Components:
Method of action:
Medically reviewed by Fedorchenko Olga Valeryevna, PharmD. Last updated on 20.03.2022
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Eneas
Enalapril, Nitrendipine
Essential hypertension (patients who are indicated for combination therapy).
Essential hypertension (patients who are indicated for combination therapy).
Inside, swallowing whole, without breaking or chewing, with a sufficient amount of water. No more than 1 tablet per day.
Patients with impaired liver function. Enanorm is contraindicated in patients with severe hepatic impairment (see "Contraindications"). In patients with mild to moderate hepatic impairment, monotherapy with neither enalapril nor nitrendipine is contraindicated, but due to the fact that there is no experience with Enanorm in such patients, the drug should be prescribed with caution.
Patients with impaired renal function. Enanorm is contraindicated in patients with severe renal impairment (creatinine Cl less than 10 ml / min) and patients undergoing hemodialysis. In patients with moderate renal insufficiency (creatinine Cl greater than 30 ml / min, serum creatinine < 3 mg/ml), there is no need to adjust the dose, at the same time, it is necessary to evaluate renal function.
Children and teenagers. The drug Enanorm should not be used in children and adolescents under 18 years of age due to the lack of data on the use.
Inside, swallowing whole, without breaking or chewing, with a sufficient amount of water. No more than 1 tablet per day.
Patients with impaired liver function. Eneas is contraindicated in patients with severe hepatic impairment (see "Contraindications"). In patients with mild to moderate hepatic impairment, monotherapy with neither enalapril nor nitrendipine is contraindicated, but due to the fact that there is no experience with Epeasa in such patients, the drug should be prescribed with caution.
Patients with impaired renal function. Eneas is contraindicated in patients with severe renal impairment (creatinine Cl less than 10 ml / min) and patients undergoing hemodialysis. In patients with moderate renal insufficiency (creatinine Cl greater than 30 ml / min, serum creatinine < 3 mg/ml), there is no need to adjust the dose, at the same time, it is necessary to evaluate renal function.
Children and teenagers. Eneas should not be used in children and adolescents under 18 years of age due to the lack of data on the use.
hypersensitivity to enalapril, nitrendipine or any excipient of the drug and other dihydropyridine derivatives,
a history of angioedema associated with treatment with ACE inhibitors,
hereditary or idiopathic angioedema,
shock,
collapse,
acute heart failure,
pathological syndromes, including chronic heart failure at the stage of decompensation, requiring inotropic therapy, accompanied by unstable hemodynamics (for example, cardiovascular shock, acute heart failure, acute coronary syndrome, acute period of stroke) with unstable hemodynamics: acute myocardial infarction (in the first 4 weeks after a myocardial infarction), chronic heart failure of the III–IV functional class according to the NYHA classification,
bilateral renal artery stenosis or single kidney artery stenosis,
hemodynamically significant aortic or mitral valve stenosis and hypertrophic obstructive cardiomyopathy,
severe renal impairment (creatinine Cl less than 10 ml / min) and hemodialysis,
severe hepatic impairment,
galactose intolerance, lactase deficiency, or glucose-galactose malabsorption (the drug contains lactose),
severe arterial hypotension (sBP less than 90 mmHg).),
pregnancy,
lactation period,
age under 18 (efficacy and safety not established).
With caution: aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary heart disease, coronary insufficiency, severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bone marrow hematopoiesis suppression, diabetes mellitus, hyperkalemia, post-kidney transplant condition, kidney failure, mild or moderate liver function disorders, salt-restricted diet, conditions accompanied by a decrease in blood pressure.BCC (including diarrhea, vomiting), elderly.
Classification of adverse reactions by frequency of development: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000, including individual reports), frequency unknown (cannot be estimated from available data).
The adverse reactions observed when using Enanorm are similar to the reactions to taking each of the components of the drug separately.
From the CCC side: often-flushes of blood to the skin of the face, peripheral edema, infrequently-tachycardia, dizziness, pronounced decrease in blood pressure, very rarely-violation of peripheral blood circulation, shortness of breath.
From the nervous system: often-headache, very rarely-asthenia, hypothermia, drowsiness, paresthesia, tremor, convulsions.
From the respiratory system: often-cough, very rarely-pharyngitis, tracheitis, dyspnea.
From the digestive system: infrequently-nausea, dyspepsia, very rarely-flatulence.
From the skin and subcutaneous tissues: infrequently-erythematous rash.
From the kidneys and urinary tract: very rarely — hematuria.
Musculoskeletal and connective tissue disorders: very rarely — muscle spasm.
Laboratory and instrumental data: very rarely — increased activity of hepatic transaminases, hypokalemia.
Adverse side effects observed when taking drugs containing similar components
Enalapril
From the CCC side:
From the kidneys and urinary tract: infrequently-the appearance or increase in renal function disorders, very rarely-acute renal failure, rarely-oliguria, proteinuria, in some cases with concomitant deterioration of renal function, pain in the iliac region.
From the respiratory system: infrequently-dry cough, sore throat, hoarseness, bronchitis, rarely-shortness of breath, sinusitis, rhinitis, very rarely-bronchospasm / asthma attack, pulmonary infiltrates, pneumonia, angioedema, affecting the pharynx, larynx and / or tongue and leading in some cases to death (more often in patients of the black race).
From the digestive system: infrequently-nausea, pain in the upper abdomen, digestive disorders, rarely-vomiting, diarrhea, constipation, loss of appetite, change or transient loss of taste, anosmia, very rarely-pancreatitis, intestinal obstruction, dry mouth, stomatitis, glossitis.
From the liver and biliary tract: very rarely-liver dysfunction, hepatitis, liver failure, a syndrome that begins with cholestatic jaundice and progresses to liver necrosis, in some cases with a fatal outcome.
From the endocrine system: very rarely — gynecomastia.
From the skin and subcutaneous tissues: infrequently — exanthema, rarely — urticaria, pruritus, angioedema of the lips, face and/or upper and lower extremities, very rarely — severe skin reactions (for example, pemphigus, pemphigus, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome or toxic epidermal necrolysis), phenomena resembling psoriasis, photosensitivity, flushes of blood to the skin of the face, increased sweating, alopecia, onycholysis. Skin manifestations may be accompanied by fever, myalgia/myositis, arthralgia/arthritis, vasculitis, serositis, eosinophilia, leukocytosis, increased erythrocyte sedimentation rate and / or antinuclear antibody titers. If a severe skin reaction is suspected, treatment is discontinued
From the nervous system: infrequently-headache, weakness, rarely-dizziness, depression, sleep disorders, impotence, peripheral neuropathy with paresthesia, balance disorders, muscle spasms, nervousness, confusion.
On the part of the hearing organ: rarely-tinnitus.
On the part of the visual organ: rarely-blurred vision, dry eyes, increased lacrimation.
Laboratory and instrumental data:
Nitrendipine
On the part of the immune system: infrequently-flu-like syndrome.
From the CCC side: infrequently: arrhythmia, tachycardia, palpitations, peripheral edema, flushes of blood to the skin of the face, increased symptoms of vasodilation, rarely-a marked decrease in blood pressure, angina, chest pain.
From the gastrointestinal tract: infrequently-nausea, diarrhea, rarely-abdominal pain, constipation, dyspepsia, vomiting, very rarely-gum hyperplasia.
From the endocrine system: very rarely — gynecomastia.
From the blood and lymphatic system: very rarely — leukopenia, agranulocytosis.
Musculoskeletal and connective tissue disorders: rarely-myalgia.
From the nervous system: infrequently-headache, asthenia, rarely-nervousness, paresthesia, tremor, dizziness.
From the respiratory system: rarely-shortness of breath.
From the skin and subcutaneous tissues: rarely-skin itching, rash, urticaria.
On the part of the visual organ: rarely-visual impairment.
From the kidneys and urinary tract: very rarely-increased frequency of urination, polyuria.
Laboratory and instrumental data: very rarely — an increase in the activity of liver enzymes. If any of the side effects described in the description are aggravated, or any other side effects not specified in the instructions have been noticed, you should inform your doctor.
Classification of adverse reactions by frequency of development: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000, including individual reports), frequency unknown (cannot be estimated from available data).
The adverse reactions observed when using Eneas are similar to the reactions to taking each of the components of the drug separately.
From the CCC side: often-flushes of blood to the skin of the face, peripheral edema, infrequently-tachycardia, dizziness, pronounced decrease in blood pressure, very rarely-violation of peripheral blood circulation, shortness of breath.
From the nervous system: often-headache, very rarely-asthenia, hypothermia, drowsiness, paresthesia, tremor, convulsions.
From the respiratory system: often-cough, very rarely-pharyngitis, tracheitis, dyspnea.
From the digestive system: infrequently-nausea, dyspepsia, very rarely-flatulence.
From the skin and subcutaneous tissues: infrequently-erythematous rash.
From the kidneys and urinary tract: very rarely — hematuria.
Musculoskeletal and connective tissue disorders: very rarely — muscle spasm.
Laboratory and instrumental data: very rarely — increased activity of hepatic transaminases, hypokalemia.
Adverse side effects observed when taking drugs containing similar components
Enalapril
From the CCC side:
From the kidneys and urinary tract: infrequently-the appearance or increase in renal function disorders, very rarely-acute renal failure, rarely-oliguria, proteinuria, in some cases with concomitant deterioration of renal function, pain in the iliac region.
From the respiratory system: infrequently-dry cough, sore throat, hoarseness, bronchitis, rarely-shortness of breath, sinusitis, rhinitis, very rarely-bronchospasm / asthma attack, pulmonary infiltrates, pneumonia, angioedema, affecting the pharynx, larynx and / or tongue and leading in some cases to death (more often in patients of the black race).
From the digestive system: infrequently-nausea, pain in the upper abdomen, digestive disorders, rarely-vomiting, diarrhea, constipation, loss of appetite, change or transient loss of taste, anosmia, very rarely-pancreatitis, intestinal obstruction, dry mouth, stomatitis, glossitis.
From the liver and biliary tract: very rarely-liver dysfunction, hepatitis, liver failure, a syndrome that begins with cholestatic jaundice and progresses to liver necrosis, in some cases with a fatal outcome.
From the endocrine system: very rarely — gynecomastia.
From the skin and subcutaneous tissues: infrequently — exanthema, rarely — urticaria, pruritus, angioedema of the lips, face and/or upper and lower extremities, very rarely — severe skin reactions (for example, pemphigus, pemphigus, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome or toxic epidermal necrolysis), phenomena resembling psoriasis, photosensitivity, flushes of blood to the skin of the face, increased sweating, alopecia, onycholysis. Skin manifestations may be accompanied by fever, myalgia/myositis, arthralgia/arthritis, vasculitis, serositis, eosinophilia, leukocytosis, increased erythrocyte sedimentation rate and / or antinuclear antibody titers. If a severe skin reaction is suspected, treatment is discontinued
From the nervous system: infrequently-headache, weakness, rarely-dizziness, depression, sleep disorders, impotence, peripheral neuropathy with paresthesia, balance disorders, muscle spasms, nervousness, confusion.
On the part of the hearing organ: rarely-tinnitus.
On the part of the visual organ: rarely-blurred vision, dry eyes, increased lacrimation.
Laboratory and instrumental data:
Nitrendipine
On the part of the immune system: infrequently-flu-like syndrome.
From the CCC side: infrequently: arrhythmia, tachycardia, palpitations, peripheral edema, flushes of blood to the skin of the face, increased symptoms of vasodilation, rarely-a marked decrease in blood pressure, angina, chest pain.
From the gastrointestinal tract: infrequently-nausea, diarrhea, rarely-abdominal pain, constipation, dyspepsia, vomiting, very rarely-gum hyperplasia.
From the endocrine system: very rarely — gynecomastia.
From the blood and lymphatic system: very rarely — leukopenia, agranulocytosis.
Musculoskeletal and connective tissue disorders: rarely-myalgia.
From the nervous system: infrequently-headache, asthenia, rarely-nervousness, paresthesia, tremor, dizziness.
From the respiratory system: rarely-shortness of breath.
From the skin and subcutaneous tissues: rarely-skin itching, rash, urticaria.
On the part of the visual organ: rarely-visual impairment.
From the kidneys and urinary tract: very rarely-increased frequency of urination, polyuria.
Laboratory and instrumental data: very rarely — an increase in the activity of liver enzymes. If any of the side effects described in the description are aggravated, or any other side effects not specified in the instructions have been noticed, you should inform your doctor.
To date, no cases of overdose of this combination have been reported.
Symptoms: the most likely manifestation of an overdose of Enanorm will be a marked decrease in blood pressure.
Treatment: gastric lavage, administration of adsorbents (if possible, in the first 30 minutes), vital functions should be monitored. In the case of a pronounced decrease in blood pressure, the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and oral administration of sodium chloride salt solution are indicated, in more severe cases, measures aimed at stabilizing blood pressure: intravenous administration of 0.9% sodium chloride solution, plasma — substituting solutions, if necessary, administration of angiotensin II, hemodialysis (the rate of elimination of enalaprilate is 62 ml/min). There is no specific antidote
To date, no cases of overdose of this combination have been reported.
Symptoms: the most likely manifestation of an overdose of Eneas will be a marked decrease in blood pressure.
Treatment: gastric lavage, administration of adsorbents (if possible, in the first 30 minutes), vital functions should be monitored. In the case of a pronounced decrease in blood pressure, the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and oral administration of sodium chloride salt solution are indicated, in more severe cases, measures aimed at stabilizing blood pressure: intravenous administration of 0.9% sodium chloride solution, plasma — substituting solutions, if necessary, administration of angiotensin II, hemodialysis (the rate of elimination of enalaprilate is 62 ml/min). There is no specific antidote
Enanorm is a combination of two antihypertensive agents with a complementary mechanism for lowering blood pressure: enalapril-an ACE inhibitor and nitrendipine-BCC.
Enalapril
Enalapril is a prodrug, as a result of its hydrolysis, an active metabolite is formed — enalaprilate, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the content of which leads to a direct decrease in the release of aldosterone. At the same time, OPSS, sAD and dBP, postload and preload on the myocardium are reduced.
Enalapril dilates the arteries to a greater extent than the veins, while there is no reflex increase in heart rate.
The antihypertensive effect is more pronounced with high plasma renin activity than with normal or reduced renin activity. A decrease in blood pressure within therapeutic limits does not affect the cerebral circulation: blood flow in the vessels of the brain is maintained at a sufficient level and against the background of reduced blood pressure. Increases coronary and renal blood flow.
With prolonged use, hypertrophy of the left ventricle of the myocardium and the myocytes of the walls of the arteries of the resistive type decreases, the progression of heart failure is prevented and the development of left ventricular dilatation slows down. Enalapril improves blood supply to the ischemic myocardium.
The time of onset of the antihypertensive effect when taken orally is 1 hour, reaches a maximum after 4-6 hours and persists for a day.
Nitrendipine
Nitrendipine-BCC from the group of dihydropyridine derivatives, has an antihypertensive effect. Reduces the flow of calcium ions into the smooth muscle cells of the coronary and peripheral arteries. Causes a slight increase in the excretion of sodium and water. Reduces afterload and the need for oxygen in the myocardium, does not inhibit the conduction of the heart muscle.
Reduces the number of functioning channels, without affecting the time of their activation, inactivation and recovery. It separates the processes of excitation and contraction in the myocardium, mediated by tropomyosin and troponin, and in the vascular smooth muscles, mediated by calmodulin. In therapeutic doses, it normalizes the transmembrane current of calcium ions, which is disturbed in a number of pathological conditions, primarily in arterial hypertension.
The results of a clinical study of Enanorm in patients with arterial hypertension who did not achieve satisfactory blood pressure control with enalapril at a dose of 10 mg or nitrendipine at a dose of 20 mg showed that Enanorm has a more pronounced effect on reducing both dBP and sAD and the severity of the therapeutic response to the therapy.
Eneas is a combination of two antihypertensive agents with a complementary mechanism for lowering blood pressure: enalapril-an ACE inhibitor and nitrendipine-BCC.
Enalapril
Enalapril is a prodrug, as a result of its hydrolysis, an active metabolite is formed — enalaprilate, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the content of which leads to a direct decrease in the release of aldosterone. At the same time, OPSS, sAD and dBP, postload and preload on the myocardium are reduced.
Enalapril dilates the arteries to a greater extent than the veins, while there is no reflex increase in heart rate.
The antihypertensive effect is more pronounced with high plasma renin activity than with normal or reduced renin activity. A decrease in blood pressure within therapeutic limits does not affect the cerebral circulation: blood flow in the vessels of the brain is maintained at a sufficient level and against the background of reduced blood pressure. Increases coronary and renal blood flow.
With prolonged use, hypertrophy of the left ventricle of the myocardium and the myocytes of the walls of the arteries of the resistive type decreases, the progression of heart failure is prevented and the development of left ventricular dilatation slows down. Enalapril improves blood supply to the ischemic myocardium.
The time of onset of the antihypertensive effect when taken orally is 1 hour, reaches a maximum after 4-6 hours and persists for a day.
Nitrendipine
Nitrendipine-BCC from the group of dihydropyridine derivatives, has an antihypertensive effect. Reduces the flow of calcium ions into the smooth muscle cells of the coronary and peripheral arteries. Causes a slight increase in the excretion of sodium and water. Reduces afterload and the need for oxygen in the myocardium, does not inhibit the conduction of the heart muscle.
Reduces the number of functioning channels, without affecting the time of their activation, inactivation and recovery. It separates the processes of excitation and contraction in the myocardium, mediated by tropomyosin and troponin, and in the vascular smooth muscles, mediated by calmodulin. In therapeutic doses, it normalizes the transmembrane current of calcium ions, which is disturbed in a number of pathological conditions, primarily in arterial hypertension.
The results of a clinical study of Eneas in patients with arterial hypertension who did not achieve satisfactory blood pressure control with enalapril at a dose of 10 mg or nitrendipine at a dose of 20 mg showed that Eneas has a more pronounced effect on reducing both dBP and sBP and the severity of the therapeutic response to the therapy.
Enalapril
After oral administration, it is absorbed from the gastrointestinal tract by 60%. Food intake does not affect the absorption of enalapril.The binding of enalapril to plasma proteins is 50-60%. Enalapril is rapidly metabolized in the liver to form the active metabolite — enalaprilate. The bioavailability of enalapril is 40%.
Cmax enalapril in blood plasma is reached after 1 h, enalaprilat-3-4 h. Enalaprilat easily passes through the histohematic barriers, excluding BBB, a small amount penetrates through the placenta and into breast milk.
T1/2 enalaprilata — about 11 hours. Enalapril is mainly excreted by the kidneys-60% (20% - in the form of enalapril and 40% - in the form of enalaprilate), through the intestine-33% (6% - in the form of enalapril and 27% - in the form of enalaprilate).
It is removed during hemodialysis (rate of 62 ml / min) and peritoneal dialysis.
Nitrendipine
It is rapidly absorbed from the gastrointestinal tract by 88%. Bioavailability is 20-30% due to the pronounced effect of primary passage through the liver. Relationship with plasma proteins (albumin) — 96–98%. Tmax in blood plasma-1-3 hours after application.
Vss it is 5-9 l / kg, hemodialysis and plasmapheresis to remove nitrendipine from the body are ineffective.
It is metabolized in the liver, mainly by oxidation. The metabolites are pharmacologically inactive. Nitrendipine is excreted mainly through the kidneys: approximately 77% of the dose is excreted as metabolites, less than 0.1% of the dose is excreted unchanged. The rest of nitrendipine is excreted through the intestine.
T1/2 nitrendipine after oral administration is 8-12 hours. Neither nitrendipine nor its metabolites accumulate in the body. In elderly patients, T increases1/2, in cirrhosis of the liver-AUC and Cmax in the blood plasma increases.
In patients with impaired renal function, dose adjustment is not required.
The study of the interaction of enalapril and nitrendipine in healthy volunteers did not reveal a change in the pharmacokinetics of nitrendipine. As for enalaprilat, its bioavailability is slightly increased when used concomitantly with nitrendipine, but this does not seem to have clinical significance. The bioavailability of nitrendipine when using a combined drug is higher than when using two drugs separately.
- Antihypertensive agent combined (blocker of "slow" calcium channels inhibitor of angiotensin converting enzyme) [ACE inhibitors in combinations]
- Antihypertensive agent combined (blocker of "slow" calcium channels inhibitor of angiotensin converting enzyme) [Calcium channel blockers in combinations]
The antihypertensive effect of Enanorm may be enhanced when used concomitantly with other antihypertensive agents, such as diuretics, beta-blockers, or alpha-blockers.
In addition, when used simultaneously, individual components of the drug may exhibit the following interactions
Enalapril
Combinations that should be used with caution
Potassium-sparing diuretics and potassium preparations. ACE inhibitors reduce the loss of potassium caused by diuretics. Potassium-sparing diuretics, potassium preparations, and other drugs that can increase the serum potassium content (for example, heparin) may have an additive effect on the serum potassium content, especially in patients with impaired renal function. If the combined use of such drugs is necessary, for example, to eliminate hypokalemia, then caution should be exercised and the content of potassium in the blood serum should be monitored frequently.
Lithium. The use of enalapril in combination with lithium is not recommended due to the risk of a significant increase in the concentration of lithium in the blood serum with the subsequent development of severe neurotoxicity. If the combined use of these drugs is necessary, then the concentration of lithium in the blood serum should be carefully monitored.
NSAIDs. In combination with ACE inhibitors, they additively increase the content of potassium in the blood serum, which can lead to deterioration of kidney function. In elderly patients and patients with reduced BCC, this combination can cause acute renal failure due to its direct effect on the glomerular filtration rate. Moreover, NSAIDs can weaken the antihypertensive effect of ACE inhibitors.
Hypoglycemic agents for oral administration. Enalapril can increase the hypoglycemic effect of these drugs, so you should carefully monitor the concentration of glucose in the blood.
Baclofen. May enhance the antihypertensive effect. If necessary, combined use should monitor blood pressure and adjust the dose.
Neuroleptics. Use in conjunction with these drugs may cause orthostatic hypotension.
Antidepressants. Use in combination with tricyclic antidepressants may cause orthostatic hypotension.
Allopurinol, cytostatics, immunosuppressants, systemic corticosteroids (used parenterally or orally), procainamide. Concomitant use may cause leukopenia.
Digoxin. Enalapril was used in combination with digoxin without any evidence of a clinically significant adverse interaction.
Combinations to consider
Amifostin. The combination enhances the antihypertensive effect.
Nitrendipine
Cimetidine and ranitidine. Cimetidine, and to a lesser extent ranitidine, may increase the concentration of nitrendipine in blood plasma, but the clinical significance of these data is unknown.
Digoxin. Simultaneous use of nitrendipine and digoxin may lead to an increase in the concentration of digoxin in the blood plasma. Therefore, the appearance of symptoms of digoxin overdose should be monitored or, if necessary, the concentration of digoxin in the blood plasma should be monitored.
Muscle relaxants. The use of nitrendipine may increase the duration and severity of the effects of muscle relaxants, for example, pancuronium bromide.
Grapefruit juice inhibits the oxidative metabolism of nitrendipine. Taking the latter with grapefruit juice increases the concentration of nitrendipine in the blood plasma, which can increase its antihypertensive effect. Nitrendipine is metabolized by the cytochrome P450 isoenzyme CYP3A4 in the intestinal mucosa and in the liver. Inducers of the CYP3A4 isoenzyme, such as anticonvulsants (phenytoin, phenobarbital, carbamazepine) and rifampicin, can significantly reduce the bioavailability of nitrendipine. Inhibitors of the isoenzyme CYP3A4, for example, antifungal imidazoles (itraconazole, etc.) can increase the concentration of nitrendipine in the blood plasma
Beta-blockers. Nitrendipine and beta-blockers act synergistically. This may be of particular importance for patients in whom additional beta-adrenoceptor blockade does not compensate for sympathetic vascular reactions, and caution is recommended for such patients.
The antihypertensive effect of Eneas may be enhanced when used concomitantly with other antihypertensive agents, such as diuretics, beta-blockers, or alpha-blockers.
In addition, when used simultaneously, individual components of the drug may exhibit the following interactions
Enalapril
Combinations that should be used with caution
Potassium-sparing diuretics and potassium preparations. ACE inhibitors reduce the loss of potassium caused by diuretics. Potassium-sparing diuretics, potassium preparations, and other drugs that can increase the serum potassium content (for example, heparin) may have an additive effect on the serum potassium content, especially in patients with impaired renal function. If the combined use of such drugs is necessary, for example, to eliminate hypokalemia, then caution should be exercised and the content of potassium in the blood serum should be monitored frequently.
Lithium. The use of enalapril in combination with lithium is not recommended due to the risk of a significant increase in the concentration of lithium in the blood serum with the subsequent development of severe neurotoxicity. If the combined use of these drugs is necessary, then the concentration of lithium in the blood serum should be carefully monitored.
NSAIDs. In combination with ACE inhibitors, they additively increase the content of potassium in the blood serum, which can lead to deterioration of kidney function. In elderly patients and patients with reduced BCC, this combination can cause acute renal failure due to its direct effect on the glomerular filtration rate. Moreover, NSAIDs can weaken the antihypertensive effect of ACE inhibitors.
Hypoglycemic agents for oral administration. Enalapril can increase the hypoglycemic effect of these drugs, so you should carefully monitor the concentration of glucose in the blood.
Baclofen. May enhance the antihypertensive effect. If necessary, combined use should monitor blood pressure and adjust the dose.
Neuroleptics. Use in conjunction with these drugs may cause orthostatic hypotension.
Antidepressants. Use in combination with tricyclic antidepressants may cause orthostatic hypotension.
Allopurinol, cytostatics, immunosuppressants, systemic corticosteroids (used parenterally or orally), procainamide. Concomitant use may cause leukopenia.
Digoxin. Enalapril was used in combination with digoxin without any evidence of a clinically significant adverse interaction.
Combinations to consider
Amifostin. The combination enhances the antihypertensive effect.
Nitrendipine
Cimetidine and ranitidine. Cimetidine, and to a lesser extent ranitidine, may increase the concentration of nitrendipine in blood plasma, but the clinical significance of these data is unknown.
Digoxin. Simultaneous use of nitrendipine and digoxin may lead to an increase in the concentration of digoxin in the blood plasma. Therefore, the appearance of symptoms of digoxin overdose should be monitored or, if necessary, the concentration of digoxin in the blood plasma should be monitored.
Muscle relaxants. The use of nitrendipine may increase the duration and severity of the effects of muscle relaxants, for example, pancuronium bromide.
Grapefruit juice inhibits the oxidative metabolism of nitrendipine. Taking the latter with grapefruit juice increases the concentration of nitrendipine in the blood plasma, which can increase its antihypertensive effect. Nitrendipine is metabolized by the cytochrome P450 isoenzyme CYP3A4 in the intestinal mucosa and in the liver. Inducers of the CYP3A4 isoenzyme, such as anticonvulsants (phenytoin, phenobarbital, carbamazepine) and rifampicin, can significantly reduce the bioavailability of nitrendipine. Inhibitors of the isoenzyme CYP3A4, for example, antifungal imidazoles (itraconazole, etc.) can increase the concentration of nitrendipine in the blood plasma
Beta-blockers. Nitrendipine and beta-blockers act synergistically. This may be of particular importance for patients in whom additional beta-adrenoceptor blockade does not compensate for sympathetic vascular reactions, and caution is recommended for such patients.
