Instructions Vanatex Combi film-coated tablets 80 mg + 12.5 mg blister No. 28
Composition
active ingredients: valsartan, hydrochlorothiazide;
1 film-coated tablet contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide
or 160 mg valsartan and 12.5 mg hydrochlorothiazide,
or 160 mg of valsartan and 25 mg of hydrochlorothiazide;
excipients:
core: lactose monohydrate, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate;
tablet coating 80 mg/12.5 mg (Mixture for coating the tablets - Type 2): hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide red (E 172);
tablet coating 160 mg/12.5 mg (Mixture for coating the tablets – Type 3): hypromellose, macrogol 400, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172), black iron oxide (E 172);
tablet coating 160 mg/25 mg (Mixture for coating the tablets - Type 4): hypromellose, macrogol 400, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172), black iron oxide (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties:
80 mg/12.5 mg: pink oblong biconvex film-coated tablets;
160 mg/12.5 mg: reddish-brown oblong biconvex film-coated tablets;
160 mg/25 mg: light brown oblong biconvex film-coated tablets.
Pharmacotherapeutic group
Angiotensin II receptor blockers (AT1 receptor blockers) and diuretics.
ATX code C09D A03.
Pharmacological properties
Pharmacodynamics.
Valsartan
Valsartan is an orally active and specific angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT1 receptor subtype, which is responsible for the known actions of angiotensin II. Increased plasma Ang II levels after blockade of the AT1 receptor with valsartan may stimulate the unblocked AT2 receptor, which is likely to counteract the action of the AT1 receptor. Valsartan does not exhibit partial agonist activity at the AT1 receptor and has a much higher affinity for the AT1 receptor than for the AT2 receptor. Valsartan does not inhibit ACE (also known as kinase II), which converts Ang I to Ang II and degrades bradykinin. In clinical trials comparing valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (P < 0.05) in patients taking valsartan than in those taking an ACE inhibitor (2.6% vs. 7.9%). In a clinical trial of patients with a history of dry cough while taking an ACE inhibitor, 19.5% of subjects taking valsartan and 19% of those taking a thiazide diuretic had cough compared with 68.5% of patients taking an ACE inhibitor (P < 0.05).
Valsartan administration to patients with arterial hypertension results in a reduction in blood pressure without affecting the pulse rate. In most patients, after a single oral dose, antihypertensive activity begins within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours. The hypotensive effect persists for 24 hours after taking the drug. With repeated doses of the drug, the maximum reduction in blood pressure at any dose is generally achieved within 2-4 weeks and is maintained during long-term treatment. In combination with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.
In patients with high blood pressure, type 2 diabetes, and microalbuminuria, valsartan has been shown to reduce urinary albumin excretion.
Conclusion: 160-320 mg of valsartan leads to a clinically significant reduction in UAE in patients with high blood pressure and type 2 diabetes.
Hydrochlorothiazide
The primary site of action of thiazide diuretics is the renal distal convoluted tubules. It has been demonstrated that there is a high-affinity receptor in the renal cortex that is the primary binding site for thiazide diuretics and inhibits sodium chloride (NaCl) transport in the distal convoluted tubules. The mechanism of action of thiazides is to inhibit the Na+ Cl- unidirectional transporter, possibly by competing for the Cl- site, which affects the mechanisms of electrolyte reabsorption: directly, increasing the excretion of sodium and chloride to approximately the same extent, and indirectly, through such a diuretic action, reducing plasma volume with subsequent increases in plasma renin activity, aldosterone secretion, urinary potassium loss, and a decrease in plasma potassium. The renin-aldosterone link is mediated by angiotensin II, therefore, with simultaneous administration of valsartan, the decrease in potassium in the blood plasma is less pronounced than with monotherapy with hydrochlorothiazide.
Pharmacokinetics.
The systemic bioavailability of hydrochlorothiazide is reduced by approximately 30% when co-administered with valsartan. 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, since in controlled clinical trials a clear antihypertensive effect of this combination was found, which exceeded the effect of the active substance alone, as well as the effect of placebo.
Valsartan
After oral administration of valsartan alone, peak plasma concentrations of valsartan are reached within 2-4 hours. The mean absolute bioavailability is 23%. Food reduces the exposure by approximately 50%.
Distribution
The steady-state volume of distribution of valsartan after intravenous administration is about 17 liters, indicating that valsartan is not widely distributed in tissues. Valsartan is extensively bound to serum proteins (94-97%), mainly to serum albumin.
Biotransformation
Valsartan is not biotransformed to a significant extent, as only approximately 20% of the dose is recovered as metabolites.
Excretion from the body
Valsartan exhibits multiexponential decay kinetics (t½α < 1 hour and t½ ß almost 9 hours). Valsartan is mainly excreted in the feces (about 83% of the dose) and urine (about 13% of the dose), mainly unchanged. After intravenous administration, the plasma clearance of valsartan is about 2 l/h, and its renal clearance is 0.62 l/h (about 30% of the total clearance). The half-life of valsartan is 6 hours.
Hydrochlorothiazide
Absorption
After oral administration, hydrochlorothiazide is rapidly absorbed (tmax about 2 hours) with similar absorption characteristics for both suspensions and tablets. The absolute bioavailability of hydrochlorothiazide is 60-80% after oral administration.
Distribution
Distribution and elimination kinetics are generally described by a bi-exponential decay function. The expected volume of distribution is 4-8 l/kg.
Circulating hydrochlorothiazide binds to serum proteins (40-70%), mainly serum albumin.
Excretion from the body
For hydrochlorothiazide, >95% of the absorbed dose is excreted unchanged in the urine. Renal clearance consists of passive filtration and active secretion in the renal tubules. The half-life is 6-15 hours.
Special patient groups
Elderly patients
Limited data indicate that the total clearance of hydrochlorothiazide is reduced in both healthy volunteers and elderly patients with high blood pressure compared to young healthy volunteers.
Kidney failure
When used at the recommended dose of Vanatex Combi, no dose adjustment is required for patients with creatinine clearance of 30-70 ml/min.
There are no data on the use of Vanatex Combi in patients with severe renal impairment (creatinine clearance < 30 ml/min) or in patients undergoing dialysis. Valsartan is extensively bound to plasma proteins and is not dialysable, whereas hydrochlorothiazide is dialysable.
Renal clearance of hydrochlorothiazide consists of passive filtration and active secretion in the renal tubules. As expected for a drug that is excreted almost exclusively by the kidneys, renal function has a marked effect on the kinetics of hydrochlorothiazide.
Liver failure
In a pharmacokinetic study in patients with mild (n=6) and moderate (n=5) hepatic dysfunction, valsartan exposure was approximately 2-fold higher compared to healthy volunteers.
There are no data on the use of valsartan in patients with severe hepatic dysfunction. Liver disease does not significantly affect the pharmacokinetics of hydrochlorothiazide.
Non-melanoma skin cancer
Results from two recent pharmacoepidemiological studies using Danish national data sources have shown a cumulative dose-dependent association between HCT and the occurrence of basal cell carcinoma and squamous cell carcinoma. One study [1] included a population of 71,533 patients with basal cell carcinoma (BCC) and 8,629 patients with squamous cell carcinoma (SCC), who were compared with 1,430,833 and 172,462 control patients, respectively. High HCT intake (≥ 50,000 mg total) was associated with an adjusted hazard ratio (HR) of 1.29 (95% confidence interval (CI): 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for SCC. A cumulative dose-response relationship has been observed for BCC and PCC. For example, a cumulative dose of 50,000 mg corresponds to 12.5 mg of GHTZ when taken daily for about 11 years.
Another study [2] showed a possible association between lip cancer (LC) and HCT use: 633 patients with lip cancer (LC) were compared with 63,067 control patients using a randomised pooled analysis. A cumulative dose-response relationship was demonstrated with an adjusted HR of 2.1 (95% CI: 1.7-2.6) for general use, increasing to 3.9 (3.0-4.9) for high use (25,000 mg) and 7.7 (5.7-10.5) for the highest cumulative dose (100,000 mg) (see section 4.4).
Indication
Arterial hypertension in patients whose blood pressure is not adequately controlled with valsartan or hydrochlorothiazide monotherapy.
Contraindication
Hypersensitivity to valsartan, hydrochlorothiazide, other sulfonamide-based drugs or to any of the excipients.
Severe hepatic insufficiency, cirrhosis and cholestasis.
Severe renal failure (creatinine clearance < 30 ml/min), anuria.
Pregnant women or women planning to become pregnant (see “Use during pregnancy or breastfeeding”).
Concomitant use of angiotensin receptor antagonists or angiotensin-converting enzyme inhibitors with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2).
Interaction with other medicinal products and other types of interactions
Interactions associated with both valsartan and hydrochlorothiazide
Concomitant use is not recommended.
Lithium
Reversible increases in plasma lithium concentrations and toxicity have been reported with concomitant use of angiotensin-converting enzyme inhibitors and thiazides, including hydrochlorothiazide. Due to the lack of experience with the concomitant use of valsartan and lithium, this combination is not recommended. If such a combination proves necessary, careful monitoring of plasma lithium levels is recommended.
Concomitant use requiring caution
Other antihypertensive drugs
Vanatex Combi may enhance the effect of other drugs with antihypertensive properties (e.g. angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers).
Pressor amines (e.g., noradrenaline, adrenaline)
There may be a reduced response to pressor amines, which is not sufficient to preclude their use.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid > 3 g/day, and nonselective NSAIDs
NSAIDs may attenuate the antihypertensive effect of both angiotensin II antagonists and hydrochlorothiazide when used concomitantly. In addition, concomitant administration of Vanatex Combi and NSAIDs may lead to deterioration of renal function and an increase in plasma potassium levels. Therefore, monitoring of renal function at the start of treatment is recommended, as well as adequate hydration of the patient.
Interactions related to valsartan
Dual blockade of the renin-angiotensin system (RAS)
Clinical studies indicate that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the simultaneous use of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of adverse reactions such as hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared to the use of either drug alone (see sections "Contraindications", "Special instructions" and "Pharmacodynamics").
Concomitant use is not recommended.
Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, and other substances that may increase potassium levels
If the use of a medicinal product that affects potassium levels is considered necessary in combination with valsartan, monitoring of plasma potassium is recommended.
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 terminating concomitant use of these medicinal products.
Lack of interaction
In drug interaction studies with valsartan, no clinically significant interactions were observed between valsartan and any of the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. Digoxin and indomethacin may interact with the hydrochlorothiazide component of Vanatex Combi (see Interactions related to hydrochlorothiazide).
Interactions related to hydrochlorothiazide
Concomitant use requiring caution
Drugs associated with potassium loss and hypokalemia (e.g., kaliuretic diuretics, corticosteroids, laxatives, ACTH, amphotericin, carbenoxolone, penicillin G, salicylic acid and derivatives).
If it is necessary to prescribe these drugs with the combination of hydrochlorothiazide and valsartan, it is recommended to monitor the level of potassium in the blood plasma. These drugs may enhance the effect of hydrochlorothiazide on the level of potassium in the blood plasma.
Drugs that can cause torsades de pointes
Class Ia antiarrhythmics (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 intravenously, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine intravenously).
Drugs that affect plasma sodium levels
The hyponatremic effect of diuretics may be enhanced by concomitant use of such drugs as antidepressants, neuroleptics, antiepileptic drugs, etc. Vanatex Combi should be prescribed with caution during long-term treatment with such drugs.
Digitalis glycosides
Thiazide-induced hypokalemia or hypomagnesemia may occur as an undesirable effect, contributing to the development of digitalis-induced cardiac arrhythmias.
Calcium salts and vitamin D
The use of thiazide diuretics, including hydrochlorothiazide, with vitamin D or calcium salts may increase plasma calcium levels. Concomitant use of thiazide diuretics with calcium salts may lead to hypercalcemia in patients with a predisposition to hypercalcemia (e.g., hyperparathyroidism, malignancy, or vitamin D-mediated conditions) by increasing calcium reabsorption.
Antidiabetic agents (oral agents and insulin)
Thiazide therapy may affect glucose tolerance. Dose adjustment of the antidiabetic medicinal product may be necessary.
Metformin should be used with caution due to the risk of lactic acidosis induced by possible functional renal failure associated with hydrochlorothiazide.
Beta-blockers and diazoxide
Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta-blockers increases the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may potentiate the hyperglycemic effect of diazoxide.
Medications used in the treatment of gout (probenecid, sulfinpyrazone, and allopurinol)
It may be necessary to adjust the dose of drugs that promote the excretion of uric acid, since hydrochlorothiazide may increase the level of uric acid in the blood plasma. It may be necessary to increase the dose of probenecid or sulfinpyrazone. Concomitant use of thiazide diuretics, including hydrochlorothiazide, may increase the frequency of hypersensitivity reactions to allopurinol.
Anticholinergics and other drugs that affect intestinal motility
The bioavailability of thiazide diuretics may be increased by anticholinergic agents (e.g. atropine, biperiden), presumably by reducing gastrointestinal motility and gastric emptying rate. On the other hand, prokinetics such as cisapride are expected to reduce the bioavailability of thiazide diuretics.
Amantadine
Thiazides, including hydrochlorothiazide, increase the risk of adverse effects caused by amantadine.
Cholestyramine and colestipol resins
The absorption of thiazide diuretics, including hydrochlorothiazide, is impaired in the presence of anionic resins. This may result in subtherapeutic effects of the thiazide diuretics. However, it is possible to minimize the potential interaction between hydrochlorothiazide and the resin by administering hydrochlorothiazide at least 4 hours before or 4-6 hours after administration of the resin.
Cytotoxic agents (e.g., cyclophosphamide, methotrexate)
Thiazides, including hydrochlorothiazide, may reduce the renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
Non-depolarizing skeletal muscle relaxants (e.g. tubocurarine)
Thiazides, including hydrochlorothiazide, enhance the effect of curare derivatives.
Cyclosporine
Concomitant administration with cyclosporine may increase the risk of hyperuricemia and gout-like complications.
Alcohol, anesthetics and sedatives
Concomitant use of thiazide diuretics with drugs that can also lower blood pressure (e.g., by reducing sympathetic activity of the central nervous system or by direct vasodilation) may potentiate orthostatic hypotension.
Methyldopa
There have been isolated reports of hemolytic anemia in patients receiving concomitant treatment with methyldopa and hydrochlorothiazide.
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.
Contrast agents containing iodine
In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially with high doses of iodine-containing preparations. The patient should be adequately rehydrated before use.
Application features
Changes in electrolyte concentration.
It is not recommended to use Vanatex Combi with potassium salts, potassium-sparing diuretics, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (e.g. heparin). Cases of hypokalaemia have been reported during treatment with thiazide diuretics. It is recommended to periodically check the potassium content in the blood serum. Thiazide diuretics reduce calcium excretion, which may cause hypercalcaemia. Patients taking diuretics should have their plasma electrolyte levels periodically determined.
Patients with a deficiency in the body of sodium and/or circulating blood volume (CBC).
Patients taking thiazide diuretics, including hydrochlorothiazide, should be monitored for clinical signs of fluid and electrolyte disturbances. 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 Vanatex Combi therapy. Therefore, correction of sodium and/or volume depletion should be considered before initiating therapy with this drug.
Patients with severe chronic heart failure or other conditions with increased activity of the renin-angiotensin-aldosterone system
In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and, rarely, with acute renal failure and/or fatal outcome. Evaluation of patients with heart failure or after myocardial infarction should always include assessment of renal function. The use of Vanatex Combi in patients with severe chronic heart failure is not justified.
Since it cannot be excluded that due to inhibition of the renin-angiotensin-aldosterone system, the use of Vanatex Combi may also be associated with impaired renal function, Vanatex Combi should not be used in such patients.
Renal artery stenosis
The drug should not be used in patients with unilateral or bilateral renal artery stenosis or stenosis caused by a single kidney, as blood urea and plasma creatinine levels may increase in such patients.
Primary hyperaldosteronism
Vanatex Combi should not be used in patients with primary hyperaldosteronism, as their renin-angiotensin system is not activated.
Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy
As with other vasodilators, patients with aortic and mitral valve stenosis or hypertrophic obstructive cardiomyopathy (HOCM) require special caution.
Kidney dysfunction
No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/min). Periodic monitoring of serum potassium, creatinine and uric acid levels is recommended when valsartan/hydrochlorothiazide is used in patients with renal impairment.
Vanatex Combi should be used with caution in severe renal insufficiency (creatinine clearance < 30 ml/min). Thiazide diuretics may provoke azotemia in patients with chronic renal impairment. They are not effective as monotherapy in severe renal insufficiency (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 currently no experience regarding the safety of the drug in patients who have recently undergone a kidney transplant.
Liver dysfunction
No dose adjustment is required in patients with mild to moderate hepatic impairment without cholestasis. However, Vanatex Combi should be used with caution. Thiazide diuretics should be used with caution in patients with impaired hepatic function or progressive liver disease, as minor disturbances of fluid and electrolyte balance may precipitate hepatic coma.
Systemic lupus erythematosus
Thiazide diuretics have been reported to exacerbate or activate the manifestations of systemic lupus erythematosus.
Other metabolic disorders
Thiazide diuretics may alter glucose tolerance and increase serum cholesterol, triglycerides, and uric acid levels. Dosage adjustments of insulin or oral hypoglycemic agents may be necessary in diabetic patients. Thiazides may decrease urinary calcium excretion and cause transient and minor increases in serum calcium in the absence of calcium metabolism disorders. Significant hypercalcemia may indicate underlying hyperparathyroidism. Thiazides should be discontinued before parathyroid function tests are performed.
Photosensitivity
Photosensitivity reactions have been reported with thiazide diuretics. If a photosensitivity reaction occurs during treatment, it is recommended to discontinue treatment. If repeated use of the diuretic is considered necessary, it is recommended to protect exposed skin from sunlight or artificial ultraviolet radiation.
Pregnancy
General recommendations
Caution should be exercised when using the drug in patients with a history of hypersensitivity to other angiotensin II receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients with allergies and asthma.
Hydrochlorothiazide may reduce the level of protein-bound iodine in the blood plasma and increase the concentration of free bilirubin in the blood serum.
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 medicinal products, including other angiotensin II receptor antagonists. If angioedema develops, treatment with angiotensin II receptor antagonists should be discontinued immediately. Re-administration is contraindicated.
Acute angle-closure glaucoma
The use of hydrochlorothiazide, a sulfonamide, has been associated with an idiosyncratic reaction that may lead to acute transient myopia and acute angle-closure glaucoma. Acute decrease in visual acuity or eye pain has been reported. These symptoms usually occur within a few hours to a week of taking the drug. Untreated glaucoma can lead to irreversible vision loss.
The drug should be discontinued immediately. Medical or surgical treatment may be required. A risk factor for the development of acute angle-closure glaucoma is an allergic reaction to the use of sulfonamides or penicillins.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that the concomitant use of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of arterial hypotension, hyperkalemia and decreased renal function (including the occurrence of acute renal failure). For dual blockade of the renin-angiotensin-aldosterone system (RAAS), the concomitant use of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections "Interaction with other medicinal products and other forms of interaction" and "Pharmacodynamics").
When the combination of these drugs (dual blockade) is considered absolutely necessary, treatment should only be carried out under medical supervision and with frequent and careful monitoring of renal function, fluid and electrolyte balance and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Doping control
It should be borne in mind that this drug may cause a positive reaction during anti-doping control.
Excipients
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Non-melanoma skin cancer
The results of pharmacoepidemiological studies have shown a high risk of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) with the use of high total doses of hydrochlorothiazide (HCTZ).
Patients taking HTZ alone or in combination with other drugs should be informed of the risk of non-melanoma skin cancer and advised to regularly check their skin for new lesions, as well as changes in existing ones, and to report any suspicious skin lesions.
Suspicious skin lesions should potentially be histologically examined by biopsy.
Patients should be advised to limit exposure to sunlight and UV rays and use appropriate protection to minimize the risk of skin cancer.
The use of GHZ should also be carefully reviewed in patients with a history of skin cancer (see section 4.8).
Choroidal effusion, acute myopia, and secondary angle-closure glaucoma
Drugs containing sulfonamide or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia, and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug.
Untreated acute angle-closure glaucoma can lead to permanent vision loss. The main treatment is to stop the medication as soon as possible. If the intraocular pressure remains uncontrolled, urgent medical or surgical treatments may be necessary. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
Very rare cases of severe acute respiratory toxicity, sometimes progressing to acute respiratory distress syndrome (ARDS), have been reported with hydrochlorothiazide. Pulmonary oedema may develop within minutes to hours of taking hydrochlorothiazide. Early signs include dyspnoea, fever and worsening pulmonary function. In such circumstances, hydrochlorothiazide should be discontinued and appropriate treatment instituted. Hydrochlorothiazide should not be given to patients with a history of ARDS following hydrochlorothiazide use.
Use during pregnancy or breastfeeding
Pregnancy
Valsartan
The use of angiotensin II receptor antagonists (ARBs) is contraindicated throughout pregnancy.
Epidemiological data on the risk of teratogenic effects following exposure to ACE inhibitors during the first trimester of pregnancy are inconclusive, but a small increase in risk cannot be excluded. Since there are no controlled epidemiological data on the risk with angiotensin II receptor antagonists, a risk of teratogenic effects may also exist for this class of drugs. 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 with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative treatments which have an approved safety profile for use in pregnancy should be started.
It is known that the use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy induces human fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia).
If AIIRAs have been used from the second trimester of pregnancy, ultrasound examination is recommended to check kidney function and the condition of the skull bones.
The condition of newborns whose mothers used ARAII should be carefully monitored for the development of arterial hypotension.
Hydrochlorothiazide
There is limited experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester. Intrauterine administration of a thiazide diuretic has been associated with thrombocytopenia in the fetus or newborn, as well as other adverse events. Hydrochlorothiazide crosses the placenta. Given the pharmacological mechanism of action of hydrochlorothiazide, its use in the second and third trimesters may compromise fetoplacental perfusion and may cause fetal and neonatal adverse events such as jaundice, electrolyte imbalance and thrombocytopenia.
Breast-feeding
Due to the lack of information on the use of valsartan during breastfeeding, Vanatex Combi is not recommended for use during this period.
Hydrochlorothiazide passes into breast milk. Therefore, Vanatex Combi is not recommended for use during breastfeeding.
If pregnancy is detected during treatment, the drug should be discontinued as soon as possible.
Ability to influence reaction speed when driving vehicles or other mechanisms
At the beginning of the use of the drug (the period is determined individually by the doctor) it is forbidden to drive a car and perform work that may lead to an accident. Later, the degree of prohibition is determined
