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Nitrendipine, Enalapril

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Clinical Pharmacology

Enanopm is a combination of two hypotensive drugs that supplement the other mechanisms to reduce the physical pressure (BP): enalapril: angiotensin-converting enzyme (APF) and Nitrendipine - a blocker of "slow" calcium channels (BMK)

Enalapril

Enalapril is a prodrug, as a result of its hydrolysis an active metabolite is formed - enaprilat, which inhibits ACE. Its mechanism of action is associated with a decrease in the formation of angiotensin I from angiotensin II, a decrease in the content of which leads to a clear decrease in the release of aldosterone. At the same time, general peripheral vascular resistance (OPS), systolic and diastolic blood pressure, afterload and preload on the myocardium decrease.

Enalapril dilates the arteries to a greater degree than the veins, while there is no reflex increase in heart rate (HR).

The angiohypertensive effect is more pronounced with high plasma renin activity than with its normal or reduced activity. Reducing blood pressure in therapeutic limits does not affect the cerebral circulation: the blood flow in the vessels of the brain is maintained at a sufficient level and against the background of low blood pressure. Strengthens coronary and renal blood flow.

With prolonged use, left ventricular myocardial hypertrophy and myocytes of resistive-type artery walls are reduced, progression of heart failure is prevented and the development of left ventricular dilatation is slowed down. Enalapril improves blood supply to the ischemic myocardium.

The time of onset of the antihypertensive effect when taken orally - 1 hour, reaches a maximum after 4-6 hours and lasts for a day.

Nitrendipine

Nitrendipine BCCA from the group of dihydropyridine derivatives has an angi-hypertensive effect. Reduces the current of calcium ions in the smooth muscle cells of the coronary and peripheral arteries. Causes some increase in excretion of sodium and water. Reduces afterload and myocardial oxygen demand, does not inhibit the conductivity of the heart muscle.

Reduces the number of functioning channels without affecting the time of their activation, inactivation and recovery. Separates the processes of excitation and contraction in the myocardium, mediated by tropomyosin and troponin, and in vascular smooth muscle, mediated by calmodulin. In therapeutic doses, it normalizes the transmembrane current of calcium ions, disturbed in a number of pathological conditions, especially 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 monorapia with enalapril at a dose of 10 mg or Nitrendipine at a dose of 20 mg showed that Enanorm has a more pronounced effect in reducing both diastolic and systolic BP and the severity of the therapeutic response to therapy.

Pharmacokinetics

Enalapril

After ingestion 60% is absorbed from the gastrointestinal tract. Eating does not affect the absorption of enalapril.

Communication enalapril with plasma proteins is 50 - 60%. Enalapril is rapidly metabolized in peppe to form the active metabolite, enalaprilat. Enalapril bio-stole - 40%.

The maximum concentration of enalapril in the blood plasma is reached after 1 hour, enalaprilat is 3-4 hours. Enalaprilat easily passes through the blood-blood barriers, excluding the blood-brain, a small amount passes through the placenta and into the thoracic modoco.

The half-life (T1/2) enalaprilat about 1 h. Enalapril is derived mainly by the kidneys - 60% (20% - as enalapril and 40% - as enalaprilat), through the intestine - 33% (6% - as enapril and 27% - as enalaprilat).

It is removed during hemodialysis (speed 62 ml / min) and peritoneal dialysis.

Nitrendipine

Rapidly absorbed from the gastrointestinal tract by 88%.Bioavailability is 20-30% due to the pronounced effect of the "primary passage" through the liver, Communication with plasma proteins (albumin) - 96-99%. Hemodialysis is ineffective. The time to reach the maximum plasma concentration of 1-3 h after application.

The volume of distribution in the equilibrium state is 5–9 l / kg, therefore hemodialysis and plasmapheresis are ineffective.

Metabolized in the liver mainly by oxidation. Metabolites are pharmacologically inactive. Nitrendipine is excreted mainly through the kidneys: approximately 77% of the taken dose is excreted as metabolites, less than 0.1, and the% of the taken dose is excreted unchanged. The rest of the Nitrendipine is excreted through the intestines.

T1/2 Nitrendipine after oral administration is 8-12 hours. Neither Nitrendipine nor its metabolites in the body accumulate. In elderly patients increases T1/2in cirrhosis of the liver - the area under the curve "concentration - time" (AUC) and the maximum concentration 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 changes in the pharmacokinetics of Nitrendipine. As for enalaprilat, its biodegradability somewhat increases with simultaneous use with Nitrendipine, but this, apparently, has no clinical significance. The bioavailability of Nitrendipine when using the combined drug is higher than when using two drugs separately.

Indications

Essential hypertension (for patients who are recommended combination therapy).

Composition

1 tablet contains:
active ingredients: Nitrendipine - 20 mg, enalapril maleate - 10 mg;
Excipients: sodium bicarbonate - 5.00 mg, microcrystalline cellulose - 20.00 mg, corn starch - 20.00 mg, sodium lauryl sulfate - 8.00 mg, povidone K25 - 6.00 mg, magnesium stearate - 1.20 mg, lactose monohydrate - 63.58 mg.

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Nitrendipine, Enalapril

Dosage and Administration

Enanorm is administered by mouth no more than 1 tablet per day. pills should be swallowed whole, do not break or chew, drinking plenty of water.

It is recommended to select the doses of the components by adjusting the dose individually.

Patients with impaired liver function

The drug Enanorm is contraindicated in patients with severely impaired liver function. In patients with mild and moderate liver dysfunction, monotherapy with either enalapril or Nitrendipine is not contraindicated, but due to the fact that there is no experience with using Enanorm in these patients, the drug should be administered with caution.

Patients with impaired renal function

Enanorm is contraindicated in patients with severe renal impairment (CC less than 10 ml / min) and patients on hemodialysis. In patients with moderate renal insufficiency (CC more than 30 ml / min, serum creatinine less than 3 mg / ml) there is no need for dose adjustment at the same time during the treatment period, renal function should be evaluated.

Kids and teens

The drug Enanorm should not be used in children and adolescents under the age of 18 years due to the lack of data on the application.

Adverse reactions

Classification of undesirable adverse reactions (NPR) development:

  • very often (1/10);
  • often (1/100, 1/10);
  • infrequently (1l1000, 1/100);
  • rarely (1/10000, 1/1000);
  • very rarely (1/10000, including individual messages);
  • frequency unknown (cannot be estimated based on available data).

Adverse reactions observed with the use of the drug Enanorm, are similar to reactions to the reception of each of the components of the drug separately.

Since the cardiovascular system: often - flushing of the skin of the face, peripheral edema; infrequently - tachycardia, dizziness, pronounced decrease in blood pressure; very rarely - a violation of the peripheral circulation, shortness of breath.

From the nervous system: often - headache; very rarely - asthenia, hypothermia, drowsiness, paresthesia, tremor, convulsions.

On the part of the respiratory system: often cough; very rarely - pharyngitis, tracheitis, dyspnea.

From the digestive system: infrequently - nausea, dyspepsia; very rarely - flatulence.

Skin and Subcutaneous Tissues: infrequently - erythematous rash.

From the kidneys and urinary tract: very rarely - hematuria.

From the musculoskeletal and connective tissue: very rarely - muscle spasm.

Laboratory and instrumental data: very rarely, increased activity of liver transaminases, hypokalemia.

The following adverse reactions were observed when taking drugs containing similar ingredients:

Enalapril

Since the cardiovascular system: infrequently - especially at the beginning of treatment and in patients with lowered BCC and / or salts, worsening Raynaud's disease, heart failure, severe arterial hypertension or renal hypertension, and also after increasing the dose of enalapril and / or using diuretics u / or in a position "standing" noted: gloving, weakness, visual disturbances; rarely - fainting; very rarely, tachycardia, rapid heartbeat, atrial bradycardia, atrial fibrillation, chest pain, angina pectoris, myocardial infarction, transient cerebral circulation disturbance occurred due to the enhancement of the antihypertensive effect. Cardiac arrest, embolism and pulmonary infarction, pulmonary edema.

From the kidneys and urinary tract: infrequently - the appearance or strengthening of renal dysfunction; very rarely, acute renal failure; rarely - oliguria, proteinuria in some cases with a concomitant deterioration in renal function, pain in the iliac region.

On the part of the respiratory system: infrequently - dry cough, sore throat, hoarseness, bronchitis; rarely - shortness of breath, sinusitis, rhinitis; very rarely - bronchospasm, bronchial asthma attack, pulmonary infiltrates, stomatitis, glossitis, dry mouth, pneumonia, angioedema, affecting the pharynx, larynx and / or tongue, and in some cases fatal; more often in patients with non-iroid race.

From the side of the digestive system: infrequently - nausea, pain in the upper abdomen, indigestion; rarely - vomiting, diarrhea, constipation, loss of appetite, change or transient loss of taste, anosmia; very rarely - pancreatitis, intestinal obstruction, stomatitis, glossitis.

Liver and biliary tract: very rarely, liver dysfunction, hepatitis, hepatic insufficiency, syndrome starting with cholestatic jaundice and progression to necrosis of the liver, in some cases fatal.

On the part of the endocrine system: very rare gynecomastia.

From the skin and subcutaneous tissues: infrequently - rash; 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, "tides" 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 titers of antinuclear antibodies. If you suspect a severe skin reaction, treatment is stopped.

From the side, the nervous system: infrequently - headache, weakness; rarely - dizziness, depression, sleep disturbances, impotence, peripheral neuropathy with paresthesia, imbalance, muscle spasms, nervousness, confusion.

From the organ of hearing: rarely tinnitus.

On the part of the organ of vision: rarely - blurred vision, dry eyes, increased tearing.

Laboratory and instrumental data: infrequently - a decrease in hemoglobin, hematocrit, leukocytes or platelets; rarely - anemia, thrombocythemia, neutropenia, eosinophilia (in some cases - agranulocytosis or pancytopenia), especially in patients with impaired renal function, with systemic diseases of the connective tissue, patients receiving allopurinol, procainamide or immunosuppressants; elevated serum urea, creatinine and potassium concentrations, decreased serum sodium and serum levels, hyperkalemia (in patients with diabetes mellitus), excretion of albumin excretion by the kidneys, especially in patients with impaired renal function, severe heart failure), renovascular hypertension; very rarely, hemolysis / hemolytic anemia (also in combination with a deficiency of glucose-6-phosphate dehydrogenase), an increase in the concentration of bilirubin, and an increase in asthenicity of biliary transaminases.

Nitrendipine

On the part of the immune system: Infrequently - flu-like syndrome.

Since the cardiovascular system: infrequently - arrhythmia, tachycardia, palpitations, peripheral edema, "flush" of blood to the skin of the face, increased symptoms of vasodilation; rarely - marked reduction in blood pressure, angina pectoris, chest pain.

From the gastrointestinal tract: infrequently - nausea, diarrhea; rarely - abdominal pain, constipation, dyspepsia, pvota; very rarely - gingival hyperplasia.

On the part of the endocrine system: very rarely - gynecomastia.

From the side of blood and lymphatic system: very rarely - leukopenia, agranulocytosis.

From the muscular and connective tissue: rarely - myalgia.

From the nervous system: infrequently - headache, asthenia; rarely - nervousness, paresthesia, tremor, dizziness.

On the part of the respiratory system: rarely - shortness of breath.

Skin and Subcutaneous Tissues: rarely - pruritus, rash, urticaria.

On the part of the organ of vision: rarely - visual impairment.

From the kidneys and urinary tract: very rarely - an increase in the frequency of urination, polyuria.

Laboratory and instrumental data: very rarely - increased activity of liver enzymes.

If any of the side effects indicated in the instruction are aggravated, or any other side effects not mentioned in the instruction have been noticed, it is necessary to inform the doctor about it.

Contraindications

Carefully: aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary artery disease, coronary insufficiency, severe autoimmune systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma), bone marrow hematopoietic oppression, diabetes mellitus, hyperkalemia, diabetes mellitus, hyperkalemia, after kidney transplantation, kidney failure, mild or moderate liver dysfunction, conditions accompanied by a decrease in BCC (including diarrhea, vomiting), a diet with limitation of salt, th age.

Drug interactions

The antihypertensive effect of Enanorm may be enhanced by simultaneous use with other hypotensive drugs, such as diuretics, beta-blockers, or alpha blockers. In addition, when used simultaneously, the individual components of the repair can exhibit the following interactions:

Enalapril

Combinations that should be used with caution:

Calicide diuretics and potassium preparations

Angiotensin-converting enzyme inhibitors (ACE inhibitors) reduce diuretic and potassium loss. Potassium-sparing diuretics, potassium preparations and other drugs that can increase the content of potassium in the blood serum (for example, heparin), can have an additive effect on the content of potassium in the blood serum, especially in patients with impaired renal function. If the combined use of such drugs is necessary, for example, to eliminate hypokalemia, then one should exercise caution and often control the potassium content in the blood serum.

Lithium

Use in combination with lithium is not recommended because of the risk of a significant increase in the concentration of lithium in the blood serum with the subsequent development of severe non-toxic toxicity. If the combined use of these drugs is necessary, you should carefully monitor the concentration of lithium in the serum.

Nonsteroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) and ACE inhibitors additively increase serum levels of cusoma, which can lead to a deterioration in renal function. In older patients and patients with reduced BCC, this combination may cause acute renal failure due to the direct effect on the glomerular filtration rate. Moreover, NIPA may weaken the antihypertensive effect of ACE inhibitors.

Oral hypoglycemic agents

Enalapril can enhance the hypoglycemic effect of these drugs, so you should carefully monitor the concentration of glucose in the blood.

Baclofen

May enhance antihyperterms effect. If necessary, the combined use of blood pressure should be monitored and to fix the dose.

Neuroleptics

Co-administration with these drugs may cause orthostatic hypotension.

Antidepressants

Use in conjunction with tricyclic antidepressants can cause orthostatic hypotension.

Allopurinol, cytostatics, immunosuppressants, systemic corticosteroids (used parenterally or orally), procainomide

Simultaneous use may cause leukopenia.

Combinations to be considered:

Amifostine

The combination enhances the antihypertensive effect.

Nitrendipine

Cimetidine and ranitidine

Cimetidine and, to a lesser extent, ranitidine, can increase the concentration of Nitrendipine in the blood plasma, but the clinical significance of these data is unknown.

Digoxin

Enalapril is used in conjunction with digoxin without any signs of a clinically significant adverse interaction.The simultaneous use of Nitrendipine and digoxin can lead to an increase in the concentration of digoxin in the blood plasma. Therefore, you should control the onset of symptoms of digoxin overdose or, if necessary, control the concentration of digoxin in the blood plasma.

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 may enhance its anti-hyperteptic effect.

Nitrendipine is metabolized by cytochrome P450 CYP3A4 isoenzyme in the intestinal mucosa and in the liver. Inductors of the isoenzyme CYPZA4, for example, anticonvulsants (phenytoin, phenobarbital, carbamazepine) and rifampicin, can significantly reduce the bioavailability of Nitrendipine. Inhibitors of the CYPZA4 isoenzyme, 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 the additional blockade of beta-adrenergic receptors does not allow to compensate for sympathetic vascular reactions, and caution is recommended for such patients.

Pregnancy and Lactation

Pregnancy

The use of ACE inhibitors in the first trimester of pregnancy is not recommended. Epidemiological data on the risk of teratogenicity of the action of ACE inhibitors in the first trimester of pregnancy are not conclusive; however, an increase in this risk cannot be ruled out. If the continuation of the use of ACE inhibitors during pregnancy is not considered absolutely necessary, then when planning pregnancy, patients should be transferred to alternative therapy, the safety of which is established during pregnancy. It is known that the use of ACE inhibitors in the second and third trimesters of pregnancy has a toxic effect on the fetus (impaired renal function, lack of water, delayed ossification of the skull) and newborns (impaired renal function, arterial hypotension, hyperkalemia). If ACE inhibitors were used in the second and third trimesters of pregnancy, it is recommended to carry out ultrasound examination to assess kidney function and the state of the bones of the skull. It should also be carefully monitored for newborns in order to detect arterial hypotension, if the mother took ACE inhibitors.

Breastfeeding period

The few pharmacokinetic data on a very low concentration of enalapril in breast milk. Although these concentrations are not clinically significant, it is not recommended to use the drug when breastfeeding premature babies, as well as in the first few weeks after birth because of the theoretical possibility of a risk of action on the cardiovascular system and kidneys of the newborn and because of the lack of sufficient clinical data. In older infants, it is possible to consider the possibility of taking the drug by nursing women, if such treatment is necessary for the mother, and if the child is monitored to detect any adverse events.

Special instructions

Use strictly prescribed by a doctor.

Quincke’s edema

When using ACE inhibitors, especially in the first weeks, as well as in rare cases after prolonged use, angioedema of the extremities, face, lips, mucous membranes, tongue, larynx or pharynx may develop. In such cases, the medical treatment is immediately canceled.

With angioedema of the tongue, larynx or golotki, death is possible, in these cases, emergency therapy should be carried out with the patient hospitalized, the patient should be monitored for at least 12-24 hours, and can be discharged from the hospital only after the complete disappearance of symptoms.

Neutropenia / Agranulocytosis

Enalapril should be used with extreme caution in patients with systemic diseases of the connective tissue, in patients receiving immunosuppressants, allopurinol or procainamide, or a combination of them, especially in the presence of impaired renal function.When using the drug Enanorm in these patients, it is recommended to control the leukocyte formula. During the treatment period, patients should be instructed to report any signs of infection to the doctor. Enanorm should be discontinued if neutropenia is detected or suspected (neutrophil count is less than 1000 / mmH).

Renal dysfunction

In patients with impaired renal function with the use of ACE inhibitors, control of renal function is necessary, especially in the first weeks of treatment. Caution should be exercised in patients with an activated renin-angiotensin system.

For patients with moderate renal dysfunction (creatinine clearance more than 30 ml / min, serum creatinine З 3 mg / ml) dose adjustment is not required, but monitoring of renal function is necessary.

In some patients, a pronounced decrease in blood pressure at the beginning of treatment with ACE inhibitors may lead to a slight further deterioration in renal function. In such circumstances, there have been cases of acute renal failure, which was usually reversible.

Experience with the use of the drug Enanorm in patients who have recently undergone kidney transplantation, no.

Proteinuria

In patients with impaired renal function, proteinuria has rarely developed. In patients with clinically significant proteinuria (more than 1 g / day), Enanorm can be used only after a thorough assessment of the risk-benefit ratio and with regular monitoring of clinical and biochemical blood parameters.

Patients with abnormal liver function

Experience with the use of the drug Enanorm in patients with mild or moderately impaired liver function is not, therefore, this drug should be used in such patients with caution, if there are indications for this.

Since individual cases of the syndrome starting with cholestatic jaundice and liver progressing to necrosis with a fatal outcome have been described, it is necessary to discontinue treatment and observe patients if jaundice appears or there is a pronounced activity of "liver" transaminases.

Orthostatic hypotension

In some cases, the drug Enanorm may cause orthostatic hypotension, the risk of which increases in patients with the activated renin-angiotensin-aldosterone system. For example, with reduced blood volume or impaired water and electrolyte balance of blood or salt deficiency due to the use of diuretics, use of low salt diet, hemodialysis, the presence of diarrhea or vomiting, as well as weakening of left ventricular function and renovascular hypertension. In these patients, you first need to adjust the blood volume or salt concentration. Patients with heart failure (with or without associated renal impairment) may develop symptomatic hypotension. The risk of hypotension in these patients is increased with severe heart failure, with high doses of loop diuretics and in the presence of hyponatremia or impaired renal function.

A transient hypotensive reaction is not a contraindication for the continued use of the drug Enanorm, and usually presents no difficulty after restoring the circulating blood volume and blood pressure.

Aortic stenosis

In patients with aortic valve stenosis, ACE inhibitors should be used with caution. In hemodynamically significant stenosis, enalapril is contraindicated.

Primary hyperaldosteronism

The use of enalapril in patients with primary aldosteronism is not recommended.

Hemodialysis patients

The use of Enanorm preparation during dialysis through high-strength membranes (from polyacrylonitrile, sodium methylallyl sulfonate, for example, AN69) can lead to anaphylactic reactions, including swelling of the face, "flushed to the skin of the face, severe orthostatic hypotension and shortness of breath for several minutes after the start of dialysis, Therefore, such combinations should be avoided.

Anaphylactoid reactions in the process of LDL apheresis and desensitization to Hymenoptera venom

The use of ACE during apheresis of low density lipoproteins (LDL) with dextran sulfate can be accompanied by life-threatening anaphylactoid reactions.The use of ACE inhibitors in the conduct of specific immunotherapy (desensitization) to the poisons of insects (bees, ocy) may be accompanied by anaphylactoid reactions, which in some cases may be life-threatening. If necessary, apheresis of LDL or specific immunotherapy (desensitization) to insect venom AGIF should be temporarily replaced by other means of treating high blood pressure or heart failure.

Surgery / Anesthesia

When performing major surgeries or anesthesia with the use of drugs that cause orthostatism, enalapril leads to blocking the synthesis of angiotensin II, due to compensatory renin release. In such cases, if orthostatic hypotension develops (and it is assumed that the development of orthostatic hypotension occurs by this mechanism), then it should be corrected by increasing the volume of blood plasma.

Impact on fertility

In some cases of in vitro fertilization, blockers of “slow” calcium channels, similar to Nitrendipine, caused reversible biochemical changes in the sperm heads, which could lead to dysfunction of sperm. When repeated unsuccessful attempts at artificial insemination should be taken into account, among other factors, the male intake of blockers of "slow" calcium channels such as Nitrendipine.

Racial differences

Like other inhibitors of the angiotensin-converting enzyme, enalapril, as a component of the fixed dose combination, is probably less effective in lowering blood pressure in precursors of the negroid race than in patients of other races. Perhaps this is due to the higher prevalence of low renin activity in the Negroid race with arterial hypertension.

Impact on the ability to drive vehicles and other mechanisms that require high concentration of attention

When using the drug Enanorm, care must be taken when driving vehicles and complex mechanisms.

Overdosage

To date, an overdose of this combination is not registered.

Symptoms: The most likely manifestation of an overdose of Enanorm will be a pronounced decrease in blood pressure.

Treatment: there is no specific antidote. Gastric lavage, the introduction of adsorbents (if possible, in the first 30 minutes. Vital functions should be monitored.

In the case of a pronounced decrease in the patient's blood pressure, the patient is transferred to a horizontal position with a low head. In mild cases, gastric lavage and ingestion of a salt solution of sodium chloride are shown, in more severe cases, measures aimed at stabilizing blood pressure; intravenous administration of 0.9% sodium chloride solution; plasma solutions; if necessary, the introduction of angiotensin II, hemodialysis (the rate of introduction of enalaprilat - 62 ml / min).

  • Brand name: Enanorm
  • Active ingredient: Nitrendipine, Enalapril
  • Dosage form: Pills.
  • Manufacturer: Ferrer Internacional S.A.
  • Country of Origin: Italy

Studies and clinical trials of Nitrendipine, Enalapril (Click to expand)

  1. Cost-Utility Analysis of Eprosartan Compared to Enalapril in Primary Prevention and Nitrendipine in Secondary Prevention in Europe—The HEALTH Model
  2. Comparison of the antihypertensive effects of the fixed dose combination enalapril 10 mg/nitrendipine 20 mg vs losartan 50 mg/hydrochlorothiazide 12.5 mg, assessed by 24-h ambulatory blood pressure monitoring, in essential hypertensive patients
  3. Optimisation and validation of liquid chromatographic and partial least-squares-1 methods for simultaneous determination of enalapril maleate and nitrendipine in pharmaceutical preparations
  4. Efficacy of four antihypertensive drugs (clonidine, enalapril, nitrendipine, oxprenolol) on stress blood pressure
  5. Comparison of the antihypertensive efficiency of nitrendipine, metoprolol, mepindolol and enalapril using ambulatory 24-hour blood pressure monitoring
  6. Effectiveness and tolerability of enalapril plus nitrendipine on a fixed dose in hypertensive patients over 65 years
  7. Long-term effectiveness and tolerability of a fixed dose combination enalapril plus nitrendipine in different hypertensive populations
  8. Effectiveness and tolerability in hypertensive patients treated with a fixed dose of enalapril plus nitrendipine followed up to one year
  9. Differential effects of enalapril and nitrendipine on the fibrinolytic system in essential hypertension
  10. Efficacy of a fixed dose combination of enalapril/nitrendipine in patients not controlled with enalapril or nitrendipine monotherapy. results of pooled analysis of two studies: ENEAS-1 and ENEAS-2
  11. ABPM study: efficacy of two fixed dose combinations, enalapril/nitrendipine vs. losartan/hidrochlorotiazide, in not controlled mild-moderate hypertensive patients
  12. Comparison of effects of enalapril and nitrendipine on cardiac sympathetic nervous system in essential hypertension
  13. Fixed-Dose Combination Enalapril/Nitrendipine
  14. Effectiveness and Tolerability of Fixed-Dose Combination Enalapril plus Nitrendipine in Hypertensive Patients
  15. Nitrendipine plus enalapril: additive antihypertensive effects
  16. Enalapril/nitrendipine is effective in reducing systolic and diastolic BP,
  17. A Sensitive and Selective RP-LC Method for the Simultaneous Determination of the Antihypertensive Drugs, Enalapril, Lercanidipine, Nitrendipine and Their Validation
  18. Comparison of the effects of nitrendipine and enalapril on development and progression of diabetic glomerulopathy in streptozotocin-diabetic rats
  19. Long-Term Treatment With Either Enalapril or Nitrendipine Stabilizes Albuminuria and Increases Glomerular Filtration Rate in Non- Insulin-Dependent Diabetic Patients
  20. Enalapril/Nitrendipine
  21. Beneficial renal effects of enalapril and nitrendipine in NIDDM
  22. Effects of Enalapril and Nitrendipine on the Excretion of Epidermal Growth Factor and Albumin in Hypertensive NIDDM Patients
  23. Opposite effects of enalapril and nitrendipine on natriuretic response to atrial natriuretic factor. Renal function evaluated with clearance studies in humans
  24. Combination treatment of enalapril with nitrendipine in rats with renovascular hypertension

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