Co-Vamloset, 10 mg+160 mg+12, 5 mg 30 pcs.

Hypotensive drug combined (slow calcium channel blocker [BMCC] + angiotensin II receptor antagonist [ARA II] + diuretic)

Indications

Grade II and III arterial hypertension.

Composition

1 film-coated tablet,5 mg + 160 mg + 12.5 mg/10 mg + 160 mg + 12.5 mg/10 mg + 160 mg + 25 mg contains:

Core:

Active substances:

Amlodipine besylate (amlodipine besylate) 6.94 mg/13.88 mg/13.88 mg, equivalent to amlodipine 5.00 mg/10.00 mg/10.00 mg

Valsartan A, substance-granules 251.35 mg/251.35 mg/251.35 mg

[Active substance of granule substance: valsartan 160.00 mg/160.00 mg/160.00 mg

Auxiliary substances of the granule substance: microcrystalline cellulose (type 200), croscarmellose sodium, povidone K-25, sodium lauryl sulfate]

Hydrochlorothiazide 12.50 mg/12.50 mg/25.00 mg

Supplements:

Mannitol, magnesium stearate, colloidal silicon dioxide

Film shell:

Film-forming compound:

– polyvinyl alcohol

– macrogol-3350

– talc

Red iron oxide dye (E172) (for 10 mg + 160 mg + 12.5 mg tablets)

Yellow iron oxide dye (E172) (for 10 mg + 160 mg + 25 mg tablets)

How to take, the dosage

The drug Co-Vamloset should be taken orally with a little water, regardless of meal times.

The recommended daily dose is 1 tablet containing amlodipine + valsartan + GXTZ at a dose of 5 mg + 160 mg + 12.5 mg, 10 mg + 160 mg + 12.5 mg (as Co-Vamloset, film-coated tablets, 5 mg + 160 mg + 12.5 mg, 10 mg + 160 mg + 12.5 mg) or 1 tablet containing amlodipine + valsartan + GXTZ at a dose of 10 mg + 160 mg + 25 mg (as Co-Vamloset, film-coated tablets, 10 mg + 160 mg + 25 mg).

The drug Co-Vamloset is taken once daily.

For convenience, patients receiving amlodipine, valsartan and GXTZ monotherapy in separate tablets can be switched to therapy with Co-Vamloset containing the same doses of active ingredients. Patients with insufficient BP control on dual combination therapy (valsartan + GXTZ, amlodipine + valsartan and amlodipine + GXTZ) may be switched to triple combination therapy with Co-Vamloset in appropriate doses. The dose of Co-Vamloset shall be adjusted after previously titrated doses of monocomponent drugs containing the active ingredients of Co-Vamloset. If it will be necessary to change a dose of one of active substances in KoVamloset (e.g. in connection with newly diagnosed disease, change of patient’s condition or drug interaction) individual selection of doses of individual components is necessary.

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

If a patient has dose-dependent side effects when using dual combination therapy with any component of Co-Vamloset, a Co-Vamloset containing a lower dose of the active component that caused the side effect may be used to achieve a comparable decrease in BP.

Increase the dose 2 weeks after starting therapy.

The maximum antihypertensive effect of Co-Vamloset is noted 2 weeks after increasing the dose. The maximum dose is 10 mg + 320 mg + 25 mg per day.

Application in patients over 65 years

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).

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.

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 dysfunction (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

Interaction

Amlodipine

When amlodipine monotherapy is used, there are no clinically significant interactions with Thiazide diuretics, beta-adrenoblockers, ACE inhibitors, long-acting nitrates, nitroglycerin for sublingual use, digoxin, warfarin, atorvastatin, sildenafil, aluminum- and magnesium hydroxide, simethicone, cimetidine, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and hypoglycemic drugs for oral administration.

Concurrent administration of amlodipine and ethanol does not affect pharmacokinetics of the latter.

CYP3A4 isoenzyme inhibitors

Concurrent use of amlodipine at a dose of 5 mg/day with diltiazem at a dose of 180 mg/day in elderly patients with arterial hypertension resulted in a 1.6-fold increase in systemic exposure to amlodipine. When using amlodipine with potent CYP3A4 isoenzyme inhibitors (e.g., ketoconazole, itraconazole and ritonavir) an even more pronounced increase in systemic exposure to amlodipine may occur. Caution is necessary when using amlodipine with CYP3A4 isoenzyme inhibitors.

Due to CYP3A4 isoenzyme inhibition, concomitant administration with grapefruit juice may increase the bioavailability of amlodipine. However, in a clinical study in healthy volunteers no significant changes in pharmacokinetics were found when taking amlodipine at a dose of 10 mg with 240 ml of grapefruit juice.

CYP3A4 isoenzyme inducers

Because the use of amlodipine with CYP3A4 isoenzyme inducers (e.g., carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone, rifampicin, herbal preparations containing St. John’s Wort

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 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 dysfunction (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

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 a 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

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 is insufficient data on the use of amlodipine in pregnant women to judge its impact 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.