Instructions for use Corsar AM film-coated tablets 5 mg + 160 mg blister No. 30
Composition
active ingredients: valsartan and amlodipine besylate;
1 tablet contains amlodipine besylate (calculated as 100% anhydrous substance) - 6.94 mg, which is equivalent to amlodipine - 5 mg; valsartan (calculated as 100% anhydrous substance) - 80 mg or
amlodipine besylate (calculated as 100% anhydrous substance) – 6.94 mg, which is equivalent to amlodipine – 5 mg; valsartan (calculated as 100% anhydrous substance) – 160 mg, or
amlodipine besylate (calculated as 100% anhydrous substance) – 13.88 mg, which is equivalent to amlodipine – 10 mg; valsartan (calculated as 100% anhydrous substance) – 160 mg;
excipients: microcrystalline cellulose, crospovidone, colloidal anhydrous silicon dioxide, magnesium stearate;
tablet coating 5 mg/80 mg: Opadry II 85F 220088 Yellow (polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc, iron oxide yellow (E 172), iron oxide red (E 172));
tablet coating 5 mg/160 mg: Opadry II 85F 220088 Yellow (polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc, iron oxide yellow (E 172), iron oxide red (E 172));
tablet coating 10 mg/160 mg: Opadry II 85F 220087 Yellow (polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc, iron oxide yellow (E 172), iron oxide red (E 172)).
Dosage form
Film-coated tablets.
Main physicochemical properties:
5 mg/80 mg tablets: round tablets with a biconvex surface, film-coated, yellow-brown in color;
5 mg/160 mg tablets: round tablets with a biconvex surface, film-coated, yellow-brown in color;
10 mg/160 mg tablets: round tablets with a biconvex surface, with a score on one side, film-coated, light yellow in color with a brown tint.
Pharmacotherapeutic group
Combination drugs of angiotensin II inhibitors.
ATX code C09D B01.
Pharmacological properties
Pharmacodynamics.
Corsar® AM contains two antihypertensive components with additional mechanisms of blood pressure control in patients with essential hypertension: amlodipine belongs to the class of calcium antagonists, and valsartan belongs to the class of angiotensin II antagonists. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a greater extent than either component alone.
Amlodipine.
Amlodipine inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. The mechanism of antihypertensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle, which leads to a decrease in peripheral vascular resistance and a decrease in blood pressure. Experimental data confirm that amlodipine binds to dihydropyridine and nonhydropyridine binding sites. Contractile processes of cardiac muscle and vascular smooth muscle depend on the passage of extracellular calcium into these cells through specific ion channels.
After administration of therapeutic doses to patients with arterial hypertension, amlodipine causes vasodilation, resulting in a decrease in blood pressure in the supine and standing positions. This decrease in blood pressure is not accompanied by a significant change in heart rate or plasma catecholamine levels with prolonged use.
The effect correlates with plasma concentrations in young and elderly patients.
In patients with arterial hypertension and normal renal function, therapeutic doses of amlodipine lead to a decrease in renal vascular resistance and an increase in glomerular filtration rate, as well as effective renal plasma flow without changes in the filtered fraction or proteinuria.
As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or walking) in patients with normal ventricular function treated with amlodipine generally showed a small increase in cardiac index without a significant effect on dP/dt or on end-diastolic pressure or left ventricular volume. In hemodynamic studies, amlodipine did not exhibit a negative inotropic effect at therapeutic doses in intact animals and humans, even when co-administered with beta-blockers in humans.
Amlodipine does not alter sinoatrial node function or atrioventricular conduction in healthy animals or humans. In clinical studies in which amlodipine was used in combination with beta-blockers in patients with arterial hypertension or angina pectoris, no changes in electrocardiogram parameters were noted.
Positive clinical effects of amlodipine have been observed in patients with chronic stable angina, vasospastic angina, and angiographically confirmed coronary artery disease.
In a study of antihypertensive and lipid-lowering therapy for the prevention of heart attack in mild to moderate hypertension in patients with at least one additional risk factor for coronary heart disease, amlodipine (2.5–10 mg/day) or lisinopril (10–40 mg/day) as first-line therapy compared with the thiazide diuretic chlorthalidone (12.5–25 mg/day) was used to compare the incidence of fatal coronary heart disease or nonfatal myocardial infarction. The incidence of heart failure was significantly higher in the amlodipine group than in the chlorthalidone group. However, there were no significant differences in all-cause mortality between the amlodipine and chlorthalidone groups.
Valsartan.
Valsartan is an active, potent and specific angiotensin II receptor antagonist for oral administration. It acts selectively on the AT1 receptor subtype, which is rare and responsible for the effects of angiotensin II. Increased levels of angiotensin II due to blockade of AT1 receptors by valsartan may stimulate free AT2 receptors, which balances the effect of AT1 receptors. Valsartan does not have any partial agonist activity at AT1 receptors and has a much higher (approximately 20,000-fold) affinity for AT1 receptors than for AT2 receptors.
Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Based on the lack of effect on ACE and potentiation of bradykinin or substance P activity, the use of angiotensin II receptor antagonists is usually not accompanied by cough. In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly lower in patients treated with valsartan than in patients taking an ACE inhibitor. In patients previously treated with an ACE inhibitor, dry cough developed, with valsartan treatment this complication being noted in 19.5% of cases and with thiazide diuretic treatment in 19% of cases, while in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases. Valsartan does not interact with or block receptors for other hormones or ion channels known to play an important role in regulating cardiovascular function.
Prescribing the drug to patients with arterial hypertension leads to a decrease in blood pressure without affecting the pulse rate.
In most patients, after a single oral dose of the drug, the onset of antihypertensive activity is noted within 2 hours, and the maximum reduction in blood pressure is achieved within 4–6 hours.
The antihypertensive effect persists for more than 24 hours after a single dose. With regular use of the drug, the maximum therapeutic effect is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. Abrupt withdrawal of valsartan does not lead to the resumption of arterial hypertension or other adverse clinical events.
Valsartan has been shown to significantly reduce hospitalization rates in patients with chronic heart failure (NYHA class II–IY). A more significant effect was achieved in patients not receiving ACE inhibitors or beta-blockers. Valsartan has also been shown to reduce cardiovascular mortality in clinically stable patients with left ventricular disease or left ventricular dysfunction after myocardial infarction.
According to research data, ACE inhibitors and angiotensinogen receptor antagonists (ARBs) should not be used together in patients with diabetic nephropathy, as an increased risk of hyperkalemia, acute kidney injury and/or hypotension has been established. When studying the feasibility of additional therapy with aliskiren to ACE/ARB therapy in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease or a combination of both, an increased risk of complications of therapy, the development of adverse events and serious adverse events of special importance (hyperkalemia, hypotension and renal dysfunction) was established with the use of aliskiren.
Valsartan/amlodipine.
The valsartan/amlodipine combination has been studied in studies involving patients with uncomplicated essential hypertension of mild to moderate severity, except for patients at high risk of cardiovascular events. Normalization of blood pressure was observed in patients whose blood pressure was not adequately controlled with valsartan 160 mg monotherapy. Blood pressure normalization was observed in 75% of patients taking 10 mg/160 mg amlodipine/valsartan, in 62% of patients taking 5 mg/160 mg amlodipine/valsartan compared with 53% of patients taking 160 mg valsartan. The addition of 10 mg and 5 mg amlodipine provided additional reductions in systolic/diastolic blood pressure compared with patients taking 160 mg valsartan alone.
The addition of valsartan has been shown to normalize blood pressure in patients whose blood pressure was not adequately controlled with amlodipine 10 mg monotherapy. Blood pressure normalized in 78% of patients receiving 10 mg/160 mg amlodipine/valsartan compared with 67% of patients who continued to receive 10 mg amlodipine alone. The addition of 160 mg valsartan resulted in an additional reduction in systolic/diastolic blood pressure compared with patients receiving 10 mg amlodipine alone.
The combination of amlodipine/valsartan from 5 mg/160 mg to 10 mg/160 mg in patients with essential hypertension more significantly reduces stable blood pressure compared to the dosing regimen of lisinopril/hydrochlorothiazide from 10 mg/12.5 mg to 20 mg/12.5 mg.
It has been proven that the effect of the valsartan/amlodipine combination was maintained for more than 1 year. Abrupt withdrawal of the drug did not lead to a rapid increase in blood pressure.
In patients whose blood pressure is adequately controlled with amlodipine and who have unacceptable edema, combination therapy may provide similar blood pressure control while reducing edema.
There is evidence that age, gender, race, and body mass index (≥ 30 kg/m2, < 30 kg/m2) do not affect the clinical response to the combination of varisartan/amlodipine.
There have been no studies of the valsartan/amlodipine combination in populations other than hypertensive patients. There are studies of valsartan in patients with heart failure and in the post-infarction period. There have been studies of amlodipine in patients with chronic stable angina, vasospastic angina, and angiographically confirmed ischemic heart disease.
Pharmacokinetics.
Linearity.
Valsartan and amlodipine exhibit linear pharmacokinetics.
Amlodipine.
Absorption. After oral administration of therapeutic doses of amlodipine alone, peak plasma concentrations (Cmax) are reached within 6–12 hours. The estimated absolute bioavailability is 64% to 80%. Food intake does not affect the bioavailability of amlodipine.
Distribution: The volume of distribution is approximately 21 L/kg. In vitro studies of amlodipine have shown that approximately 97.5% of the circulating drug is bound to plasma proteins in patients with essential hypertension.
Biotransformation: Amlodipine is extensively (approximately 90%) metabolized in the liver to inactive metabolites.
Elimination: Elimination of amlodipine from plasma is biphasic, with a half-life of approximately 30–50 hours. Steady-state plasma levels are reached after continuous administration for 7–8 days. 10% of the parent amlodipine and 60% of the amlodipine metabolites are excreted in the urine.
Valsartan.
Absorption. After oral administration of the drug, Cmax of valsartan in blood plasma is achieved within 2–4 hours. The average absolute bioavailability of the drug is 23%. Food reduces exposure, as shown by AUC (plasma concentration - time), of valsartan by approximately 40%, and Cmax - by 50%, although 8 hours after administration, the plasma concentration of valsartan is the same for the group that took the drug on an empty stomach and the group of patients that took the drug after a meal. A 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 steady-state volume of distribution of valsartan after intravenous administration is approximately 17 L, indicating that valsartan is not extensively distributed into tissues. Valsartan is highly bound to plasma proteins (94–97%), mainly to serum albumin.
Biotransformation: Valsartan is not significantly transformed, with only 20% of the dose converted to metabolites. A hydroxymetabolite, which is pharmacologically inactive, has been identified in plasma at low concentrations (less than 10% of the AUC of valsartan).
Elimination: Valsartan exhibits multi-exponential elimination kinetics (half-life T1/2a < 1 hour and T1/2b approximately 9 hours). Valsartan is excreted mainly unchanged in the feces (approximately 83% of the dose) and urine (approximately 13% of the dose). After intravenous administration, the plasma clearance of valsartan is approximately 2 l/h, and its renal clearance is approximately 0.62 l/h (approximately 30% of the total clearance). The elimination half-life of valsartan is 6 hours.
Valsartan/amlodipine.
Special populations.
Children
There are no data on the pharmacokinetics of the drug in children.
Elderly patients (aged 65 years and over)
The time to reach Cmax of amlodipine in plasma is approximately the same in young and elderly patients. In elderly patients, the clearance of amlodipine tends to decrease, which leads to an increase in AUC and a prolongation of the half-life. The average systemic AUC of valsartan in elderly patients is 70% higher than in younger patients, so caution should be exercised when increasing the dose.
Kidney failure.
Renal impairment does not significantly affect the pharmacokinetics of amlodipine. As expected for a compound whose renal clearance accounts for only 30% of total plasma clearance, there was no correlation between renal function status and systemic exposure to valsartan.
Liver dysfunction.
In patients with hepatic impairment, the clearance of amlodipine is reduced, resulting in an increase in AUC by approximately 40–60%. On average, in patients with mild to moderate chronic liver disease, the exposure (determined by AUC values) of valsartan is on average twice that of healthy volunteers (selected for age, sex and body weight). Patients with liver disease should use the drug with caution.
Indication
Essential hypertension in adult patients whose blood pressure is not controlled with amlodipine or valsartan monotherapy.
Contraindication
Hypersensitivity to the active substance, dihydropyridine derivatives or to any of the excipients of the drug.
Severe liver dysfunction, biliary cirrhosis or cholestasis.
Concomitant use of angiotensin receptor antagonists (ARBs), including valsartan, or angiotensin-converting enzyme (ACE) inhibitors with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mg/min/1.73 m2).
Pregnant women and women planning to become pregnant (see section "Use during pregnancy or breastfeeding").
Severe hypotension.
Shock (including cardiogenic shock).
Left ventricular outflow tract obstruction (e.g. hypertrophic obstructive cardiomyopathy and severe aortic stenosis).
Hemodynamically unstable heart failure after acute myocardial infarction.
Interaction with other medicinal products and other types of interactions
Interactions common to the combination
Studies on the interaction of Corsar® AM with other drugs have not been conducted.
Medicines that require caution when used concomitantly
Other antihypertensive drugs
Commonly used antihypertensive drugs (e.g. alpha-blockers, diuretics) and other drugs that may cause hypotensive adverse events (e.g. tricyclic antidepressants, alpha-blockers used to treat benign prostatic hyperplasia) may potentiate the hypotensive effect of the combination.
Interactions related to amlodipine
Concomitant use not recommended
Grapefruit or grapefruit juice
The use of amlodipine with grapefruit juice or grapefruit is not recommended, as bioavailability may be increased in some patients, leading to increased hypotensive effect of the drug.
Medicines that require caution when used concomitantly
CYP3A4 inhibitors
Concomitant use of amlodipine with more or less potent CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in systemic exposure to amlodipine. The clinical manifestations of such pharmacokinetic changes may be enhanced in elderly patients. Clinical monitoring and dose adjustment may be necessary.
CYP3A4 inducers (anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, St. John's wort (Hypericum perforatum)
Plasma concentrations of amlodipine may be altered when used concomitantly with known CYP3A4 inducers. Therefore, blood pressure should be monitored and the dosage adjusted during and after concomitant use, especially with strong CYP3A4 inducers (e.g. rifampicin, Hypericum perforatum).
Simvastatin
Multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in simvastatin exposure compared to simvastatin alone. It is recommended that the daily dose of simvastatin be reduced to 20 mg for patients taking amlodipine.
Dantrolene (infusion)
Fatal cases of ventricular fibrillation and cardiovascular collapse have been observed in animals in association with hyperkalemia following intravenous administration of verapamil and dantrolene. Due to the risk of hyperkalemia, it is recommended that concomitant use of calcium channel blockers such as amlodipine be avoided in patients predisposed to malignant hyperthermia and in the treatment of malignant hyperthermia.
Medicines that require caution when used concomitantly
Others
In clinical studies, amlodipine did not affect the pharmacokinetics of atorvastatin, dioxin, warfarin, or cyclosporine.
Interactions related to valsartan
Lithium
When lithium is used concomitantly with ACE inhibitors or angiotensin II receptor antagonists, including valsartan, reversible increases in serum lithium concentrations and toxicity have been reported. Concomitant 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 lithium toxicity may be further increased by concomitant use of Corsar® AM and diuretics.
Potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may increase potassium levels
If drugs that affect potassium channels are prescribed in combination with valsartan, frequent monitoring of potassium plasma levels should be considered.
Medicines that require caution when used concomitantly
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day), and nonselective NSAIDs
Concomitant use of angiotensin II antagonists and NSAIDs may result in attenuation of the hypotensive effect. Concomitant use of angiotensin II antagonists and NSAIDs may also increase the risk of worsening of renal function and an increase in serum potassium. Therefore, at the beginning of treatment, it is recommended to monitor renal function and ensure adequate fluid intake.
Inhibitors of the accumulation transporter (rifampicin, cyclosporine) or efflux transporter (ritonavir)
In vitro studies with human liver tissue have shown that valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. Concomitant use of inhibitors of the uptake transporter (rifampicin, cyclosporine) or efflux transporter (ritonavir) may increase systemic exposure to valsartan.
Dual blockade of the RAAS with ARBs, ACE inhibitors, or aliskiren
Clinical studies have shown that dual blockade of the RAAS with the combined use of ACE inhibitors, ARBs or aliskiren leads to an increased incidence of adverse events such as hypotension, hyperkalemia and decreased renal function (including acute renal failure) compared with treatment with a single drug that affects the RAAS. Therefore, the concomitant use of ARBs, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR < 60 mg/min/1.73 m2).
Others
With valsartan monotherapy, no clinically significant drug interactions have been established with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Application features
The safety and efficacy of amlodipine in the treatment of hypertensive crisis have not been established.
Patients with a deficiency in the body of sodium and/or circulating blood volume.
In patients with uncomplicated hypertension, excessive hypotension has been observed in placebo-controlled studies with valsartan/amlodipine. In patients with an activated renin-angiotensin system (RAS) (sodium and/or volume depletion and high doses of diuretics) receiving angiotensin receptor blockers, symptomatic hypotension may occur. Correction of this condition before the use of Corsar® AM or close medical supervision at the beginning of therapy is recommended.
If hypotension occurs during the use of Corsar® AM, the patient should be placed on his back and, if necessary, an intravenous infusion of saline should be performed. After stabilization of blood pressure, treatment can be continued.
Hyperkalemia.
Concomitant treatment with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may increase potassium levels (heparin, etc.) should be undertaken with caution, and frequent monitoring of potassium levels should be considered.
Renal artery stenosis.
Corsar® AM should be used with caution for the treatment of hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, as serum urea and creatinine levels may increase.
Kidney transplantation.
There is no experience with the safe use of Corsar® AM in patients with a recent kidney transplant.
Liver dysfunction.
Valsartan is excreted mainly unchanged in the bile. The half-life of amlodipine is prolonged and the AUC (plasma concentration - time) is higher in patients with impaired liver function; dosage recommendations have not been established. Special caution is required when using Corsar® AM in patients with mild to moderate liver dysfunction or obstructive gallbladder disease.
The maximum recommended dose for patients with mild or moderate hepatic impairment without cholestasis is 80 mg of valsartan.
Kidney dysfunction.
Concomitant use of angiotensin receptor antagonists, including valsartan, or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with renal impairment (GFR < 60 mg/min/1.73 m2).
Primary hyperaldosteronism.
Patients with primary hyperaldosteronism should not take the angiotensin II antagonist valsartan because their renin-angiotensin system is impaired due to the underlying disease.
Angioedema.
Angioedema, including swelling of the larynx and glottis, which may lead to airway obstruction and/or swelling of the face, lips, pharynx and/or tongue, has been reported in patients taking valsartan. Some of these patients had a history of angioedema while taking other drugs, including angiotensin-converting enzyme (ACE) inhibitors. Corsar® AM should be discontinued immediately if angioedema occurs; repeated use is not recommended.
Heart failure/post-myocardial infarction
Renal function may be impaired in susceptible patients due to inhibition of the renin-angiotensin-aldosterone system (RAAS). In patients with severe heart failure, in whom renal function may depend on RAAS activity, the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia, and (in rare cases) acute renal failure and/or fatal outcome. Similar results have been reported with valsartan. Renal function should be assessed in patients with heart failure or after myocardial infarction.
In a study of amlodipine in patients with non-ischemic heart failure of NYHA class III and IV, the incidence of pulmonary edema was higher with amlodipine than with placebo, but there was no significant difference in the incidence or worsening of heart failure. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure because they may increase the risk of cardiovascular events and mortality.
Aortic and mitral valve stenosis
As with other vasodilators, particular caution should be exercised in patients with known mitral valve stenosis or severe low-grade aortic stenosis.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that the combined use of ACE inhibitors, ARBs or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by the combined use of ACE inhibitors, ARBs or aliskiren is not recommended.
If dual blockade is absolutely necessary, it should be carried out only under specialist supervision with frequent and careful monitoring of renal function, electrolyte concentrations and blood pressure. ACE inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy.
The use of the valsartan/amlodipine combination has not been studied in patients with diseases other than arterial hypertension.
Use during pregnancy or breastfeeding
Pregnancy
The drug is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this drug, its use should be immediately discontinued and replaced with another drug approved for use in pregnant women.
Epidemiological evidence on the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however, a small increased risk cannot be excluded. Although there are no controlled epidemiological studies of angiotensin II receptor antagonists (ARBs), a similar risk may exist with this class of drugs.
Exposure to ARAII in the 2nd and 3rd trimesters is known to have a toxic effect on the human fetus (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the newborn (renal failure, arterial hypotension, hyperkalemia).
If ARVI has been used from the second trimester of pregnancy, ultrasound examination of renal function and fetal skull is recommended.
Infants whose mothers have taken ARVIs should be closely observed for the development of hypotension.
Breastfeeding period
Amlodipine is excreted in breast milk. The proportion of the maternal dose received by the infant is estimated with an interquartile range of 3–7%, with a maximum of 15%. The effects of amlodipine on the infant are unknown.
Because no information is available regarding the use of valsartan/amlodipine during breastfeeding, the drug is not recommended during breastfeeding; alternative treatments with better established safety profiles during breastfeeding are preferable, especially while breastfeeding a newborn or preterm infant.
Fertility
Clinical studies on the effect on fertility have not been conducted.
Valsartan did not cause adverse reproductive effects in male and female rats when administered orally at doses up to 200 mg/kg/day, which is 6 times the maximum recommended human dose on a mg/m2 basis (calculated using a dose of 320 mg/day for a 60 kg patient).
Amlodipine
Reversible biochemical changes in the heads of sperm have been reported in some patients treated with calcium channel blockers. Clinical data on the effects of amlodipine on fertility are insufficient. In one study in rats, adverse effects on male fertility were observed.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients using Corsar® AM may experience dizziness or a feeling of weakness after taking the drug, so they should take this into account when driving vehicles and working with potentially dangerous mechanisms.
Amlodipine may have minor or moderate influence on the ability to drive or use machines. If patients experience dizziness, headache, fatigue or nausea while taking amlodipine, their reactions may be impaired.
Method of administration and doses
Patients whose blood pressure is inadequately controlled with amlodipine or valsartan monotherapy may be switched to combination therapy with Corsar® AM. The recommended dose is 1 tablet per day. Corsar® AM tablets can be taken regardless of meals. It is recommended to take Corsar® AM with a small amount of water. The tablets cannot be divided.
Patients taking valsartan and amlodipine separately can be switched to Corsar® AM, which contains the same doses of the components.
Individual dose titration with the components (i.e. amlodipine and valsartan) is recommended before switching to a fixed-dose combination. If clinically indicated, direct conversion from monotherapy to a fixed-dose combination may be considered.
The maximum daily dose is 1 tablet of Corsar® AM 5 mg/80 mg or 1 tablet of Corsar® AM 5 mg/160 mg, or 1 tablet of Corsar® AM 10 mg/160 mg (maximum permissible doses of the drug components are 10 mg of amlodipine content, 320 mg of valsartan content).
Dosage for specific patient groups
Kidney dysfunction
There are no clinical data available on the use in patients with severe renal impairment.
No dose adjustment is required in patients with mild or moderate renal impairment. In patients with moderate renal impairment, it is recommended to monitor potassium and creatinine levels in the blood.
Concomitant use of Corsar® AM with aliskiren is contraindicated in patients with impaired renal function (GFR < 60 mg/min/1.73 m2).
Diabetes mellitus
Concomitant use of Corsar® AM with aliskiren is contraindicated in patients with diabetes mellitus.
Liver dysfunction
The drug Corsar® AM is contraindicated in patients with severe liver dysfunction.
Corsar® AM should be used with caution in patients with impaired liver function or obstructive biliary tract diseases. For patients with mild to moderate liver dysfunction without cholestasis, the maximum recommended dose is 80 mg of valsartan.
Dosage recommendations for amlodipine in patients with mild or moderate hepatic impairment have not been developed. When transferring such patients with arterial hypertension (see section "Indications") and impaired hepatic function to amlodipine or Corsar® AM, the lowest recommended dose of amlodipine should be prescribed in monotherapy or as part of combination therapy.
Elderly patients (aged 65 years and over)
For elderly patients, the usual dosage regimens are recommended.
Caution should be exercised when increasing the dose of the drug in elderly patients.
When transferring such patients with arterial hypertension (see section "Indications") and impaired liver function to amlodipine or Corsar® AM, the lowest recommended dose of amlodipine should be prescribed in monotherapy or as part of combination therapy.
Pediatric populations
The safety and efficacy of valsartan/amlodipine in children (under 18 years of age) have not been studied. Data are not available.
Children.
