Ko-Valsartan

Valsartan / Hydrochlorothiazide

Film-coated tablets

Round, biconvex, red-brown, film-coated tablets.

Each tablet contains:
Active substances: valsartan and hydrochlorothiazide (active substances) 160 / 12.5 mg respectively;
Excipients: microcrystalline cellulose, crospovidone, anhydrous colloidal silicon dioxide, magnesium stearate;
Shell composition: Opadry II 85G25455 Red (polyvinyl alcohol, talc, macrogol, titanium dioxide (E 171), iron dye red oxide (E 172), sunset yellow dye (E 110), lecithin).

Agents acting on the renin–angiotensin system. Angiotensin II receptor blockers and diuretics.

С09DA03

Pharmacodynamics
Valsartan and hydrochlorothiazide are the active ingredients of Ko-Valsartan.

Valsartan is an orally active selective angiotensin II receptor blocker (ARB II). It selectively acts on the AT₁ receptors, which are responsible for the known effects of angiotensin II. Valsartan has no AT₁ receptor agonist activity. Its affinity for AT₁ receptors is approximately 20,000 times greater than for AT₂ receptors.

Valsartan does not inhibit angiotensin-converting enzyme (ACE), also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Due to the lack of influence on ACE, the effects of bradykinin and substance P are not potentiated. Therefore, when taking angiotensin II receptor antagonists, development of dry cough is unlikely. Valsartan does not interact with, and does not block the receptors of other hormones or ion channels involved in regulation of the cardiovascular system functions. In the treatment of arterial hypertension, valsartan lowers blood pressure (BP) without affecting the heart rate.

After ingestion of a single dose of the drug, the antihypertensive effect develops within 2 hours, and the maximum decrease in blood pressure is achieved within 4-6 hours. After taking Ko-Valsartan, the antihypertensive effect persists for more than 24 hours. With repeated administration of Ko-Valsartan, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. Combination with hydrochlorothiazide is more effective in lowering blood pressure.

Hydrochlorothiazide is a thiazide diuretic. The point of application of the action of thiazide diuretics is the cortical section of the distal renal tubules, where the receptors (highly sensitive to the action of diuretics) are located, and where Na and C1 ion transport is inhibited. The mechanism of thiazide action is associated with inhibition of the Na+Cl- pump, which obviously occurs due to competition for C1- transport sites. As a result, the excretion of sodium and chloride ions increases approximately equally. As a result of the diuretic action, a decrease in the volume of circulating plasma is observed, resulting in increased renin activity, aldosterone secretion, excretion of potassium in the urine and, consequently, a decrease in serum potassium concentration. The relationship between renin and aldosterone is mediated by angiotensin II. Therefore, the prescription of an angiotensin II receptor antagonist reduces the loss of potassium associated with the use of a thiazide diuretic.

Treatment of arterial hypertension in adult patients who fail to achieve adequate control of blood pressure with monotherapy with valsartan or hydrochlorothiazide.

Tablets are taken orally, without chewing, with a sufficient amount of water, regardless of the meal.

The recommended dose of Ko-Valsartan is 1 tablet per day. Dose titration of the individual components is recommended. In each case it is necessary to control the titration with an increase in the dose of individual components in order to reduce the risk of hypotension and other side effects.

When clinically indicated, a direct crossover from monotherapy to a fixed-dose combination may be considered in patients whose blood pressure is not adequately controlled with valsartan or hydrochlorothiazide alone, provided that the recommended dose titration sequence for the individual components is followed.

When necessary for blood pressure control, the dosage may be increased after 1-2 weeks of treatment to a maximum daily dose of 320 mg of valsartan and 25 mg of hydrochlorothiazide.

The antihypertensive effect is achieved within 2 weeks. In most patients, the maximum antihypertensive effect is achieved within 4 weeks. However, for some patients, 4-8 weeks of treatment may be required. This should be taken into account while dosage titration.

Special population

Patients with impaired renal function
Dose adjustment is not required in patients with mild to moderate renal insufficiency (glomerular filtration rate (GFR) ≥30 ml / min / 1.73 m²). Ko-Valsartan is contraindicated in patients with severe renal insufficiency (GFR <30 ml/min / 1.73 m²) and anuria, since it contains hydrochlorothiazide. Co-administration of valsartan with aliskiren is contraindicated in patients with moderate or severe renal insufficiency (GFR <60 ml/min / 1.73 m²) (see Section Contraindications).

Patients with diabetes
The simultaneous use of valsartan with aliskiren is contraindicated in patients with diabetes mellitus (see Section Contraindications).

Patients with impaired liver function
In patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg. Dose modification of hydrochlorothiazide is not required in patients with mild to moderate hepatic impairment. Ko-Valsartan is contraindicated in patients with severe hepatic impairment, biliary cirrhosis and patients with cholestasis, because it contains valsartan.

Elderly patients
Elderly patients do not need to change the dose of Ko-Valsartan.

Children and adolescents
Taking the drug Ko-Valsartan is not recommended for patients under the age of 18 due to the lack of data on efficacy and safety.

Listed below are side effects for which a possible association has been recognized with the use of valsartan in combination with hydrochlorothiazide. Classification of the incidence of side effects: very common (≥ 1/10); common (≥1/100, but <1/10); uncommon (≥1/1000, but <1/100); rare (≥1/10000 but <1/1000), very rare (<1/10000).

When using a combination of valsartan and hydrochlorothiazide, the following side effects are possible:

Metabolism and nutritional disorders: dehydration (uncommon).

Nervous system disorders: paresthesia (uncommon); dizziness (very rare); fainting, when used after myocardial infarction (frequency unknown).

Eye disorders: blurred vision (uncommon).

Ear and labyrinth disorders: tinnitus (uncommon).

Vascular disorders: hypotension (uncommon).

Respiratory, thoracic, and mediastinal disorders: cough (uncommon); non-cardiogenic pulmonary edema (frequency unknown).

Gastrointestinal disorders: diarrhea (very rare).

Musculoskeletal and connective tissue disorders: myalgia (uncommon); arthralgia (very rare).

Renal and urinary disorders: impaired renal function (frequency unknown).

General disorders and administration site conditions: increased fatigue (uncommon).

Laboratory tests and instrumental studies interaction: an increase in the concentration of uric acid, creatinine and bilirubin in serum, hypokalemia, hyponatremia, an increase in the content of urea nitrogen in the blood, neutropenia (frequency unknown).

Adverse events previously noted with each of the components may occur with the use of Ko-Valsartan, even if they were not observed during clinical studies.

Valsartan

The following adverse events were observed with valsartan monotherapy, regardless of the causal relationship with this medicinal product:

Blood and lymphatic system disorders: a decrease in the concentration of hemoglobin and hematocrit, thrombocytopenia (frequency unknown).

Immune system disorders: hypersensitivity reactions, including serum sickness (frequency unknown).

Metabolism and nutrition disorders: an increased concentration of potassium in the blood serum, hyponatremia (frequency unknown).

Ear and labyrinth disorders: vertigo (uncommon).

Vascular disorders: vasculitis (frequency unknown).

Gastrointestinal disorders: abdominal pain (uncommon).

Hepatobiliary disorders: an increase in indicators characterizing liver function (frequency unknown).

Skin and subcutaneous tissue disorders: angioedema, bullous dermatitis, skin rash, pruritus (frequency unknown).

Renal and urinary disorders: renal failure (frequency unknown).

Hydrochlorothiazide

The following adverse events have been reported with thiazide diuretic monotherapy, including hydrochlorothiazide:

Neoplasms benign, malignant and unspecified, including cysts and polyps: non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma).

Blood and lymphatic system disorders: thrombocytopenia, sometimes with purpura (rare); agranulocytosis, leukopenia, hemolytic anemia, depression of bone marrow function (very rare); aplastic anemia (frequency unknown).

Immune system disorders: hypersensitivity reactions (very rare).

Metabolism and nutrition disorders: hypokalemia, increased blood lipid levels, mainly when taking high doses of hydrochlorothiazide (very common); hyponatremia, hypomagnesemia, hyperuricemia (common); hypercalcemia, hyperglycemia, glucosuria and deterioration in the condition of patients with diabetes (rare); hypochloremic alkalosis (very rare).

Mental disorders: depression, sleep disorder (rare).

Nervous system disorders: headache, dizziness, paresthesia (rare).

Eye disorders: visual impairment (rare); acute angle-closure glaucoma (frequency unknown).

Cardiac disorders: arrhythmia (rare).

Vascular disorders: orthostatic hypotension (common).

Respiratory, thoracic and mediastinal disorders: respiratory distress syndrome with pneumonitis and pulmonary edema (very rare).

Gastrointestinal disorders: loss of appetite, nausea, vomiting (common); constipation, discomfort in the gastrointestinal tract, diarrhea (rare); pancreatitis (very rare).

Hepatobiliary disorders: intrahepatic cholestasis or jaundice (rare).

Renal and urinary disorders: impaired renal function, acute renal failure (frequency unknown).

Skin and subcutaneous tissue disorders: urticaria and other forms of rash (common); photosensitivity reactions (rare); necrotizing vasculitis, toxic epidermal necrolysis = Lyell’s syndrome, skin reactions resembling systemic lupus erythematosus (SLE), exacerbation of SLE (very rare); erythema multiforme (frequency unknown).

General disorders and administration site conditions: fever, asthenia (frequency unknown).

Musculoskeletal and connective tissue disorders: muscle spasms (frequency unknown).

Reproductive system and breast disorders: erectile dysfunction (common).

Description of individual adverse reactions

Non-melanoma skin cancer. Based on the available data from clinical studies, there was a dose-dependent relationship between the use of hydrochlorothiazide and the development of non-melanoma skin cancer.

If any of the side effects listed in this leaflet get worse, or if you notice any other side effects not listed in this leaflet, inform your healthcare provider.

• Hypersensitivity to valsartan, hydrochlorothiazide, sulfonamides or any other component of Ko-Valsartan;
• Pregnancy and breast-feeding;
• Severe liver dysfunction, biliary cirrhosis and cholestasis;
• Anuria, severe renal failure (GFR < 30 ml/min/1.73 m²);
• Refractory hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia;
• Children and adolescents under 18 years of age (safety and efficacy in children under 18 years of age have not been established);
• Simultaneous use of ARB II, including valsartan, or ACE inhibitors with aliskiren in patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml/min / 1.73 m²).

When taking a larger dose than prescribed by a healthcare provider, immediately seek medical advice for timely medical assistance!

Symptoms: an overdose of valsartan can cause severe hypotension, which in turn can lead to impaired consciousness, circulatory collapse and/or shock. With an overdose of hydrochlorothiazide, nausea, drowsiness, hypovolemia, electrolyte imbalance, accompanied by cardiac arrhythmias and muscle spasms, may develop.

Treatment: therapeutic measures depend on the time passed since the overdose, as well as the type and severity of symptoms. While the primary measure is stabilization of the cardiovascular system. In case of overdose, depending on the time elapsed after taking Ko-Valsartan, the measures taken should include induction of vomiting, gastric lavage and / or administration of activated charcoal.

In case of hypotension, the patient should be placed in a horizontal position and immediately ensure the restoration of the water-salt balance by injecting isotonic saline.

Valsartan is not excreted by hemodialysis due to its strong binding to plasma proteins. However, hemodialysis is effective for removing hydrochlorothiazide from the body.

If you forget to take Ko-Valsartan, do not make up for the missed dose by taking a double dose. Just take your regular dose of Ko-Valsartan.

If you stop taking Ko-Valsartan, your blood pressure may rise again. You should continue taking Ko-Valsartan even if you feel well. Consult your healthcare provider if you intend to stop taking Ko-Valsartan.

If you have any further questions on the use of Ko-Valsartan, ask your doctor or pharmacist for advice.

Your healthcare provider should be informed about all medicines you are taking. Talk to your healthcare provider before taking any medicine while taking Ko-Valsartan.

Interactions related to valsartan and hydrochlorothiazide

Lithium: a reversible increase in serum lithium concentrations and an increase in toxicity have been reported with simultaneous use with ACE inhibitors, angiotensin II receptor antagonists and thiazides, including hydrochlorothiazide. Because the renal clearance of lithium decreases with thiazides, the risk of lithium toxicity most likely increases with Ko-Valsartan. If the simultaneous administration of these drugs is necessary, careful monitoring of the serum concentration of lithium is recommended.

Other antihypertensive medications: Ko-Valsartan may increase the effect of other antihypertensive drugs (guanethidine, methyldopa, vasodilators, ACE inhibitors, beta-blockers, calcium channel blockers, and direct renin inhibitors).

Sympathomimetics (adrenaline, norepinephrine): possible weakening of the therapeutic response to sympathomimetics.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid (more than 3 g/day) and other non-selective NSAIDs: with simultaneous administration, it is possible to weaken the antihypertensive effect of both angiotensin II antagonists and hydrochlorothiazide , as well as an increased risk of deterioration in renal function and an increase in plasma potassium concentration. If it is necessary to use such a combination, adequate hydration of patients and monitoring of renal function should be ensured from the start of treatment.

Interactions that occur during treatment with individual active components of the drug may also occur during treatment with Ko-Valsartan.

Interactions related to valsartan

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ARB II, ACE inhibitors, or aliskiren: Clinical data suggest that dual blockade of the renin-angiotensin-aldosterone system (RAAS) with combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with a higher incidence of adverse events such as hypotension, hyperkalemia, or impaired renal function (including acute renal failure) compared with monotherapy with agents acting on the RAAS.

Potassium-sparing diuretics, potassium preparations and salt substitutes containing potassium: if a simultaneous use of valsartan with a medicine that affects concentration of potassium in the blood serum is considered necessary, it is recommended to control concentration of potassium in the blood serum.

Transporters: In vitro data indicate that valsartan is a substrate for the OATP1B1/OATP1B3 and MRP2 transport proteins. Simultaneous use with inhibitors of OATP1B1 / OATP1B3 transport proteins (rifampin, cyclosporine) or the efflux transport protein MRP2 (ritonavir) may increase the systemic exposure of valsartan. Special precautions should be taken at the beginning or end of co-therapy with such medicinal products.

Other agents: no clinically significant interactions with agents such as: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide have been identified.

Interactions related to hydrochlorothiazide

Medicines affecting the level of potassium in the blood: the hypokalemic effect of the diuretic may be enhanced while taking other kaliuretic diuretics, corticosteroids, laxatives, adrenocorticotropic hormone, amphotericin, carbenoxolone, penicillin G, salicylic acid and salicylates). It is recommended to regularly monitor the concentration of potassium in the plasma.

Medicines causing cardiac arrhythmia: due to the risk of developing hypokalemia, caution should be exercised with the simultaneous use of medicines that cause cardiac arrhythmia of the “torsades de pointes” type: antiarrhythmic drugs of class 1a and III, some antipsychotics.

Medicines affecting the level of sodium in the blood: The hyponatraemic effect of diuretics may be enhanced when used simultaneously with certain medicines, such as antidepressants, antipsychotics and antiepileptics. Caution is advised in the long-term use of these medicinal products.

Cardiac glycosides: Hypokalemia and hypomagnesemia caused by taking thiazide diuretics contribute to the development of cardiac arrhythmias when taking cardiac glycosides.

Calcium salts and vitamin D: The use of thiazide diuretics, including hydrochlorothiazide, with vitamin D or calcium salts may lead to an increase in serum calcium concentration and the development of hypercalcemia in patients with a predisposition (for example, in hyperparathyroidism, malignancies and conditions mediated by vitamin D intake) due to increased tubular reabsorption of calcium.

Antidiabetic agents (oral hypoglycemic agents and insulin): Thiazides may impair glucose tolerance. When using thiazide diuretics, dose adjustment of antidiabetic agents may be required. Caution should be exercised when using metformin, because. it is possible to develop lactic acidosis due to the development of functional renal failure while taking hydrochlorothiazide.

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

Medicines for the treatment of gout (probenecid, sulfinpyrazone and allopurinol): dose adjustment of medicines for the treatment of gout may be required due to the possible increase in serum uric acid concentrations of hydrochlorothiazide. If necessary, increase the dose of probenecid or sulfinpyrazone. The simultaneous use of thiazide diuretics, including hydrochlorothiazide, may increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergics and other medicines affecting gastrointestinal motility: Anticholinergics (atropine, biperiden) may increase the bioavailability of thiazide diuretics, apparently due to inhibition of gastrointestinal motility and a decrease in the rate of gastric emptying. Conversely, prokinetics such as cisapride may decrease the bioavailability of thiazide diuretics.

Amantadine: Thiazide diuretics may increase the risk of adverse effects of amantadine.

Ion exchange resins: Absorption of hydrochlorothiazide is impaired in the presence of cholestyramine and colestipol. It is recommended to take hydrochlorothiazide 4 hours before or 4-6 hours after taking ion exchange resins.

Cytotoxicants: Hydrochlorothiazide may reduce the renal excretion of cytotoxicants (cyclophosphamide, methotrexate) and potentiate their myelosuppressive effect.

Non-depolarizing muscle relaxants (tubocurarine): Hydrochlorothiazide potentiates the action of curare-like muscle relaxants.

Cyclosporine: When used simultaneously with cyclosporine, there is an increasing risk of developing hyperuricemia and complications, such as gout.

Alcohol, barbiturates and narcotic drugs: Combined use of thiazide diuretics with substances that have an antihypertensive effect may increase the risk of orthostatic hypotension.

Methyldopa: Isolated cases of hemolytic anemia have been reported in patients receiving hydrochlorothiazide and methyldopa concomitantly.

Iodine-containing contrast agents: With dehydration caused by the use of thiazide diuretics, there is an increased risk of developing acute renal failure, especially when using high doses of iodine-containing drugs. Patients require rehydration before introduction of iodine-containing agents.

Electrolyte balance changes
Simultaneous prescription of valsartan with potassium supplements, salt substitutes containing potassium, potassium-sparing diuretics or other agents that can increase concentration of potassium in the blood serum (heparin, etc.) is not recommended. It is recommended to control concentration of potassium in the blood serum.

Cases of hypokalemia have been reported during treatment with thiazide diuretics. It is recommended to control the level of potassium in the blood serum.

Treatment with thiazide diuretics is often associated with the occurrence of hyponatremia and hypochloremic alkalosis. Thiazides, including hydrochlorothiazide, increase the excretion of magnesium in the urine, which can lead to the development of hypomagnesemia. Thiazides reduce urinary calcium excretion, which can lead to the development of hypercalcemia. Periodic monitoring of the concentration of electrolytes in the blood serum is recommended.

Patients with sodium deficiency and/or reduced circulating blood volume (CBV)
In patients with severe sodium deficiency and/or reduced CBV, for example, receiving high doses of diuretics. In rare cases symptomatic hypotension may occur at the beginning of treatment with Ko-Valsartan. Before starting treatment, it is necessary to correct the content of sodium and/or CBV in the body.

Patients with severe heart failure and other conditions accompanied by activation of the renin-angiotensin-aldosterone system
In patients with severe heart failure whose renal function is dependent on RAAS activity, treatment with ACE inhibitors may cause oliguria and/or progressive azotemia, and in rare cases, acute renal failure and/or death. Evaluation of patients with heart failure or post-infarction should always include an assessment of renal function. The use of Ko-Valsartan in patients with severe heart failure has not been studied. Therefore, it cannot be ruled out that inhibition of the RAAS by Ko-Valsartan may also lead to deterioration in renal function. In this regard, it is not recommended to use Ko-Valsartan in this patient population.

Renal artery stenosis
Ko-Valsartan 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. It is possible to increase the concentration of urea in the blood and the concentration of creatinine in the blood serum in these patients.

Primary hyperaldosteronism
Patients with primary hyperaldosteronism are not recommended to prescribe Ko-Valsartan, since their renin-angiotensin system is not active.

Stenosis of the aortic or mitral valve, obstructive hypertrophic cardiomyopathy
As for other vasodilators, special care should be taken when using Ko-Valsartan in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.

Impaired kidney function
In patients with impaired renal function (creatinine clearance> 30 ml / min), dose adjustment of Ko-Valsartan is not required. Periodic monitoring of serum concentrations of potassium, creatinine and uric acid is recommended in patients with impaired renal function taking Ko-Valsartan.

Simultaneous use of Ko-Valsartan with aliskiren is contraindicated in patients with renal insufficiency (GFR <60 ml/min / 1.73 m²) (see Sections Contraindications and Dosage and administration).

Kidney transplant
Currently, there are no data on the safety of the use of Ko-Valsartan in patients who have recently undergone kidney transplantation.

Impaired liver function
In patients with mild to moderate hepatic impairment without cholestasis, Ko-Valsartan should be used with caution. Thiazide diuretics should be used with caution in patients with impaired hepatic function or advanced liver disease, as mild hypovolemia and electrolyte imbalance may precipitate hepatic coma.

Angioedema in history
Cases of angioedema, including laryngeal and glottic edema leading to airway obstruction and/or swelling of the face, lips, pharynx and/or tongue, have been reported in patients treated with valsartan. Some of these patients had a history of angioedema after taking other medicines, including ACE inhibitors. In the event of angioedema, patients should immediately stop taking Ko-Valsartan. Re-administration of the drug is not allowed.

Systemic lupus erythematosus
Thiazide diuretics have been reported to exacerbate or activate manifestations of systemic lupus erythematosus.

Other metabolic disorders
Thiazide diuretics, including hydrochlorothiazide, may cause changes in glucose tolerance and an increase of cholesterol, triglycerides, and uric acid in serum. Patients with diabetes may need to adjust the dose of insulin or oral hypoglycemic agents.

Thiazides can reduce excretion of calcium ions in the urine and cause a temporary and slight increase in serum calcium concentration. Severe hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended to stop treatment with thiazide diuretics until a test to assess the function of the parathyroid glands.

Photosensitivity
Taking thiazide diuretics can provoke development of photosensitivity reactions. If a photosensitivity reaction develops, it is recommended to stop treatment with Ko-Valsartan. If it is necessary to take diuretics again, it is recommended to protect exposed skin from sunlight and UV radiation.

Pregnancy
Treatment with ARB II (including Ko-Valsartan) should not be initiated during pregnancy unless it is not possible to replace an ARB II with another alternative therapy. Patients planning pregnancy should be switched to antihypertensive therapy with medicinal products that have a well-established safety profile for pregnant women.

If pregnancy occurs, ARB II should be discontinued immediately and other antihypertensive therapy initiated as needed.

General disorders
Caution should be exercised in patients with hypersensitivity to other angiotensin II receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are most common in patients with allergies or asthma.

Acute angle-closure glaucoma
Hydrochlorothiazide, being a sulfonamide derivative, can cause an idiosyncratic reaction in the form of acute transient myopia and acute angle-closure glaucoma. Symptoms of these disorders include an unexpected decrease in visual acuity or pain in the eyes, which occur within a few hours to several weeks after the start of the drug. If left untreated, acute angle-closure glaucoma can lead to vision loss.

If these symptoms appear, the drug should be discontinued. If intraocular pressure remains uncontrolled, urgent conservative or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma may include a history of allergy to sulfonamides or penicillin.

Double blockade of the renin-angiotensin-aldosterone system (RAAS)
Hypotension, syncope, stroke, hyperkalemia, and impaired renal function (including acute renal failure) have been reported in individuals with hypersensitivity, especially when combining medicines that affect the RAAS. In this regard, a double blockade of the RAAS is not recommended while prescribing aliskiren with ACE inhibitors or ARB II (including valsartan).

If RAAS dual blockade therapy cannot be avoided, then it should be performed under supervision of specialists and the patient’s condition should be regularly monitored for renal function, electrolyte levels, and blood pressure.

Simultaneous use of Ko-Valsartan with aliskiren is contraindicated in patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m²).

Non-melanoma skin cancer
In two epidemiological studies, based on data from the Danish National Cancer Registry, the risk of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) was found to be dependent on the cumulative dose of hydrochlorothiazide. Photosensitivity in a patient taking hydrochlorothiazide is a possible mechanism for the development of non-melanoma skin cancer.

Patients taking hydrochlorothiazide should be informed of the risk of developing non-melanoma skin cancer and should be advised to regularly examine the skin for new lesions and immediately report any suspicious skin lesions. Possible preventive measures include limiting exposure to the sun and exposure to UV rays, sufficient protection, which will allow patients to reduce the risk of developing skin cancer. The need for the use of hydrochlorothiazide in patients who have previously had non-melanoma skin cancer should be carefully considered.

Consult your healthcare provider before taking Ko-Valsartan if you have one of the listed diseases or conditions.

Pregnancy
The use of Ko-Valsartan is contraindicated during pregnancy.

Valsartan
The use of ARB II is not recommended in the first trimester of pregnancy and is contraindicated in the second and third trimesters of pregnancy.

Epidemiological data have shown an increased risk of teratogenic effects with the use of ACE inhibitors in the first trimester of pregnancy. A similar risk may also exist when taking ARB II (including valsartan). If necessary, an alternative antihypertensive treatment should be prescribed in patients planning a pregnancy. The alternative treatment should have an established safety profile for use during pregnancy.

If pregnancy occurs, ARB II (including Ko-Valsartan) should be discontinued immediately and, another antihypertensive therapy should be prescribed when necessary.

ARB II use in the second and third trimesters is known to cause fetotoxicity (decreased renal function, oligohydramnios, and delayed skull ossification) and neonatal toxicity (renal failure, hypotension, and hyperkalemia).

If a woman takes an ARB II during the second trimester of pregnancy, then ultrasound monitoring of the function of the kidneys and the skull of the fetus is necessary. Newborns from mothers taking ARB II should be under close medical supervision due to possible hypotension.

Hydrochlorothiazide
Experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester, is limited. Data from animal studies are insufficient. Hydrochlorothiazide crosses the placental barrier. Based on the mechanism of the pharmacological action of hydrochlorothiazide, when used in the second and third trimesters of pregnancy, fetoplacental perfusion may be disturbed and jaundice, electrolyte imbalance and thrombocytopenia may develop in the fetus or newborn.

Breast-feeding
Data on the possibility of prescribing valsartan during breast-feeding are not available. Hydrochlorothiazide passes into breast milk. Therefore, it is not recommended to use Ko-Valsartan during breast-feeding. Patients should be switched to alternative therapy with medicines that possess a well-established safety profile when breast-feeding, especially if the child is newborn or premature.

Studies evaluating the effect of Ko-Valsartan on the ability to drive a car and work with mechanisms have not been conducted. When driving vehicles or working with mechanisms, the possibility of dizziness or weakness should be considered.

Film-coated tablets, 160 mg/12.5 mg.

10 tablets in a blister pack. 3 blister packs with a patient information leaflet in an outer carton.

15 tablets in a blister pack. 2 blister packs with a patient information leaflet in an outer carton.

Protect from light and moisture. Store at a temperature not exceeding 25°C.
Keep out of the reach of children.

2 years. Do not use after the expiry date.

State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus
Phone / Fax +375 17 268 63 64
production@academpharm.by
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en