Exforge and Co-Exforge - instructions for use, analogs, reviews and release forms (tablets 5 + 80, 5 + 160, 5 + 320, 10 + 160, 10 + 320 mg) of the drug for the treatment of hypertension and pressure reduction in adults, children and during pregnancy. Composition

In this article, you can read the instructions for using the drug Exforge and Ko-Exforge. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of experts on the use of Exforge in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Exforge in the presence of existing structural analogues. Use to treat hypertension and reduce blood pressure in adults, children, as well as during pregnancy and lactation.Composition of the preparation.

Exforge and Ko-Exforge - a combined antihypertensive drug containing active substances with a complementary mechanism for monitoring blood pressure. Amlodipine, a derivative of dihydropyridine, belongs to the class of slow calcium channel blockers (BCCC), Valsartan to the class of antagonists of angiotensin 2 receptors. The combination of these components has a mutually complementary antihypertensive effect, which leads to a more pronounced decrease in blood pressure compared to that of monotherapy with each drug .

Composition

Amlodipine besylate + Valsartan + auxiliary substances (Exforge).

Amlodipine besylate + Valsartan + Hydrochlorothiazide (Co-Exforge).

Pharmacokinetics

The pharmacokinetic parameters of amlodipine, valsartan and hydrochlorothiazide are characterized by linearity.

Amlodipine

After ingestion of Amlodipine in therapeutic doses, Cmax in the blood plasma is reached after 6-12 hours. Absolute bioavailability averages 64-80%. Eating food does not affect the bioavailability of amlodipine. In studies with amlodipine, it was shown that in patients with arterial hypertension, approximately 97.5% of the circulating drug binds to proteinsblood plasma. Amlodipine is intensively (approximately 90%) metabolized in the liver with the formation of active metabolites. 10% is excreted unchanged, 60% - in the form of metabolites.

Valsartan

After oral administration of valsartan Cmax in blood plasma is achieved after 2-4 hours. The average absolute bioavailability is 23%.

The pharmacokinetic curve of valsartan is of a downward multi-exponential nature. When taken with food, the bioavailability is reduced by 40% and Cmax in blood plasma by almost 50%, although approximately 8 hours after taking the drug inside the concentration of valsartan in the blood plasma in people taking it with food and in the group receiving fast-acting valsartan, are aligned. Valsartan largely binds to serum proteins (94-97%), mainly with albumins. Valsartan does not undergo a pronounced metabolism (about 20% of the dose is determined in the form of metabolites). The hydroxyl metabolite is determined in blood plasma at low concentrations. This metabolite is pharmacologically inactive. Valsartan is excreted mainly unchanged through the intestine (about 83% of the dose) and kidneys (about 13% of the dose).

Hydrochlorothiazide

Absorption of hydrochlorothiazide after ingestion is rapid (time to reach Cmax about 2 h). With simultaneous intake of food, both the increase and decrease in the systemic bioavailability of hydrochlorothiazide were reported compared with the administration of the drug on an empty stomach. The magnitude of this effect is small and clinically insignificant. The absolute bioavailability of hydrochlorothiazide after oral administration is 70%. Hydrochlorothiazide is excreted unchanged. More than 95% of the absorbed dose of hydrochlorothiazide is excreted unchanged in kidneys with urine.

Indications

• arterial hypertension (for patients who are shown combined therapy);
• arterial hypertension 2 and 3 degrees (Co-Exforge).

Forms of release

The tablets covered with a cover 5 + 80, 5 + 160, 5 + 320, 10 + 160, 10 + 320 mg (Exforge).

The tablets covered with a cover 5 + 160 + 12,5; 5 + 160 + 25; 10 + 160 + 12.5; 10 + 160 + 25; 10 + 320 + 25 mg (Co-Exforge).

Instructions for use and dosage

Exforge

The drug should be taken orally, washed down with a small amount of water, once a day, regardless of the time of ingestion.

The recommended daily dose is 1 tablet in a dose of 5/80 mg or 5/160 mg or 10/160 mg.

When appointing patients of advanced age, patients with initial or moderate impairment of kidney function (CK> 30 ml / min),with impaired liver function or with liver disease, with cholestasis, a change in the dosing regimen is not required.

Ko-Exforge

The drug should be taken orally (preferably in the morning), washed down with a small amount of water, regardless of food intake.

For convenience, patients treated with amlodipine, valsartan, and hydrochlorothiazide in individual tablets can be transferred to Co-Exforge therapy containing the same doses of active components, as well as inadequate control of blood pressure on a background of double combination therapy (valsartan + hydrochlorothiazide, amlodipine + valsartan and amlodipine + hydrochlorothiazide), patients can be transferred to triple combined treatment with Ko-Exforge in appropriate doses.

If the patient has a dose-dependent side effect when using a dual combination therapy with any components of the Ko-Exforge preparation, a Ko-Exforge preparation containing a lower dose of the active ingredient that causes this side effect may be prescribed to achieve a similar reduction in blood pressure.

The recommended daily doses of Ko-Exforge are:

• 5 mg + 160 mg + 12.5 mg (1 tablet containing amlodipine + valsartan + hydrochlorothiazide at doses of 5 mg + 160 mg + 12.5 mg);
• 10 mg + 160 mg + 12.5 mg (1 tablet containing amlodipine + valsartan + hydrochlorothiazide at doses of 10 mg + 160 mg + 12.5 mg);
• 10 mg + 320 mg + 25 mg (2 tablets containing amlodipine + valsartan + hydrochlorothiazide at doses of 5 mg + 160 mg + 12.5 mg).

The maximum antihypertensive effect of the drug is noted 2 weeks after the dose is increased. The maximum dose of the drug is 10 mg + 320 mg + 25 mg per day.

Patients over 65 years of age are not required to adjust the dose.

Since the safety and efficacy of Co-Exforge in children and adolescents (under 18 years of age) have not yet been established, the drug is not recommended for use in this category of patients.

In patients with mild and moderate renal impairment (QC more than 30 ml / min) and liver (5-9 points on the Child-Pugh scale), dose adjustment is not required.

Side effect

• anorexia;
• weight gain;
• hypokalemia, hypercalcemia, hyperlipidemia, hyponatremia;
• leukopenia, thrombocytopenia;
• dizziness;
• headache;
• insomnia;
• sleep disorders;
• lack of coordination;
• dizziness due to physical exertion;
• flavoring disorders;
• retardation;
• drowsiness;
• fainting;
• visual disturbances;
• vertigo;
• marked decrease in blood pressure;
• tachycardia;
• orthostatic hypotension;
• phlebitis;
• thrombophlebitis;
• cough;
• dyspnea;
• irritation in the throat;
• dyspepsia;
• discomfort in the abdomen;
• pain in the upper abdomen;
• bad breath;
• diarrhea;
• dry mouth;
• nausea, vomiting;
• increased sweating;
• itching;
• backache;
• edema in the joint region;
• muscle spasms;
• muscle weakness;
• myalgia;
• pain in the limbs;
• acute renal insufficiency;
• erectile disfunction;
• gynecomastia;
• noise in ears;
• peripheral edema;
• increased fatigue;
• violation of gait;
• asthenia;
• general weakness;
• pain in the chest.

Contraindications

• expressed violations of the liver (more than 9 points on the scale Child-Pugh), biliary cirrhosis and cholestasis;
• severe renal dysfunction (CK less than 30 ml / min), anuria, patients on hemodialysis;
• severe arterial hypotension (systolic blood pressure less than 90 mm Hg), collapse, cardiogenic shock;
• clinically significant aortic stenosis;
• refractory to adequate therapy hypokalemia, hyponatremia, hypercalcemia, as well as hyperuricemia with clinical manifestations;
• hereditary angioedema, or edema in patients on the background of previous therapy with antagonists of AT2 receptors;
• pregnancy and pregnancy planning;
• the period of breastfeeding;
• age under 18 years (effectiveness and safety not established);
• hypersensitivity to amlodipine, valsartan, hydrochlorothiazide, other derivatives of sulfonamide, dihydropyridine derivative and other auxiliary components of the drug.

Application in pregnancy and lactation

It is known that the appointment of ACE inhibitors that affect RAAS, pregnant in 2 and 3 trimesters, leads to damage or death of the developing fetus. Given the mechanism of action of angiotensin 2 receptor antagonists, the risk to the fetus can not be ruled out. According to the retrospective analysis of the use of ACE inhibitors in the first trimester of pregnancy, the development of fetal and newborn pathology was accompanied. Hydrochlorothiazide penetrates the placental barrier. With the use of thiazide diuretics, including hydrochlorothiazide, embryonic or neonatal thrombocytopenia, as well as other unwanted reactions observed in adult patients, is possible during pregnancy.In case of unintended admission of valsartan in pregnant women, cases of spontaneous abortion, malignancy and renal dysfunction in newborns are described. Exforge and Co-Exforge, like any other drug that directly affects RAAS, should not be prescribed in pregnancy and in women planning a pregnancy.

Patients of childbearing age should be informed of the possible risk to the fetus associated with the use of drugs that affect RAAS. If the pregnancy is diagnosed during treatment with Exforge or Co-Exforge, the drug should be discontinued as soon as possible.

It is not known whether valsartan and / or amlodipine penetrates into breast milk. In experimental studies, valsartan has been identified with breast milk. Hydrochlorothiazide is excreted into breast milk. Ko-Exforge should not be used during breastfeeding.

Application in elderly patients

Patients over 65 years of age are not required to adjust the dose.

Use in children

Contraindicated in children and adolescents under the age of 18 years (safety of use in children and adolescents under 18 years is not established).

special instructions

Caution should be exercised in prescribing Exforge to patients with liver disease (especially with obstructive diseases of the biliary tract). Valsartan is excreted mainly unchanged with bile, while amlodipine is extensively metabolized in the liver.

Renal impairment

When using the drug Ko-Exforzh it is necessary to conduct regular monitoring of the creatinine and potassium content in the blood plasma.

Abolition of beta-blockers

If it is necessary to cancel beta-blockers before starting therapy with Co-Exforge, the dose of beta-blockers should be reduced gradually. Since the composition of the drug Ko-Exforge does not include a beta-blocker, the use of the drug does not prevent the development of the "withdrawal" syndrome that occurs when the beta-blockers are abruptly discontinued.

Marked decrease in blood pressure

In controlled studies with the use of Ko-Exforge in the maximum daily dose (10 mg + 320 mg + 25 mg) in patients with arterial hypertension of 2 and 3 degrees, a marked decrease in blood pressure was observed in 1.7% of cases, including orthostatic hypotension (in comparison with 1.8%0.4% and 0.2% on a combination therapy of valsartan + hydrochlorothiazide at a dose of 320 mg + 25 mg, amlodipine + valsartan 10 mg + 320 mg and amlodipine + hydrochlorothiazide 10 mg + 25 mg, respectively). In case of development of arterial hypotension, the patient should be placed with raised legs, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After the stabilization of blood pressure, treatment with Ko-Exforge can be continued.

Hyponatremia and / or decrease in BCC

In patients with activated RAAS (eg, with a deficiency of bcc and / or hyponatremia, as well as in patients receiving high doses of diuretics), the development of symptomatic arterial hypotension is possible with angiotensin receptor antagonists. Before starting treatment with Ko-Exforge, you should adjust the sodium content in the body and / or BCC, or start therapy under close medical supervision. When using the drug Ko-Exforge it is necessary to conduct regular monitoring of the content of plasma electrolytes.

Change in the concentration of potassium in the blood plasma

In controlled trials with the combination of amlodipine + valsartan + hydrochlorothiazide in a maximum daily10 mg + 320 mg + 25 mg in patients with moderate to severe hypertension, the incidence of hypokalemia (the potassium content in the blood plasma was less than 3.5 mmol / l) was 9.9% compared to 24.5%, 6.6% and 2.7% Amlodipine + hydrochlorothiazide 10 mg + 25 mg, valsartan + hydrochlorothiazide 320 mg + 25 mg and amlodipine + valsartan 10 mg + 320 mg, respectively. The frequency of cancellation of therapy due to the development of hypokalemia was 0.2% (one patient) in the groups of the drug Ko-Exforge and amlodipine + hydrochlorothiazide. In patients treated with Co-Exforge, hyperkalemia (the content of potassium in the blood plasma was more than 5.7 mmol / L) was observed in 0.4% of cases (compared to 0.2-0.7% when double combinations were used). When using Co-Exforge in a controlled study, the mutual opposite effects of valsartan at a dose of 320 mg / day and hydrochlorothiazide at a dose of 25 mg / day on serum potassium content practically balanced each other in many patients. In other cases, patients either had hypo- or hyperkalemia. When using the drug Ko-Exforge it is necessary to conduct regular monitoring of the potassium content in the blood plasma.

Systemic lupus erythematosus

With the use of thiazide diuretics, including hydrochlorothiazide, there was reported worsening of the course or development of systemic lupus erythematosus.

Other metabolic disorders

Thiazide diuretics can impair glucose tolerance and increase plasma concentrations of cholesterol, triglycerides and uric acid.

With the use of thiazide diuretics, a decrease in the excretion of calcium, leading to the development of moderate hypercalcemia, is possible. Expressed hypercalcemia on the background of therapy with the drug Ko-Exforge may indicate a latent hyperparathyroidism.

Impact on the ability to drive vehicles and manage mechanisms

Some side effects of the drug, incl. dizziness or visual disturbances, can adversely affect the ability to drive vehicles and carry out potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Amlodipine

In monotherapy with amlodipine, there is no clinically significant interaction with thiazide diuretics, beta-adrenoblockers, ACE inhibitors, long-acting nitrates,nitroglycerin for sublingual use, digoxin, warfarin, atorvastatin, sildenafil, antacid preparations (magnesium hydroxide, aluminum hydroxide gel, simethicone), cimetidine, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics and hypoglycemic drugs for oral administration.

Inhibitors of the isoenzyme CYP3A4. When amlodipine is used together with diltiazem, in elderly patients slowed metabolism of amlodipine, probably due to inhibition of the isoenzyme CYP3A4, which leads to an increase in the concentration of amlodipine in the blood plasma by approximately 50% and increase its systemic exposure. When using amlodipine together with powerful inhibitors of CYP3A4 (eg, ketoconazole, Itraconazole and ritonavir), a marked increase in systemic exposure to amlodipine is possible.

Inductors of isoenzyme CYP3A4. Since the use of amlodipine together with inducers of the isoenzyme CYP3A4 (for example, carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidone, rifampicin, grapefruit juice, herbal preparations containing St. John's wort) can lead to a marked decrease in its concentration in the blood plasma, with amlodipine with inducers CYP3A4, it should monitor its content in the blood plasma.

Valsartan

It was found that with monotherapy valsartan there is no clinically significant interaction with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indometacin, hydrochlorothiazide, amlodipine, glibenclamide.

When used simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that can cause an increase in the potassium content in the blood (for example, with heparin), care should be taken and regular monitoring of potassium in the blood.

When valsartan is used together with NSAIDs, a decrease in the antihypertensive effect of valsartan is possible.

Hydrochlorothiazide

Lithium. With simultaneous use with ACE inhibitors and diuretics, cases of a reversible increase in the plasma concentration of lithium and its toxic effect were reported. Therefore, with the simultaneous use of hydrochlorothiazide and lithium preparations, it is recommended to monitor the concentration of lithium in the blood plasma.

Muscle relaxants of peripheral action.Thiazide diuretics, including hydrochlorothiazide, potentiate the action of muscle relaxants of peripheral action.

NSAIDs. It is possible to reduce the diuretic and antihypertensive effect of the thiazide component of the Ko-Exforge preparation when used simultaneously with NSAIDs, for example, with acetylsalicylic acid, indomethacin. Concomitant hypovolemia can lead to the development of acute renal failure.

Medicines that can cause an increase in the potassium content in the blood plasma. The risk of hypokalemia increases with the simultaneous appointment of other diuretics, GCS, ACTH, amphotericin B, carbenoxolone and Acetylsalicylic acid (at a dose of more than 3 g). Caution should be exercised while using Ko-Exforge with potassium salts, potassium-sparing diuretics, potassium-containing substitutes for edible salt, as well as with drugs that can cause an increase in potassium in the blood (for example, heparin).

Cardiac glycosides. Thiazide diuretics can cause such undesirable effects as hypokalemia or hypomagnesemia; these conditions increase the risk of arrhythmia with the simultaneous use of cardiac glycosides.

Hypoglycemic agents for oral administration and insulin. When using the drug in patients with diabetes mellitus, it may be necessary to adjust the dose of insulin or hypoglycemic agents for oral administration. Since the use of hydrochlorothiazide together with Metformin may develop lactic acidosis (due to a violation of the function against hydrochlorothiazide therapy), caution should be exercised when using Co-Exforge in patients receiving metformin treatment.

Anticholinergics. It is possible to increase the bioavailability of the thiazide diuretic with the simultaneous use of m-holinoblokatorov (for example, atropine, biperiden), which, apparently, is associated with a decrease in gastrointestinal motility and slowing down the rate of gastric emptying.

Methyldopa. There have been reports of cases of hemolytic anemia with simultaneous administration of hydrochlorothiazide and methyldopa.

Kolestyramin reduces the absorption of thiazide diuretics, including hydrochlorothiazide.

Vitamin D and calcium salts. With the joint use of thiazide diuretics, including hydrochlorothiazide, with vitamin D or calcium salts, an increase in the serum calcium content is possible.

Cyclosporine.Simultaneous administration of cyclosporine may increase the risk of hyperuricemia and the appearance of symptoms resembling an exacerbation of gout.

Carbamazepine. In patients taking hydrochlorothiazide concomitantly with carbamazepine, hyponatremia may develop. Since in patients receiving both hydrochlorothiazide and Carbamazepine therapy, hyponatremia may develop, when prescribing Co-Exforge together with carbamazepine, appropriate monitoring of the sodium content in the blood plasma should be carried out.

Other types of interaction. Simultaneous administration of thiazide diuretics, including hydrochlorothiazide, may lead to an increased incidence of hypersensitivity reactions to allopurinol; increased risk of side effects of amantadine; enhancing the hyperglycemic effect of diazoxide; cytotoxic agents (for example, cyclophosphamide, methotrexate), and potentiation of their myelosuppressive effects.

Analogues of Exforge medicinal product

Structural analogs for the active substance:

• Vylloset;
• Ko-Exforge.

Analogues on the curative effect (remedies for the treatment of primary hypertension):

• Adelphan;
• Altiazem PP;
• Amlodipine;
• Amprilan;
• Anaprilin;
• Arifon;
• Atenolol;
• Berlipril;
• Betalk;
• Vasocardine;
• Vasotensis;
• Verapamil;
• Veroshpiron;
• Hypothiazide;
• Diazepec;
• Dibazol;
• Diltiazem;
• Diroton;
• Indap;
• Indapamide;
• Kalchek;
• Kapoten;
• Captopril;
• Carvedilol;
• Cardura;
• Clopheline;
• Co-Diroton;
• Co-Renitek;
• Concor;
• Corvitol;
• Cordaflex;
• Corinfar;
• Lasix;
• Lysinopril;
• Lozap;
• Losartan;
• Lorist;
• Metocard;
• Nifedipine;
• Noliprel;
• Norvasc;
• Obsidan;
• Prazosin;
• Prestan;
• Prestarium;
• Propranolol;
• Raunatin;
• Spironolactone;
• Tenox;
• Physiotherapy;
• Furosemide;
• Egilok;
• Egilok Retard;
• Enalapril;
• Enam;
• Enap;
• Enarenal.

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