Co-Vamloset, 10 mg+160 mg+25 mg 30 pcs.

Special Instructions

If you have any of the following conditions, inform your doctor before taking this medicine.

Caution should be exercised when using the drug in patients with unilateral or bilateral renal artery stenosis or artery stenosis of the single kidney, with conditions accompanied by decreased CER and water-electrolyte disturbances: nephropathies accompanied by salt loss, prerenal (cardiogenic) renal dysfunction, in patients with hypercalcemia, in patients with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, hypokalemia, hyponatremia, hypomagnesemia, hypochloremia In patients with CHF class III-IV according to NYHA classification, with acute coronary syndrome, with diabetes, with systemic lupus erythematosus, with hyperuricemia, with elevated concentrations of cholesterol and triglycerides in plasma, in patients with closed-angle glaucoma, in patients with a history of nonmelanoma skin cancer (NMSc) (see “Administration Instructions”). see section “Special indications”), as well as in patients after kidney transplantation. Caution should be exercised when using the drug in elderly patients.

Caution should be exercised when using Co-Vamloset concomitantly with potassium salts, potassium-saving diuretics, potassium-containing salt substitutes, and with drugs that may increase plasma potassium levels (e.g., heparin).

Application in children and adolescents under the age of 18

“Since the safety and effectiveness of Co-Vamloset in children and adolescents (under 18 years) has not been established, the drug is not recommended for use in this patient population.

Application in patients over age 65

No adjustment of the drug dose is necessary. In patients in this category, if necessary, it is possible to reduce the initial dose to contain the lowest dose of amlodipine, i.e. 1 tablet containing amlodipine + valsartan + GXTZ at a dose of 5 mg + 160 mg + 12.5 mg (as Co-Vamloset, film-coated tablets, 5 mg + 160 mg + 12.5 mg) or 5 mg + 160 mg + 25 mg (as Co-Vamloset, film-coated tablets, 5 mg + 160 mg + 25 mg).

Patients with impaired renal function

For patients with renal dysfunction of mild to moderate degree (FFR ≥ 30 ml/min/1.73 m² of body surface area, but ≤ 90 ml/min/1.73 m² of body surface area) the initial dose adjustment is not required. The drug should not be used in patients with severe renal dysfunction (GFR < 30 ml/min/1.73 m² body surface area) due to the presence of HCTS in the drug.

The use of thiazide diuretics in monotherapy in patients with severe renal function impairment (GFR < 30 ml/min/1.73 m² body surface area) is ineffective, however simultaneous use with “loop” diuretics in patients of this category is possible.

Patients with impaired liver function

Safety and effectiveness of amlodipine in hypertensive crisis have not been established.

Sodium deficiency and/or hypovolemia

Severe arterial hypotension, including orthostatic hypotension, was noted in 1.7% of patients receiving the maximum dose combination of amlodipine + valsartan + GXTZ (10 mg + 320 mg + 25 mg) compared with 1.8% of patients receiving the combination of valsartan + GXTZ (320 mg + 25 mg), 0.4% of patients receiving amlodipine + valsartan (10 mg + 320 mg) combination and 0.2% of patients receiving amlodipine + GXTZ (25 mg + 10 mg) combination in a controlled trial involving patients with uncomplicated moderate to severe arterial hypertension.

Patients with sodium deficiency and/or hypovolemia, such as those receiving high-dose diuretics, may develop symptomatic hypotension at the start of therapy with Co-Vamloset. This combination should be used only after correction of hyponatremia and/or hypovolemia.

In case of severe arterial hypotension during Co-Vamloset therapy, the patient should be placed in supine position and, if necessary, given intravenous infusion of 0.9% sodium chloride solution. Treatment with the drug can be continued after BP stabilization.

Changes in plasma electrolyte content

Co-Vamloset

In a controlled study in many patients, when the combination of amlodipine + valsartan + GXTZ was used, the effects of valsartan at 320 mg and GXTZ at 25 mg on serum potassium levels nearly balanced each other. In other patients, one of the effects may have predominated. Periodic plasma electrolyte determinations to detect possible electrolyte imbalances should be performed at set intervals.

Periodic determination of serum electrolytes, particularly potassium, should be performed at appropriate intervals to detect possible electrolyte imbalances, especially in patients with risk factors such as impaired renal function, use of other medications or a history of electrolyte imbalances.

Valsartan

Concurrent use with potassium-containing supplements, potassium-saving diuretics, eplerenone, potassium-containing salt substitutes, or other drugs that may cause an increase in plasma potassium (e.g., heparin) is not recommended. Plasma potassium levels should be monitored.

GCTZ

Therapy with Co-Vamloset should be started only after hypokalemia and concomitant hypomagnesemia have been eliminated. Thiazide diuretics may contribute to recurrence of hypokalemia or aggravate existing hypokalemia. Thiazide diuretics should be used with caution in patients with conditions with increased potassium loss, such as nephropathy, and prerenal (cardiogenic) renal dysfunction. If hypokalemia develops during treatment with HCTS, Co-Vamloset should be discontinued until steady normalization of plasma potassium.

Thiazide diuretics can promote hyponatremia and hypochloremic alkalosis again or aggravate already existing hyponatremia. Hyponatremia accompanied by neurological symptoms (nausea, progressive disorientation, apathy) has been observed. HCTH treatment should be started only after elimination of already existing hyponatremia. In case of severe or rapidly developing hyponatremia during combination amlodipine + valsartan + GXTZ treatment should be stopped until normalization of plasma sodium content.

All patients receiving thiazide diuretics should be monitored periodically for electrolyte disturbances, especially plasma potassium, sodium, and magnesium.

Kidney function impairment

Thiazide diuretics may contribute to azotemia in patients with chronic kidney disease. When using Co-Vamloset in patients with impaired renal function, it is recommended to monitor periodically electrolytes (including potassium), serum creatinine and uric acid concentrations. Co-Vamloset is contraindicated in patients with severe renal impairment (CK < 30 ml/min), anuria and patients on dialysis (see section “Contraindications”).

Patients with mild to moderate renal dysfunction (GFR ≥ 30 ml/min/1.73 m² body surface area) do not require dose adjustment of Co-Vamloset.

renal artery stenosis

In patients with unilateral or bilateral renal artery stenosis or stenosis of the artery of the single kidney, administration of Co-Vamloset may be accompanied by elevated serum urea and creatinine concentrations, so Co-Vamloset should be used with caution in such patients.

Kidney transplantation

Today, there are no data on the safe use of the combination amlodipine + valsartan + GXTZ in patients after kidney transplantation.

Hdisordered liver function

Ndisordered liver

Valsartan is excreted mainly in unchanged form with bile. T_½ amlodipine is prolonged, and AUC values are higher in patients with impaired hepatic function; there are no dose recommendations. In patients with mild to moderate hepatic impairment without cholestasis, the maximum recommended dose is 80 mg of valsartan, so Co-Vamloset is contraindicated in these patients.

Angioneurotic edema

Angioneurotic edema, including laryngeal and pharyngeal edema causing airway obstruction and/or swelling of the face, lips, larynx, and/or tongue, has been noted in patients receiving valsartan. Some of these patients had previously noted angioedema against the background of the use of other drugs, including ACE inhibitors. If angioedema develops, Co-Vamloset should be discontinued immediately and the drug should not be used again.

CHF and coronary heart disease/after myocardial infarction

In susceptible patients, there may be changes in renal function due to inhibition of the RAAS. In patients whose renal function depends on RAAS activity (e.g., patients with CHF of functional class III-IV [according to NYHA classification]), therapy with ACE inhibitors and ARA II may be accompanied by oliguria and/or progressive azotemia and in rare cases may lead to acute renal failure and death. Similar outcomes have been reported with valsartan therapy. Assessment of patients with CHF or post-myocardial infarction should always include renal function assessment.

In a long-term placebo-controlled trial (PRAISE-2) of amlodipine in patients with CHF of NYHA functional class III-IV nonischemic etiology, there was an increased incidence of pulmonary edema with amlodipine despite a slight difference in the incidence of worsening heart failure compared with placebo.

In patients with NYHA functional class III-IV CHF, BMCCs, including amlodipine, should be used with caution because they may increase the risk of cardiovascular events and death.

Caution is advised in patients with CHF and coronary heart disease because available data are limited in these patient populations.

Aortic and mitral valve stenosis

As with other vasodilators, caution should be exercised in patients with low-grade mitral valve stenosis or severe aortic valve stenosis.

Pregnancy

ARA II therapy should not be started during pregnancy. Patients planning to become pregnant should switch to an alternative hypotensive therapy with an established safety profile for use during pregnancy. If pregnancy is diagnosed, APA II therapy should be discontinued immediately or switched to an alternative hypotensive therapy with an established safety profile of use in pregnancy.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism should not use ARA II (including valsartan) because the RAAS is not activated in such patients. Therefore, Co-Vamloset should not be used in this population.

Systemic lupus erythematosus

A worsening of the course or development of systemic lupus erythematosus has been reported with thiazide diuretics, including GXTZ.

Other metabolic disorders

Thiazide diuretics, including HCTC, may alter glucose tolerance and increase serum cholesterol, triglycerides, and uric acid concentrations. In patients with diabetes mellitus it may be necessary to adjust the dose of insulin or hypoglycemic drugs for oral administration.

Due to the HCTS component, Co-Vamloset is contraindicated in symptomatic hyperuricemia. HCTS may increase serum uric acid concentration due to decreased uric acid clearance and may cause or aggravate hyperuricemia and contribute to gout in susceptible patients.

Thiazides decrease renal calcium excretion and may cause intermittent and small increases in serum calcium concentrations in the absence of known calcium metabolism disorders. Co-Vamloset is contraindicated in patients with hypercalcemia and should be used only after the existing hypercalcemia has been resolved. Co-Vamloset should be discontinued if hypercalcemia develops during treatment. Serum calcium concentration should be periodically monitored during thiazide therapy. Severe hypercalcemia may be a sign of occult hyperparathyroidism. Thiazide therapy should be interrupted before parathyroid function is investigated.

Photosensitivity

Photosensitivity reactions have been reported when using thiazide diuretics (see See section “Side effects”). If photosensitivity reactions develop during treatment with Co-Vamloset, it is recommended to discontinue therapy. If repeated use of the diuretic is necessary, it is recommended to protect the skin areas exposed to sunlight or artificial UV radiation.

acute closed angle glaucoma

HCHTZ, being a sulfonamide, causes an idiosyncratic reaction leading to the development of acute transient myopia and acute closed-angle glaucoma. Symptoms include a sudden decrease in visual acuity or pain in the eye, usually within a few hours or a week after starting the drug. Left untreated, acute closed angle glaucoma can lead to permanent vision loss.

Initial therapy consists of stopping use of HCTZ as soon as possible. If intraocular pressure remains uncontrolled, urgent conservative or surgical treatment may be necessary. A history of allergic reactions to sulfonamides and penicillin may be risk factors for acute closed angle glaucoma.

General

Caution should be exercised in patients with previous hypersensitivity to other ARA II. Hypersensitivity reactions to HCTS are more likely in patients with allergies and bronchial asthma.

Elderly patients (≥65 years)

Caution, including frequent BP monitoring, should be exercised in elderly patients because available data in this patient population are limited.

Double RAAS blockade

The concomitant use of ACE inhibitors, ARA II, or aliskiren is accompanied by a higher incidence of adverse events, such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure). If combined therapy by dual RAAS blockade is considered absolutely necessary, it should be performed only under the supervision of a specialist and with careful monitoring of renal function, plasma electrolytes and blood pressure.

The concomitant use of ARA IIc drugs containing aliskiren is contraindicated in patients with diabetes and/or with moderate or severe renal impairment (FFR < 60 ml/min/1.73 m² body surface area) and is not recommended in other patients. Concomitant use of ARA IIc with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Hypertensive crises

Co-Vamloset should not be used to control hypertensive crises.

Doping test

When using Co-Vamloset, athletes may have a positive doping test (due to the presence of HCTS in the drug).

NMRC

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between HCTC intake and an increased risk of developing basal cell carcinoma and squamous cell carcinoma (SCC). The risk of NSCLC development increased with increasing total (cumulative) dose of HCTS. A possible mechanism of NMRK development is the photosensitizing effect of HCTS.

Patients taking HCTC as monotherapy or in combination with other medications should be aware of the risk of developing NMR. It is recommended that such patients have regular skin examinations to detect any new suspicious lesions as well as changes in existing skin lesions.

Any suspicious skin changes should be reported to the physician immediately. Suspicious skin areas should be examined by a specialist. Histological examination of skin biopsy specimens may be required to confirm the diagnosis.

Patients should be advised to follow preventive measures such as limiting exposure to sunlight and ultraviolet (UV) rays and use appropriate protective equipment to minimize the risk of developing SLE.

In patients with a history of NMRCC, it is recommended that the appropriateness of HCTC be reconsidered.

Some side effects of the drug, including dizziness or visual disturbances, may adversely affect the ability to perform potentially hazardous activities requiring increased concentration and rapid psychomotor reactions (driving vehicles, operating moving machinery). Patients taking Co-Vamloset should be cautious when driving vehicles and operating moving mechanisms.

Synopsis

Tablets 5 mg + 160 mg + 12.5 mg:

Oval, biconvex, film-coated tablets in white or nearly white with K1 engraved on one side.

Fracture appearance: white or almost white rough surface with white or almost white film coating.

Tablets 10 mg + 160 mg + 12.5 mg:

Oval, biconvex, film-coated tablets in pink with K2 engraved on one side.

Fracture appearance: white or almost white rough surface with pink film coating.

Tablets 10 mg + 160 mg + 25 mg:

Oval, biconvex, film-coated tablets brown-yellow with K4 engraved on one side.

Fracture appearance: white or almost white rough surface with brown-yellow film coating.

Contraindications

Hypersensitivity to amlodipine, valsartan, GXTZ, other sulfonamide derivatives and dihydropyridine series, as well as other excipients of the drug.

– Hereditary angioedema, or edema in patients on prior therapy with ARA II.

– Pregnancy, pregnancy planning and breastfeeding period.

– Liver failure, biliary cirrhosis and cholestasis.

– Severe renal function impairment (CK < 30 ml/min), anuria, hemodialysis patients.

– Hypokalemia, hyponatremia, hypercalcemia, and hyperuricemia with clinical manifestations refractory to adequate therapy.

– Age <18 years (effectiveness and safety not established).

– Severe arterial hypotension (systolic BP < 90 mm Hg), collapse, cardiogenic shock.

– Clinically significant aortic stenosis.

– Hemodynamically unstable heart failure after acute myocardial infarction.

– Concurrent use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal function impairment (FFR < 60 ml/min/1.73 m² body surface area).

– Concurrent use with ACE inhibitors in patients with diabetic nephropathy.

Overdose

There are currently no data on cases of drug overdose.

Amlodipine

Alodipine overdose may result in excessive peripheral vasodilation and possible reflex tachycardia. Severe and prolonged BP lowering up to the development of shock with lethal outcome has also been reported.

Valsartan

In an overdose of valsartan, you can expect to develop a marked decrease in BP and dizziness.

In case of pronounced BP decrease, the patient should be in a horizontal position with elevated legs and take active measures to support cardiovascular activity, including regular monitoring of cardiac and respiratory system activity, CPR, and urine output.

Vasopressor drugs may be used to maintain normal vascular tone if there are no contraindications. If Co-Vamloset has been taken recently, vomiting or gastric lavage may be effective. The use of activated charcoal in healthy volunteers was accompanied by a decrease in absorption of amlodipine.

Valsartan and amlodipine are not eliminated by hemodialysis, whereas hemodialysis may be effective for HCTC elimination.

Pregnancy use

As with any drug that affects the renin-angiotensin-aldosterone system (RAAS), Co-Vamloset should not be used in women planning to become pregnant. When prescribing any drug that affects the RAAS, the physician should inform women of childbearing age about the potential dangers of these drugs during pregnancy.

The use of Co-Vamloset in pregnancy is contraindicated.

It is known that the use of ACE inhibitors that affect the RAAS in the II and III trimesters of pregnancy leads to the damage or death of the developing fetus. Given the mechanism of action of ARA II, the risk to the fetus cannot be excluded. According to a retrospective analysis, the use of ACE inhibitors in the first trimester of pregnancy was accompanied by the development of fetal and neonatal pathology. HCTC penetrates through the placenta. Thiazide diuretics, including HCTC, may cause fetal or neonatal jaundice or thrombocytopenia during pregnancy, as well as other adverse reactions seen in adult patients. Inadvertent administration of valsartan in pregnant women has resulted in cases of spontaneous abortions, scarcity of water, and renal dysfunction in the newborn. There are insufficient data on the use of amlodipine in pregnant women to judge its effect on the fetus.

If pregnancy is diagnosed during treatment with Co-Vamloset, the drug should be discontinued as soon as possible.

It is unknown whether valsartan and/or amlodipine are excreted with breast milk. Excretion of valsartan with breast milk has been reported in experimental studies. HCTS is also excreted with breast milk. Co-Vamloset is contraindicated during breastfeeding.