea nitrogen (mainly renal failure).
Treatment
Therapeutic measures depend on how long ago the large dose of the drug was taken and the severity of symptoms, with the most important being stabilization of hemocirculation.
If the drug was taken recently, vomiting should be induced, but if a long time has passed since ingestion, a sufficient amount of activated charcoal should be administered.
In the event of hypotension, the patient should be placed in a horizontal position and immediately administered intravenously with isotonic saline to restore water-salt balance.
Valsartan is not removed by hemodialysis due to its high plasma protein binding, however, clearance of hydrochlorothiazide is achieved by dialysis.
Side effects
Adverse reactions occurring when taking the combination of valsartan/hydrochlorothiazide
Metabolism and nutrition disorders: dehydration.
Nervous system: dizziness, paresthesia, syncope, confusion, disorientation, nervousness, mood changes, xanthopsia.
From the organs of vision: blurred vision.
From the side of the organs of hearing and labyrinth: ringing in the ears.
Vascular disorders: arterial hypotension.
Respiratory, thoracic and mediastinal disorders: cough, non-cardiogenic pulmonary edema, respiratory distress, pneumonitis.
Gastrointestinal: diarrhea, thirst, inflammation of the salivary glands, cholecystitis.
