Instructions for use NOLIPREL® FORTE A (NOLIPREL FORTE A)
Perindopril
Neutropenia, agranulocytosis
Neutropenia/agranulocytosis, thrombocytopenia and anemia were observed while taking ACE inhibitors. In patients with normal liver function and in the absence of other complicating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with pre-existing liver dysfunction. Some of these patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.
Hypersensitivity/angioedema
When taking ACE inhibitors, incl. and perindopril, in rare cases, the development of angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and/or larynx may occur. These reactions may occur at any time during therapy. In such cases, the drug should be stopped immediately and the necessary monitoring should be carried out until the symptoms disappear completely. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used to treat symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. If these symptoms appear, you should immediately administer epinephrine solution 1:
- 1000 (0.3-0.5 ml) subcutaneously and/or ensure airway patency.
There are reports that black patients are more likely to experience angioedema when taking ACE inhibitors than white patients.
Patients who have had angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain (with or without nausea and vomiting), in some cases, without previous angioedema of the face and with normal C1-esterase levels. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.
Anaphylactoid reactions during desensitization
There are isolated reports of the development of persistent, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteric venom (including bee and aspen). ACE inhibitors should be prescribed with extreme caution to patients prone to allergic reactions and undergoing desensitization; their use should be avoided in patients undergoing immunotherapy with insect venom allergens. However, if the patient requires both treatment with ACE inhibitors and desensitization, then the onset of such reactions can be prevented by temporarily stopping the use of ACE inhibitors at least 24 hours before starting the course of desensitization therapy.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Patients on hemodialysis
Anaphylactoid reactions have been reported in some patients undergoing hemodialysis using high-flux membranes (eg, AN69®) and concomitantly receiving one of the ACE inhibitors. For such patients, the use of a different type of membrane or a different class of antihypertensive drug should be considered.
Cough
Taking an ACE inhibitor may cause a dry cough. The cough persists for a long time while taking the drug, but disappears when the drug is discontinued. This symptom may have an iatrogenic etiology. If the need to take an ACE inhibitor remains, then continued treatment should be considered.
Risk of arterial hypotension and/or renal failure (in case of heart failure, water and electrolyte deficiency)
With significant loss of water and electrolytes (strict salt-free diet or long-term treatment with diuretics), especially in patients with initially low blood pressure, with renal artery stenosis, congestive heart failure or cirrhosis of the liver, accompanied by edema and ascites, pronounced stimulation of the RAAS occurs. Therefore, inhibition of RAAS activity when taking an ACE inhibitor may lead to a sudden decrease in blood pressure and/or an increase in serum creatinine, indicating functional renal failure. This is most likely when you first take the drug and during the first 2 weeks of treatment. In some, albeit very rare cases, such a disorder develops acutely, and the onset of the process is difficult to predict. In such cases, treatment should be resumed with a lower dose, gradually increasing it.
Elderly patients
Before starting treatment, kidney function and potassium levels should be monitored. To avoid sudden arterial hypotension, the initial dose of the drug is adjusted depending on the degree of decrease in blood pressure, especially in the case of dehydration and loss of electrolytes.
Patients with established atherosclerosis
The risk of arterial hypotension exists in all patients, but the drug should be used with extreme caution in patients with coronary artery disease or cerebrovascular insufficiency. In such cases, treatment should be started with a low dose.
Renovascular hypertension
Renovascular hypertension is treated by revascularization. However, the use of ACE inhibitors may be beneficial in patients with renovascular hypertension awaiting surgery or when surgery is not available.
In patients with an established diagnosis of renal artery stenosis or if it is suspected, treatment with Noliprel® forte A should begin in the hospital with a small dose under monitoring of renal function and potassium levels, because Some patients developed renal failure, which was reversible when treatment was discontinued.
Other risk groups
In patients with severe acute heart failure (grade IV) and in patients with insulin-dependent diabetes mellitus (a tendency to spontaneously increase potassium levels), treatment with Noliprel® forte A should be started with low doses and carried out under constant medical supervision.
Patients with arterial hypertension and coronary insufficiency should not stop taking beta-blockers:
- An ACE inhibitor should be used in addition to a beta blocker.
Diabetes
In diabetic patients already taking oral hypoglycemic agents or insulin, glycemic levels should be carefully monitored, especially during the first month of taking an ACE inhibitor.
Ethnic differences
Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of black race compared to representatives of other races. Perhaps this difference is due to the fact that arterial hypertension in black patients very often occurs against the background of low renin activity.
Surgery/anesthesia
ACE inhibitors can cause a drop in blood pressure during anesthesia, especially if the anesthetic used has a hypotensive effect. Therefore, long-acting ACE inhibitors such as perindopril should, if possible, be discontinued 24 hours before surgery.
Aortic or mitral valve stenosis/hypertrophic cardiomyopathy
Use ACE inhibitors with caution in patients with left ventricular outflow tract obstruction.
Liver dysfunction
In rare cases, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not yet clear. In patients receiving ACE inhibitors, if jaundice or a marked increase in liver enzyme activity develops, the ACE inhibitor should be discontinued and a thorough medical examination should be performed.
Hyperkalemia
Elevated serum potassium levels have been reported in some patients treated with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalemia include renal failure, deterioration of renal function, age (> 70 years), diabetes mellitus, intercurrent events such as dehydration, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or taking other drugs that cause increases in serum potassium (eg, heparin). Taking potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes, especially in patients with impaired renal function, may result in significant increases in serum potassium levels. Hyperkalemia can cause serious arrhythmias, sometimes fatal. If concomitant administration of perindopril or the above drugs is considered necessary, they should be taken with caution and with regular monitoring of serum potassium levels.
Indapamide
In patients with impaired liver function, taking thiazide and thiazide-like diuretics can cause hepatic encephalopathy. In this case, the diuretic should be stopped immediately.
Photosensitivity
Cases of photosensitivity have been reported with the use of thiazide and thiazide-like diuretics. If photosensitivity is noted during treatment, it is recommended to stop taking the drug. If re-administration of a diuretic is considered necessary, it is recommended to protect the skin from the sun and artificial UV radiation.
Water and electrolyte balance
Sodium level.
Before starting treatment, it is necessary to evaluate the sodium content, and further such studies should be carried out regularly. Taking any diuretic medication can cause a decrease in sodium levels, which sometimes leads to a number of serious complications. Initially, a decrease in sodium levels may be asymptomatic, which is why it is necessary to regularly monitor its content. In elderly patients and patients with liver cirrhosis, monitoring should be carried out even more often.
Potassium level.
The main danger when taking thiazide and thiazide-like diuretics is potassium deficiency and, accordingly, hypokalemia. Consideration of the risk of potassium levels falling below acceptable levels (< 3.4 mmol/L) is necessary in persons at increased risk, such as elderly patients and/or patients with impaired or malnutrition, regardless of whether they are taking one or more medications drugs, in patients with liver cirrhosis, which is accompanied by edema and ascites, in patients with coronary artery disease and in patients with heart failure. In such cases, hypokalemia increases the toxicity of cardiac glycosides and increases the risk of developing arrhythmias. Patients with congenital or iatrogenic prolongation of the QT interval are also at risk. Hypokalemia, like bradycardia, is a risk factor for the development of serious cardiac arrhythmias, especially torsade de pointes (TdP), which can be fatal. In any case, potassium levels should be monitored as often as possible. The first determination of plasma potassium should be carried out within the first week after the start of treatment. If potassium levels decrease, dose adjustment is necessary.
Calcium level.
Thiazide and thiazide-like diuretics can reduce the excretion of calcium in the urine, which leads to a temporary and slight increase in the concentration of calcium in the blood. A marked increase in calcium levels may be associated with undiagnosed hyperparathyroidism. In this case, treatment should be stopped until the function of the parathyroid gland is examined.
Blood glucose level
In patients with diabetes mellitus, it is necessary to constantly monitor blood glucose levels, especially if potassium levels are simultaneously low.
Uric acid
Patients with high levels of uric acid in the blood may be predisposed to developing gout.
Effect on kidney function
Thiazide and thiazide-like diuretics are most effective when renal function is normal or only slightly impaired (serum creatinine is below approximately 2.5 mg/dL, i.e. 220 µmol/L for an adult patient). In elderly patients, plasma creatinine levels should be adjusted for age, weight and gender using the Cockcroft formula:
- For men: CC (ml/min) = (140 – age) x body weight (kg)/0.814 x serum creatinine (µmol/l)
- the calculation result should be multiplied by 0.85.
For women:
At the beginning of treatment, taking diuretics can lead to loss of water and sodium, which in turn leads to hypovolemia. Hypovolemia causes a decrease in glomerular filtration rate. It may be accompanied by an increase in creatinine and urea in the blood. This renal failure is temporary and does not cause undesirable consequences in patients with normal renal function, but in cases of existing impairment, renal failure may worsen.
Athletes
Please note that indapamide may cause a positive reaction during doping control.
Noliprel® forte A
The combination of lithium and the combination of perindopril with indapamide is generally not recommended.
Kidney failure.
In patients with severe renal failure (creatinine clearance <30 ml/min), this combination is contraindicated. Treatment should be discontinued if a patient suffers from arterial hypertension without visible kidney damage, but in whom renal failure is detected during a blood test (renal complex). Treatment can be resumed either with this combination at lower doses or with only one component. Such patients should usually undergo frequent monitoring of serum creatinine and potassium levels for the first time - after 2 weeks of treatment, then once every 2 months during the period of therapeutic stability.
Renal failure was mainly observed in patients with acute heart failure and was also observed in renal artery stenosis. This drug is generally not recommended for patients with bilateral renal artery stenosis or for patients with only one kidney.
Arterial hypotension, deficiency of water and electrolytes.
The risk of a sudden drop in blood pressure increases with low sodium levels (especially in patients with renal artery stenosis). Therefore, during treatment, the state of water and electrolyte balance should be periodically monitored, which may be disturbed due to diarrhea or vomiting. In case of severe arterial hypotension, intravenous infusion of an isotonic solution may be necessary.
Transient arterial hypotension is not a contraindication for continued treatment. After restoration of adequate blood volume and blood pressure, treatment can be resumed either with this combination at lower doses, or with only one component.
Potassium content.
The combination of perindopril and indapamide does not prevent the onset of hypokalemia, especially in patients with diabetes mellitus and in patients with renal failure. As with any antihypertensive drug taken in combination with a diuretic, plasma potassium levels should be regularly monitored during treatment with this combination.
Excipients.
Noliprel® forte A should not be prescribed to patients with lactose intolerance, lapp lactase deficiency or impaired absorption of glucose-galactose.
Use in pediatrics
The effectiveness and tolerability of perindopril in children and adolescents as mono- or as part of combination therapy has not been sufficiently studied.
Impact on the ability to drive vehicles and operate machinery
Perindopril and indapamide in the form of monotherapy or in combination as part of the drug Noliprel® forte A do not affect the ability to concentrate and the speed of psychomotor reactions. However, in some patients, especially at the beginning of treatment or when combined with another antihypertensive drug, individual reactions may develop with a decrease in blood pressure. This leads to impaired ability to drive vehicles or other mechanisms.
Results of preclinical safety studies
The toxicity of the perindopril/indapamide combination is slightly higher than the toxicity of each component. No renal toxicity was detected in rats. However, this combination causes gastrointestinal toxicity in dogs; in rats, the toxic effect on the maternal body increases (compared to perindopril). These undesirable effects occurred at doses with a very high safety margin compared to the therapeutic doses used.
Preclinical studies conducted separately with perindopril and indapamide revealed neither genotoxic nor teratogenic potential.
Compound
The drug Noliprel is offered in several different forms. All variations of the drug include perindopril and indapamide . Combined Noliprel contain 2 mg of perindopril and 0.625 mg of indapamide. The composition of Noliprel Forte includes 4 mg of perindopril and 1.25 mg of indapamide. Noliprel A contains 2.5 mg of perindopril and 0.625 mg of indapamide.
In this drug, perindopril is associated with the amino acid arginine, which has a beneficial effect on the condition of the cardiovascular system. Noliprel A Forte tablets contain 5 mg of perindopril and 1.25 mg of indapamide. Noliprel A Bi-forte contains 10 mg of perindopril and 2.5 mg of indapamide.
As additional substances in the composition of the drug Noliprel there is magnesium stearate, lactose monohydrate, colloidal hydrophobic silicon dioxide, microcrystalline cellulose.
pharmachologic effect
Noliprel is a combination drug that contains perindopril (an angiotensin-converting factor inhibitor) and indapamide (a diuretic that is part of the sulfonamide group).
The pharmacological effect of a drug is determined by a combination of some of the effects of these components. In this combination, both components mutually increase the effect. Noliprel is an antihypertensive drug that effectively lowers both diastolic and systolic blood pressure. The severity of the effect depends on the dose. After taking the drug, there is no rapid heartbeat. The clinical effect is observed 1 month after treatment was started. The antihypertensive effect lasts for one day. After therapy is suspended, the patient does not experience withdrawal symptoms. During treatment, the severity of left ventricular hypertrophy decreases, and the degree of total precardiac and postcardiac load decreases. Large vessels become more elastic, the walls of small vessels are restored. The medicine has no effect on the metabolic processes that occur in the body.
Perindopril reduces the level of aldosterone secretion, resulting in increased renin activity in the blood. Blood pressure decreases in people with different levels of renin . Under the influence of this component, blood vessels dilate.
When taking the drug, the likelihood of hypokalemia . The mechanism of action of indapamide is similar to thiazide diuretics: urination and excretion of sodium and chloride ions in the urine will increase.
Vascular hyperreactivity decreases under the influence of adrenaline. The amount of lipids in the blood does not change.
Pharmacokinetics and pharmacodynamics
The pharmacokinetics of perindopril and indapamide when used in combination is the same as when used separately. After oral administration, perindopril is rapidly absorbed. Bioavailability level - 65-70%. About 20% of total absorbed perindopril is later converted to perindoprilat (the active metabolite). The maximum concentration of perindoprilate in plasma is observed after 3-4 hours. Less than 30% binds to blood proteins, depending on the concentration in the blood plasma. The half-life is 25 hours. The substance penetrates the placental barrier. Perindoprilat is excreted from the body through the kidneys. Its half-life is 3-5 hours. There is a slower administration of perindoprilate in older people, as well as in patients with heart failure and renal failure.
Indapamide is completely and relatively quickly absorbed from the gastrointestinal tract. The maximum concentration of the substance in plasma is observed one hour after oral administration.
The substance binds to plasma proteins by 79%. Half-life is 19 hours. The substance is excreted in the form of inactive metabolites by the kidneys (approximately 70%) and intestines (approximately 22%). In people with renal failure, no changes in the pharmacokinetics of the substance are observed.
Noliprel's analogs
Level 4 ATX code matches:
Akkuzid
Enap-N
Iruzid
Co-Diroton
Enalozide
Enap NL
Enapril-N
Capozide
Tritace Plus
Enzix
Liprazid
Co-Renitec
Hartil N
Hartil D
Ko-Perineva
Kaptopres
Analogs of Noliprel, as well as the drugs Noliprel A Bi Forte, Noliprel A Forte, are other drugs that are used to lower blood pressure and contain similar active ingredients, that is, perindopril and indapamide. Such drugs are Co-prenesa , Prestarium , etc. The price of analogues may be lower than the cost of Noliprel and its varieties.
Overdose
In case of an overdose of the drug, there is a severe decrease in blood pressure, nausea, vomiting, dizziness , mood instability, symptoms of renal failure, and electrolyte imbalance. In this case, you need to immediately bring the water-electrolyte balance back to normal, rinse the stomach, and take enterosorbents. Noliprel metabolites can be removed using dialysis. If necessary, intravenous saline is administered.
special instructions
People who have been prescribed treatment with Noliprel need adequate dehydration of the body to prevent a sharp decrease in blood pressure.
People with heart failure may be treated with beta blockers at the same time.
When treated with Noliprel, a positive reaction is observed during a doping test.
In the first weeks of treatment, it is important to drive vehicles or operate precision machinery carefully when treating with Noliprel.
If during treatment there is a significant decrease in pressure, it may be necessary to administer 0.9% sodium chloride intravenously.
Treatment of patients with cerebral circulatory insufficiency or coronary heart disease should begin with small doses of Noliprel.
In people who have very high levels of uric acid in the blood, when treated with varieties of the drug Noliprel, the risk of developing gout .
Interaction
Noliprel should not be taken at the same time as lithium medications. If it is impossible to discontinue one of the drugs, the lithium level in the blood should be closely monitored.
With simultaneous treatment with potassium-sparing diuretics or drugs with potassium, the concentration of potassium in the blood may increase. This combination is recommended only for hypokalemia.
When indapamide with vincamine, bepridil, sultopride, halofantrine, as well as with simultaneous intravenous administration of erythromycin , arrhythmia and bradycardia may occur.
Sometimes, with simultaneous treatment with Insulin and Noliprel, hypoglycemia may develop.
When taking non-steroidal anti-inflammatory drugs, the antihypertensive properties of Noliprel are inhibited. If you are dehydrated, this combination of medications can cause kidney problems or kidney failure.
When treated with Noliprel and antipsychotics or tricyclic antidepressants, orthostatic hypotension may develop.
Due to the retention of water and electrolytes in the body, with simultaneous treatment with Noliprel and mineralocorticoids, glucocorticosteroids, stimulant laxatives, tetracosactide, amphotericin B, the hypotensive effect is reduced and the likelihood of hypokalemia increases.
Due to the possibility of developing hypokalemia, the risk of toxic effects of cardiac glycosides increases.
When combined with Metformin, acidosis may develop .
Before using iodine-containing X-ray contrast agents with Noliprel, the body must be adequately hydrated.
The simultaneous use of calcium salts can provoke hypercalcemia.
Concomitant treatment with cyclosporine may increase blood creatinine levels.
Contraindications
Contraindications to the use of all types of the drug Noliprel are the following diseases and conditions:
- high sensitivity to the components of the drug or the presence of allergic reactions to its components;
- renal failure , in which creatinine clearance is less than 30 ml/min;
- liver failure , in which there is a tendency to encephalopathy ;
- combination with drugs that prolong the QT interval, as well as antiarrhythmic drugs;
- hypokalemia;
- renal artery stenosis;
- lactase deficiency, glucose-galactose malabsorption syndrome, galactosemia;
- history of angioedema;
- pregnancy , lactation ;
- age up to eighteen years.
Also, you should not take the drug at the same time as potassium supplements or potassium-sparing diuretics if the patient has hyperkalemia.
Due to the lack of sufficient information, it is not recommended to use the tablets for treatment in people who are on hemodialysis , as well as in patients with decompensated heart failure.
It is prescribed with caution to people with systemic connective tissue diseases, those taking antidepressants, and suppression of bone marrow hematopoiesis. angina pectoris are also treated with caution .
Side effects
- In the functions of the cardiovascular system : severe hypotension, orthostatic collapse, in rare cases: arrhythmia , stroke , myocardial infarction .
- In the functions of the genitourinary system : deterioration of kidney function, proteinuria in people with glomerular nephropathy, in rare cases - acute renal failure. There may be a decrease in potency.
- In the functions of the central and peripheral nervous system : severe fatigue, dizziness , headache , asthenia, unstable mood, impaired hearing, vision, decreased appetite, convulsions, and in some cases, stupor.
- In the functions of the respiratory system : cough, difficulty breathing, bronchospasm, nasal discharge.
- In the functions of the gastrointestinal tract : dyspepsia, abdominal pain, pancreatitis , cholestasis, increased transaminase activity, hyperbilirubinemia.
- In the functions of the blood system : against the background of hemodialysis or after a kidney transplant, patients may develop anemia, in rare cases - thrombocytopenia, pancytopenia, agranulocytosis, hemolytic anemia.
- Allergic manifestations : skin itching, rash, swelling, urticaria.
- Patients with liver failure may develop hepatic encephalopathy. People with impaired water-electrolyte balance may experience hyponatremia, hypovolemia, hypokalemia, and dehydration.
