The shape of the tablets and engraving depend on the dosage of the active ingredients:
- amlodipine besilate – 5 mg/valsartan – 80 mg: round tablets with beveled edges, coated with a dark yellow film coating with the engraving “NV” on one side and “NVR” on the other;
- amlodipine besilate – 5 mg/valsartan – 160 mg: oval tablets with beveled edges, coated with a dark yellow film coating with engraving “ECE” on one side and “NVR” on the other;
- amlodipine besilate – 10 mg/valsartan – 160 mg: oval tablets with beveled edges, coated with a light yellow film coating with the engraving “UIC” on one side and “NVR” on the other.
- microcrystalline cellulose;
- magnesium stearate;
- titanium dioxide;
- macrogol 4000;
- iron oxide is yellow.
- Pharmacological properties
- Co-Exforge, instructions for use: method and dosage
- Dosage and Administration
- для взрослых
- for children
- Children, during pregnancy and lactation
- Drug Interactions
- special instructions
- Conditions of leave from pharmacies
- Form of issue and composition
Valsartan and amlodipine exhibit linear pharmacokinetics.
Suction. After taking therapeutic doses of amlodipine separately, the maximum plasma concentration (max) is reached within 6-12 hours. The bioavailability calculated is from 64% to 80%. Eating does not affect the bioavailability of amlodipine.
Distributions. The distribution volume is approximately 21 l/kg. In vitro studies of amlodipine have shown that in patients with essential hypertension, approximately 97,5% of the circulating drug binds to plasma proteins.
Metabolism. Amlodipine is intensively (about 90%) metabolized in the liver to inactive metabolites.
Conclusion. The withdrawal of amlodipine from plasma is biphasic, with a half-life of about 30-50 hours. Equilibrium plasma levels are achieved after continuous administration for 7-8 days. 10% of the initial amlodipine and 60% of amlodipine metabolites are excreted in the urine.
Suction. After oral administration, C max of valsartan in blood plasma is reached within 2-4 hours. The average bioavailability of the drug is 23%. Food reduces exposure, as shown by AUC (plasma concentration – time), of valsartan by about 40%, and C max by 50%, although after 8:00 after application, the concentration of valsartan in plasma is the same for the fasting group and the group patients who took the drug after meals. The decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be taken regardless of food intake.
Distribution. The equilibrium volume of distribution of valsartan after intravenous administration is about 17 L, which indicates that valsartan is distributed in tissues – not intensely.
Valsartan is strongly bound to plasma proteins (94-97%), mainly from albumin.
Metabolism. Valsartan is not significantly transformed, since only 20% of the dose passes into metabolites. In plasma in low concentrations (less than 10% AUC of valsartan), hydroxymetabolite has been identified, which is pharmacologically inactive.
After oral administration of Exforge, C max of valsartan and amlodipine in blood plasma is achieved after 3 and 6-8 hours, respectively. Exforge’s rate and extent of absorption are equivalent to the bioavailability of valsartan and amlodipine when administered in separate tablets.
Detonic – a unique medicine that helps fight hypertension at all stages of its development.
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.
Co-Exforge is a combined drug that includes three antihypertensive components: amlodipine (a derivative of dihydropyridine) – a slow calcium channel blocker (BMCC), valsartan – an angiotensin II receptor antagonist (ARA II), and hydrochlorothiazide (GHTZ) – thiazide. 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.
Exforge is used to lower blood pressure, the effect can be recorded within two hours after taking the pill. To improve well-being, it will take an average of five hours, while the effect will persist throughout the day. The manufacturer guarantees that the patient will not notice any surges in pressure or pulse.
Also, if necessary, you can abruptly cancel the drug without consequences, this means that there is no withdrawal syndrome. It is also clinically proven that when admitted by patients with heart failure, the number of hospitalizations or sudden cardiac arrest is much lower.
The instructions for the use of Exforge pressure pills indicate situations where therapy is allowed only under the supervision of a doctor:
- in the presence of a patient’s history of Quincke’s edema, as well as swelling of the vocal cords and larynx, oral organs (as there is information about treatment with valsartan), you should be extremely careful while using Exforge;
- if the risk of hyperkalemia is increased (for example, against the background of potassium-sparing diuretics), control of the amount of potassium in the blood is mandatory;
- in case of liver diseases not listed in contraindications, a controlled intake of a medication containing amlodipine should still be ensured;
- with hypovolemia or a deficiency of sodium in the blood – due to the increased risk of developing severe hypotension;
- with CHF III-IV of functional classes – the risk of conditions causing acute renal failure and even death is increased;
- in severe IHD – due to the increased likelihood of developing myocardial infarction due to treatment with amlodipine;
- the same applies to moderate renal dysfunction, renal artery stenosis – admission is only under control.
When the slightest signs of edema appear, the medication should be irrevocably canceled. When working with mechanisms or driving, you need to remember the likelihood of dizziness due to Exforge.
The drug Exforge is a combined antihypertensive drug, which includes amlodipine and valsartan. The active components have a synergistic effect, mutually increasing therapeutic efficacy, which favorably distinguishes Exforge among single-component antihypertensive drugs.
Amlodipine belongs to the pharmacological group of slow calcium channel blockers. The substance provokes relaxation of the smooth muscle layer of the vascular wall, thereby causing a decrease in total peripheral vascular resistance and a decrease in blood pressure. Therapeutic doses of amlodipine cause expansion of the vascular lumen without significant changes in heart rate and catecholamine levels.
Valsartan is a specific active angiotensin II receptor antagonist. The mechanism of action of the substance is the selective effect on AT1 receptors. Valsartan does not inhibit the angiotensin converting enzyme (ACE) and does not cause the accumulation of bradykinin.
The maximum concentration of amlodipine in the blood is reached 6-12 hours after taking the Exforge tablet. Bioavailability varies from 65 to 80%. The ability to bind to plasma proteins is 98%. Metabolized in the liver. The elimination half-life can make from 30 to 50 hours. It is excreted by the kidneys in the form of metabolic products.
The concentration of valsartan in the blood reaches its maximum values 2-3 hours after taking the medicine. Bioavailability is 23%. The ability to form bonds with serum proteins ranges from 94 to 97%. Almost not metabolized in the liver. It is excreted mainly by the intestine unchanged. The elimination half-life is 6 hours.
Co-Exforge, instructions for use: method and dosage
Patients whose blood pressure is inadequately regulated by a single drug of amlodipine or valsartan can be transferred to a combination therapy with the drug
. The recommended dose is 1 tablet per day. Exforge tablets can be taken regardless of food intake. It is recommended to take Exforge with a little water.
Patients taking valsartan and amlodipine separately can be transferred to Exforge, which contains the same doses of the components.
Before switching to a fixed-dose combination, individual dose selection with components (i.e., amplodipine and valsartan) is recommended. In case of clinical need, you can consider the possibility of a direct replacement of monotherapy with a combination of fixed doses.
The maximum daily dose is 1 tablet of Exforge 5 mg/80 mg or 1 tablet of Exforge 5 mg/160 mg, or 1 tablet of Exforge 10 mg/160 mg (the maximum allowable dose of the components of the drug is 10 mg by the content of amlodipine, 320 mg by the content of valsartan) .
Dosage for individual groups of patients
There are no clinical data available for use in patients with severe renal impairment.
Patients with impaired renal function of mild or moderate severity do not need dose adjustment.
In patients with moderate renal impairment, it is recommended to monitor the level of potassium and creatinine in the blood.
The simultaneous use of Exforge with aliskiren is contraindicated in patients with impaired renal function (GFR lt; 60 mg/min/1,73 m 2).
The simultaneous use of Exforge with aliskiren is contraindicated in patients with diabetes mellitus.
Violation of the function of the liver.
Exforge is contraindicated in patients with severely impaired liver function.
Exforge should be used with caution in patients with impaired liver function or obstructive biliary tract disease. For patients with mild or moderate hepatic impairment without cholestasis, the maximum recommended dose is 80 mg of valsartan.
Recommendations for dosing amlodipine in patients with mild or moderate impaired liver function have not been developed. When transferring such patients with arterial hypertension (see the “Indications” section) and liver dysfunction to amlodipine or Exforge, the smallest recommended dose of amlodipine should be prescribed in monotherapy or as part of combination therapy.
Elderly patients (over 65 years old)
For older patients, the usual dosage regimens are recommended.
Caution should be exercised when increasing the dose of the drug to elderly patients.
When transferring such patients with arterial hypertension (see the “Indications” section) and liver dysfunction to amlodipine or Exforge, the smallest recommended dose of amlodipine should be prescribed in monotherapy or as part of combination therapy.
The safety and effectiveness of Exforge for children (under the age of 18 years) has not been investigated. No data available.
Children. A study of the treatment of children with this drug (under the age of 18 years) has not been conducted. Therefore, until further information is obtained, Exforge is not recommended for the treatment of children.
Co-Exforge tablets are taken orally, 1 time per day (preferably in the morning), regardless of the meal time, with a small amount of water.
The recommended daily dose of the drug is 1 tablet, the dosage of amlodipine/valsartan/GHTZ 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 GHTZ in separate tablets can switch to Co-Exforge, which includes the same doses of active ingredients. Patients with insufficient control can also be transferred to a triple combined intake of drugs in the form of Co-Exforge in appropriate doses. Blood pressure during dual combination therapy – amlodipine GHTZ, amlodipine valsartan or valsartan GHTZ.
If dose-related adverse events occur against the background of a double combined treatment with any active components of the drug, Co-Exforge containing a lower dose of the active substance causing the violation can be prescribed to achieve a similar reduction in blood pressure.
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.
Dosage and Administration
Exforge tablets should be taken orally, washed down with a sufficient volume of ordinary water, regardless of the meal. Do not crush or chew tablets.
Exforge’s recommended dosage for adult patients is 1 tablet 1 time per day. The maximum daily rate of the drug in terms of the number of active elements amlodipine/valsartan is 10/320 mg. The choice of tablets with various dosages of active ingredients is carried out exclusively by a doctor.
For children and adolescents under the age of 18, taking Exforge is contraindicated.
During breastfeeding and bearing a child, it is forbidden to use the drug Exforge for therapeutic purposes.
Children, during pregnancy and lactation
The use of Exforge is contraindicated during gestation and breastfeeding.
If pregnancy occurs while taking Exforge, therapy should be stopped immediately.
Exforge is not recommended for the treatment of children under the age of 18 due to a lack of safety information.
contraindicated for pregnant women or women planning a pregnancy. If pregnancy is confirmed during treatment with this agent, its use must be stopped immediately and replaced with another drug approved for use in pregnant women.
Epidemiological studies of the risk of teratogenicity after exposure to ACE inhibitors during the first trimester of pregnancy were convincing; however, a slight increase in risk cannot be ruled out. Although data from controlled epidemiological studies of angiotensin II receptor antagonists (ARAII) are not available, a similar risk may arise with the use of drugs of this class.
The exposure of ARAI in the second and third trimester is known to have a toxic effect on the human fetus (decreased renal function, oligohydramnios, delayed ossification of the bones of the skull) and a newborn (renal failure, arterial hypotension, hyperkalemia).
If ARAI has been used since the second trimester of pregnancy, ultrasound examination of the kidneys and bones of the fetal skull is recommended.
Infants whose mothers took ARAI should be closely monitored in case of development of arterial hypotension.
Since there is no information on the use of Exforge during breastfeeding, it is not recommended to use the drug during breastfeeding, it is advisable to use alternative drugs with a studied safety profile, especially in case of breastfeeding of newborns or premature babies.
The use of Co-Exforge during pregnancy planning, as well as during its course is contraindicated, since this tool has an effect on the renin-angiotensin-aldosterone system (RAAS). The use of ACE inhibitors acting on RAAS in the II and III trimesters of pregnancy causes damage or death to the developing fetus, and in the first trimester – the development of fetal/newborn pathology.
It was established that GHTZ passes through the placenta. The use of thiazide diuretics, including GHTZ, during pregnancy can provoke the appearance of thrombocytopenia or embryonic/neonatal jaundice, as well as other disorders recorded in adults. Cases of the occurrence of oligohydramnios, spontaneous abortion, and renal dysfunction in newborns against the background of an unintentional intake of valsartan by a pregnant woman are described.
If pregnancy has occurred during Co-Exforge therapy, the drug must be urgently canceled.
HCT is detected in breast milk, whether valsartan and/or amlodipine is excreted in human milk is not clear. Co-Exforge is contraindicated in the period of breastfeeding.
The study of drug interactions
with other medicines were not carried out.
Medicines, with the simultaneous use of which should be careful
Other antihypertensive drugs
Frequently used antihypertensive drugs (e.g. alpha-blockers, diuretics) and other drugs that can cause the appearance of antihypertensive adverse events (e.g. tricyclic antidepressants, alpha-blockers used to treat benign prostatic hyperplasia) can enhance the hypotensive effect of the combination.
Simultaneous use is not recommended.
The simultaneous use of amlodipine with more or less powerful CYP3A4 inhibitors (protease inhibitors, azole antifungal, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to an increase in the systemic effect of amlodipine.
Clinical manifestations of such pharmacokinetic changes may be exacerbated in elderly patients. Clinical monitoring and dose adjustment may be required.
Inducers of CYP3A4 (anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidone), rifampicin, perforated hypericum (Hypericum perforatum)
There are no studies on the effects of CYP3A4 inducers on amlodipine. The simultaneous use of CYP3A4 inducers (e.g. rifampicin, Hypericum perforatum) can lead to a decrease in the concentration of amlodipine in blood plasma. Caution is advised to use amlodipine with CYP3A4 inducers.
Simvastatin. Repeated use of doses of 10 mg of amlodipine with 80 mg of simvastatin leads to an increase in the exposure of simvastatin by 77% compared with the use of simvastatin alone. It is recommended that the dose of simvastatin be reduced to 20 mg for patients taking amlodipine.
Dantrolene (infusion). In animals, fatal cases of ventricular fibrillation and cardiovascular collapses were observed in connection with hyperkalemia after the use of verapamil and dantrolene. Due to the risk of hyperkalemia, it is recommended to avoid the combined use of calcium channel blockers, such as amlodipine, in patients prone to developing malignant hyperthermia and in the treatment of malignant hyperthermia.
In clinical studies, amlodipine did not affect the pharmacokinetics of atorvastatin, dioxin, warfarin, or cyclosporine.
Interactions associated with valsartan
Lithium. With the simultaneous use of lithium with ACE inhibitors or angiotensin II receptor antagonists, including valsartan, a reversible increase in serum lithium concentrations and its toxicity was noted. The simultaneous use of valsartan and lithium is not recommended. If the use of such a combination is necessary, serum lithium levels should be carefully monitored. The risk of increased lithium toxicity may be further increased when combined with Exforge and diuretics.
Potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, or other drugs that can increase potassium levels
If drugs that affect potassium channels are prescribed in combination with valsartan, regular monitoring of plasma potassium should be considered.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (gt; 3 g/day) and non-selective NSAIDs
With the simultaneous use of angiotensin II antagonists and NSAIDs, hypotensive effects may be weakened.
Also, the simultaneous use of angiotensin II antagonists and NSAIDs may increase the risk of impaired renal function and serum potassium levels. Therefore, at the beginning of treatment, it is recommended to monitor the state of renal function, as well as ensure the proper fluid level in the patient’s body.
Accumulation vector inhibitors (rifampicin, cyclosporin) or the reflux vector (ritonavir)
The results of in vitro studies with human liver tissue showed that valsartan is a substrate of the hepatic transporter of OATP1B1 accumulation and the hepatic reflux transporter of MRP2. The simultaneous use of accumulation vector inhibitors (rifampicin, cyclosporine) or the reflux vector (ritonavir) can increase the systemic exposure of valsartan.
Double blockade of RAAS with ARA, ACE inhibitors or aliskiren
The results of clinical studies have shown that the double blockade of RAAS with the combined use of ACE inhibitors, ARA or aliskiren leads to an increase in the frequency of adverse events such as hypotension, hyperkalemia and decreased renal function (including acute renal failure), compared with treatment with a single drug, affecting the RAAS.
When monotherapy with valsartan, no clinically significant drug interactions with such drugs have been established: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
With amlodipine monotherapy, there is no clinically significant drug interaction with ACE inhibitors, thiazide diuretics, warfarin, NSAIDs, maalox, antibiotic agents, prolonged-action nitrates, beta-adrenergic blockers, digoxin, cimetidine, and hypoglycemic drugs for oral use.
When combining valsartan with biologically active additives, drugs and salt substitutes containing potassium, as well as potassium-sparing diuretics, special care should be taken. To prevent negative consequences, monitoring of potassium in the blood plasma should be carried out.
Possible drug interaction of amlodipine with the simultaneously 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), non-steroidal anti-inflammatory drugs, anti-inflammatory drugs and oral antidiabetic drugs: there is no clinically significant interaction when combined with amlodipine;
- diltiazem (inhibitor of the CYP3A4 isoenzyme): there is a decrease in the rate of metabolism of amlodipine in elderly patients, which causes an increase in its blood level by about 50% and an increase in systemic exposure;
- ethanol: changes in the pharmacokinetics of this substance when combined with amlodipine are not recorded;
- 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, fosphenytoin, rifampicin; herbal remedies containing Hypericum perforatum; grapefruit juice (inducers of the CYP3A4 isoenzyme): a marked decrease in the plasma concentration of amlodipine is observed, in connection with which its level should be monitored;
- simvastatin (at a dose of 80 mg): there is an increase in the systemic exposure of this substance by 77% when combined with amlodipine at a dose of 10 mg; Simvastatin in a dose exceeding 20 mg is not recommended to be used simultaneously with Co-Exforge.
Possible drug interaction of valsartan with the simultaneously used drugs/substances:
- warfarin, cimetidine, digoxin, furosemide, indomethacin, atenolol, amlodipine, hydrochlorothiazide, glibenclamide: there is a lack of clinically significant interaction of these substances with valsartan used in monotherapy mode;
- NSAIDs: the antihypertensive and diuretic effect of valsartan may be reduced; in elderly patients with concomitant hypovolemia or impaired renal activity, the combined use of ARA II and NSAIDs (including selective COX-2 inhibitors) may worsen renal activity;
- other drugs that affect RAAS: the risk of hyperkalemia, arterial hypotension, impaired renal activity with the combined use of these drugs with ARA II is exacerbated;
- rifampicin, ritonavir, cyclosporine: increased systemic bioavailability of valsartan.
Possible drug interaction of thiazide diuretics, including HCTZ, with the simultaneously used drugs/substances:
- other antihypertensive drugs (including methyldopa, guanethidine, vasodilating agents, slow calcium channel blockers, beta-blockers, ACE inhibitors, ARA II, direct renin inhibitors): it is likely to increase their antihypertensive effectiveness;
- peripheral muscle relaxants (curariform muscle relaxants, for example, tubocurarine chloride): the effect of these agents 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 risk of hypokalemia increases;
- insulin, antidiabetic oral agents: lactic acidosis may occur with the combination of HCTZ with metformin; Co-Exforge therapy should be used with caution in patients with diabetes mellitus, adjusting doses of hypoglycemic agents or insulin if necessary;
- cardiac glycosides: the risk of heart rhythm disturbances caused by hypokalemia and hypomagnesemia (adverse reactions of thiazide diuretics) may be aggravated;
- methyldopa: hemolytic anemia may occur in the treatment of HCT 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 developing hyperuricemia and the appearance of symptoms similar to signs of exacerbation of gout is increased;
- anticholinergics (biperiden, atropine): increased bioavailability of HCT, which is possibly due to a decrease in gastrointestinal motility and a slower rate of gastric emptying;
- carbamazepine: the threat of hyponatremia is exacerbated; it is necessary to exercise appropriate control of the plasma level of sodium in the blood;
- calcium salts and vitamin D: an increase in serum calcium concentration is possible with a combination of these substances with HCTZ;
- allopurinol: an increase in the frequency of hypersensitivity reactions is possible;
- cyclophosphamide, methotrexate (cytotoxic drugs): kidney excretion of these drugs is reduced and their myelosuppressive effect is enhanced;
- diazoxide: its hyperglycemic effect increases;
- amantadine: the risk of developing its side effects is increasing;
- pressor amines (norepinephrine): GHTZ 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.
In the case when it is necessary to cancel the intake of beta-adrenoreceptor blockers before starting the use of Exforge, the dosage should be reduced gradually. With a sharp cessation of the use of beta-adrenergic blockers, withdrawal syndrome may develop.
Throughout the therapeutic course of Exforge, particular care should be taken when driving vehicles, practicing extreme sports and working with dangerous and high-precision mechanical devices.
During therapy, regular monitoring of the content of potassium and creatinine in blood plasma is required.
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-adrenergic blockers, it is not able to prevent the occurrence of withdrawal syndrome, which develops when their intake is suddenly terminated.
Treatment with thiazide diuretics can cause hypochloremia, hyponatremia or aggravate existing hyponatremia. In patients with this disorder, individual cases of the appearance of neurological symptoms were recorded, such as nausea, disorientation, asthenia, apathy. In patients with severe deficiency of bcc and/or hyponatremia, including
when using high doses of diuretics, while taking ARA II in rare cases, the development of symptomatic arterial hypotension is possible. Before starting the course, it is required to correct the concentration of sodium in the blood and/or BCC, or to begin treatment under close medical supervision. If arterial hypotension occurs, the patient should be laid with raised legs, if necessary, infuse iv with a solution of sodium chloride 0,9%. After stabilization of blood pressure is achieved, the drug can be continued.
In the treatment of Co-Exforge, it is necessary to regularly determine the plasma electrolyte content.
The use of thiazide diuretics can cause the development of hypokalemia, or in the presence of this violation, exacerbate its manifestations. It is necessary to take HCTZ with caution in patients with nephropathy, cardiogenic impaired renal function or with other lesions accompanied by potassium deficiency. If there is a development of clinical symptoms of hypokalemia in the form of muscle weakness, paresthesias, ECG changes, Co-Exforge should be discontinued.
With the use of HCTZ, there is a chance of a change in glucose tolerance, as well as an increase in the level of serum triglycerides, cholesterol and uric acid. A decrease in clearance of the latter can provoke hyperuricemia and the occurrence of gout in susceptible 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.
Cases of transient myopia and acute attacks of angle-closure glaucoma were recorded with the use of HCT as sulfonamide, the risk factors for which may be indications of a history of allergic reactions caused by sulfonamides and penicillin. Symptoms of the angle-closure form of glaucoma, as a rule, appear in the period from several hours to 7 days after the start of the course of therapy. Untimely treatment of this complication can cause permanent vision loss.
Patients driving vehicles or working with other complex/moving mechanisms should be careful when taking Co-Exforge because of the possible development of adverse reactions in the form of visual disturbances, weakness and dizziness.
Before starting Exforge therapy, previously taken beta-blockers, if necessary, should be canceled by gradually lowering the dose to avoid the development of withdrawal syndrome. The appointment of the drug is recommended based on laboratory indicators of sodium in the body and the volume of circulating blood (BCC), since their deficiency can cause severe arterial hypotension.
With a deficiency of bcc and/or sodium, it is necessary to carry out their correction and begin treatment under close medical supervision. With the development of arterial hypotension, the patient should take a horizontal position with raised legs. Saline is indicated. When blood pressure stabilizes, Exforge can be continued.
Some side effects of the drug, incl. dizziness or visual impairment, may adversely affect the ability to drive vehicles and perform potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.
There is still no overdose experience
. The main symptom of an overdose of valsartan is probably severe arterial hypotension with dizziness. An overdose of amlodipine can lead to increasing peripheral vasodilation and, possibly, to reflex tachycardia. Significant and potentially prolonged systemic hypotension has been reported, right down to shock and death.
If the drug is taken recently, you should induce vomiting or rinse the stomach. The absorption of amlodipine is significantly reduced when using activated carbon immediately or within two hours after taking amlodipine.
Clinically significant arterial hypotension caused by an overdose of Exforge requires active support of the state of the cardiovascular system, including frequent monitoring of the cardiac and respiratory functions, elevation of the extremities, attention to the volume of circulating fluid and urination.
To restore vascular tone and blood pressure, a vasoconstrictor drug can be used in the absence of contraindications for its use. With a persistent decrease in blood pressure, which is a consequence of the blockade of calcium channels, it may be appropriate to administer calcium gluconate.
Withdrawal of valsartan and amlodipine via hemodialysis is unlikely.
With an overdose of Exforge, dizziness and a sharp decrease in blood pressure may occur.
To eliminate the symptoms of intoxication, induce artificial vomiting, rinse the stomach and take a large amount of activated charcoal.
Information on overdose cases of Co-Exforge is currently not available.
An overdose of amlodipine can cause excessive peripheral vasodilation and reflex tachycardia, as well as a sometimes pronounced and prolonged decrease in blood pressure, up to the development of a shock with a fatal outcome.
Against the background of an overdose of valsartan, dizziness and a significant decrease in blood pressure may occur.
The main clinical manifestations of HCT 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 an overdose are drowsiness and nausea, hypokalemia can cause muscle cramps.
If an excessive dose of the drug has been taken recently, it is necessary to induce vomiting or rinse the stomach. The use of activated carbon immediately or within 2 hours after taking amlodipine significantly weakened its absorption.
Against the background of a marked decrease in blood pressure, the patient should be laid with raised legs and measures aimed at increasing blood pressure and maintaining the activity of the cardiovascular system, including monitoring of 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.
Conditions of leave from pharmacies
Store at a temperature not exceeding 30 ° C, in the original packaging, in a place protected from moisture, out of reach of children.
Store in a dry place inaccessible to children at a temperature not exceeding 25 ° C.
Shelf life is 2 years.
Released by prescription.
Exforge should be stored in a well-protected place from children, moisture and direct sunlight. Storage temperature should not exceed 30˚C.
Shelf life is 3 years.
The average cost of Exforge (tablets 5 mg 80 mg, 28 pcs.) In Moscow is 1800 rubles. Released by prescription.
Keep out of the reach of children. Store at temperatures up to 25 ° C in a dry place. Shelf life is 2 years.
Form of issue and composition
5 mg/80 mg film-coated tablets; 5 mg/160 mg; 10 mg/160 mg.
Packing: 14 or 28 tablets per pack.
Drugs are available in tablet form.
Exforge tablets have such active ingredients 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 components – amlodipine, valsartan, hydrochlorothiazide (diuretic component);
- additional substances: MCC, colloidal silicon dioxide, hypromellose, crospovidone, macrogol, magnesium stearate, titanium dioxide, talc.
Exforge differs from Co-Exforge and Exforge H in its constituent components. In the last two, the substance hydrochlorothiazide is additionally used, which has a diuretic effect and is used for an additional hypotensive effect, as it removes excess fluid from the body.
Co-Exforge is released in the form of film-coated tablets:
- dosage 5 mg 160 mg 12,5 mg: biconvex, oblong, with oblique edges, white shell, NVR embossing on one side, VCL on the other;
- dosage of 10 mg 160 mg 12,5 mg: biconvex, oblong, with beveled edges, the shell is pale yellow, on one side is embossed with NVR, on the other – VDL;
- dosages of 5 mg 160 mg 25 mg: biconvex, oval, with a bevel, yellow shell, the inner layer on the cross section is almost white or white, on one side is embossed NVR, on the other – VEL;
- 10 mg 160 mg 25 mg: biconvex, oval, beveled, brownish-yellow shell, the inner layer on the cross section is almost white or white, on one side is embossed NVR, on the other – VHL;
- 10 mg 320 mg 25 mg: biconvex, oval, beveled, brown-yellow shell, the inner layer on the cross section is almost white or white, on one side is embossed NVR, on the other – VFL.
Packing: 7 pcs. in a blister, in a cardboard bundle of 1, 4 or 18 blisters; 14 pcs. in a blister, in a cardboard bundle 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 besilate – 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 (iron dye yellow oxide, hypromellose, talc, macrogol), Premix red (iron dye oxide red, hypromellose, talc, macrogol).
1 tablet in 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 besilate – 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 coating: Premix yellow (macrogol 4000, hypromellose, iron dye oxide yellow, talc); in addition, for a dosage of 5 mg 160 mg 25 mg – Premix white (macrogol 4000, hypromellose, titanium dioxide, talc).
Analogues of Co-Exforge are: Co-Vamloset, Tritensin.
The structure determines the analogues:
The means for the treatment of primary hypertension include analogues:
- Egiloc Retard;
- Altiazem PP;
The drug is an absolute analogue of Exforge. Due to the presence of similar dosages of the active ingredients per 1 tablet, Amlosartan can be used as an alternative to Exforge in the process of drug use.
A tablet preparation containing amlodipine in combination with potassium losartan. Not inferior in therapeutic efficacy to Exforge medication. It is used for the treatment of essential hypertension in patients who are shown combination treatment with losartan and amlodipine. It is contraindicated for children under 18 years of age, patients with hypersensitivity to the composition of the drug, severe renal failure, hypotension, shock, heart failure after acute myocardial infarction, as well as pregnant and lactating women.
Antihypertensive drug, which includes amlodipine and irbesartan. The drug is indicated for the treatment of arterial hypertension, provided that the patients do not have the proper effect of monotherapy with amlodipine or irbesartan. Contraindicated in case of hypersensitivity, cardiogenic shock, pregnancy, unstable angina, aortic stenosis, breast-feeding in children under 18 years of age.
The safety and effectiveness of amlodipine in the treatment of hypertensive crisis have not been established.
Patients with a deficiency of sodium and/or circulating blood volume in the body.
In patients with uncomplicated arterial hypertension (0,4%), excessive hypotension was observed with Exforge as part of a placebo-controlled study. In patients with an activated renin-angiotensin system (with a low sodium and/or volume and in the case of high doses of diuretics) who take angiotensin receptor blockers, symptomatic hypotension may occur. Recommended correction of this condition before Exforge or careful medical supervision at the beginning of therapy.
If arterial hypotension occurs during the use of Exforge, the patient should be placed on his back and, if necessary, infused with saline. After stabilization of blood pressure, treatment can be continued.
Caution should be given to simultaneous treatment with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that can increase potassium levels (heparin, etc.), and also provide for regular monitoring of potassium content.
Renal artery stenosis.
Exforge should be used with caution in hypertension in patients with unilateral or bilateral renal artery stenosis or single kidney stenosis since serum urea and creatinine levels may increase.
There is no experience with the safe use of Exforge in patients with recent kidney transplantation.
Valsartan is excreted mainly unchanged with bile. The half-life of amlodipine is lengthened and the AUC (plasma concentration – time) is higher in patients with impaired liver function, dosage recommendations are not established. Particular caution is necessary when applying Exforge to patients with impaired liver function of mild or moderate degrees or obstructive diseases of the gallbladder.
The maximum recommended dose for patients with mild or moderate hepatic impairment without cholestasis is 80 mg of valsartan.
Impaired renal function.
The simultaneous use of angiotensin receptor antagonists, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with impaired renal function (GFR lt; 60 mg/min/1,73 m 2).
Patients with primary hyperaldosteronism should not take the angiotensin II valsartan antagonist because their renin-angiotensin system is impaired due to the underlying disease.
Quincke edema, including swelling of the larynx and glottis, which can lead to airway obstruction, and/or swelling of the face, lips, pharynx, and/or tongue, was observed in patients treated with valsartan. Some of these patients had a history of Quincke edema when taking other drugs, including ACE inhibitors (ACE). Exforge should be discontinued immediately if Quincke edema occurs; repeated use is not recommended.
Heart failure/after myocardial infarction
Due to inhibition of renin-angiotensin-sensitive patients, impaired renal function is possible. In patients with severe heart failure, in which renal function may depend on the activity of renin-angiotensin-, the use of ACE inhibitors (ACE) and angiotensin receptor antagonists caused the development of oliguria and/or progressive azotemia, as well as (in rare cases) acute renal failure and/or death.
In a long-term placebo-controlled study (PRAISE-2) of amlodipine in patients with heart failure of non-ischemic origin of class III and IV according to the NYHA classification (New York Cardiology Association) with amlodipine, the incidence of pulmonary edema was higher compared to that with placebo however, there was no significant difference in the appearance or worsening of heart failure.
Aortic stenosis and mitral valve
As with other vasodilators, patients who have a mitral valve stenosis or severe aortic stenosis of a low degree should be especially careful.
Double blockade of renin-angiotensin- (RAAS)
There is evidence that the combined use of ACE inhibitors, ARA or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, it is not recommended to conduct a double blockade of RAAS by the combined use of ACE inhibitors, ARA or aliskiren.
If double blockade is absolutely necessary, it should be carried out exclusively under the supervision of a specialist with frequent close monitoring of renal function, electrolyte concentration and blood pressure. ACE and ARA inhibitors should not be used together in patients with diabetic nephropathy.
The use of Exforge has not been studied in patients with diseases other than arterial hypertension.
The ability to influence the reaction rate when driving vehicles or other mechanisms.
Patients using Exforge may experience dizziness or a feeling of weakness after taking the drug, so they should take this into account when driving and working with potentially dangerous mechanisms.
Amlodipine can slightly or moderately affect the ability to drive vehicles or work with mechanisms. If patients experience dizziness, headache, fatigue, or nausea when using amlodipine, their reaction may be impaired.