Co-Vamloset, 30 pcs., 5 mg+160 mg+12.5 mg, film-coated tablets

Vamloset®

The drug Vamloset®

Common drug interactions for Vamloset® (amlodipine/valsartan)

Concomitant use requiring attention

Other antihypertensive drugs (eg, alpha-blockers, diuretics) and drugs that have a hypotensive effect (eg, tricyclic antidepressants, alpha-blockers for the treatment of benign prostatic hyperplasia) may enhance the antihypertensive effect.

Drug interactions for amlodipine

Undesirable simultaneous use

Grapefruit or grapefruit juice

Concomitant use is not recommended due to the possibility of increased bioavailability in some patients and enhanced antihypertensive effects.

Concomitant use requiring caution

CYP3A4 isoenzyme inhibitors

Concomitant use with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, verapamil or diltiazem, azole antifungals, macrolides such as erythromycin or clarithromycin) may lead to a significant increase in the systemic exposure of amlodipine. In elderly patients, these changes are of clinical significance, so medical supervision and dosage adjustment are necessary.

Inducers of the CYP3A4 isoenzyme (anticonvulsants (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort)

With simultaneous use of inducers of the CYP3A4 isoenzyme, the concentration of amlodipine in the blood plasma may vary. Therefore, blood pressure control and dose adjustment of amlodipine are indicated both during treatment with inducers of the CYP3A4 isoenzyme and after their withdrawal, especially when using strong inducers of the CYP3A4 isoenzyme (for example, rifampicin, drugs containing St. John's wort).

Simvastatin

Simultaneous repeated use of amlodipine at a dose of 10 mg/day and simvastatin at a dose of 80 mg/day increases the exposure of simvastatin by 77% compared with that of simvastatin monotherapy. For patients receiving amlodipine, it is recommended to use simvastatin at a dose of no more than 20 mg/day.

Dantrolene (intravenous administration)

In animal experiments, cases of fatal ventricular fibrillation and cardiovascular failure associated with hyperkalemia were observed after oral administration of verapamil and intravenous administration of dantrolene. Given the risk of developing hyperkalemia, simultaneous use of slow calcium channel blockers, including amlodipine, should be avoided in patients prone to developing malignant hyperthermia.

Tacrolimus

When used concomitantly with amlodipine, there is a risk of increasing the concentration of tacrolimus in the blood plasma, but the pharmacokinetic mechanism of this interaction has not been fully studied. To prevent the toxic effect of tacrolimus when used concomitantly with amlodipine, the concentration of tacrolimus in the blood plasma should be monitored and the dose of tacrolimus should be adjusted if necessary.

Cyclosporine

Drug interaction studies have not been conducted with cyclosporine and amlodipine in healthy volunteers or other patient populations, except for renal transplant patients in whom variable trough concentrations (mean: 0%-40%) of cyclosporine were observed. With the simultaneous use of amlodipine in patients who have undergone kidney transplantation, the concentration of cyclosporine in the blood plasma should be monitored and, if necessary, its dose should be reduced.

Clarithromycin

Clarithromycin is an inhibitor of the CYP3A4 isoenzyme. With simultaneous use of amlodipine and clarithromycin, the risk of developing arterial hypotension is increased. Close medical monitoring of patients receiving amlodipine concomitantly with clarithromycin is recommended.

Mammalian target of rapamycin (mTOR) inhibitors

mTOR inhibitors such as sirolimus, temsirolimus and everolimus are substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of the CYP3A isoenzyme. When used concomitantly with mTOR inhibitors, amlodipine may increase their exposure.

Concomitant use requiring attention

Other

In clinical studies of amlodipine, there was no significant interaction with thiazide diuretics, alpha-blockers, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, Maalox (aluminum- or magnesium-containing antacids, simethicone) , cimetidine, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and oral hypoglycemic agents.

Simultaneous use of amlodipine and ethanol

does not affect the pharmacokinetics of the latter.

Calcium preparations

may reduce the effect of BMCC.

With simultaneous use of BMCC with lithium preparations

(no data available for amlodipine) their neurotoxicity may increase (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Glucocorticosteroids

Decreased antihypertensive effect (retention of fluid and sodium ions as a result of action (retention of fluid and sodium ions as a result of the action of corticosteroids).

Drug interactions for valsartan

Concomitant use is contraindicated

Concomitant use of ARB II, including valsartan, with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.

Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Undesirable simultaneous use

Lithium

Simultaneous use with lithium preparations is not recommended, since a reversible increase in the concentration of lithium in the blood plasma and the development of intoxication are possible. If simultaneous use with lithium preparations is necessary, the concentration of lithium in the blood plasma should be carefully monitored. The risk of toxic effects associated with the use of lithium preparations may further increase when used simultaneously with Vamloset® and diuretics.

Potassium-sparing diuretics, potassium supplements, potassium-containing dietary supplements, and other drugs and substances that may increase serum potassium levels (eg, heparin)

If simultaneous use with drugs that affect potassium levels is necessary, it is recommended to monitor the potassium content in the blood plasma.

Concomitant use requiring caution

NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid in a dose of more than 3 g/day and non-selective NSAIDs

With simultaneous use, it is possible to weaken the antihypertensive effect, increase the risk of developing renal dysfunction and increase the potassium content in the blood plasma. At the beginning of therapy, it is recommended to assess renal function, as well as correct water and electrolyte imbalances.

Transport protein inhibitors

in vitro study results

valsartan is a substrate for the transporter proteins OATP1B1 and MRP2. Concomitant use of valsartan with OATP1B1 transporter protein inhibitors (eg, rifampicin, cyclosporine) and an MRP2 transporter protein inhibitor (eg, ritonavir) may increase the systemic exposure of valsartan (Cmax and AUC). This should be taken into account at the beginning and at the end of concomitant therapy.

Double blockade of the RAAS when using ARA II, ACE inhibitors or aliskiren

The simultaneous use of ARA II with other drugs that affect the RAAS leads to an increase in the incidence of cases of arterial hypotension, hyperkalemia, and renal dysfunction. It is necessary to monitor blood pressure, renal function, and the content of blood plasma electrolytes when using Vamloset® with other drugs that affect the RAAS.

Other

When monotherapy with valsargan, no clinically significant interactions were identified with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.

Compound

Side effects

WHO classification of the incidence of side effects: very often - ≥1/10; often - from ≥1/100 to <1/10; uncommon - from ≥1/1000 to <1/100; rarely - from ≥1/10000 to <1/1000; very rarely - <1/10000; frequency unknown—cannot be estimated from available data.

Vamloset

Infectious and parasitic diseases: often - nasopharyngitis, influenza.

From the immune system: rarely - hypersensitivity.

Metabolism and nutrition: often - hypokalemia; uncommon - anorexia, hypercalcemia, hyperlipidemia, hyperuricemia, hyponatremia.

Mental disorders: rarely - anxiety.

From the nervous system: often - headache; uncommon - loss of coordination, dizziness, postural dizziness, paresthesia, drowsiness.

From the side of the organ of vision: infrequently - visual impairment; rarely - visual impairment.

From the organ of hearing and labyrinthine disorders: infrequently - vertigo; rarely - tinnitus.

From the side of the heart: infrequently - palpitations, tachycardia; rarely - fainting.

From the side of blood vessels: infrequently - orthostatic hypotension; rarely - a pronounced decrease in blood pressure.

From the respiratory system, chest and mediastinal organs: infrequently - cough, pain in the pharynx and larynx.

From the digestive system: uncommon - diarrhea, nausea, abdominal discomfort, pain in the upper abdomen, constipation, dry oral mucosa.

From the skin and subcutaneous tissues: infrequently - erythema, skin rash; rarely - exanthema, hyperhidrosis, itching.

From the musculoskeletal and connective tissue side: infrequently - arthralgia, back pain, swelling of the joints; rarely - muscle spasms, a feeling of heaviness throughout the body.

From the kidneys and urinary tract: rarely - pollakiuria, polyuria.

From the genital organs and breast: rarely - erectile dysfunction.

General disorders and disorders at the injection site: often - asthenia, increased fatigue, facial swelling, a feeling of a rush of blood to the facial skin, edema, peripheral edema, pastosity.

Additional Information

In patients receiving the amlodipine/valsartan combination, peripheral edema was less common (5.8%) than in patients receiving amlodipine therapy alone (9%).

Amlodipine

From the blood and lymphatic system: very rarely - leukopenia, thrombocytopenia, sometimes with purpura.

From the immune system: very rarely - hypersensitivity.

Metabolism and nutrition: very rarely - hyperglycemia.

Mental disorders: uncommon - depression, insomnia/sleep disorders, mood lability; rarely - confusion.

From the nervous system: often - dizziness, headache, drowsiness; uncommon - taste disturbance, paresthesia, fainting, tremor, hypoesthesia; very rarely - muscle hypertonicity, peripheral neuropathy, neuropathy; frequency unknown - extrapyramidal disorders.

From the organ of vision: infrequently - blurred vision, blurred vision.

From the organ of hearing and labyrinthine disorders: infrequently - tinnitus.

From the side of the heart: often - palpitations; very rarely - arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction.

From the side of blood vessels: often - a feeling of a rush of blood to the skin of the face, a pronounced decrease in blood pressure; very rarely - vasculitis.

From the respiratory system, chest and mediastinal organs: infrequently - shortness of breath, rhinitis; very rarely - cough.

From the digestive system: often - nausea, abdominal discomfort, pain in the upper abdomen; uncommon - changes in stool, diarrhea, dry oral mucosa, dyspepsia, vomiting; rarely - gastritis, gingival hyperplasia, pancreatitis.

From the liver and biliary tract: very rarely - increased activity of liver enzymes (usually with symptoms of cholestasis), increased concentration of bilirubin in the blood plasma, hepatitis, intrahepatic cholestasis, jaundice.

From the skin and subcutaneous tissues: infrequently - alopecia, exanthema, erythema, photosensitivity reactions, itching, hyperhidrosis, purpura, skin rash, change in skin color; very rarely - erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema.

From the musculoskeletal and connective tissue side: often - swelling of the ankles; uncommon - arthralgia, back pain, muscle spasms, myalgia.

From the kidneys and urinary tract: infrequently - urinary disorders, nocturia, pollakiuria.

From the genital organs and breast: uncommon - erectile dysfunction, gynecomastia.

General disorders and disorders at the injection site: often - increased fatigue, peripheral edema; uncommon - asthenia, discomfort, malaise, non-cardiogenic heart pain, pain.

Laboratory and instrumental data: infrequently - decrease/increase in body weight.

Valsartan

From the blood and lymphatic system: frequency unknown - decrease in hemoglobin and hematocrit, leukopenia, neutropenia, thrombocytopenia, sometimes with purpura.

From the immune system: very rarely - hypersensitivity.

From the organ of hearing and labyrinthine disorders: infrequently - vertigo.

From the side of blood vessels: frequency unknown - vasculitis.

From the respiratory system, chest and mediastinal organs: infrequently - cough.

From the digestive system: infrequently - a feeling of discomfort in the abdomen, pain in the upper abdomen.

From the liver and biliary tract: frequency unknown - increased activity of liver enzymes, increased concentration of bilirubin in the blood plasma.

From the skin and subcutaneous tissues: frequency unknown - skin itching, skin rash, angioedema.

Musculoskeletal and connective tissue disorders: frequency unknown - myalgia.

From the kidneys and urinary tract: frequency unknown - increased concentration of creatinine in the blood plasma, impaired renal function, including acute renal failure.

General disorders and disorders at the injection site: uncommon - increased fatigue.

Laboratory and instrumental data: frequency unknown - increased potassium levels in the blood serum.

Additional information about the components of the drug

Adverse events previously reported with each of the components may occur with Vamloset, even if they were not observed in clinical studies.

Amlodipine

Often - drowsiness, dizziness, palpitations, abdominal pain, nausea, swelling of the ankles.

Uncommon: insomnia, mood lability (including anxiety), depression, tremor, taste disturbance, fainting, hypoesthesia, visual impairment (including diplopia), tinnitus, marked decrease in blood pressure, shortness of breath, rhinitis, vomiting , dyspepsia, alopecia, purpura, skin discoloration, hyperhidrosis, itching, exanthema, myalgia, muscle cramps, pain, urinary disturbance, increased frequency of urination, impotence, gynecomastia, chest pain, malaise, weight gain, weight loss.

Rarely - confusion.

Very rarely - leukopenia, thrombocytopenia, allergic reactions, hyperglycemia, muscle hypertonicity, peripheral neuropathy, myocardial infarction, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis, pancreatitis, gastritis, gingival hyperplasia, hepatitis, jaundice, increased activity of liver enzymes (most often due to cholestasis), angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity.

Isolated cases of extrapyramidal syndrome have been described.

Valsartan

Frequency unknown - decreased hemoglobin and hematocrit, neutropenia, thrombocytopenia, increased serum potassium, increased liver enzyme activity, increased plasma bilirubin concentration, increased plasma creatinine concentration, impaired renal function, including renal failure, angioedema, myalgia , vasculitis, hypersensitivity, including serum sickness.

Use during pregnancy and breastfeeding

Vamloset is contraindicated during pregnancy.

Considering the mechanism of action of ARA II, a risk to the fetus cannot be excluded when using the drug in the first trimester of pregnancy.

Like any other drug that directly affects the RAAS, Vamloset should not be used during pregnancy, or in women planning pregnancy. When prescribing drugs that affect the RAAS, it is necessary to inform women of childbearing age about the potential risk of negative effects of these drugs on the fetus during pregnancy. When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile. If pregnancy is diagnosed, you should stop taking Vamloset and, if necessary, switch to alternative antihypertensive therapy.

The drug Vamloset, like other drugs that have a direct effect on the RAAS, is contraindicated in the II–III trimesters of pregnancy, since it can cause fetotoxic effects (impaired renal function, delayed ossification of fetal skull bones, oligohydramnios) and neonatal toxic effects (renal failure, arterial hypotension , hyperkalemia) and fetal death. If, however, the drug was used in the II–III trimesters of pregnancy, then it is necessary to conduct an ultrasound of the kidneys and bones of the fetal skull. Newborns whose mothers took Vamloset during pregnancy should be monitored because the development of arterial hypotension in the newborn is possible.

It is not recommended to use Vamloset during breastfeeding. If therapy with Vamloset is necessary during lactation, breastfeeding should be discontinued.

Contraindications

hypersensitivity to amlodipine, other dihydropyridine derivatives, valsartan or other components of the drug;

severe liver failure (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis;

severe renal failure (creatinine Cl less than 30 ml/min), patients on hemodialysis;

severe arterial hypotension (SBP less than 90 mm Hg), collapse, shock (including cardiogenic shock);

obstruction of the LV outflow tract (including hypertrophic obstructive cardiomyopathy and severe aortic stenosis);

hemodynamically unstable heart failure after acute myocardial infarction;

primary hyperaldosteronism;

simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml/min);

pregnancy;

breastfeeding period.

The safety of using Vamloset in patients after kidney transplantation, as well as in children and adolescents under 18 years of age, has not been established.

With caution: mild (5–6 points on the Child-Pugh scale) and moderate (7–9 points on the Child-Pugh scale) liver dysfunction; obstructive diseases of the biliary tract; mild to moderate renal dysfunction (creatinine clearance 30–50 ml/min); unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney; chronic heart failure of functional class III–IV according to the NYHA classification; hyperkalemia; hyponatremia; diet with limited salt intake; decreased blood volume (including diarrhea, vomiting); hereditary angioedema or edema due to previous therapy with ARA II. As with the use of other vasodilators, special caution should be exercised when used in patients with mild to moderate mitral and aortic stenosis.