Co-Exforge - Instructions For Use, Analogs, Reviews, Price Of Tablets

Table of contents:

Co-Exforge - Instructions For Use, Analogs, Reviews, Price Of Tablets
Co-Exforge - Instructions For Use, Analogs, Reviews, Price Of Tablets

Video: Co-Exforge - Instructions For Use, Analogs, Reviews, Price Of Tablets

Video: Co-Exforge - Instructions For Use, Analogs, Reviews, Price Of Tablets
Video: Эксфорж 2023, April


Co-Exforge: instructions for use and reviews

  1. 1. Release form and composition
  2. 2. Pharmacological properties
  3. 3. Indications for use
  4. 4. Contraindications
  5. 5. Method of application and dosage
  6. 6. Side effects
  7. 7. Overdose
  8. 8. Special instructions
  9. 9. Application during pregnancy and lactation
  10. 10. Use in childhood
  11. 11. In case of impaired renal function
  12. 12. For violations of liver function
  13. 13. Use in the elderly
  14. 14. Drug interactions
  15. 15. Analogs
  16. 16. Terms and conditions of storage
  17. 17. Terms of dispensing from pharmacies
  18. 18. Reviews
  19. 19. Price in pharmacies

Latin name: Co-Exforge

ATX code: C09DX01

Active ingredient: amlodipine (Amlodipine) + valsartan (Valsartan) + hydrochlorothiazide (Hydrochlorothiazide)

Manufacturer: Novartis Pharma Stein, AG (Novartis Pharma Stein, AG) (Switzerland); Novartis Pharmaceuticals, S. A. (Novartis Farmaceutica, SA) (Spain)

Description and photo update: 2019-06-02

Prices in pharmacies: from 1866 rubles.


Film-coated tablets, Co-Exforge
Film-coated tablets, Co-Exforge

Co-Exforge is a combined antihypertensive drug.

Release form and composition

Co-Exforge is produced in the form of film-coated tablets:

  • dosage 5 mg + 160 mg + 12.5 mg: biconvex, oblong, with beveled edges, white shell, embossed NVR on one side, VCL on the other;
  • dosage 10 mg + 160 mg + 12.5 mg: biconvex, oblong, with beveled edges, pale yellow shell, embossed NVR on one side, VDL on the other;
  • dosages 5 mg + 160 mg + 25 mg: biconvex, oval, beveled, yellow shell, the inner layer on the cross-section is almost white or white, NVR embossed on one side, VEL on the other;
  • 10 mg + 160 mg + 25 mg: biconvex, oval, beveled, brownish-yellow shell, the inner layer on the cross-section is almost white or white, NVR embossed on one side, VHL on the other;
  • 10mg + 320mg + 25mg: biconvex, oval, chamfered, brown-yellow shell, the inner layer on the cross-section is almost white or white, NVR embossed on one side, VFL on the other.

Packing: 7 pcs. in a blister, in a cardboard box of 1, 4 or 18 blisters; 14 pcs. in a blister, in a cardboard box of 1, 2, 4 or 7 blisters and instructions for use of Co-Exforge.

1 tablet at a dosage of 5 mg + 160 mg + 12.5 mg / 10 mg + 160 mg + 12.5 mg contains:

  • active substances: amlodipine besylate - 6.94 / 13.87 mg (which is equivalent to amlodipine base - 5/10 mg, respectively); valsartan - 160/160 mg; hydrochlorothiazide - 12.5 / 12.5 mg;
  • additional components: colloidal silicon dioxide, microcrystalline cellulose, magnesium stearate, crospovidone;
  • film coating: Premix white (macrogol 4000, hypromellose, titanium dioxide, talc), additionally for a dosage of 10 mg + 160 mg + 12.5 mg - Premix yellow (dye iron oxide yellow, hypromellose, talc, macrogol), Premix red (dye iron oxide red, hypromellose, talc, macrogol).

1 tablet at a dosage of 5 mg + 160 mg + 25 mg / 10 mg + 160 mg + 25 mg / 10 mg + 320 mg + 25 mg contains:

  • active substances: amlodipine besylate - 6.94 / 13.87 / 13.87 mg (which is equivalent to amlodipine base - 5/10/10 mg, respectively); valsartan - 160/160/320 mg; hydrochlorothiazide - 25/25/25 mg;
  • additional components: magnesium stearate, crospovidone, microcrystalline cellulose, colloidal silicon dioxide;
  • film shell: Premix yellow (macrogol 4000, hypromellose, iron dye yellow oxide, talc); additionally for a dosage of 5 mg + 160 mg + 25 mg - Premix white (macrogol 4000, hypromellose, titanium dioxide, talc).

Pharmacological properties


Co-Exforge is a combined agent that includes three antihypertensive components: amlodipine (a dihydropyridine derivative) - a slow calcium channel blocker (BMCC), valsartan - an angiotensin II receptor antagonist (ARA II), and hydrochlorothiazide (HCTZ) - a thiazide diuretic. The combination of these components with a complementary mechanism for controlling blood pressure (BP) provides a more pronounced decrease in the latter than each of these drugs during monotherapy.


Amlodipine prevents the transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of the antihypertensive action of this active substance is due to a direct relaxing effect on the smooth muscles of the vascular walls, leading to a decrease in total peripheral vascular resistance (OPSS) and a decrease in blood pressure. In the presence of arterial hypertension, after taking the drug in therapeutic doses, vasodilation occurs, which causes a decrease in blood pressure (in the supine and standing position). With this decrease in blood pressure, there is no pronounced change in heart rate (HR) and catecholamine activity against the background of prolonged use.

Plasma levels of the active ingredient in the blood correlate with the effect in young and elderly patients. In patients with normal renal function and arterial hypertension, amlodipine in therapeutic doses helps to reduce renal vascular resistance, increase the glomerular filtration rate (GFR) and improve effective renal plasma blood flow without changing the filtration fraction and the severity of proteinuria.

When treating with amlodipine in patients with normal left ventricular (LV) function, the active substance can cause, both at rest and during exercise, a slight increase in the cardiac index without a significant effect on the maximum rate of pressure rise in the LV, LV volume, and of course - diastolic pressure. According to the results of hemodynamic studies, a decrease in blood pressure against the background of the use of amlodipine in therapeutic doses is not accompanied by a negative inotropic effect even when combined with the use of β-blockers. The drug does not change the function of the sinoatrial node and does not affect the atrioventricular conduction in healthy volunteers and intact animals. The combined use of amlodipine with β-blockers in the presence of arterial hypertension or angina pectoris,leading to a decrease in blood pressure, did not cause unwanted changes in the electrocardiogram (ECG) indicators. The clinical effects of amlodipine in patients with chronic stable angina pectoris, vasospastic angina pectoris, and coronary artery disease have been confirmed angiographically.


Valsartan is an active and specific ARA II intended for oral administration. The substance selectively acts on the AT 1 subtype receptors responsible for the effects produced by angiotensin II. An increase in the level of unbound angiotensin II in plasma, due to blockade of AT 1 receptors caused by valsartan, can initiate free AT 2 receptors, which interfere with the results of stimulation of AT 1 receptors.

The substance does not exhibit any significant agonist activity towards AT 1 receptors and has an affinity for the latter approximately 20,000 times greater than for AT 2 receptors.

Valsartan does not lead to inhibition of the angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II, causing the destruction of the vasodilator bradykinin. Since there is no effect on ACE and the accumulation of bradykinin or substance P while taking angiotensin II antagonists, the occurrence of a dry cough is unlikely. The agent does not interact and does not suppress ion channels or receptors of other hormones that play an important role in the mechanism of regulation of the functions of the cardiovascular system. In the presence of arterial hypertension, valsartan leads to a decrease in blood pressure, but does not change the heart rate.

As a rule, the antihypertensive effect of the drug manifests itself within 2 hours after a single oral administration and lasts for more than 24 hours. The maximum therapeutic effect is observed 4–6 hours after administration.

With repeated use of the drug, the maximum decrease in blood pressure, regardless of the dose taken, is recorded on average within 2-4 weeks and is maintained at the achieved level during long-term treatment. Abrupt withdrawal of valsartan does not lead to a sharp increase in blood pressure or the appearance of other undesirable clinical events.

Drug therapy against the background of chronic heart failure (CHF) of functional class II-IV according to the classification of the New York Heart Association (NYHA) provides a significant decrease in the number of hospitalizations associated with cardiovascular diseases (which is especially pronounced in patients who do not take β-blockers or ACE inhibitors).

When using the drug in patients with left ventricular failure (in the case of stable hemodynamic parameters) or with LV pathology after myocardial infarction, a decrease in cardiovascular mortality is recorded.

Hydrochlorothiazide (HCTZ)

Under the influence of thiazide diuretics on the highly sensitive receptors of the distal convoluted tubules of the renal cortex, inhibition of the reabsorption of chlorine (Cl -) and sodium (Na +) ions occurs. Inhibition of the Cl - and Na + co-transport presumably occurs as a result of competition for the binding sites of Cl - ions in the co-transport system. As a result, the excretion of Cl - and Na + increases on average equally.

Due to the diuretic effect, there is a decrease in the volume of circulating blood plasma, which contributes to an increase in renin activity, aldosterone production, renal excretion of potassium and, as a consequence, a decrease in the level of the latter in blood serum.

Amlodipine + Valsartan + HCTZ

With the combination therapy of amlodipine + valsartan + HCTZ, a stronger decrease in systolic and diastolic blood pressure (SBP and DBP) was observed, compared with the use of double combinations: amlodipine + HCTZ, amlodipine + valsartan and valsartan + HCTZ.

In patients with an initial mean blood pressure of 170/107 mm Hg. Art. (arterial hypertension of II – III severity) in the case of combined therapy with amlodipine + valsartan + HCTZ for 8 weeks in a daily dose of 10 mg + 320 mg + 25 mg, the average decrease in SBP / DBP was 39.7 / 24.7 mm Hg. Art., compared to 31.5 / 19.5 mm Hg. Art., 33.5 / 21.5 mm Hg. Art., 32.0 / 19.7 mm Hg. Art., noted against the background of combined treatment amlodipine + HCTZ at a dose of 10 mg + 25 mg, amlodipine + valsartan at a dose of 10 mg + 320 mg, and valsartan + HCTZ at a dose of 320 mg + 25 mg, respectively.

During treatment with Co-Exforge, 71% of patients achieved the target blood pressure (below 140/90 mm Hg), compared with 45–54% recorded with the use of double combinations.

The antihypertensive effect of Co-Exforge after oral administration persists for 24 hours.

Age, gender and race do not affect the therapeutic effect of the drug.


Amlodipine, valsartan and HCTZ have been found to have linear pharmacokinetics.


After oral administration in therapeutic doses in the blood plasma, the maximum concentration (C max) of the substance is observed after 6-12 hours, the absolute bioavailability is on average 64-80%, the volume of distribution (V d) is approximately 21 l / kg. Food intake does not affect the bioavailability of the substance.

According to in vitro studies in patients with arterial hypertension, about 97.5% of circulating amlodipine binds to blood plasma proteins.

Approximately 90% of amlodipine is metabolized in the liver, forming active metabolites. The half-life (T 1/2) varies from 30 to 50 hours, excretion from plasma is biphasic. Stationary blood concentrations are recorded after taking the drug for 7–8 days. It is excreted unchanged - 10% of the substance, in the form of metabolites - 60%.


After oral administration, C max of the substance is reached after 2–4 hours, the absolute bioavailability averages 23%. In the case of ingestion with food, a decrease in bioavailability by 40% is revealed in terms of the area under the pharmacokinetic curve (AUC), and C max in plasma is approximately 50%. However, approximately 8 hours after ingestion, the blood levels of valsartan in patients who took it on an empty stomach and those who received it with food level out. The decrease in AUC recorded in this case does not lead to a clinically significant weakening of the therapeutic effect; therefore, valsartan can be used regardless of the meal time.

After intravenous (i / v) administration during the equilibrium state, V d of valsartan was approximately 17 liters, which indicates the absence of its extensive distribution in the tissues. The connection with serum proteins, mainly albumin, is 94–97%. The substance does not undergo pronounced biotransformation, only 20% of the administered dose is detected in the form of metabolites. In blood plasma, a hydroxyl metabolite, which is pharmacologically inactive, is determined in low concentrations (less than 10% of the AUC of the parent substance).

The pharmacokinetic curve of the active substance has a descending multi-exponential character: T 1 / 2α is less than 1 hour, T 1 / 2β is about 9 hours.

It is excreted mainly unchanged with feces (~ 83%) and urine (~ 13%) of the dose. After intravenous administration, the clearance of valsartan in plasma is approximately 2 l / h, its renal clearance is 0.62 l / h (on average, 30% of the total clearance), T 1/2 is 6 hours.

Hydrochlorothiazide (HCTZ)

HCTZ is characterized by rapid absorption. After oral administration, the time to reach the C max of the substance is approximately 2 hours. The increase in AUC is on average linear and proportional to the dose. In the case of simultaneous use with food when compared with taking the drug on an empty stomach, the systemic bioavailability of HCTZ can both decrease and increase. The degree of this effect is insignificant and clinically insignificant, the absolute bioavailability is 60–80%. In general, the kinetics of distribution and elimination is presented in the form of a biexponential decreasing function with Т 1/2 = 6–15 hours. The kinetics of HCTZ does not change with repeated administration, the cumulation when using it once a day is minimal.

The apparent V d - 4-8 l / kg, bound to plasma proteins, mainly albumin 40-70% of circulating blood substance. HCTZ also accumulates in erythrocytes at concentrations approximately 3 times higher than those in blood plasma. Excreted unchanged by the kidneys over 95% of the absorbed dose.

After oral administration of Co-Exforge, C max HCTZ, valsartan and amlodipine are noted after 2, 3 and 6-8 hours, respectively. The degree and rate of absorption of Co-Exforge are equivalent to the bioavailability of its active components when each of them is used as separate oral preparations.

Indications for use

Co-Exforge is recommended for the treatment of grade II and III arterial hypertension.



  • hemodynamically unstable heart failure after acute myocardial infarction;
  • clinically significant aortic stenosis;
  • severe arterial hypotension (SBP below 90 mm Hg), cardiogenic shock, collapse;
  • severe renal impairment (GFR below 30 ml / min / 1.73 m²), anuria, hemodialysis treatment;
  • severe liver dysfunctions (over 9 points on the Child - Pough scale), cholestasis, biliary cirrhosis;
  • hypercalcemia, hyponatremia, hypokalemia, refractory to adequate treatment, as well as hyperuricemia with clinical symptoms;
  • hereditary angioedema or edema against the background of previous use of ARA II;
  • planning pregnancy, the period of pregnancy and lactation;
  • combination with aliskiren against the background of type 2 diabetes mellitus;
  • age up to 18 years;
  • hypersensitivity to any of the constituent tablets of Co-Exforge, as well as to other sulfonamide derivatives and dihydropyridine derivatives.

Relative (Co-Exforge should be taken with extreme caution):

  • mitral / aortic stenosis, hypertrophic obstructive cardiomyopathy;
  • CHF III-IV functional class according to the NYHA classification (treatment with ACE inhibitors and ARA II can cause oliguria and / or often progressive azotemia, and in rare cases - acute renal failure with a fatal outcome);
  • sick sinus syndrome (SSS), ischemic heart disease (IHD) (after starting or increasing the dose of amlodipine, an attack of angina pectoris may occur or the risk of myocardial infarction may worsen);
  • conditions leading to a decrease in the BCC;
  • violations of water and electrolyte balance (including hyponatremia, hyperkalemia);
  • functional kidney disorders of moderate severity (estimated GFR is more than 30 ml / min / 1.73 m², but below 90 ml / min / 1.73 m²);
  • stenosis of an artery of a single kidney, unilateral or bilateral stenosis of the renal arteries;
  • kidney transplant;
  • mild / moderate functional disorders of the liver, especially against the background of obstruction of the biliary tract (below 9 points on the Child - Pough scale);
  • diabetes;
  • systemic lupus erythematosus (HCTZ can provoke an aggravation of the course of this disease);
  • hyperuricemia;
  • high cholesterol and triglyceride levels;
  • history of angle-closure glaucoma;
  • elderly age;
  • simultaneous use with potassium-containing substitutes for table salt, potassium-sparing diuretics, potassium salts, as well as drugs that can lead to an increase in the level of potassium in the blood (including heparin).

Co-Exforge, instructions for use: method and dosage

Co-Exforge tablets are taken orally, 1 time per day (preferably in the morning), regardless of mealtime, with a small amount of water.

The recommended daily dose of the drug is 1 tablet, the dosage of amlodipine / valsartan / HCTZ is selected by the doctor. The maximum daily dose of the drug is 10 mg + 320 mg + 25 mg.

For convenience, patients taking amlodipine, valsartan and HCTZ in separate tablets can switch to Co-Exforge, which contains the same doses of active ingredients. Patients with insufficient control of blood pressure during double combination therapy - amlodipine + HCTZ, amlodipine + valsartan or valsartan + HCTZ can also be transferred to a triple combined administration of drugs in the form of Co-Exforge in appropriate doses.

If, against the background of double combined treatment with any active components of the drug, dose-dependent adverse events occur, to achieve a similar decrease in blood pressure, Co-Exforge can be prescribed, containing the active substance causing this violation in a lower dose.

You can increase the dose 14 days after the start of the course of therapy.

The maximum antihypertensive effect is achieved 14 days after increasing the dose.

Side effects

Adverse events recorded when using Co-Exforge (a combination of amlodipine, valsartan and HCTZ):

  • nervous system: often - headache, dizziness; infrequently - lethargy, drowsiness, taste disturbances, dizziness caused by physical activity; postural dizziness, impaired coordination, paresthesia, fainting, neuropathy, including peripheral;
  • mental disorders: infrequently - insomnia / sleep disturbances;
  • cardiovascular system: often - a marked decrease in blood pressure; infrequently - orthostatic hypotension, tachycardia, thrombophlebitis, phlebitis;
  • metabolism and nutritional disorders: often - hypokalemia; infrequently - hyperlipidemia, hypercalcemia, hyponatremia, hyperuricemia, anorexia;
  • senses: infrequently - blurry vision, vertigo;
  • digestive system: often - dyspepsia; rarely - bad breath, dry mouth, pain in the upper abdomen, abdominal discomfort, nausea, diarrhea, vomiting;
  • respiratory system: infrequently - shortness of breath, throat irritation, cough;
  • musculoskeletal system and connective tissue: infrequently - muscle weakness, muscle spasms, swelling in the joints, myalgia, pain in the limbs, back pain;
  • skin and subcutaneous tissues: infrequently - itchy skin, increased sweating;
  • genitals and mammary gland: infrequently - erectile dysfunction;
  • kidneys and urinary tract: often - pollakiuria; infrequently - an increase in the plasma level of creatinine in the blood, acute renal failure;
  • laboratory and instrumental data: infrequently - an increase in body weight, hypokalemia, hyperuricemia, an increase in the blood plasma level of urea nitrogen;
  • general disorders: often - increased fatigue, peripheral edema; infrequently - gait disturbances, general weakness, asthenia, abasia, chest pain (non-cardiac nature).

Side effects observed with amlodipine monotherapy:

  • nervous system: often - headache, drowsiness, dizziness; infrequently - taste disturbances, tremors, paresthesia, hypesthesia, fainting; extremely rare - neuropathy, muscle hypertonia; with an unknown frequency - extrapyramidal disorders;
  • immune system: extremely rare - hypersensitivity reactions;
  • mental disorders: infrequently - mood lability, insomnia / sleep disturbances, anxiety;
  • blood and lymphatic system: extremely rare - thrombocytopenia, leukopenia;
  • metabolism and nutritional disorders: extremely rare - hyperglycemia;
  • cardiovascular system: often - flushing of the face, palpitations; infrequently - a marked decrease in blood pressure; extremely rare - arrhythmias (including ventricular tachycardia, bradycardia, atrial fibrillation), vasculitis, myocardial infarction;
  • sense organs: infrequently - diplopia, visual disturbances, tinnitus;
  • respiratory system: infrequently - rhinitis, shortness of breath; extremely rare - cough;
  • liver and biliary tract: extremely rarely - an increase in the activity of liver enzymes, an increase in the content of bilirubin in the plasma, cholestatic jaundice, intrahepatic cholestasis, hepatitis;
  • gastrointestinal tract (GIT): often - nausea, pain in the upper abdomen, abdominal discomfort; infrequently - thirst, dryness of the oral mucosa, dyspepsia, changes in the frequency of bowel movements, constipation, vomiting, diarrhea; extremely rare - gingival hyperplasia, gastritis, pancreatitis;
  • musculoskeletal system and connective tissue: infrequently - muscle spasms, arthralgia, myalgia, back pain;
  • kidneys and urinary tract: infrequently - nocturia, urinary disorders, pollakiuria;
  • skin and subcutaneous tissues: infrequently - hyperhidrosis, alopecia, pruritus, discoloration of the skin, skin rash (including exanthema, photosensitivity), purpura; extremely rarely - urticaria, erythema multiforme / multiforme, angioedema, Stevens-Johnson syndrome;
  • general disorders: often - increased fatigue, peripheral edema (feet, ankles); infrequently - general weakness, asthenia, pain of various localization, including in the chest area;
  • genitals and mammary gland: infrequently - gynecomastia, erectile dysfunction;
  • laboratory and instrumental data: infrequently - increase / decrease in body weight; extremely rarely - an increase in the activity of hepatic transaminases.

Adverse events observed when using valsartan in monotherapy mode:

  • immune system: with unknown frequency - hypersensitivity reactions;
  • blood and lymphatic system: with an unknown frequency - a decrease in the level of hemoglobin and hematocrit, thrombocytopenia, neutropenia;
  • vessels: with an unknown frequency - vasculitis;
  • Gastrointestinal tract: infrequently - pain in the upper abdomen, abdominal discomfort;
  • sense organ: infrequently - vertigo;
  • respiratory system: infrequently - cough;
  • liver and biliary tract: with an unknown frequency - an increase in the activity of liver enzymes, an increase in the plasma content of bilirubin in the blood;
  • musculoskeletal system and connective tissue: with unknown frequency - myalgia;
  • skin and subcutaneous tissues: with an unknown frequency - itching, rash, bullous dermatitis, angioedema;
  • general disorders: infrequently - increased fatigue;
  • kidneys and urinary tract: with an unknown frequency - an increase in plasma creatinine levels, impaired renal function (including acute renal failure);
  • laboratory and instrumental data: with an unknown frequency - an increase in the plasma concentration of potassium in the blood.

In the course of clinical studies in the treatment of valsartan in monotherapy, the following disorders were recorded (regardless of their causal relationship with this substance): insomnia, decreased libido, neutropenia, rhinitis, sinusitis, pharyngitis, upper respiratory tract infections, viral infections.

Adverse reactions recorded when using HCTZ as a monotherapy drug:

  • immune system: extremely rare - hypersensitivity reactions;
  • blood and lymphatic system: rarely - thrombocytopenia, in some cases in combination with purple; extremely rarely - hemolytic anemia, inhibition of bone marrow hematopoiesis, agranulocytosis, leukopenia; with an unknown frequency - aplastic anemia;
  • nervous system: rarely - headache, dizziness, paresthesia;
  • mental disorders: rarely - sleep disorders, depression;
  • cardiovascular system: often - orthostatic hypotension (aggravated by taking ethanol, painkillers or sedatives); rarely - arrhythmias;
  • liver and biliary tract: rarely - jaundice or intrahepatic cholestasis;
  • Gastrointestinal tract: often - loss of appetite, vomiting, nausea; rarely - diarrhea, constipation, abdominal discomfort; extremely rare - pancreatitis;
  • endocrine system: rarely - worsening of the course of diabetes mellitus;
  • genitals and mammary gland: often - impotence;
  • sense organs: rarely - visual impairment (especially in the first weeks of the course); with an unknown frequency - acute development of angle-closure glaucoma;
  • respiratory system: extremely rare - respiratory distress syndrome, including pneumonitis (pulmonitis) and pulmonary edema;
  • kidneys and urinary tract: with an unknown frequency - impaired renal function, acute renal failure;
  • skin and subcutaneous tissue: often - urticaria, skin rash; rarely - photosensitivity; extremely rarely - lupus-like reactions, toxic epidermal necrolysis, necrotizing vasculitis, exacerbation of cutaneous manifestations of systemic lupus erythematosus; with an unknown frequency - erythema multiforme;
  • laboratory and instrumental data: very often - an increase in the level of lipids in the blood, hypokalemia; often - hyperuricemia, hypomagnesemia, hyponatremia; rarely - glucosuria, hyperglycemia, hypercalcemia; extremely rare - hypochloremic alkalosis.


There is currently no data on cases of overdose of Co-Exforge.

An overdose of amlodipine can cause excessive peripheral vasodilation and reflex tachycardia, as well as sometimes a pronounced and prolonged decrease in blood pressure, up to the development of fatal shock.

Against the background of an overdose of valsartan, dizziness and a significant decrease in blood pressure may appear.

The main clinical manifestations of HCTZ overdose include effects due to loss of electrolytes (including hypochloremia and hypokalemia) and dehydration as a result of stimulation of diuresis. The most common symptoms of overdose are drowsiness and nausea, hypokalemia can cause muscle spasms. When used in combination with antiarrhythmic drugs, including cardiac glycosides, hypokalemia can aggravate cardiac arrhythmias.

If an excessive dose of the drug has been recently taken, it is necessary to induce vomiting or gastric lavage. The use of activated charcoal immediately or within 2 hours after taking amlodipine significantly weakened its absorption.

Against the background of a pronounced decrease in blood pressure, the patient should be laid with raised legs and measures should be taken to increase blood pressure and maintain the activity of the cardiovascular system, including monitoring cardiac and respiratory functions, BCC and the volume of urine excreted. In order to restore vascular tone and normalize blood pressure, it is possible to prescribe (in the absence of contraindications) a vasoconstrictor. To eliminate the blockade of calcium channels, intravenous infusion of solutions of calcium salts is allowed. HCTZ can be removed from the systemic circulation using hemodialysis, but this procedure is ineffective for valsartan and amlodipine.

special instructions

During therapy, it is required to regularly monitor the content of potassium and creatinine in the blood plasma.

Before taking the drug, if it is necessary to cancel treatment with β-blockers, the dose of the latter should be reduced gradually. Due to the fact that Co-Exforge does not contain β-blockers, it is not able to prevent the onset of the withdrawal syndrome that develops when they are abruptly stopped.

Treatment with thiazide diuretics may cause hypochloremia, hyponatremia, or exacerbate existing hyponatremia. In patients with this disorder, isolated cases of the appearance of neurological symptoms were recorded, such as nausea, disorientation, asthenia, apathy. In patients with severe BCC deficiency and / or hyponatremia, including when using high doses of diuretics, while taking ARA II, in rare cases, symptomatic arterial hypotension may develop. Before starting the course, it is required to correct the concentration of sodium in the blood and / or BCC, or to start treatment under close medical supervision. In the event of arterial hypotension, the patient should be laid down with raised legs, if necessary, infusion of sodium chloride 0.9% solution intravenously. After reaching the stabilization of blood pressure, the drug can be continued.

When treating Co-Exforge, it is necessary to regularly determine the content of blood plasma electrolytes.

The use of thiazide diuretics can cause hypokalemia, or, in the presence of this disorder, aggravate its manifestations. It is necessary to take HCTZ with caution in patients with nephropathy, cardiogenic renal dysfunction or with other lesions accompanied by potassium deficiency. If the development of clinical symptoms of hypokalemia is noted in the form of muscle weakness, paresthesias, changes in the ECG, Co-Exforge should be discontinued.

With the use of HCTZ, there is a possibility of a change in glucose tolerance, as well as an increase in the level of triglycerides, cholesterol and uric acid in the blood serum. A decrease in the clearance of the latter can provoke hyperuricemia and the occurrence of gout in predisposed patients.

HCTZ should be used with extreme caution in patients with hypercalcemia, since it leads to a decrease in calcium excretion and moderately increases the concentration of calcium in the blood. The development of severe hypercalcemia when using Co-Exforge may indicate latent hyperparathyroidism.

While taking HCTZ as a sulfonamide, cases of transient myopia and acute attacks of angle-closure glaucoma have been recorded, the risk factors for which may be indications of a history of allergic reactions caused by sulfonamides and penicillin. The symptoms of angle-closure glaucoma usually appear within a few hours to 7 days after the start of the course of therapy. Failure to treat this complication in a timely manner can cause permanent loss of vision.

Influence on the ability to drive vehicles and complex mechanisms

Patients who drive vehicles or work with other complex / moving mechanisms should be careful while taking Co-Exforge, because of the possible development of adverse reactions in the form of visual disturbances, weakness and dizziness.

Application during pregnancy and lactation

The use of Co-Exforge during pregnancy planning, as well as during pregnancy, is contraindicated, since this agent affects the renin-angiotensin-aldosterone system (RAAS). The use of ACE inhibitors acting on the RAAS in the II and III trimesters of pregnancy causes damage or death of the developing fetus, and in the I trimester - the development of fetal / newborn pathology. It has been established that HCTZ passes through the placenta. The use of thiazide diuretics, including HCTZ, during pregnancy can cause thrombocytopenia or embryonic / neonatal jaundice, as well as other disorders recorded in adults. Cases of oligohydramnios, spontaneous abortions and impaired renal function in newborns against the background of unintentional intake of valsartan by a pregnant woman are described.

If pregnancy occurs during the period of Co-Exforge therapy, the drug must be urgently canceled.

HCTZ is detected in breast milk, it has not been determined whether valsartan and / or amlodipine is excreted in breast milk. Co-Exforge is contraindicated to take during breastfeeding.

Pediatric use

The efficacy and safety of Co-Exforge in children and adolescents under 18 years of age have not been established, therefore, drug treatment is contraindicated in patients of this category.

With impaired renal function

In the presence of severe renal dysfunction (GFR less than 30 ml / min / 1.73 m²), anuria, as well as in hemodialysis treatment, taking Co-Exforge is contraindicated because of the HCTZ it contains.

In patients with mild / moderate functional renal impairment (GFR above 30 ml / min, but less than 90 ml / min), stenosis of an artery of a solitary kidney, unilateral or bilateral stenosis of the renal arteries (due to an increased risk of increased serum creatinine and urea levels blood), the drug must be used with caution, there is no need to adjust the initial dose in this case.

For violations of liver function

In the presence of severe liver dysfunction (more than 9 points on the Child - Pough scale), cholestasis or biliary cirrhosis, Co-Exforge is contraindicated.

Patients with mild / moderate hepatic impairment (5-9 points on the Child-Pough scale), especially with biliary obstruction, should use the drug with caution. In patients of this category, if necessary, it is possible to reduce the initial dose of the drug to one containing the minimum dose of amlodipine - 5 mg + 160 mg + 12.5 mg or 5 mg + 160 mg + 25 mg.

Use in the elderly

Elderly people do not need to adjust the dose of the drug. If necessary, in patients of this age group, it is allowed to reduce the initial dose of Co-Exforge to the one containing the lowest dose of amlodipine - 5 mg + 160 mg + 12.5 mg or 5 mg + 160 mg + 25 mg.

Drug interactions

Possible drug interaction of amlodipine with concomitantly used drugs / substances:

  • thiazide diuretics, β-blockers, long-acting nitrates, ACE inhibitors, digoxin, nitroglycerin for sublingual administration, sildenafil, atorvastatin, warfarin, antacids (aluminum hydroxide gel, magnesium hydroxide, simethicone), nonsteroidal anti-inflammatory drugs (NSAIDs), anti-inflammatory drugs and oral antidiabetic drugs: there is no clinically significant interaction when used in combination with amlodipine;
  • diltiazem (an inhibitor of the isoenzyme CYP3A4): there is a decrease in the metabolic rate of amlodipine in elderly patients, which causes an increase in its level in the blood by about 50% and an increase in systemic exposure;
  • ethanol: no changes in the pharmacokinetics of this substance are recorded when combined with amlodipine;
  • itraconazole, ketoconazole, ritonavir (potent inhibitors of CYP3A4): a significant increase in systemic exposure to amlodipine is possible; with this combination, caution should be exercised;
  • carbamazepine, phenytoin, phenobarbital, primidone, phosphenytoin, rifampicin; herbal remedies containing St. John's wort; grapefruit juice (inducers of the CYP3A4 isoenzyme): there is a pronounced decrease in the plasma concentration of amlodipine, and therefore its level should be monitored;
  • simvastatin (at a dose of 80 mg): there is an increase in systemic exposure of this substance by 77% when it is combined with amlodipine at a dose of 10 mg; it is not recommended to use simvastatin in a dose exceeding 20 mg simultaneously with Co-Exforge.

Possible drug interactions of valsartan with concurrently used drugs / substances:

  • warfarin, cimetidine, digoxin, furosemide, indomethacin, atenolol, amlodipine, hydrochlorothiazide, glibenclamide: there is no clinically significant interaction of these substances with valsartan used in monotherapy;
  • NSAIDs: the antihypertensive and diuretic effect of valsartan may decrease; in elderly patients with concomitant hypovolemia or impaired renal function, the combined use of ARA II and NSAIDs (including selective COX-2 inhibitors) may impair renal function;
  • other drugs that affect the RAAS: the risk of hyperkalemia, arterial hypotension, and renal dysfunction is aggravated when these drugs are used together with ARA II;
  • rifampicin, ritonavir, cyclosporin: the systemic bioavailability of valsartan increases.

Possible drug interactions of thiazide diuretics, including HCTZ, with concurrently used drugs / substances:

  • other antihypertensive drugs (including methyldopa, guanethidine, vasodilating agents, slow calcium channel blockers, beta-blockers, ACE inhibitors, ARA II, direct renin inhibitors): their antihypertensive efficacy may increase;
  • muscle relaxants of peripheral action (curariform muscle relaxants, for example, tubocurarine chloride): the effect of these drugs is enhanced;
  • glucocorticosteroids (GCS), diuretics, adrenocorticotropic hormone (ACTH), carbenoxolone, amphotericin B; acetylsalicylic acid (ASA) in a dose of more than 3000 mg (drugs that cause a decrease in the plasma concentration of potassium in the blood): the threat of hypokalemia increases;
  • insulin, antidiabetic oral agents: lactic acidosis may occur when HCTZ is combined with metformin; care should be taken to carry out Co-Exforge therapy in patients with diabetes mellitus, adjusting the dose of hypoglycemic agents or insulin if necessary;
  • cardiac glycosides: the risk of heart rhythm disturbances caused by hypokalemia and hypomagnesemia (unwanted reactions of thiazide diuretics) may be aggravated;
  • methyldopa: hemolytic anemia may occur when treating HCTZ with this substance;
  • colestipol and colestyramine (anion exchange resins): reduce the absorption of thiazide diuretics, including HCTZ; the drug should be taken 4-6 hours after these compounds or 4 hours before them;
  • cyclosporine: the threat of hyperuricemia and the appearance of symptoms similar to those of an exacerbation of gout increases;
  • anticholinergics (biperiden, atropine): the bioavailability of HCTZ increases, which is possibly due to a decrease in gastrointestinal motility and a slowdown in the rate of gastric emptying;
  • carbamazepine: the threat of hyponatremia is aggravated; it is necessary to carry out appropriate monitoring of plasma sodium levels in the blood;
  • calcium salts and vitamin D: an increase in the concentration of calcium in the blood serum is possible when these substances are combined with HCTZ;
  • allopurinol: an increase in the frequency of hypersensitivity reactions is possible;
  • cyclophosphamide, methotrexate (cytotoxic drugs): the excretion of these drugs by the kidneys decreases and their myelosuppressive effect increases;
  • diazoxide: its hyperglycemic effect increases;
  • amantadine: the threat of the development of its side effects increases;
  • pressor amines (norepinephrine): HCTZ is able to reduce the body's response to their administration, this effect has no clinical significance;
  • barbiturates, ethanol, narcotic substances: with simultaneous use with HCTZ, the likelihood of developing orthostatic hypotension increases.

For valsartan and HCTZ, a general drug interaction with lithium preparations is inherent: there is a reversible increase in the concentration of lithium in the plasma and its toxic effect during therapy with diuretics and ACE inhibitors. Blood lithium should be monitored when combined with HCTZ. The likelihood of a toxic effect associated with the use of lithium preparations when used simultaneously with Co-Exforge may be further enhanced, since the renal clearance of lithium preparations is inhibited under the influence of thiazide diuretics. If necessary, combined use requires careful monitoring of the serum lithium concentration in the blood.


Co-Exforge analogues are: Co-Vamloset, Tritensin.

Terms and conditions of storage

Store in a dry place out of the reach of children at a temperature not exceeding 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Co-Exforge

According to reviews, Co-Exforge is an effective treatment for arterial hypertension of II and III severity. The drug, which is a combination of three active components, according to patients, demonstrates a more pronounced ability to lower blood pressure than its individual components. Everyone recommends taking Co-Exforge only after consulting a doctor and under his supervision. They also indicate that during the period of therapy, it is necessary to monitor the content of creatinine and potassium in the blood.

Almost everyone considers its high cost to be a disadvantage of the tool.

Price for Co-Exforge in pharmacies

The price of Co-Exforge, film-coated tablets for a pack containing 28 pcs., Can be:

  • dosage of 5 mg + 160 mg + 12.5 mg - 2,100-2,500 rubles;
  • dosage 10 mg + 160 mg + 12.5 mg - 2150-2650 rubles.

Co-Exforge: prices in online pharmacies

Drug name



Co-Exforge 10 mg + 160 mg + 12.5 mg film-coated tablets 28 pcs.

1866 RUB


Co-Exforge 5 mg + 160 mg + 12.5 mg film-coated tablets 28 pcs.

2143 RUB


KO-Exforge tablets p.o. 10mg + 160mg + 12.5mg 28 pcs.

2179 RUB


KO-Exforge tablets p.p. 5mg + 160mg + 12.5mg 28 pcs.

2233 RUB


Maria Kulkes
Maria Kulkes

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!

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