Hypertension, arterial

Benazepril tablets may be taken before, during or after meals, taking foods that do not alter the bioavailability but delaying absorption.

Benazepril is administered as a daily intake.

Hypertension, essential

- In the absence of prior hydrosodic depletion or renal insufficiency (in common practice), the effective dosage is 10 mg per day in a single dose.
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If necessary, a non-hyperkalaemic diuretic may be combined in order to achieve an additional decrease in blood pressure.
In arterial hypertension previously treated with diuretics

Either stop the diuretic 3 days before to reintroduce it, thereafter if necessary

Either administer initial doses of 2.5mg and adjust them according to the response obtained.

It is recommended to dose plasma creatinine and serum potassium prior to treatment and within 15 days of initiation of treatment.
- In subjects over 70 years of age (see Warnings and Precautions for Use), initiate treatment with a lower dose (5mg / day), increased, if necessary, up to 10mg / Day at the end of a month of treatment.

- In hypertension, renovascular, it is recommended to start the treatment at the dosage of 2.5mg / day and to adjust it to the patient's blood pressure response. Serum creatinine and serum potassium will be monitored for the onset of any functional renal insufficiency (see Warnings and Precautions for Use)
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In case of renal insufficiency, the dosage of benazepril is adjusted to the degree of this deficiency

If the creatinine clearance is greater than or equal to 30 ml / min, there is no need to change the dosage.
If the creatinine clearance is less than 30 ml / min, a daily dose of 5 mg per day is recommended.
In these patients, normal medical practice includes periodic control of potassium and creatinine, for example every two months in periods of stability, therapeutic.
The diuretics to be combined in this case are the so-called diuretics of the loop.

This results in

· Decreased secretion of aldosterone

· Elevated renin activity, plasma, aldosterone no longer having negative feedback

A decrease in total peripheral resistance with a preferential action on the muscular and renal territories, without this drop being accompanied by hydrosodic retention or reflex tachycardia in chronic treatment
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The antihypertensive action of benazepril also occurs in subjects with low or normal renin concentrations

Benazepril acts through its active metabolite, benazeprilate, the other metabolites, being inactive.


Benazepril is active in all stages of arterial hypertension: mild, moderate or severe, decreased pressure, systolic and diastolic arterial pressure, decubitus, and orthostatism with no change in cardiac rhythm.

The antihypertensive activity, after a single dose is manifested as of 1 hour, is maximum between 2 and 4 hours and keeps for 24 hours. >
The residual blockade of the 24-hour conversion enzyme is very high, ranging from about 90% to 95%.


Discontinuation of treatment is not accompanied by a rebound in hypertension.

If necessary, the addition of a thiazide diuretic results in additive synergy. The combination of an enzyme-conversion inhibitor and a thiazide also reduces the risk of hypokalemia induced by the diuretic alone.
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The use of the combination of an ACE inhibitor with an angiotensin II receptor antagonist (ARA II) was analyzed in two large randomized controlled trials (ONTARGET ONLY Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes). The ONTARGET study was performed in patients with a history of disease, cardiovascular disease or cerebrovascular disease, or with type 2 diabetes with target organs. The VA NEPHRON-D study was performed in type 2 diabetic patients with diabetic nephropathy

Compared to monotherapy, these studies did not demonstrate any significant beneficial effect on the progression of renal and / or cardiovascular disease and mortality, while there was an increase Of the risk of hyperkalemia, acute renal failure and / or hypotension

These results are also applicable to other IEC and ARA II, taking into account the similarity of their pharmacodynamic properties.

IEC and ARA II should therefore not be combined in patients with diabetic nephropathy.

The ALTITUDE study (Aliskiren Trial, in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was carried out with the aim of evaluating the benefit of the addition of aliskiren to standard treatment with IEC or ARA II In patients with type 2 diabetes and chronic renal insufficiency, with or without cardiovascular disorders. This study was terminated prematurely due to an increased risk of adverse events. Cardiovascular, vascular and cerebral deaths were more frequent in the aliskiren group than in the placebo group, even in adverse events and in some serious adverse events such as hyperkalemia, hypotension And renal insufficiency were reported more frequently in the aliskiren group than in the placebo group.

This drug should never be used in case of

· Hypersensitivity to benazepril.

· Antecedent of angioedema (edema of Quincke) related to the taking of an enzyme inhibitor, conversion

· 2nd and 3rd trimesters of pregnancy (see sections Precautions and Precautions for Pregnancy and Breastfeeding)

· In case of intestinal occlusion, due to the presence of castor oil.

The combination of BRIEM with drugs containing aliskiren is contraindicated in patients with diabetes or renal insufficiency (GFR)

This medicine contains castor oil and can cause digestive problems (laxative effect, mild, diarrhea).


It is established that the combination of ACE inhibitors, angiotensin II receptor antagonists (ARA II) or aliskiren increases the risk of hypotension, Hyperkalaemia and impairment of renal function (including the risk of acute renal failure)

As a result, the double blockade of RAAS by the combination of IEC, ARA II or aliskiren is not recommended (see sections Interactions with other medicinal products and other forms of interactions and properties Pharmacodynamics).

Nevertheless, if such an association is considered absolutely necessary, it can only be done under the supervision of a specialist and with close and frequent control of renal function, ionogram, blood pressure Arterial pressure. ACE inhibitors and ARBs II should not be combined in patients with diabetic nephropathy

Risk of neutropenia / agranulocytosis in the field, immunosuppressed

ACE inhibitors have unusually resulted in agranulocytosis and / or bone marrow depression when administered
· At high doses

· In patients with renal insufficiency associated with systemic diseases (collagenases such as lupus, disseminated erythematosus or scleroderma) with immunosuppressive and / or potentially leucopenic treatment
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The strict observance of the recommended dosages seems to constitute the best prevention of the occurrence of these events. However, if a conversion enzyme inhibitor is to be administered to this type of patient, the benefit / risk ratio will be carefully measured.


An angioedema of the face, extremities, lips, tongue, glottis and / or larynx has been rarely reported, in patients treated with a conversion enzyme inhibitor, including benazepril . In such cases, benazepril should be discontinued immediately and the patient should be monitored until the edema has disappeared.


Angioedema associated with laryngeal edema may be fatal When the tongue, glottis or larynx is affected, which may result in airway obstruction, a subcutaneous adrenaline solution at; 1/1000 (0.3 ml to 0.5 ml) should be administered promptly and other appropriate treatments should be applied.
The prescription of an ACE inhibitor should no longer be considered in these patients (see section Contraindications).

The incidence of angioedema when converting enzyme therapy is higher in black patients than in other patients.
Patients with a history of unrelated angioedema, an angiotensin-converting enzyme (ACE) inhibitor, have an increased risk of angioedema under inhibition of the enzyme.

Hemodialysis

Anaphylactoid reactions (edema of the tongue and lips with dyspnea and decreased blood pressure) have also been observed during hemodialysis using high permeability membranes (polyacrylonitrile) in patients treated with anti - Conversion enzyme. It is recommended to avoid this association

Pregnancy

ACE inhibitors should not be started during pregnancy. Unless ACE treatment is considered essential, it is recommended that patients considering pregnancy modify their antihypertensive treatment for a drug with a well established safety profile during pregnancy. In case of diagnosis of pregnancy, treatment with ACE inhibitors should be discontinued immediately and should an alternative treatment be started (see sections Contraindications and Pregnancy and Breastfeeding)
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Precautions for use

Cough

A dry cough has been reported with the use of enzyme conversion inhibitors.

It is characterized by its persistence as well as by its disappearance when the treatment is stopped.
The iatrogenic etiology should be considered in the presence of this symptom.
In cases where the prescription of an ACE inhibitor is essential, further processing may be considered.

Risk of arterial hypotension and / or renal insufficiency (in case of heart failure, depletion, hydrosodic, etc.)

An important stimulation of the renin-angiotensin-aldosterone system is observed, especially during depletions, large hydrosodic events (deodorized diet, strict or prolonged diuretic treatment), in patients with initially low blood pressure, Renal artery stenosis, congestive heart failure or cirrhosis, edema-ascitic,

The blocking of this system by an inhibitor of the conversion enzyme can then cause a sudden drop in blood pressure and / or rarely and in the first two weeks of treatment, especially during the first dose. More variable delay, elevation of plasma creatinine indicative of acute functional renal failure

In all these cases, the initiation of the treatment must be progressive (see section Dosage and mode of administration).

Subject: aged

Renal function and serum potassium are assessed prior to onset of treatment (see Dosage and Mode of Administration). The starting dose is subsequently adjusted as a function of the blood pressure response, a fortiori in the case of water-depleted depletion, in order to avoid any sudden onset hypotension. >
Renal insufficiency

In patients with renal insufficiency (creatinine clearance less than 30 ml / min), the dosage is reduced (see section 4.2).

In these patients, and in patients with glomerular nephropathy, normal medical practice includes periodic control of potassium and creatinine (see section Dosage and Mode of Administration).

Subject with known atherosclerosis

Since the risk of hypotension exists, especially in patients with ischemic heart disease or cerebral circulatory insufficiency, starting with low-dose therapy.
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Hypertension, renovascular

The treatment of renal arterial hypertension is revascularization.


Treatment should then be instituted with a low dose and monitoring of renal function and serum potassium should be performed, some patients having developed functional renal insufficiency, reversible, discontinuation of treatment.

Anemia

Anemia with decreased hemoglobin has been demonstrated, and in renal transplant patients or hemodialysis patients, the decrease is even more pronounced when the baseline values ​​are high. This effect does not appear to be dose-dependent but would be related to the mechanism of action of the enzyme inhibitors of
This decrease is moderate, occurs within 1 to 6 months and then remains stable. It is reversible upon cessation of treatment. This can be prosecuted in this type of patient, by performing a regular hematological control.

Other populations at risk

In patients with severe cardiac insufficiency (Stage IV) or in patients with insulin-dependent diabetes (tendency, spontaneous hyperkalaemia), treatment will be initiated under medical supervision with a reduced initial dose. Code>
In a hypertensive patient with coronary artery disease, do not discontinue treatment with: beta-blocker: IEC will be added to the beta-blocker. >
Surgical intervention

In the case of anesthesia, and more, when anesthesia is performed with hypotensive agents, inhibitors of the enzyme of conversion are at the origin of hypotension. It is possible, therefore, is recommended the day before the intervention for long-acting conversion enzyme inhibitors, such as benazepril.
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Data from clinical trials have shown that double-blockade of the renin-angiotensin-aldosterone (RAAS) system by the concomitant use of angiotensin II receptor antagonists Or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and impairment of renal function (including acute renal failure) in comparison to The use of a single medicinal product acting on the RAAS (see sections 4.3, 4.4)
Some drugs or classes of therapeutics are likely to promote the occurrence of hyperkalaemia: potassium salts, potassium-sparing diuretics, inhibitors, angiotensin II inhibitors, anti-angiotensin II Non-steroidal inflammatory drugs, heparins (low molecular weight or non-fractionated), ciclosporin and tacrolimus, trimethoprim.

In all cases: monitor renal function (creatinine) in the first few weeks of treatment with IEC.

NSAIDs, including inhibitors, selective COX-2 and acetylsalicylic acid (aspirin and salicylates ≥ 3 g / d)
Acute renal failure in the patient at risk (elderly and / or dehydrated) by decreased filtration, glomerular, by inhibition of prostaglandins, vasodilators, due to NSAIDs. Furthermore, reduction of the antihypertensive effect.

Hydrate the patient, monitor the function, renal at the beginning of treatment.
+; Baclofen

Increased effect, antihypertensive.

Monitoring blood pressure and dosage adjustment of antihypertensive drugs if necessary

Associations to be taken into account

+ Alphabloquants for urological purposes: alfuzosin, doxazosin, prazosin tamsulosin, terazosin

Increase in hypotensive effect. Risk of increased orthostatic hypotension.

+ Amifostine

Increase in antihypertensive effect.

+ Antidepressants imipraminic, neuroleptic

Antihypertensive effect and risk of increased orthostatic hypotension (additive effect)

Corticosteroids, tetracosactide (pathway, general) (except hydrocortisone used as a replacement therapy in Addison's disease).
Decreased antihypertensive effect (hydrosodic retention of corticosteroids).

Not applicable.

Pregnancy

Linked to: BENAZEPRIL

Use of ACE inhibitors is not recommended during the first trimester of pregnancy (see Warnings and Precautions for Use). The use of ACE inhibitors is contraindicated in the 2 nd and 3 rd trimesters of pregnancy (see sections Contraindications and Warnings and Precautions for Use)

The available epidemiological data concerning the risk of malformation after exposure to IEC in the first trimester of pregnancy are not conclusive. However, a small increase in the risk of congenital malformations can not be ruled out. A, unless treatment with ACE inhibitors is considered essential, it is recommended that patients considering pregnancy modify their antihypertensive treatment for a drug with a well-established safety profile during pregnancy. In case of pregnancy diagnosis, treatment with IEC should be discontinued immediately and, if necessary, an alternative treatment will be started.

Exposure to ACE inhibitors during the 2 nd and 3 rd trimesters of pregnancy is known to cause fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of skull bones) and toxicity to Newborn (insufficiency, renal, hypotension, hyperkalaemia) (see section Safety data, preclinical). In case of exposure to an ACE from the 2nd trimester of pregnancy, it is recommended to perform a fetal ultrasound in order to verify the renal function and the bones of the vault of the skull. IEC-treated mothers should be monitored for blood pressure (see sections 4.3 and 4.4).

Breastfeeding

Related to benazepril

Limited pharmacokinetic data have shown low concentrations in breast milk (see section 5.2 Pharmacokinetic Properties). Although these concentrations do not appear to be clinically relevant, the use of BRIEM 5 mg film-coated tablets is not recommended during breast-feeding, premature infants and during the first weeks after delivery , Because of the possible risk of cardiovascular and renal adverse reactions and because the clinical experience is limited.

In the case of an older infant, the use of BRIEM 5 mg film-coated tablet capable of breastfeeding can be considered if this treatment is necessary for the mother and the follow-up of The occurrence of the least adverse effect in the child is performed.

At the clinical level

Have been found

· Headache, asthenia, vasomotor reactions, sensations, dizziness, palpitations

· Hypotension, orthostatic or non (see Warnings and Precautions)
· Rashes, pemphigus, Stevens Johnson syndrome

· Digestive disorders especially because of the presence of castor oil (nausea, vomiting, abdominal pain), dysgeusia

· Isolated cases of liver disease

· A dry cough has been reported with the use of ACE inhibitors. It is characterized by its persistence as well as by its disappearance at the end of the treatment The iatrogenic etiology should be considered in the presence of this symptom.
· Exceptionally, angioedema (angioedema) (see Warnings and Precautions for Use Special warnings and precautions for use

Biologically speaking

· Moderate increase in urea and creatinine, plasma, reversible at cessation of treatment. This increase is more frequently encountered in cases of arterial stenosis, renal arterial hypertension, diuretics, renal insufficiency

· In the case of glomerular nephropathy, administration of an enzyme inhibitor, conversion may cause proteinuria.

· Hyperkalemia, usually transient.

· Anemia (see Warnings and Precautions for Use) has been reported with enzyme inhibitors, conversion, on special sites (transplanted, renal, hemodialysis). Hemolytic anemia has been observed.