Exforge and Co-Exforge: instructions for use, price, reviews, analogues

Compound

Exforge tablets have active ingredients such as amlodipine and valsartan , as well as the following additional components: talc, MCC, magnesium stearate, hypromellose, colloidal silicon dioxide, titanium dioxide, crospovidone, yellow iron oxide, macrogol 4000. Co
-Exforge, in turn , has the following composition:

active ingredients – amlodipine , valsartan , hydrochlorothiazide ;
additional substances: MCC, colloidal silicon dioxide, hypromellose, crospovidone, macrogol, magnesium stearate, titanium dioxide, talc.

Pharmacodynamics and pharmacokinetics

The active components of Exforge have a complementary mechanism of action to control blood pressure . Amlodipine belongs to the blockers of “slow” calcium channels. The second active component valsartan , is an angiotensin II receptor antagonist . The combination of these two components has a mutually complementary hypotensive effect, which causes a decrease in arterial (blood) pressure.

Amlodipine acts as a relaxant on vascular smooth muscle. It dilates the walls of blood vessels, which causes a decrease in peripheral vascular resistance and a decrease in blood pressure. With long-term use, this is not accompanied by significant changes in heart rate and catecholamine , as well as negative inotropic effects .

In people with normal left ventricular function, the drug may cause a slight increase in cardiac index without a significant effect on the rate of rise of pressure (maximum) in the left ventricle, left ventricular volume and final blood pressure.

The action of amlodipine is effective in those who have chronic stable and vasospastic angina , as well as angiographically confirmed damage to the coronary arteries .

Valsartan selectively affects AT1 receptors , blocking them, which can lead to stimulation of AT2 receptors .

With arterial hypertension , those taking valsartan experience a decrease in blood pressure without changes in heart rate . The antihypertensive effect in this case persists throughout the day. In case of heart failure (chronic) class II–IV, the number of hospitalizations decreases. In case of left ventricular failure or dysfunction of the left ventricle after myocardial infarction, a decrease in cardiovascular mortality is recorded.

The antihypertensive effect after taking the medicine becomes noticeable no later than 2 hours. The maximum reduction in blood pressure occurs after about 5 hours.

The hypotensive effect is observed for more than a day. The maximum reduction in blood pressure with repeated use can be achieved within 2-4 weeks; it remains at this level with long-term therapy. If you stop taking valsartan, there is no sharp increase in blood pressure or other undesirable consequences.

At a dosage of 10/160 mg, the drug normalizes blood pressure in most patients with inadequate blood pressure control when using amlodipine 10 mg.

When using dosages of 10/160 and 5/160 mg after using the drug, blood pressure is normalized in most patients with inadequate blood pressure control when taking valsartan 160 mg per day.

The effect of Exforge does not depend on age, race or gender.

The pharmacokinetics of this drug is characterized by linearity. After oral administration of Exforge, the maximum plasma levels of amlodipine and valsartan are achieved after approximately 7 and 3 hours, respectively.

Amlodipine is actively broken down in the liver, resulting in the formation of active metabolites . It is eliminated in two stages with a half-life of 30-50 hours. Equilibrium plasma concentrations are observed after approximately a week. 10% of the substance is excreted from the body unchanged and about 60% in the form of metabolites through the kidneys.

About 20% of the beneficial dose of valsartan is determined as metabolites . The active substance is excreted mainly unchanged through the kidneys and intestines. The half-life is about 6 hours.

The pharmacodynamics of the drug Co-Exforge, in turn, is characterized by the combined effect of three antihypertensive components, which have a complementary mechanism of action to control blood pressure . At the same time, a more significant decrease in SBP and DBP is observed when compared with the use of combinations of only two active substances included in the drug. Blood pressure targets are achieved faster.

The maximum antihypertensive effect when taking Co-Exforge can be noticed 2 weeks after the start of the course. The therapeutic effect does not depend on age, race and gender.

The maximum concentration of amlodipine , valsartan and hydrochlorothiazide after taking Co-Exforge appears after 7, 3 and 2 hours, respectively.

The bioavailability of hydrochlorothiazide when administered orally is about 70%. The half-life is 6-15 hours. The substance is excreted unchanged from the body in urine.

Use during pregnancy and children

Exforge, like any other drug that has a direct effect on the renin-angiotensin-aldosterone system (RAAS), should not be prescribed during pregnancy or to women planning pregnancy. If pregnancy is detected during treatment with Exforge, the drug should be discontinued as soon as possible. Patients of childbearing age should be informed of the possible risk to the fetus associated with the use of drugs that affect the RAAS. Given the mechanism of action of angiotensin II receptor antagonists, a risk to the fetus cannot be excluded. It is known that the administration of ACE inhibitors, which affect the RAAS, to pregnant women in the second and third trimesters leads to damage or death of the developing fetus. According to a retrospective analysis, the use of ACE inhibitors in the first trimester of pregnancy was accompanied by the development of pathology in the fetus and newborn. With the unintentional use of valsartan in pregnant women, cases of spontaneous abortion, oligohydramnios and renal dysfunction in newborns have been described. It is not known whether valsartan and/or amlodipine are excreted in breast milk. Since experimental studies have shown that valsartan is excreted in breast milk, the use of Exforge during lactation (breastfeeding) is not recommended.

Contraindications

Exforge is contraindicated in case of individual intolerance to the components of the drug and pregnancy . This drug should be taken with caution in case of liver disease, mitral or aortic stenosis , hyperkalemia , hypertrophic obstructive cardiomyopathy , severe renal impairment, sodium deficiency and/or decreased volume .

Co-Exforge is contraindicated in:

significant liver dysfunction;
hypersensitivity to the components of the drug;
hypokalemia , hypercalcemia , hyponatremia and hyperuricemia refractory to adequate therapy ;
pregnancy;
lactation;
significant impairment of kidney function;
childhood.

The drug should be taken with caution when:

renal artery stenosis , as well as the artery of a single kidney, mitral or aortic stenosis ;
decrease in BCC ;
systemic lupus erythematosus;
mild to moderate liver dysfunction;
disturbances of water and electrolyte balance;
hypertrophic obstructive cardiomyopathy ;
diabetes mellitus.

special instructions

If it is necessary to discontinue β-blockers before starting Exforge® therapy, the dose of β-blockers should be reduced gradually. Since amlodipine is not a β-blocker, the use of Exforge® does not prevent the development of withdrawal syndrome that occurs when treatment with β-blockers is abruptly stopped.

Sodium deficiency in the body and/or decrease in blood volume. In placebo-controlled studies in patients with uncomplicated arterial hypertension, severe arterial hypotension was observed in 0.4% of cases. In patients with an activated renin-angiotensin-aldosterone system (for example, with BCC and/or sodium deficiency in patients receiving high doses of diuretics), symptomatic arterial hypotension may develop when taking angiotensin receptor blockers. Before starting treatment with Exforge®, sodium levels in the body and/or blood volume should be corrected or therapy should be initiated under close medical supervision. If arterial hypotension develops, the patient should be placed with legs elevated and, if necessary, given an intravenous infusion of saline solution. After stabilization of blood pressure, treatment with Exforge® can be continued.

Hyperkalemia. When using the drug simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that may cause an increase in the concentration of potassium in the blood (for example, heparin), caution should be exercised and regular monitoring of the concentration of potassium in the blood should be carried out.

Impact on the ability to drive vehicles and operate machinery. There is no data on the effect of the drug on the ability to drive vehicles and operate machinery. Due to the possible occurrence of dizziness or increased fatigue, caution should be exercised when driving vehicles or operating machinery.

Side effects

When taking Exforge, the following side effects are observed:

from the respiratory system: nasopharyngitis , flu , cough, pain in the larynx and pharynx;
from the central nervous system: paresthesia , headache , drowsiness , dizziness ;
from the cardiovascular system: tachycardia , orthostatic hypotension , palpitations;
skin reactions: rash, erythema ;
from the digestive system: diarrhea / constipation , abdominal pain, dry mouth, nausea;
from the musculoskeletal system: joint swelling, arthralgia , back pain;
other: pastiness , peripheral edema, asthenia , flushing of the face, feeling of heat, facial swelling, increased fatigue.

In rare cases, the following were observed: increased sensitivity, visual impairment, marked decrease in blood pressure, tinnitus, anxiety , syncope, hyperhidrosis , itching, feeling of heaviness, exanthema , muscle spasms, pollakiuria , erectile dysfunction , polyuria .

In addition, side effects from each of the components may manifest themselves when consuming Exforge, even if they have not previously been observed in clinical studies.

The drug Co-Exforge has the following side effects:

from the metabolic side: hypokalemia , anorexia , hyperlipidemia , hyponatremia , hypercalcemia ;
from the nervous system: paresthesia , fainting , lethargy, dizziness , taste disturbances, headache , coordination problems, neuropathy ;
from the hearing organs: vertigo ;
from the respiratory system: cough, irritation in the throat, shortness of breath ;
from the skin: itching, increased sweating ;
from the kidneys and urinary tract: pollakiuria , increased plasma creatinine, renal failure ;
general disorders: abasia , peripheral edema, increased fatigue, asthenia , pain in the chest, gait disturbances, general weakness;
from the psyche : drowsiness , sleep disturbances;
from the organs of vision: visual disturbances ;
from the cardiovascular system: phlebitis , significant decrease in blood pressure, orthostatic hypotension , tachycardia , thrombophlebitis ;
from the digestive system: dyspepsia , bad breath, abdominal discomfort, diarrhea , dry mouth, vomiting, nausea;
from the musculoskeletal system: pain in the limbs and back, swelling of the joints, muscle spasms, muscle weakness, myalgia ;
from the reproductive system: erectile dysfunction ;
other: weight gain, hyperuricemia .

Instructions for use of Exforge

Instructions for use of Exforge include preoral use. The drug is taken once a day with some water, regardless of the time of meals. Dosages Exforge 10/160, 10/320, 5/80, 5/160, 5/320 mg. The maximum daily dose is 10/320 mg.

For those who have been prescribed Co-Exforge, the instructions for use advise using it once daily in tablets, depending on the doctor’s prescription, containing:

5 mg amlodipine in combination with 160 mg valsartan and 12.5 mg hydrochlorothiazide;
10 mg amlodipine in combination with 160 mg valsartan and 12.5 mg hydrochlorothiazide;
10 mg amlodipine in combination with 320 mg valsartan and 25 mg hydrochlorothiazide (2 tablets).

The tablets are taken orally regardless of meals. They must be washed down with water.

Description of the dosage form

Film-coated tablets, 5/80 mg: dark yellow, round with beveled edges, imprinted “NVR” on one side and “NV” on the other.

Film-coated tablets, 5/160 mg: dark yellow, oval with beveled edges, imprinted “NVR” on one side and “ECE” on the other.

Film-coated tablets, 10/160 mg: light yellow, oval with beveled edges, imprinted “NVR” on one side and “UIC” on the other.

Overdose

Valsartan in high doses can lead to a pronounced decrease in blood pressure and dizziness , and amlodipine can lead to reflex tachycardia , arterial hypotension , and excessive peripheral vasodilation .

An overdose of hydrochlorothiazide may cause symptoms associated with electrolyte loss and dehydration . The most likely manifestations: nausea, muscle spasms, cardiac arrhythmia and drowsiness .

As treatment, induce vomiting or perform gastric lavage. activated charcoal may help .

In case of arterial hypotension, the patient must take a “lying” position with his legs elevated; in addition, measures are provided to maintain the normal functioning of the cardiovascular system. To normalize blood pressure, a vasoconstrictor can be prescribed .

Interaction

Clinically significant interaction is not observed when amlodipine with thiazide diuretics, Nitroglycerin for sublingual use, ACE inhibitors, Warfarin , Sildenafil , Cimetidine , antibiotics , beta-blockers, long-acting nitrates, Digoxin , Atorvastatin , Maalox , NSAIDs, oral hypoglycemic drugs .

The combination of amlodipine with Diltiazem in elderly patients causes a slowdown in the breakdown of amlodipine, which causes an increase in its plasma content by approximately half. Together with more potent CYP3A4 inhibitors, the systemic exposure of amlodipine increases.

The combination of amlodipine with inducers of the CYP3A4 isoenzyme , on the contrary, leads to a decrease in its concentration. Therefore, its content in plasma should be monitored.

There is no clinically significant interaction when valsartan with Cimetidine, Furosemide , Atenolol , Hydrochlorothiazide , Glibenclamide , Warfarin , Digoxin , Indomethacin and Amlodipine .

It is necessary to constantly monitor the potassium concentration when simultaneous use of Exforge with dietary supplements that contain potassium-sparing diuretics , potassium and potassium-containing salt substitutes, as well as with other drugs that cause an increase in potassium levels in the blood.

When taking Co-Exforge, you should also consider the interaction of hydrochlorothiazide with other drugs. Therefore, it is necessary to monitor the use of this drug in combination with lithium preparations, hypoglycemic drugs for oral administration and insulin . Dosage adjustments may be necessary.

In addition, hydrochlorothiazide potentiates the effect of peripheral muscle relaxants, can cause an increase in the hyperglycemic effect of Diazoxide , increased sensitivity to Allopurinol , an increased risk of developing side effects of Amantadine cytotoxic drugs through the kidneys , as well as their potentiation of myelosuppressive effects . In turn, combination with NSAIDs leads to a decrease in the diuretic and antihypertensive effects of hydrochlorothiazide. Together with drugs that reduce potassium concentrations, the risk of hypokalemia . Cardiac glycosides also increase the risk of its occurrence, as well as hypomagnesemia and arrhythmia .

Together with m-anticholinergics, the bioavailability of hydrochlorothiazide increases. When combined with Methyldopa cases of hemolytic anemia , with Cyclosporine - the risk of developing hyperuricemia and the development of gout , with Cabamazepine - hyponatremia , and with vitamin D and calcium salts, an increase in calcium levels in the blood serum is likely. Cholestyramine reduces the absorption of hydrochlorothiazide.

Pharmacokinetics

The pharmacokinetics of valsartan and amlodipine are linear.

Amlodipine

Suction. After oral administration of amlodipine in therapeutic doses, the Cmax of amlodipine in the blood plasma is achieved within 6–12 hours. The absolute bioavailability averages 64–80%. Food intake does not affect the bioavailability of amlodipine.

Distribution. The apparent VSS is approximately 21 L/kg. In vitro studies with amlodipine have shown that in patients with arterial hypertension, approximately 97.5% of the circulating drug is bound to plasma proteins.

Metabolism. Amlodipine is extensively (approximately 90%) metabolized in the liver to form active metabolites.

Excretion. The elimination of amlodipine from plasma is biphasic with a T1/2 of approximately 30 to 50 hours. Equilibrium plasma concentrations are achieved after use for 7–8 days. 10% of unchanged amlodipine and 60% of amlodipine in the form of metabolites are excreted by the kidneys.

Valsartan

Suction. After oral administration of valsartan, Cmax in blood plasma is achieved within 2–3 hours. The average absolute bioavailability is 23%. The pharmacokinetic curve of valsartan has a descending multi-exponential character (T1/2α <1 hour and T1/2β - about 9 hours). When taking valsartan with food, there is a decrease in bioavailability (according to AUC value) by 40% and Cmax in the blood plasma by almost 50%, although approximately 8 hours after taking the drug, the concentration of valsartan in the blood plasma in the group of patients taking it with food and in group taking on an empty stomach are leveled off. The decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be prescribed regardless of the timing of meals.

Distribution. The VSS of valsartan at steady state after intravenous administration was approximately 17 L, indicating the absence of extensive tissue distribution of valsartan. Valsartan is highly bound to serum proteins (94–97%), mainly to albumin.

Metabolism. Valsartan is not subject to significant metabolism (about 20% of the dose taken is determined in the form of metabolites). The hydroxyl metabolite is detected in blood plasma in low concentrations (less than 10% of the AUC of valsartan). This metabolite is pharmacologically active.

Excretion. Valsartan is excreted mainly unchanged through the intestines (about 83% of the dose) and by the kidneys (about 13% of the dose). After intravenous administration, plasma Cl of valsartan is about 2 l/h, renal Cl is 0.62 l/h (about 30% of total clearance). T1/2 of valsartan - 6 hours.

Amlodipine/Valsartan

After oral administration of the drug Exforge®, the Cmax of valsartan and amlodipine is achieved after 3 and 6–8 hours, respectively. The rate and extent of absorption of the drug is equivalent to the bioavailability of valsartan and amlodipine when each of them is taken in the form of separate tablets.

Pharmacokinetics in special clinical situations

The pharmacokinetic features of the use of Exforge® in children under 18 years of age have not been established.

Elderly patients. The time to reach Cmax of amlodipine in blood plasma is the same in young and elderly patients. In elderly patients, the clearance of amlodipine is slightly reduced, which leads to an increase in AUC and T1/2.

In elderly patients, the systemic exposure to valsartan was slightly more pronounced than in younger patients, but these indicators were not clinically significant. Since the tolerability of the drug components in older and younger patients is equally good, it is recommended to use the usual dosage regimens.

Patients with impaired renal function. In patients with impaired renal function, the pharmacokinetic parameters of amlodipine do not change significantly. There was no correlation between renal function (clearance) and systemic exposure of valsartan (AUC) in patients with varying degrees of renal impairment. No change in the initial dose is required in patients with initial and moderate renal impairment (Cl creatinine - 30-50 ml/min).

Patients with Hepatic Impairment: Patients with hepatic impairment have reduced clearance of amlodipine, resulting in an increase in AUC of approximately 40–60%. On average, in patients with mild to moderate chronic liver disease, the bioavailability (AUC) of valsartan is doubled compared to healthy volunteers (matched for age, sex and body weight).

Reviews of Exforge

Reviews about Exforge are both positive and negative. Many patients note its effectiveness. Some, however, say that they experienced side effects that forced them to stop taking the drug.

In fact, no specialist can rule out the occurrence of undesirable effects in advance. The drug is much more effective than taking amlodipine or valsartan alone, but its use should be well controlled. For many, in addition, it is more profitable to buy analogs of Exforge.

Reviews of Co-Exforge are generally positive. Patients note the undoubted effectiveness of this remedy and recommend it to others.

Exforge price, where to buy

The price of Exforge is considered quite high. You can buy this product in Moscow and other Russian cities for, on average, 1,400–1,800 rubles.

The price of Co-Exforge, on average, is about 2000 rubles.

Online pharmacies in RussiaRussia
Online pharmacies in KazakhstanKazakhstan

LuxPharma* special offer

Exforge table
10 mg/160 mg No. 28 RUR 1,590 order
Exforge tab. 5 mg/160 mg No. 28
1650 rub. order

ZdravCity

Exforge tablets p.p.o. 5mg+80mg 28 pcs. Siegfried Barbera S.L./Novartis Pharmaceuticals S.A.
RUB 1,906 order
Exforge tablets p.p.o. 10mg+160mg 28 pcs. Siegfried Barbera S.L./Novartis Pharmaceuticals S.A.
RUB 2,238 order
Exforge tablets p.p.o. 5mg+160mg 28 pcs. Siegfried Barbera S.L./Novartis Pharmaceuticals S.A.
2300 rub. order
Co-exforge tab. p.p.o. 10mg+160mg+12.5mg n28 Siegfried Barbera S.L./Novartis Pharma GmbH
RUB 2,755 order

Pharmacy Dialogue

Co-exforge (0.005+0.16/0.0125 No. 28)Novartis
RUB 2,514 order
Exforge (tablet p/o 10mg+160mg No. 28)Novartis
2300 rub. order
Co-exforge (0.01+0.16/0.0125 No. 28)Novartis
RUB 2,512 order
Exforge (tab.p.pl/vol.5mg+80mg No. 28)Novartis
RUB 2,056 order
Exforge (tab.p.pl/vol.5mg+160mg No. 28)Novartis
RUB 2,555 order

Release form

Film-coated tablets, 5 mg/80 mg, 5 mg/160 mg or 10 mg/160 mg. 7, 10 or 14 pcs. in a blister; 1, 2, 4, 8, 14 or 40 blisters of 7 tablets; 3, 9 or 28 blisters of 10 tablets; 1. 2, 4, 7, or 20 blisters of 14 tablets are placed in a cardboard box.

Film-coated tablets, 5 mg + 320 mg or 10 mg + 320 mg. 7 or 14 tablets in a PVC/PVDC blister. 1 blister of 7 tablets; 1, 2, 4, 7 blisters of 14 tablets each are placed in a cardboard box.