LINKS TO QUINAPRIL

This medicinal product should NEVER be used in cases of

· Hypersensitivity to quinapril or any of the excipients mentioned under Composition

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

(See Precautions and Precautions for Use and Pregnancy and Breastfeeding).

This medication is GENERALLY NOT RECOMMENDED in case

· Associations with hypercalcemic diuretics, potassium salts, estramustine and lithium (see section Interactions with other medicinal products and other forms of interaction)

· Bilateral stenosis of the renal artery or functionally unique kidney

· Hyperkalemia

· 1st trimester of pregnancy

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This medicinal product should NEVER be used in cases of

· Hypersensitivity to sulfonamides

· Severe renal insufficiency (creatinine clearance less than 30 ml / min)

· Hepatic encephalopathy

This drug is GENERALLY NOT RECOMMENDED for use in combination with lithium (and non-arrhythmic drugs, giving torsades de pointes) (see section Interactions with other medicinal products and other forms of interactions) Code>
Warnings, special

This medicine contains lactose. Its use is not recommended in patients with galactose intolerance, lactase deficiency or a glucose or galactose malabsorption syndrome (rare hereditary diseases).
>

LINKS TO QUINAPRIL

Risk of neutropenia / agranulocytosis in the field: Immunodepressed: Conversion enzyme inhibitors have unusually resulted in agranulocytosis and / or medullary depression, when administered at high doses, in patients with renal impairment, Systemic diseases (collagenases, such as systemic lupus erythematosus, or scleroderma), with immunosuppressive and / or potentially leucopenic treatment.
However, if an ACE inhibitor should be administered to this type of patient, the benefit / risk ratio should be carefully monitored Measured.

Angioedema (edema of Quincke): angioedema of the face, extremities, lips, tongue, glottis and / or larynx has been rarely reported, in patients treated with an inhibitor Of the enzyme conversion, quinapril included. In such cases, ACUILIX should be stopped immediately and the patient monitored until the edema has disappeared.When the edema is of interest only to the face and lips, the course is generally regressive without Treatment, although antihistamines have been used to relieve symptoms.

Angioedema associated with laryngeal edema may be fatal When the tongue, glottis or larynx is affected, which can lead to airway obstruction, a subcutaneous adrenaline , 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).



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 inhibitors of The conversion enzyme. It is recommended to avoid this association

Pregnancy: ACE inhibitors should not be started during pregnancy. Unless IEC treatment is considered essential, it is recommended that patients considering pregnancy modify their antihypertensive therapy for a drug with a well established safety profile during pregnancy. In case of diagnosis of pregnancy, treatment with IEC should be stopped immediately and if necessary an alternative treatment will be started (see sections Contraindications and Pregnancy and lactation). >

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In liver disease, thiazide and related diuretics may induce hepatic encephalopathy. In this case, the administration of the diuretic should be immediately interrupted.

Reactions of photosensitivity have been reported in the use of thiazide diuretics (see section 4.4).


Precautions for use

RELATED TO THE QUINAPRIL

Cough: 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.iatrogenic etiology should be considered in the presence of this symptom. In cases where the prescription of an inhibitor of the conversion enzyme is essential, further processing may be considered.

Child: The efficacy and safety of quinapril in children have not been established.

Risk of arterial hypotension and / or renal insufficiency (in case of cardiac insufficiency, hydrosodic depletion, etc.): an important stimulation of the system, renin-angiotensin-aldosterone is observed, especially during (Deodorized, strict diuretic or prolonged diuretic treatment) in patients with initially low blood pressure, renal artery stenosis, congestive heart failure or cirrhosis, edema-ascitic. Br>

The blockage of this system by an ACE inhibitor may then cause, especially during the first dose and during the first two weeks of treatment, a sudden fall in blood pressure and / or, rarely and in a More variable, elevated creatinine, plasma showing functional renal failure, sometimes acute

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

Elderly: renal function and serum potassium are appreciated prior to initiation of therapy (see Dosage and Mode of Administration). The starting dose is subsequently adjusted according to the function of the blood pressure response, a fortiori in cases of hydrosodic depletion, in order to avoid any sudden onset hypotension. >

Renal insufficiency: in cases of renal insufficiency (creatinine clearance, less than 80 ml / min), the treatment is initiated by a low initial dose and then adjusted according to the therapeutic response . 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).

Hepatic Pathology: In patients with alcoholic cirrhosis, concentrations of quinaprilate, the active metabolite of quinapril, are reduced. The metabolism of quinapril in quinaprilate is normally dependent on hepatic esterase and in alcoholic cirrhotic patients the de-esterification of quinapril is weaker.
Renovascular hypertension, treatment of high blood pressure, renovascular is revascularization. However, ACE inhibitors may be useful for patients with hypertension, renovascular awaiting corrective intervention, or when this is not possible. The treatment should be instituted with a low dose and monitoring of renal function and serum potassium should be performed, some patients having developed renal insufficiency, functional, reversible upon discontinuation of treatment. >

Other populations at risk

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

Anemia: anemia with decreased hemoglobin has been demonstrated in transplanted patients, renal or hemodialysis, decline all the more important as initial values ​​are high, this effect does not appear -dependent but would be linked to the mechanism of action of the enzyme-converting inhibitors.

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.

Surgical intervention: in cases of anesthesia, and more so when anesthesia is performed with agents with hypotensive potential, inhibitors of the conversion enzyme are at the origin of hypotension. Therapeutic interruption, if feasible, is therefore recommended on the day before surgery for long-acting converting enzyme inhibitors, such as quinapril.

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Balance, hydro-electrolytic

It should be checked before start-up, treatment, and at regular intervals thereafter. Any diuretic treatment may indeed cause hyponatremia, sometimes with serious consequences. Since the decline in serum sodium can initially be asymptomatic, regular monitoring is essential and should be even more frequent in populations at risk represented by elderly subjects, a fortiori malnourished, and cirrhotic patients (see sections Effects , Undesirable and overdose).

Kalaemia: Potassium depletion with hypokalaemia is the major risk of thiazide and related diuretics. The risk of occurrence of hypokalaemia (

* Cl cr '= (140 - age) x; weight / 0.814 x serum creatinine.
With

· Age in years

· Weight in kg

· Serum creatinine in micromol / l.

This formula is valid for male elderly subjects and must be corrected for women by multiplying the result by 0.85

Hypovolemia, secondary to loss of water and sodium induced by the diuretic at the beginning of treatment, results in a reduction in glomerular filtration. This may result in increased blood urea and serum creatinine. This transient functional renal failure is of no consequence in the subject, with normal renal function but may aggravate a pre-existing renal insufficiency

Hepatic Pathology

In patients with hepatic impairment or progressive liver disease, the prescription of ACUILIX, due to the presence of hydrochlorothiazide, should be performed with caution due to the possible occurrence of alterations in the balance Which can result in hepatic coma. If signs of hepatic coma occur, discontinuation of treatment should be immediate.
Sportsmen

The attention of athletes is drawn to the fact that this specialty contains an active ingredient which can induce a positive reaction of the tests carried out during the antidoping tests. Code>
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Renal impairment, functional

In some hypertensive patients without a pre-existing apparent renal lesion whose biological check-up shows functional renal insufficiency, treatment will be discontinued and may be resumed either at a reduced dosage or with only one of the constituents.

Hypotension and hydroelectrolytic imbalance

Clinical signs of hydroelectrolytic imbalance, which may occur during an intercurrent episode of diarrhea or vomiting, will be systematically investigated.


Significant hypotension may require the placement of an intravenous infusion of isotonic saline serum.
Transient hypotension is not a contraindication to further treatment. After restoration of a blood volume and a satisfactory arterial pressure, it is possible to resume the treatment either at reduced dosage or with only one of the constituents. >
Kalémie

The association of an enzyme inhibitor, conversion to a hypokalemic diuretic, does not exclude the occurrence of hypokalaemia, especially in patients with diabetes or renal insufficiency. Regular monitoring of plasma potassium will be carried out.

Pregnancy

Effects Linked to QUINAPRIL

The 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)

Available epidemiological data on the risk of malformation after exposure to ACE inhibitors in the first trimester of pregnancy are not conclusive. However, a small increase in the risk of congenital malformations can not be excluded. Unless IEC 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 IEC should be stopped 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 result in fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of skull bones) and toxicity in; Newborn (renal insufficiency, hypotension, hyperkalaemia) (see section on safety data, preclinical). In case of exposure to an IEC from the second 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. Newborns of mothers treated with IEC should be monitored for blood pressure (see section Contraindications and Warnings and Precautions for Use)


Effects associated with hydrochlorothiazide

The decline in use of hydrochlorothiazide during pregnancy is limited. Animal studies are insufficient. Hydrochlorothiazide crosses the placental barrier. Given the mechanism of pharmacological action of hydrochlorothiazide and its use during the second and third trimesters of pregnancy may decrease the fetal-placental perfusion and cause fetal and neonatal effects such as jaundice, Electrolyte imbalance and thrombocytopenia. Hydrochlorothiazide should not be used to treat gestational edema, gestational hypertension or preeclampsia due to the risk of decreased blood volume and placental hypoperfusion, with no beneficial effect on the development of The disease.

Hydrochlorothiazide should not be used to treat hypertension, essential arterial blood in pregnant women except in the rare cases where no other treatment is possible. >
Breastfeeding

Effects Related to quinapril

Limited pharmacokinetic data show very low concentrations in milk (see Properties, Pharmacokinetics). Although these concentrations do not appear to have any real clinical consequences, administration of ACUILIX 20 mg / 12.5 mg film-coated tablet is not recommended in children, premature and in the first weeks following delivery, Because of the hypothetical risk, cardiovascular and renal side effects and insufficient clinical experience

In the case of breastfeeding of an older child, administration of ACUILIX 20 mg / 12.5 mg scored film-coated tablet may be considered in a nursing mother if this treatment is necessary for the mother and That the child is monitored for the purpose of detecting possible side effects.

Effects Related to Hydrochlorothiazide

Hydrochlorothiazide is excreted in human milk in low amounts. High dose thiazides, causing severe diuresis, may inhibit the production of milk. The use of ACUILIX 20 mg / 12.5 mg film-coated tablets during lactation is not recommended. If ACUILIX 20 mg / 12.5 mg film-coated tablet is used during breast-feeding, the doses used should be as low as possible. >
To the plan, clinical

RELATED TO QUINAPRIL

Have been found

· Headache, asthenia, dizziness, discomfort

Hypotension, orthostatic or not (see section Caveats and precautions for use), more rarely chest pain, angina pectoris, syncope
Pruritus, rash, photosensitisation or other manifestations, cutaneous, more rarely pemphigus, increased sweating, very rare cases of exfoliative dermatitis and erythroderma have been reported with other IEC

· Gastralgia, anorexia, nausea, abdominal pain, more rarely pancreatitis

A dry cough has been reported with the use of ACE inhibitors It is characterized by its persistence as well as by its disappearance upon discontinuation of treatment The iatrogenic etiology must be; Considered in the presence of this symptom

Anaphylactoid / angioedema (angioedema) (see Warnings and Precautions for Use)

· Pneumopathy

· More rarely: hepatitis.

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· In case of liver failure, possibility of occurrence of hepatic encephalopathy (see sections 4.3), Contraindications and Warnings and precautions for use.
Lupus, worsening of lupus, disseminated acute erythematosus, preexisting, necrotizing vasculitis, exceptional Lyell's syndrome

Skin and subcutaneous tissue: uncommon: cases of photosensitivity reaction have been reported (see section 4.4).

Nausea, constipation, dizziness, asthenia, paresthesia, headache, rarely observed and most often giving rise to a reduction in dosage


· Thrombocytopenia.

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· Potassium depletion with hypokalaemia, especially in cases of severe diuresis, and particularly severe in certain populations at risk (see section Caveats and Precautions for Use)

· Hyponatremia with hypovolemia at the origin, dehydration and orthostatic hypotension, or even a confusional syndrome. The concomitant loss of ions, chlorine can secondarily cause an alkalosis, metabolic compensating: the incidence and amplitude of this effect are low

· Elevation of uricemia and blood glucose during treatment: use of these diuretics will be carefully discussed in gouty and diabetic subjects

· An increase in high-dose plasma lipids

Thrombocytopenia, leukopenia, agranulocytosis, aplasia, bone marrow, haemolytic anemia

· Exceptional hypercalcemia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the drug is important. It permits continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (Ansm) and network of Regional Pharmacovigilance Centers -