Tablets for pressure Vamloset instructions for use, at what pressure

Irbesartan is an oral drug that does not need biotransformation to manifest its activity. After oral administration, irbesartan is rapidly and completely absorbed. Tmax of irbesartan in blood plasma – 1,5–2 hours after ingestion. The absolute bioavailability of irbesartan when administered is 60–80%. Eating does not affect the bioavailability of irbesartan.

Irbesartan is approximately 96% bound to plasma proteins and practically does not bind to blood cells.

Vd of irbesartan is 53–93 l/kg.

After oral or intravenous administration of 14C of irbesartan, unchanged irbesartan in the blood plasma accounts for 80–85% of the radioactivity circulating in the systemic circulation. Irbesartan is metabolized in the liver by conjugation with glucuronic acid and oxidation. The main metabolite in the systemic circulation is irbesartan glucuronide (approximately 6%).

Irbesartan undergoes oxidation, mainly using the cytochrome P450 isoenzyme – CYP2C9; CYP3A4 isoenzyme plays an insignificant role in the metabolism of irbesartan. Irbesartan is not metabolized by most isoenzymes commonly involved in drug metabolism, such as isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6 or CYP2E1, and does not significantly induce or inhibit these isoenzymes. Irbesartan does not inhibit the CYP3A4 isoenzyme.

Irbesartan and its metabolites are excreted both by the liver (with bile) and by the kidneys. After oral or intravenous administration of 14C irbesartan, about 20% of the radioactivity is found in the urine with a small residual amount in the feces. Less than 2% of the dose is excreted by the kidneys as unchanged irbesartan. T1/2 of irbesartan is 11–15 hours. The total clearance with iv administration of irbesartan is 157–176 ml/min, of which 3–3,5 ml/min is accounted for by the renal clearance.

In elderly patients without arterial hypertension (men and women 65–80 years old) with clinically normal renal and hepatic function, AUC and Cmax in plasma were approximately 20–50% higher than in patients of a younger age (18–40 years) however, T1/2 in patients of young and old age were comparable. No significant age-related differences in the clinical efficacy of irbesartan were observed.

Patients of the Negroid Race with Normal Numbers Blood pressure AUC and T1/2 of irbesartan were approximately 20–25% higher than patients of the Caucasian race with normal BP, but the Cmax of irbesartan was almost the same.

In patients with renal failure (regardless of its severity) and in patients on hemodialysis, the pharmacokinetics of irbesartan does not change significantly.

Irbesartan is not removed from the blood via hemodialysis.

In patients with hepatic insufficiency due to cirrhosis of the liver of mild or moderate severity, the pharmacokinetics of irbesartan does not significantly change.

The effectiveness and safety of irbesartan in children has not been established.

After oral administration in therapeutic doses, amlodipine is well absorbed with Tmax in the blood – between 6 and 12 hours after its administration. Absolute bioavailability is 64–90%. Eating does not interfere with the absorption of amlodipine.

Amlodipine Vd is approximately 21 L/kg. In vitro studies have shown that approximately 97,5% of amlodipine in the systemic circulation binds to plasma proteins.

Amlodipine is extensively metabolized in the liver with the formation of inactive metabolites.

Through the kidneys, 10% of unchanged amlodipine and 60% of its metabolites are excreted; T1/2 from blood plasma is approximately 35-50 hours when dosed once a day.

In elderly and younger people, the Tmax of amlodipine in the blood is the same. In elderly patients, amlodipine clearance tends to decrease, resulting in increased AUC and T1/2.

In children 6-12 years old and adolescents 13-17 years old, amlodipine clearance when taking the drug inside was 22,5 and 27,4 l/h, respectively, for boys and 16,4 and 21,3 l/h, respectively, for girls. There was a large variability in systemic exposure to amlodipine in different children and adolescents. Data obtained on the use of the drug in children under 6 years of age are limited.

As with other CCBs, with liver failure, an increase in T1/2 of amlodipine is possible (see “Contraindications”, with caution and “Special Instructions”).

Patients with heart failure (in all age groups) showed an increase in AUC and T1/2.

Pharmacokinetics with the use of a combination of amlodipine/irbesartan in adults

The simultaneous administration of irbesartan and amlodipine in the form of fixed combinations in tablets or in the form of free combinations did not affect the pharmacokinetics of each of the active substances of this combination.

Three fixed dose combinations of amlodipine and irbesartan (10/150 mg, 5/300 mg and 10/300 mg) are bioequivalent to free dose combinations (10/150 mg, 5/300 mg and 10/300 mg), both in terms of speed, so in relation to the degree of absorption. When taken individually or simultaneously in doses of 10 and 300 mg, the time to reaching the median Cmax of amlodipine and irbesartan in blood plasma remains unchanged, i.e.

Pharmacokinetics in the application of the combination of amlodipine/irbesartan in children

There is no information on taking a fixed combination of amlodipine and irbesartan in children.

aprovask - Tablets for pressure Vamloset instructions for use, at what pressure

After oral administration in therapeutic doses, amlodipine is well absorbed with the achievement of Cmax in the blood – between 6 and 12 hours after its administration. Absolute bioavailability is 64–90%. Eating does not interfere with the absorption of amlodipine.

In elderly and young patients, Cmax of amlodipine in the blood is the same. In elderly patients, amlodipine clearance tends to decrease, resulting in increased AUC and T1/2.

As with other BMCC, with liver failure, an increase in T1/2 of amlodipine is possible (see Caution and “Special Instructions”).

Impaired liver function. There is an extremely limited amount of clinical data on the use of amlodipine in patients with impaired liver function. In patients with hepatic insufficiency, a decrease in amlodipine clearance was observed, which led to an extension of T1/2 and an increase in AUC by approximately 40-60%.

Elderly: Tmax of amlodipine in blood plasma is comparable in elderly patients and in patients of a younger age group. In elderly patients, the amlodipine clearance rate tends to decrease with a corresponding increase in AUC and an extension of T1/2.

Irbesartan is an oral drug that does not need biotransformation to manifest its activity. After oral administration, irbesartan is rapidly and completely absorbed. Cmax of irbesartan in blood plasma is achieved 1,5–2 hours after ingestion. The absolute bioavailability of irbesartan when administered is 60–80%. Eating does not affect the bioavailability of irbesartan.

e19f4dd9df0ffd760a4c078c948f98b8 - Tablets for pressure Vamloset instructions for use, at what pressure

Irbesartan is approximately 96% bound to plasma proteins and practically does not bind to blood cells. Vd of irbesartan is 53–93 l/kg.

After oral or intravenous administration of 14C of irbesartan, unchanged irbesartan in the blood plasma accounts for 80–85% of the radioactivity circulating in the systemic circulation. Irbesartan is metabolized in the liver by conjugation with glucuronic acid and oxidation. The main metabolite in the systemic circulation is irbesartan glucuronide (approximately 6%).

Irbesartan undergoes oxidation, mainly using the cytochrome P450 isoenzyme – CYP2C9; CYP3A4 isoenzyme plays an insignificant role in the metabolism of irbesartan. Irbesartan is not metabolized by most isoenzymes commonly involved in drug metabolism, such as isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6 or CYP2E1, and does not significantly induce or inhibit these isoenzymes. Irbesartan does not inhibit the CYP3A4 isoenzyme.

In patients of the Negroid race with normal blood pressure, AUC and T1/2, irbesartan was approximately 20–25% higher than in patients of the European race with normal blood pressure, but the Cmax of irbesartan was almost the same.

In patients with renal failure (regardless of its severity) and patients on hemodialysis, the pharmacokinetics of irbesartan does not change significantly. Irbesartan is not removed from the blood via hemodialysis.

Studies of the efficacy and safety of irbesartan in children have not been conducted.

The use of a combination of amlodipine/irbesartan in adults

The simultaneous administration of irbesartan and amlodipine in the form of fixed combinations in tablets or free combinations did not affect the pharmacokinetics of each of the active substances of this combination.

Dosing and Administration

Inside. The tablet is swallowed with water.

can be taken both simultaneously with a meal, and on an empty stomach (ie, regardless of the meal time).

Adults Usually, the initial and maintenance dose of Aprovask is 1 tablet/day. Aprovask should be used in patients who cannot achieve their target blood pressure with monotherapy with irbesartan or monotherapy with amlodipine, or to continue treatment of patients already taking irbesartan and amlodipine in separate tablets.

Doses should be selected individually, first with the use of separate preparations of irbesartan and amlodipine. Doses are selected depending on the reaction of arterial pressure on the therapy and the target value of blood pressure. The maximum recommended dose of Aprovask® is 10 150 or 10 300 mg/day (due to the fact that the maximum daily dose of amlodipine is 10 mg).

Children. The safety and effectiveness of Aprovask have not been established.

Elderly patients and impaired renal function. Usually, there is no need for dose reduction in elderly patients (see Pharmacodynamics) and patients with impaired renal function.

Impaired liver function. The drug Aprovask should be used with caution, due to the presence of amlodipine in the composition of the drug (see

“Contraindications”, with caution and “special instructions”).

Aprovask is taken orally, regardless of the time of meal. The tablet is swallowed whole, washed down with water.

The initial and maintenance dose of the drug is 1 tablet per day.

Aprovask is prescribed for patients in whom it is not possible to achieve the necessary blood pressure (BP) values ​​with monotherapy with irbesartan or amlodipine. Also, the drug is prescribed to continue therapy for patients taking irbesartan and amlodipine separately.

Doses are selected individually, first with the use of irbesartan and amlodipine separately, depending on the therapeutic effect and the target value of blood pressure.

The maximum daily dose of Aprovask is 10 mg 150 mg or 10 mg 300 mg (the amount of amlodipine should not exceed 10 mg per day).

Inside. The tablet is swallowed with water. Aprovask® can be taken both at the same time as eating, and on an empty stomach (i.e., regardless of the time of eating).

Adults The initial and maintenance dose of Aprovask® is 1 tablet/day.

Aprovask® should be used in patients who cannot achieve their target blood pressure with monotherapy with irbesartan or monotherapy with amlodipine, or to continue treatment of patients already taking irbesartan and amlodipine in separate tablets. Doses should be selected individually, first with the use of separate preparations of irbesartan and amlodipine. Doses are selected depending on the reaction of arterial pressure on the therapy and the target value of blood pressure.

The maximum recommended dose of Aprovask® is 10 150 or 10 300 mg/day (due to the fact that the maximum daily dose of amlodipine is 10 mg).

If a change in the dose of one of the active substances in the composition of the drug is required (for example, in connection with a newly diagnosed disease, a change in the patient’s condition or drug interaction), then an individual selection of doses of the individual components is necessary.

Children. The use of the drug in pediatric patients is contraindicated, the safety and effectiveness of Aprovask® have not been established.

Elderly patients and patients with impaired renal function. Dose adjustment is not required.

lekarstvo aprovask - Tablets for pressure Vamloset instructions for use, at what pressure

Impaired liver function. The drug Aprovask® should be used with caution, due to the presence of amlodipine in the composition of the drug (see Precautions and “Special Instructions”).

In elderly patients with impaired liver function, it is necessary to reduce the initial dosage of Aprovask® to the lowest dose of amlodipine (i.e., to 1 table. 5 150 mg or 5 300 mg).

Pharmacological groups

Heading ICD-10ICD-10 disease synonyms
I10 Essential (primary) hypertensionHypertension
Arterial hypertension
Crisis arterial hypertension
Arterial hypertension complicated by diabetes
Hypertension
Sudden increase in blood pressure
Hypertensive circulatory disorders
Hypertensive state
Hypertensive crises
Hypertension
Arterial hypertension
Malignant hypertension
Essential hypertension
Hypertonic disease
Hypertensive crises
Hypertensive crisis
Hypertension
Malignant hypertension
Malignant hypertension
Isolated systolic hypertension
Hypertensive crisis
Exacerbation of hypertension
Primary arterial hypertension
Transient arterial hypertension
Essential arterial hypertension
Essential arterial hypertension
Essential hypertension
Essential hypertension
I15 Secondary hypertensionHypertension
Arterial hypertension
Crisis arterial hypertension
Arterial hypertension complicated by diabetes
Hypertension
Vasorenal hypertension
Sudden increase in blood pressure
Hypertensive circulatory disorders
Hypertensive state
Hypertensive crises
Hypertension
Arterial hypertension
Malignant hypertension
Symptomatic hypertension
Hypertensive crises
Hypertensive crisis
Hypertension
Malignant hypertension
Malignant hypertension
Hypertensive crisis
Exacerbation of hypertension
Renal hypertension
Renovascular arterial hypertension
Renovascular hypertension
Symptomatic arterial hypertension
Transient arterial hypertension

Pregnancy

The use of the drug Aprovask® is contraindicated during pregnancy and during breastfeeding.

Amlodipine. The safety of amlodipine during pregnancy has not been established. In preclinical studies in animals, signs of reproductive toxicity were observed with high doses of amlodipine.

Irbesartan. Sufficient and well-controlled studies of irbesartan use in pregnant women are lacking. Exposure to the fetus of ACE inhibitors, which were taken by pregnant women in the II and III trimesters of pregnancy, led to damage and death of the developing fetus. Like any other drugs that directly affect RAAS, irbesartan is contraindicated during pregnancy.

Amlodipine. It penetrates into breast milk in an amount of 3-7% of the maternal dose (up to a maximum of 15%). The effect of amlodipine on newborns is unknown. In the case of treatment of lactating women, preference should be given to alternative drugs with a more studied safety profile during breastfeeding, especially when feeding a newborn or premature baby. A decision should be made to stop breastfeeding or to discontinue the drug, taking into account the need for its use for the mother.

Irbesartan. Excreted in the milk of lactating rats. It is not known whether irbesartan/its metabolites can be excreted in human breast milk. During breastfeeding, irbesartan is contraindicated. After assessing the ratio of the expected benefits of taking the drug to the mother and the potential risk to the child, either breastfeeding or taking irbesartan should be discontinued.

Amlodipine. Clinical evidence regarding the potential effect of amlodipine on fertility is insufficient. In one study, rats were found to have adverse effects on male fertility.

When using BMCC in some patients, biochemical changes in the sperm head were observed. There is insufficient clinical data on the potential effect of amlodipine on fertility.

Irbesartan. In studies in male and female rats, irbesartan did not affect fertility and reproductive function even in doses that have some toxic effect on parents (up to 650 mg/kg/day). There was no significant effect on the number of corpus luteum, implantable embryos or live fetuses. Irbesartan did not affect the survival, development or reproduction of offspring.

When taking irbesartan in doses of ≥50 mg/kg/day (which, when converted to 1 kg of body weight, is approximately equivalent to the maximum recommended dose of irbesartan in humans (MRI) of 300 mg/day) in pregnant rats from days 0 to 20 gestation in fetuses of rats, transient effects were observed (slight or moderate expansion of the renal pelvis, hydroureter, and/or absence of the renal papillae).

aprovask org - Tablets for pressure Vamloset instructions for use, at what pressure

When irbesartan was administered in doses of ≥180 mg/kg/day (approximately equivalent to 4 × MRDIC per 1 kg of body weight), pregnant rats developed subcutaneous edema in rats from 0 to 20 days of gestation. Since these developmental abnormalities were not observed with the restriction of oral administration of irbesartan at doses of 50, 150, and 450 mg/kg/day to pregnant rats from the 6th to the 15th day of gestation, they are likely to be late gestational effects of irbesartan.

In rabbits, the use of irbesartan at a dose of 30 mg/kg/day was associated with maternal mortality and abortion. Surviving females who received this dose equivalent to 1,5 × MRDIC when converted to kg body weight had a slight increase in fetal resorption and, accordingly, a decrease in the number of live fetuses in the litter. It was found that irbesartan crosses the placental barrier in rats and rabbits.

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The interaction of aprovask with other dosage forms

As part of the drug, pharmacological tests proved the absence of an interaction harmful to the human body between amlodipine and irbesartan. Interaction with other means is as follows:

  • you can not use aprovask with medicines that contain aliskiren for those patients who suffer from moderate to severe renal insufficiency, have diabetes, and other patients are not recommended to use a combination of these components;
  • simultaneous administration of aprovask with drugs including ACE inhibitors for patients with diabetic nephropathy and other people is not recommended; analogues of the drug should be used.

The use in the treatment of irbesartan at the same time is not shown:

  • with potassium-containing drugs;
  • with salt analogues including potassium;
  • diuretics, potassium-sparing action;
  • other means, the action of which is aimed at increasing potassium in the body;
  • in elderly patients with hypokalemia after using diuretics or with impaired renal function at the same time as non-steroidal anti-inflammatory drugs, side effects are reversible after drug withdrawal;
  • the combined use of irbesartan with lithium preparations increases the content of the latter in the blood, which poisons the body with toxins.

This medicine is harmlessly combined with thiazide diuretics, alpha-blockers, long-acting nitrates, beta-blockers, ACE inhibitors, non-steroidal anti-inflammatory drugs, hypoglycemic drugs for internal use, antibiotics, nitroglycerin in tablets.

Vamloset - Tablets for pressure Vamloset instructions for use, at what pressure

When combined with phenytoin, indomethacin, digoxin, warfarin, amlodipine does not have a weakening effect on protein binding of the above drugs. Cimetidine does not affect the pharmacological effect of amlodipine while taking it, as taking a glass of grapefruit juice is not contraindicated.

The combined use of amplodipine and tacrolimus affects the increase in the concentration of the latter in the blood, so the simultaneous use is allowed, but laboratory monitoring is required. The combined use of amlodipine and simvastatin leads to an increase in the exposure of the latter in order to reduce unpleasant consequences, its norm is reduced to 20 mg.

Aprovask is a combined antihypertensive drug with irbesartan and amlodipine.

The latter is a derivative of dihydropyridine, a slow calcium channel blocker.

The drug has an antianginal, antihypertensive effect.

Taking the drug in a single dose for hypertension provides a decrease in blood pressure (this effect is observed within 24 hours).

The drug is prescribed to patients suffering from arterial hypertension in the event that monotherapy with irbesartan or amlodipine does not bring the desired result (it turns out to be ineffective).

Detonic – a unique medicine that helps fight hypertension at all stages of its development.

Detonic for pressure normalization

The complex effect of plant components of the drug Detonic on the walls of blood vessels and the autonomic nervous system contribute to a rapid decrease in blood pressure. In addition, this drug prevents the development of atherosclerosis, thanks to the unique components that are involved in the synthesis of lecithin, an amino acid that regulates cholesterol metabolism and prevents the formation of atherosclerotic plaques.

Detonic not addictive and withdrawal syndrome, since all components of the product are natural.

Detailed information about Detonic is located on the manufacturer’s page www.detonicnd.com.

Mode of application

According to official instructions, Aprovask is intended for oral use. The tablets are swallowed on an empty stomach or during meals (regardless of food) and washed down with water.

The maintenance dose for adult patients coincides with the initial dose and is 1 tablet/day. The drug is prescribed for patients for whom monotherapy with amlodipine or irbesartan is ineffective (does not allow to achieve blood pressure targets).

Aprovask can also be used to continue the treatment of people taking amlodipine, irbesartan in separate tablets. As for the doses, they are selected individually depending on the target value Blood pressure and reactions Blood pressure on therapy. The maximum recommended daily dose is 10 150 or 10 300 mg.

Safety, efficacy of the drug in relation to children have not been established.

Elderly patients, impaired renal function. As a rule, there is no need for dose reduction in elderly patients, as in people with impaired renal function.

Impaired hepatic function. In this case, Aprovask should be used carefully, as it contains amlodipine.

Aprovask is available in the form of oval, biconvex tablets of pink, white or yellow color, coated with a film membrane.

Each tablet consists of:

  • active substances: amlodipine, irbesartan;
  • inactive components: hypromellose, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, croscarmellose sodium;
  • film sheath: opadra white, opadra yellow or opadra pink.

In studies in which the listed components were taken in combination and separately, PCV between amlodipine and irbesartan was absent.

Studies on the interaction of Aprovask with other drugs have not been conducted.

Irbesartan. Interactions with drugs metabolized by cytochrome P450 isoenzymes such as CYP1A1, CYP2A6, CYP1A2, CYP2B6, CYP2E1, CYP2D6, CYP3A4 should not be expected.

With the combined use of irbesartan with hydrochlorothiazide, nifedipine, the pharmacokinetic parameters of the former are not violated.

Patients with moderate/severe renal failure and diabetes mellitus are not allowed to take Aprovask along with medicines containing aliskiren. This combination is undesirable for other people.

ACE inhibitors. Joint administration of potassium preparations, potassium-sparing diuretics containing potassium salts can cause an increase in serum potassium concentration.

The simultaneous use of NSAIDs (including irbesartan) in elderly patients, people with impaired renal function and hypovolemia, can lead to deterioration of renal function (up to the development of acute renal failure). Such effects are reversible.

Lithium. The combination of lithium with irbesartan can increase the toxic effect of lithium, increasing its concentration in blood plasma. That is why patients taking this combination should monitor the plasma lithium concentration with medical help.

Digestive tractinfrequently – constipation, nausea, pain in the upper abdomen; often – swelling of the gums.
Respiratory systeminfrequently – coughing.
Heart and blood vesselsinfrequently – sinus bradycardia, a strong decrease in blood pressure; often – palpitations, orthostatic hypotension.
Metabolismhyperkalemia is rare.
Nervous systeminfrequently – paresthesia; often – dizziness, headaches, drowsiness.
sensesrarely seen vertigo.
The urinary systeminfrequently – azotemia, hypercreatinemia.
Sexual systemerectile dysfunction is rare.
Bones and musclesinfrequently – myalgia, joint stiffness, arthralgia.
Other reactionsinfrequently – an asthenic state, often – swelling, peripheral edema.
Respiratory systemextremely rarely – coughing; infrequently – shortness of breath, rhinitis; often a cough.
CASextremely rare – vasculitis, ventricular tachycardia, atrial fibrillation, myocardial infarction, heart rhythm disturbance; often – palpitations, hot flashes, redness of the skin.
Bones, musclesinfrequently – arthralgia, muscle cramps, myalgia, back pain.
Psyche, nervous systemextremely rare – peripheral neuropathy; infrequently – taste perversion, insomnia, tremor, mood lability, paresthesia, syncope, hypesthesia; often – headache, dizziness, drowsiness.
Sexual systeminfrequently – impotence, gynecomastia.
sensesinfrequent ringing in the ears, visual disturbances, vertigo.
The immune systemextremely rarely – angioedema, urticaria, other allergic reactions.
The urinary systeminfrequently – nocturia, increased frequency of urination, the appearance of painful urges.
Other reactionsrarely – swelling of the face; infrequently – aches, chest pains, asthenic state, feeling of malaise.

5. Contraindications

Aprovask is not allowed in patients under 18, pregnant and lactating women, as well as in people with:

  • hypersensitivity to amlodipine, irbesartan, other derivatives of dihydropyridine, additional (inactive) ingredients of drugs;
  • cardiogenic shock;
  • unstable angina (except for Prinzmetal angina);
  • clinically significant aortic stenosis;
  • diabetes mellitus or severe/moderate renal failure, provided that it is used simultaneously with drugs containing aliskiren;
  • diabetic nephropathy, provided the combined use of ACE inhibitors.

Recommended storage temperature – not higher than 30 degrees. Keep out of the reach of children. Do not use after three years from the date of release.

7. Price

As a rule, the price of Aprovask in pharmacies in the Russian Federation starts from 650 rubles per pack of drug.

c30355c012ffcd8db6e10db40f659e2b - Tablets for pressure Vamloset instructions for use, at what pressure

The approximate average cost of Aprovask in Ukraine is 700-900 hryvnias.

8. Analogs

Such drugs as Amlodipine, Amlodak, Amzaar, Amlodigamma, Amlovas, etc. are referred to the analogues of the Aprovask drug.

9. Reviews

Since Aprovask is prescribed to patients for whom monotherapy with irbesartan/amlodipine has proven ineffective, reviews are mostly positive.

According to patients and doctors, the drug quickly and carefully removes the symptoms of arterial hypertension, leading a person’s blood pressure to normal levels. To read the reviews of people about this medicine, you must go to the end of the article.

10. Summary

Thus, Aprovask is an effective drug for the treatment of hypertension. The drug is used to treat all categories of patients, except for children and adolescents under 18, as well as pregnant/lactating women.

To purchase Aprovask in a pharmacy you will have to present a prescription with a seal, a doctor’s signature.

kak upotreblyat lekarstvo aprovask - Tablets for pressure Vamloset instructions for use, at what pressure

The combination of irbesartan and amlodipine

Overdose

Symptoms: when adults take irbesartan in doses up to 900 mg/day, there is no toxicity.

Available data for amlodipine suggest that a severe overdose can lead to severe peripheral vasodilation and, possibly, the development of reflex tachycardia. It was reported about the development of a pronounced and prolonged excessive decrease in blood pressure, up to the development of shock with a fatal outcome.

Treatment: the patient should be under close medical supervision. Treatment should be symptomatic and supporting the basic vital functions of the body. There is no specific information on the treatment of an overdose of irbesartan.

Proposed measures for an overdose of Aprovask® include gastric lavage. The intake of activated charcoal by healthy volunteers immediately after or 2 hours after oral administration of 10 mg of amlodipine showed a slight decrease in the absorption of amlodipine.

Due to the fact that amlodipine has a high bond with blood proteins, and irbesartan is not excreted by hemodialysis, it is unlikely that hemodialysis can be useful in case of an overdose.

If a very large overdose has occurred, active monitoring of cardiac activity and respiration should begin. Frequent blood pressure measurement is needed. A clinically significant reduction in blood pressure due to an overdose of amlodipine requires the active maintenance of cardiovascular activity, including elevating the limbs.

Symptoms of an overdose of the drug

: when adults take irbesartan in doses up to 900 mg/day, the absence of toxicity is established. Available data for amlodipine suggest that a severe overdose can lead to severe peripheral vasodilation and, possibly, the development of reflex tachycardia. It was reported about the development of a pronounced and prolonged excessive decrease in blood pressure, up to the development of shock with a fatal outcome.

Treatment: the patient should be under close medical supervision. Treatment should be symptomatic and supporting the basic vital functions of the body. There is no specific information on the treatment of an overdose of irbesartan. Proposed measures for an overdose of Aprovask® include gastric lavage.

The intake of activated charcoal by healthy volunteers immediately after or 2 hours after oral administration of 10 mg of amlodipine showed a slight decrease in the absorption of amlodipine. Due to the fact that amlodipine has a high bond with blood proteins, and irbesartan is not excreted by hemodialysis, it is unlikely that hemodialysis can be useful in case of an overdose.

If a very large overdose has occurred, active monitoring of cardiac activity and respiration should begin. Frequent blood pressure measurement is needed. A clinically significant reduction in blood pressure due to an overdose of amlodipine requires the active maintenance of cardiovascular activity, including elevating the limbs.

Description of dosage form

The composition of the drug includes irbesartan and amlodipine, which are antagonists of the receptors for angioezin and BKK. They reduce blood pressure, weakening the resistance of blood vessels on the periphery, block the emission of calcium into the cell and narrow the pit outside.

The substance belongs to strong selective ARAII, angiotensin stops the pathological development of arterial hypertension and takes part in the homeostasis of sodium ions, for which it does not require activation of the metabolic plan. Irbesartan stops the sharp vasoconstrictor effect of angiotensin II, is not active against AT! Receptors. The component does not inhibit enzymes, for example, renin, ACE, and does not affect such hormonal receptors or ion delivery channels.

The use of irbesartan leads to a decrease in the plasma number of aldosterone, when taken in the dosage shown, the concentration of potassium in the blood serum does not change. The substance does not affect the number of triglycerides, glucose in the blood serum, does not change the concentration of uric acid or the intensity of its excretion by the kidneys.

Pressure indicators decrease regardless of body position, while there is a rare appearance of an orthostatic effect, which does not apply to patients with hypovolemia or hyponatremia. Irbesartan monotherapy is not always possible to obtain the required blood pressure indicators, in this case, a diuretic is added to the substance to additively reduce the pressure by 7-10 mm Hg. Art. and 3–6 mmHg. Art. dystolic and systolic indicators. Cancellation of the drug leads to a gradual return of blood pressure to its previous level.

Amlodipine

The tablets block the entry of calcium into the smooth vascular muscle and myocardial cells by inhibiting the ion entry membrane. The mechanism of lowering blood pressure is directly related to the relaxation of smooth vascular muscles, although until now a mechanism for reducing the intensity of angina attacks has not been specifically identified, but there is a decrease in ischemic pathologies.

Amlodipine dilates arterioles on the periphery of blood vessels, which leads to a decrease in subsequent load on the heart muscle. Myocardial oxygen demand is not expressed so sharply and reduces its energy costs. The effect of the drug is associated with an increase in the lumen of the coronary arteries and arterioles in healthy and ischemic areas of the myocardium. Vasodilatation allows an increase in oxygen supply to the myocardial muscles in those patients who suffer from spasm of the coronary arteries.

The use of the drug once a day for therapy for hypertension shows a decrease in blood pressure within 24 hours, while the patient should stand or sit. For stopping a hypertensive crisis, amlodipine is not an effective medicine due to the slow start of work.

For patients with angina pectoris, a single use of the drug per day can increase the duration of physical activity before the onset of the attack and the interval before the onset of depression of the ST segment on a cardiogram one millimeter deep. Amlodipine therapy is relevant for reducing the number of angina attacks and can reduce nitroglycerin intake per day; it is allowed for patients with diabetes mellitus, asthma and gout.

To obtain evidence of greater efficacy of the combined use of fixed doses of amlodipine and irbesartan, open clinical trials were conducted in parallel groups. Studies have led to the identification of increased effectiveness of the combination of two active substances compared to their use alone.

Composition of tablets

The drug contains irbesartan and amlodipine in different dosages, so that it is convenient to use for patients with different intensity of the disease.

As additional components used:

  • croscarmellose sodium – 24 mg;
  • microcellulose 100 μm – 10 mg;
  • hydromellose – 10 mg;
  • colloidal silicon dioxide – 2,5 mg;
  • magnesium stearate – 2,5 mg.

Only the amount of microcrystalline cellulose of 50 μm varies, which is calculated depending on the content of active ingredients. The shell includes:

  • titanium dioxide;
  • Opadra color shell;
  • macrogol 800;
  • macrogol 400;
  • dye depending on the color of the capsule.

Aprovask should be used in patients with arterial hypertension with ineffective treatment with one of the active ingredients individually (amlodipine or irbesartan).

To reduce the number of side effects during treatment, you should carefully read the list of diseases and conditions that make the use of the drug impossible:

  • cardiac shock;
  • increased reaction to amlodipine and irbesartan or auxiliary components of the drug;
  • aortic stenosis confirmed by a clinical diagnosis;
  • temporary angina (does not apply to angina pectoris);
  • pregnancy and breastfeeding time;
  • children under the age of 18;
  • the simultaneous administration of funds, in which there is aliskiren, for patients with diabetes or moderate renal failure;
  • simultaneous use of ACE inhibitors in patients with diabetic nephropathy.
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Some conditions and diseases allow the use of aprovask, but caution is observed, which is expressed in constant laboratory monitoring:

  • patients with hypokalemia or a lack of sodium, such conditions can occur after intensive use of diuretics, following a salt-free diet, gastrointestinal upset, expressed in profuse vomiting and diarrhea;
  • if in patients the renal function depends on the intensity of the RAAS (for example, patients with stenosis of the arteries of the kidneys, hypertension, heart failure of chronic course in grades 3 and 4 according to the NYHA classification);
  • if in patients with heart failure of classes 2–4 of a non-ischemic cause, pulmonary edema develops as a result of the use of amlodipine, the progression of the disease remains unchanged;
  • in patients with renal failure and after an organ transplant, the amount of potassium and blood creatinine should be monitored;
  • in patients with obstructive hypertrophic cardiomyopathy or stenosis of the mitral or aortic valve;
  • in patients with coronary heart disease, confirmed by a diagnosis of cerebral arteriosclerosis (with a significant decrease in pressure, there is a risk of an increase in the intensity of ischemic pathology, sometimes an acute stroke or heart attack develops).

Tablets, 5 150 mg: oval biconvex, covered with a white film coating, with an engraving of “150/5” on one side.

Tablets, 10 150 mg: oval biconvex, covered with a pink film sheath, engraved with “150/10” on one side.

Tablets, 5 mg: oval biconvex, coated with a yellow film coating, engraved with “300/300” on one side.

Tablets, 10 300 mg: oval biconvex, covered with a white film membrane, with a risk and a bevel to the risk on one side.

Composition and graduation form

film-coated tablets, 5 mg 150 mg, 10 mg 150 mg, 5 mg 300 mg and 10 mg 300 mg.

In a blister PVC/PE/PVDC/aluminum, 7 pcs. 2 or 4 bl. in a cardboard bundle.

Film-coated tablets, 5 mg 150 mg, 10 mg 150 mg, 5 mg 300 mg and 10 mg 300 mg. In a blister PVC/PE/PVDC/aluminum, 7 pcs. 2 or 4 bl. in a cardboard bundle.

The combined action drug Vamloset contains two active components that can be used individually: amlodipine and valsartan. Amlodipine belongs to calcium ion inhibitors and has a vasodilating effect, reduces the load on the heart. Valsartan blocks angiotensin II receptors, responsible for pressure drops, reduces myocardial hypertrophy.

Their joint presence increases the hypotensive effect due to mutually complementary various mechanisms of action. Therefore, a lower dose is required to control pressure. This reduces the likelihood of unwanted side effects, for example, edema that occurs during treatment with Amlodipine.

The medicine is intended for internal use, dispensed in pharmacies with a prescription exclusively in tablet form. Vamlocet pressure-coated tablets are available in various contents and ratios of active ingredients:

  • 5 mg 80 mg;
  • 5 mg 160 mg;
  • 10 mg 160 mg.

The first number corresponds to the content of besilate amlodipine in terms of amlodipine, and the second indicates the amount of valsartan in the granular substance Valsartan A – it is in these forms that the active ingredients are present in the medicine. The composition is complemented by a standard complex of neutral binders and excipients that color the preparation in yellow-brown color.

The package is a blister of 14 round tablets with a minimum dosage or 7 oval with a high content of active substance. From 1 to 7 plates and instructions for the preparation are placed in cardboard boxes.

Dosage form Aprovask – film-coated tablets, oval, biconvex:

  • 5 mg 150 mg: white film coating, engraving “150/5” on one side;
  • 10 mg 150 mg: pink film coating, engraving “150/10” on one side;
  • 5 mg 300 mg: yellow film coating, engraving “300/5” on one side;
  • 10 mg 300 mg: white film coating, on one side of the risk and bevel to risk.

Tablets are packaged in blisters for 7 pcs., 2 or 4 blisters in a cardboard box.

1 film-coated tablet contains:

  • active substances: amlodipine irbesartan – 5 mg 150 mg/10 mg 150 mg/5 mg 300 mg/10 mg 300 mg;
  • auxiliary components: microcrystalline cellulose 50 microns, microcrystalline cellulose 100 microns, croscarmellose sodium 6 MPa.s, colloidal silicon dioxide, magnesium stearate;
  • Shell: Opadry white (Aprovask 5 mg 150 mg and 10 mg 300 mg), Opadry pink (Aprovask 10 mg 150 mg), Opadry yellow (Aprovask 5 mg 300 mg).

Pharmacodynamics

The pharmacodynamic properties of each of the active substances that make up the drug Aprovask®, irbesartan and amlodipine contribute to their additive antihypertensive effect when used in combination compared with that when using each of these drugs separately. Both ARAII and BMCC reduce blood pressure by reducing peripheral vascular resistance, but the blockade of calcium intake into the cell and the reduction of the vasoconstrictor effect due to the action of angiotensin II are complementary mechanisms.

Amlodipine is a BMKK from the group of dihydropyridine derivatives, which inhibits the transmembrane entry of calcium ions into the myocardial cells and vascular smooth muscle. The mechanism of the antihypertensive effect of amlodipine is associated with a direct relaxing effect on the smooth muscles of blood vessels.

Amlodipine expands peripheral arterioles and due to this reduces the round fist, so-called. afterload Since the heart rate is practically not increased when taking amlodipine, this reduction in the load on the heart muscle reduces myocardial energy expenditure and its oxygen demand.

In patients with arterial hypertension, taking amlodipine once a day provides a clinically significant reduction in blood pressure while lying and standing for 24 hours. Due to the slow onset of its action, amlodipine is not intended to stop hypertensive crises.

In patients with angina pectoris, taking amlodipine once a day during a physical exercise test increases the total exercise time, the time before the onset of angina pectoris, and the time before the ST segment depression on the ECG by 1 mm. In addition, taking the drug reduces the daily number of angina attacks and the daily need for taking nitroglycerin tablets.

When taking amlodipine, no undesirable metabolic effects or changes in blood lipid concentrations were observed. Amlodipine can be taken in patients with asthma, diabetes and gout.

Irbesartan is a selective highly potent ARA II (subtype AT1). Angiotensin II is an important component of RAAS involved in the pathophysiology of the development of arterial hypertension and the homeostasis of sodium ions. For the manifestation of its action, irbesartan does not need metabolic activation.

Irbesartan blocks the strong vasoconstrictor and aldosterone-secreting effect of angiotensin II due to selective antagonism to angiotensin II receptors (subtype AT1) located in the smooth muscle cells of the vessels and adrenal cortex. Irbesartan has no agonistic activity towards AT1 receptors.

Irbesartan does not inhibit RAAS enzymes (such as renin, ACE), and does not affect other hormonal receptors or ion channels in the CVS involved in the regulation of blood pressure and sodium ion homeostasis. Blockade of irbesartan AT1 receptors breaks the feedback loop in the renin-angiotensin system, increasing plasma concentrations of renin and angiotensin II.

When irbesartan is used, the plasma concentration of aldosterone decreases, but when using the drug in the recommended doses, there are no significant changes in the serum potassium content (the average increase in serum potassium is less than 0,1 mEq/l). Irbesartan has no significant effect on the concentration of triglycerides, cholesterol or glucose in the blood serum. Irbesartan does not affect serum uric acid concentrations or kidney excretion of uric acid.

The antihypertensive effect of irbesartan develops after taking the first dose and becomes significant during 1 – 2 weeks of treatment, with a maximum effect occurring through 4 – 6 weeks. In long-term observational studies, the effect of irbesartan persisted over 1 of the year.

A single dose of irbesartan in doses up to 900 mg/day caused a dose-dependent decrease in blood pressure. A single dose of irbesartan in doses of 150-300 mg/day led to a greater decrease in blood pressure/dArterial pressure (24 hours after taking the dose) in the supine position or sitting position (on average, 8–13/5–8 mm Hg), than with a placebo. The effect of the drug 24 hours after taking the dose was 60–70% of the corresponding maximum decrease in dArterial pressure and blood pressure. Optimum effectiveness in reducing blood pressure within 24 hours is achieved with a single dose of the drug per day.

Blood pressure decreases approximately equally when standing and lying down. The orthostatic effect is rare, and, as with the use of ACE inhibitors, its occurrence can be expected in patients with hyponatremia or hypovolemia. The antihypertensive effect of irbesartan and thiazide diuretics is additive.

In patients who cannot achieve their blood pressure targets with irbesartan monotherapy, the addition of small doses of hydrochlorothiazide (1 mg) to irbesartan once a day leads to an additional (compared with the placebo effect) decrease in blood pressure and dad determined 12,5 hours after their administration, by 24–7/10–3 mm Hg. Art. respectively.

Age and gender do not affect the effectiveness of irbesartan. As in the case of treatment with other drugs that affect RAAS, patients of the Negroid race have a weaker antihypertensive effect with monotherapy with irbesartan. When irbesartan is taken with small doses of hydrochlorothiazide (for example, 12,5 mg/day), the antihypertensive effect in patients of the Negroid race approaches that of patients of the Caucasian race.

After the abolition of irbesartan, blood pressure gradually returns to its original level. Withdrawal syndrome upon discontinuation of irbesartan was not observed.

Clinical evidence for the efficacy of a fixed-dose combination of irbesartan and amlodipine was obtained in two multicenter, prospective, open-label studies of parallel groups with a blind assessment of performance indicators: I-ADD and I-COMBINE studies. The results of both studies demonstrated significantly greater efficacy of fixed dose combinations of irbesartan and amlodipine compared with amlodipine monotherapy or irbesartan monotherapy.

special instructions

Patients with heart failure. In a long-term placebo-controlled study (PRAISE-2) of amlodipine in patients with functional class III – IV CHF (but NYHA classification) of non-ischemic etiology, an increase in the incidence of pulmonary edema was observed despite the absence of a significant difference in the rate of progression of heart failure compared with placebo .

Liver failure. As with other BMCC, T1/2 of amlodipine increases in patients with impaired liver function, and recommendations on the dosage regimen for impaired liver function have not been established. In this regard, the drug combination irbesartan amlodipine should be used with caution in such patients.

Hypertensive crisis. The safety and effectiveness of amlodipine in hypertensive crisis have not been established.

Withdrawal syndrome. Despite the absence of withdrawal syndrome in BMCC, it is advisable to discontinue treatment with amlodipine, gradually reducing the dose.

Peripheral edema. Minor or mild peripheral edema was the most common amlodipine AE in clinical trials. The incidence of peripheral edema increases with increasing dose (when using amlodipine at a dose of 2,5; 5, 10 mg/day, edema occurred in 1,8; 3 and 10,8% of patients, respectively).

It is necessary to maintain dental hygiene and observation at the dentist (to prevent pain, bleeding and gum hyperplasia).

Excessive decrease in blood pressure: patients with hypovolemia and hyponatremia. Irbesartan rarely caused an excessive decrease in blood pressure in patients with hypertension without any other concomitant pathology. As with ACE inhibitors, an excessive decrease in blood pressure may be expected with appropriate symptoms in patients with hypovolemia and hyponatremia, which include patients undergoing intensive diuretic therapy and/or patients with sodium chloride restrictions or those on hemodialysis. .

Effect on renal function. Due to inhibition of RAAS, changes in renal function in predisposed patients can be expected. In patients with renal function dependent on RAAS activity (patients with arterial hypertension with bilateral or unilateral renal artery stenosis or patients with NYHA functional class III – IV CHF), treatment with other drugs that affect RAAS was associated with the development of oliguria and/or progressive azotemia and rarely with acute renal failure and/or death. It is impossible to exclude the possibility of such an effect when using ARA II, including irbesartan.

Kidney transplantation. There are no clinical data on the use of Aprovask® in patients who have recently undergone kidney transplantation.

Hyperkalemia As with other drugs that affect RAAS, hyperkalemia may develop during treatment with Aprovask®, especially in the presence of renal failure and/or heart disease. In such patients, it is recommended that serum potassium levels be monitored.

Stenosis of the aortic or mitral valve, GOKMP. As with other vasodilators, patients with aortic or mitral stenosis or with GOKMP should be careful when taking Aprovask®.

Primary hyperaldosteronism. Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting through inhibition of RAAS, therefore the use of Aprovask® in such cases is impractical.

Patients with ischemic heart disease and/or clinically significant cerebral arteriosclerosis. As with other antihypertensive drugs, a significant decrease in blood pressure in patients with coronary artery disease and/or severe atherosclerosis of the brain vessels can lead to the development of myocardial infarction or stroke. Treatment of such patients should be carried out under the strict control of blood pressure.

Double blockade of RAAS with the simultaneous use of irbesartan with ACE inhibitors or with aliskiren. The double blockade of RAAS when using a combination of irbesartan with ACE inhibitors or aliskiren is not recommended, because there is an increased risk of a sharp decrease in blood pressure, hyperkalemia and impaired renal function.

The simultaneous use of ARA II, including irbesartan, which is part of the drug Aprovask®, with drugs containing aliskiren, is contraindicated in patients with diabetes mellitus and/or moderate or severe renal failure (GFR lt; 60 ml/min/1,73 m2) and is not recommended in other patients.
The simultaneous use of ARA II, including

Psoriasis. In patients with psoriasis (including a history), the decision to use the drug should be made only after a thorough assessment of the risk/benefit ratio due to a possible exacerbation of the course of psoriasis.

gde kupit amlodipin - Tablets for pressure Vamloset instructions for use, at what pressure

Use in elderly patients (65 years and older). Patients who took irbesartan in clinical trials did not show any difference in the efficacy or safety of irbesartan in older patients (65 years or older) compared with younger patients.

Use in children and adolescents under 18 years of age. Safety and efficacy in children and adolescents under 18 years of age have not yet been established.

Influence on the ability to drive vehicles and mechanisms. The effect of the drug on the ability to drive vehicles or engage in other potentially hazardous activities requiring increased attention has not been studied. However, based on its pharmacodynamic properties, the effect of Aprovask® on this ability is unlikely. In case of dizziness, vertigo, weakness, it is necessary to refrain from driving vehicles, mechanisms.

In patients with hypovolemia and hyponatremia, an excessive decrease in blood pressure is possible, therefore, this category of patients is recommended to correct these conditions before starting therapy, and start taking Aprovask with low doses.

In chronic heart failure, a 2-3 functional class of non-ischemic etiology, amlodipine can cause pulmonary edema.

With caution, Aprovask should be taken in patients with impaired liver function, since they have an increased half-life of amlodipine.

amlodipin mepha tabl mg stk - Tablets for pressure Vamloset instructions for use, at what pressure

If the patient’s kidney function depends on the activity of the renin-angiotensin-aldosterone system, the likelihood of developing oliguria and/or progressive azotemia, as well as renal failure and/or death, cannot be ruled out.

When the drug is used by women of childbearing age, they should use reliable methods of contraception. In the event of pregnancy, Aprovask is immediately discontinued.

The influence of Aprovask on driving and other potentially dangerous mechanisms is unlikely, however, with the appearance of vertigo, dizziness, weakness, drowsiness, one should refrain from activities that require an increased concentration of attention.

Tatyana Jakowenko

Editor-in-chief of the Detonic online magazine, cardiologist Yakovenko-Plahotnaya Tatyana. Author of more than 950 scientific articles, including in foreign medical journals. He has been working as a cardiologist in a clinical hospital for over 12 years. He owns modern methods of diagnosis and treatment of cardiovascular diseases and implements them in his professional activities. For example, it uses methods of resuscitation of the heart, decoding of ECG, functional tests, cyclic ergometry and knows echocardiography very well.

For 10 years, she has been an active participant in numerous medical symposia and workshops for doctors - families, therapists and cardiologists. He has many publications on a healthy lifestyle, diagnosis and treatment of heart and vascular diseases.

He regularly monitors new publications of European and American cardiology journals, writes scientific articles, prepares reports at scientific conferences and participates in European cardiology congresses.

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