Indications for use
Noliprel is considered one of the best drugs for essential hypertension. For those who do not know, doctors understand this term as a disease characterized by a chronic increase in blood pressure. The most unpleasant thing is that the deterioration of the condition often occurs slowly and the person simply does not have time to respond to his illness in time. The same thing happened to me.
I noticed the first symptoms of pathology quite a long time ago. I often had noise in my ears, a headache, and spots in my eyes. I thought it was just manifestations of fatigue. I work hard, so I couldn’t find time for normal rest.
I decided to go to the doctor after my friends started saying that my face was constantly red. At the hospital, the therapist referred me to a cardiologist.
“Despite your relatively young age, you have all the signs of essential hypertension.
You need to resolve the issue now, otherwise you will end up with complications. I recommend starting with ACE inhibitors, diuretics and potassium antagonists. The list of such drugs is quite long...” Grigory Sergeevich, cardiologist, arrhythmologist, Moscow
After talking with the doctor, I began to look for medications that would relieve my symptoms. And, in the end, I opted for Noliprel tablets. Now I will try to explain why.
Customer reviews about Noliprel
Returning home from the clinic, I started looking for descriptions of drugs for hypertension on the Internet. The choice of tablets, injections and powders was really huge. The doctor recommended a couple of names, but judging by the reviews of patients, there were more interesting options. The cardiologist prescribed the most affordable means, but I didn’t want to save money, but to actually eliminate the problem (or at least keep it under control).
While reading different opinions about medications, I came across a description of Noliprel tablets. Some people wrote that this drug reduces blood pressure very quickly. Moreover, the remedy sometimes has an overly strong effect. This is exactly what interested me - it means it definitely works! I went online to specifically look for reviews on a specific substance.
“Hypertension is a real punishment. It was especially difficult in the fall. Any overexertion, both physical and mental, caused severe headaches and nausea. I was worried that I would have a heart attack or stroke. I started taking Noliprel on the advice of a colleague. Great pills. I drink them in advance and no longer suffer from weather changes...”
We often came across reviews of people who started drinking Noliprel after trying a bunch of its analogues. As far as I understand, these tablets are quite strong, which is why the price is high.
“I couldn’t cope with the swelling on my face and legs. Doctors said that it was because of chronic high blood pressure that the kidneys were not working well and fluid was accumulating in the body. I tried many different drugs, but the results were not impressive. I accidentally overheard a conversation between two pensioners about Noliprel. I decided to buy it for testing and realized that I had finally found what I needed..."
There were, of course, negative reviews. They concerned the side effects of the drug. Most often, people complained that after a course of Noliprel they had sleep disturbances and dry mouth. It didn't really scare me, so I decided to ignore it.
Noliprel A forte tablets 1.25 mg+5 mg 30 pcs.
From the circulatory and lymphatic system. Very rare: thrombocytopenia, leukopenia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. Anemia: In certain clinical situations (kidney transplant patients, hemodialysis patients), ACE inhibitors may cause anemia. From the central nervous system. Common: paresthesia, headache, dizziness, asthenia, vertigo. Uncommon: sleep disturbance, mood lability. Very rare: confusion. Unspecified frequency: fainting. From the side of the organ of vision. Common: blurred vision. From the side of the hearing organ. Common: tinnitus. From the cardiovascular system. Often: marked decrease in blood pressure, including orthostatic hypotension. Very rare: cardiac arrhythmias, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients. Unspecified frequency: ari (possibly fatal). From the respiratory system, chest organs and mediastinum. Often: while using ACE inhibitors, a dry cough may occur, which persists for a long time while taking drugs of this group and disappears after their discontinuation. Dyspnea. Uncommon: bronchospasm. Very rare: eosinophilic pneumonia, rhinitis. From the digestive system. Often: dryness of the oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste perception, decreased appetite, dyspepsia, constipation, diarrhea. Very rare: angioedema of the intestine, cholestatic jaundice, pancreatitis. Unspecified frequency: hepatic encephalopathy in patients with liver failure, hepatitis. From the skin and subcutaneous fat. Common: skin rash, pruritus, maculopapular rash. Uncommon: angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and/or larynx; hives; hypersensitivity reactions in patients predisposed to broncho-obstructive and allergic reactions; purpura. In patients with acute form of systemic lupus erythematosus, the course of the disease may worsen. Very rare: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Cases of photosensitivity reactions have been reported. From the musculoskeletal system and connective tissue. Common: muscle spasms. From the urinary system. Uncommon: renal failure. Very rare: acute renal failure. From the reproductive system. Uncommon: impotence. General disorders and symptoms. Often: asthenia. Uncommon: increased sweating.
How do blood pressure pills work?
I honestly tried to figure out the composition and carefully studied the available information on each component of the drug. Fortunately, there are only two of them, so you can describe these elements separately.
Perindopril is an inhibitor that converts angiotensin 1 into angiotensin 2. I understand that for many this is a meaningless set of letters. Now I’ll try to decipher the terms. The substance works on the principle of feedback, that is, if necessary, it expands or, conversely, constricts blood vessels, equalizing blood pressure. In reviews of people who have undergone treatment, Noliprel read that, if used correctly, the tablets have a positive effect on the heart, reducing pre- and afterload. All this thanks to perindopril.
Indapamide is considered one of the best diuretics. Such drugs inhibit the reabsorption of water and salts in the kidneys. Again, complex “gibberish” - in fact, everything is extremely simple. Noliprel accelerates the removal of fluid from tissues, while swelling disappears and the load on internal organs is significantly reduced.
That's the entire composition of the drug. A small number of components in the composition significantly reduces the list of contraindications. The description of the medicine states that it should not be taken if:
- renal failure;
- liver problems;
- pregnancy, lactation;
- hypersensitivity to the elements of the drug.
In the reviews I came across another feature of the product. It is very important to be as careful as possible for people suffering from lactose intolerance. This element is also included in Noliprel.
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.
Special instructions and analogues of the drug
It was very important to me that the pills did not affect the reaction. I have to drive a lot, so I specifically checked this parameter. I did not find any side effects related to driving. I’ll write a few words about the possible replacement of Noliprel with analogues. I came across reviews from people who were looking for an alternative to the product (usually due to allergies). The list was not very long. The most frequently mentioned were "Perindid" and "Co-Perineva".
Well, at the end of my review I will write about my feelings. At first I didn’t notice any special effect from taking Noliprel, I was even a little upset. It’s good that I didn’t give up treatment, since positive changes in my condition began to appear after about 2 weeks. I noticed the absence of sock marks on my feet in the evening (which means the swelling disappeared) and a clear improvement in my sleep. The dizziness stopped and the nausea went away. The doctor said that most likely later I will have to buy a larger dosage, but so far everything is fine.
Noliprel®
Perindopril, indapamide
The use of Noliprel® is not accompanied by a significant reduction in the frequency of side effects, with the exception of hypokalemia, compared with perindopril and indapamide in the lowest approved doses (see section “Side Effects”). When initiating therapy with two antihypertensive drugs that the patient has not previously received, an increased risk of idiosyncrasy cannot be excluded. Careful monitoring of the patient can minimize this risk.
Lithium preparations
The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see section “Interaction with other drugs”).
Renal dysfunction
Therapy is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment should be stopped. In the future, you can resume combination therapy using low doses of drugs, or use drugs in monotherapy.
Such patients require regular monitoring of serum potassium and creatinine levels - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure occurs more often in patients with severe heart failure or underlying renal impairment, including stenosis of one or two renal arteries.
As a rule, the use of perindopril and indapamide is not recommended for patients with bilateral renal artery stenosis or stenosis of a single functioning kidney.
Arterial hypotension and water-electrolyte imbalance
Hyponatremia is associated with a risk of sudden development of arterial hypotension (especially in patients with stenosis of one or two renal arteries). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased levels of electrolytes in the blood plasma, for example, after diarrhea or vomiting. Such patients require regular monitoring of plasma electrolyte levels.
In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for continued therapy. After restoration of circulating blood volume and blood pressure, therapy can be resumed using low doses of drugs, or drugs can be used as monotherapy.
Potassium level
The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of antihypertensive drugs and a diuretic, regular monitoring of the level of potassium in the blood plasma is necessary.
Excipients
It should be taken into account that the excipients of the drug include lactose monohydrate. Noliprel® should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.
Perindopril
Neutropenia/agranulocytosis
The risk of developing neutropenia while taking ACE inhibitors is dose-dependent and depends on the drug taken and the presence of concomitant diseases. Neutropenia rarely occurs in patients without concomitant diseases, but the risk increases in patients with impaired renal function, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma).
After discontinuation of ACE inhibitors, signs of neutropenia disappear on their own.
Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressive drugs, allopurinol or procainamide, and with simultaneous exposure to these factors, especially in patients with underlying renal impairment. Some 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 (Quincke's edema)
When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, glottis and/or larynx may occur. If symptoms appear, perindopril should be discontinued immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction. If such symptoms appear, you should immediately administer epinephrine (adrenaline) subcutaneously at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency.
Patients with a history of angioedema, not associated with taking ACE inhibitors, may have an increased risk of developing it when taking drugs of this group (see section "Contraindications").
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C-1 esterase. The diagnosis is made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis.
Anaphylactoid reactions during desensitization
There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the procedure.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Hemodialysis
Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.
Potassium-sparing diuretics and potassium supplements
As a rule, the combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing table salt substitutes is not recommended (see section “Interaction with other drugs”).
Cough
During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the attending physician believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.
Children and teenagers
Noliprel® should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of perindopril as monotherapy or as part of combination therapy in patients in this age group.
Risk of arterial hypotension and/or renal failure (in patients with heart failure, fluid and electrolyte imbalance, etc.)
In some pathological conditions, significant activation of the renin-angiotensin-aldosterone system may be observed, especially with severe hypovolemia and a decrease in the level of plasma electrolytes (against the background of a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, stenosis of one or two kidneys arteries, chronic heart failure or cirrhosis of the liver with the presence of edema and ascites.
The use of an ACE inhibitor causes a blockade of this system and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine levels, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and during other periods of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.
Elderly patients
Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the concentration of potassium in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.
Atherosclerosis
The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should be started with low doses.
Patients with renovascular hypertension
The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in patients both awaiting surgery and in cases where such surgery cannot be performed.
Treatment with Noliprel® in patients with diagnosed or suspected renal artery stenosis should begin with a low dose of the drug in a hospital setting, monitoring renal function and potassium concentration in the blood plasma. Some patients may develop functional renal failure, which disappears when the drug is discontinued.
Other risk groups
In persons with chronic heart failure (stage IV) and patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium concentration), treatment should begin with a low dose of the drug (half a tablet) and under constant medical supervision.
Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: ACE inhibitors should be used together with beta-blockers.
Patients with diabetes mellitus
When prescribing the drug to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose levels should be carefully monitored during the first month of therapy.
Ethnic differences
Perindopril, like other ACE inhibitors, apparently has a less pronounced hypotensive effect in patients of the Negroid race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race more often have low renin activity.
Surgery/General anesthesia
The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.
It is recommended to stop taking long-acting ACE inhibitors, including perindopril, 12 hours before surgery.
Aortic stenosis / Mitral stenosis / Hypertrophic cardiomyopathy
ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction.
Liver failure
In rare cases, it occurs while taking ACE inhibitors. cholestatic jaundice. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs while taking ACE inhibitors, you should stop taking the drug and consult a doctor (see section “Side Effects”).
Anemia
Anemia can develop in patients after kidney transplantation or in people on hemodialysis. In this case, the decrease in hemoglobin concentration is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, decreased renal function, advanced age, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensated heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), and potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). The use of potassium supplements, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If combined use of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of potassium levels in the blood serum (see section “Interaction with other drugs”).
Indapamide
When thiazide and thiazide-like diuretics are prescribed to patients with impaired liver function, hepatic encephalopathy may develop. In this case, diuretics should be stopped immediately.
Photosensitivity
While taking thiazide and thiazide-like diuretics, cases of photosensitivity reactions have been reported (see section "Side effects"). If photosensitivity reactions develop while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial UV rays.
Water and electrolyte balance
Content of sodium ions in blood plasma
Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and the elderly (see sections “Side effects” and “Overdose”).
Content of potassium ions in blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. Hypokalemia (less than 3.4 mmol/l) should be avoided in the following high-risk patients: elderly patients, debilitated patients or those receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema or ascites, coronary artery disease, heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmias.
Patients with an increased QT interval are also at increased risk, and it does not matter whether this increase is caused by congenital causes or the effect of drugs.
Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, especially arrhythmias, which can be fatal. In all the cases described above, more regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion concentration should be carried out within the first week from the start of therapy.
If hypokalemia is detected, appropriate treatment should be prescribed.
Content of calcium ions in blood plasma
Thiazide and thiazide-like diuretics reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid gland, you should stop taking diuretic drugs.
Plasma glucose levels
It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.
Uric acid
In patients with elevated levels of uric acid in the blood plasma during therapy, the frequency of gout attacks may increase.
Diuretics and kidney function
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adults below 25 mg/l or 220 µmol/l). In elderly patients, creatinine clearance is calculated taking into account age, body weight and gender.
At the beginning of treatment with diuretics, patients due to hypovolemia and hyponatremia may experience a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.
Athletes
Indapamide may give a positive reaction during doping control.
