High blood pressure

High blood pressure

Treatment will be initiated by a capsule of Diltiazem LP 200 mg, sustained-release capsule in a single dose per day, especially in the elderly patient, insufficient, renal and hepatic insufficiency. >

The dosage may be increased to one capsule of DILTIAZEM MYLAN, PHARMA LP 300 mg, release capsule, prolonged daily depending on the response, therapeutic and tolerance. Br>
In children: tolerance and efficacy have not been established, diltiazem is not recommended for use in children

The time taken during the day is indifferent, but it must remain relatively constant in the same patient

The capsule must be swallowed without being opened or chewed.

Diltiazem should be used with caution in patients with renal or hepatic impairment (see Warnings and Precautions for Use).


(C08DB01: system, cardiovascular)

Diltiazem reduces selectively the entry of calcium into the channel, slow calcium, voltage dependent, muscle fiber, smooth vessels and myocardial muscle fiber. By this mechanism, diltiazem decreases the calcium concentration, intracellular at the level of the contractile proteins.

Diltiazem is recognized as the class III reference product of calcium antagonists (WHO classification).


In different models, hypertensive animals, especially in the rat, genetically hypertensive, diltiazem reduced, arterial pressure without reflex tachycardia. It does not alter cardiac output and maintains renal flow rate.

In addition, it preferentially inhibits the vasoconstrictor effects of noradrenaline and angiotensin II.

In hypertensive rats, diltiazem increases diuresis without altering the urinary sodium / potassium ratio

Diltiazem decreases myocardial hypertrophy in spontaneously hypertensive rats

Diltiazem reduces the development of arterial calcinosis in rats

The two main circulating active metabolites (deacetyl diltiazem and N-monodemethyl diltiazem) have a pharmacological activity of about 50% of that of diltiazem. Code>
In humans, on the vascular level, the calcium antagonistic action of diltiazem is expressed by moderate arterial vasodilation and improves the compliance of the large arteries. This vasodilatation leads to a decrease in blood pressure in hypertension, which is related to the decrease of the peripheral resistances without causing a tachycardia, a reflex. On the contrary, there is a slight slowing down of the heart rate.
Blood, visceral flows, in particular renal and coronary flow, are maintained or increased

A discrete natriuretic effect is observed after acute administration.
In prolonged treatment, diltiazem does not stimulate the renin-angiotensin-aldosterone system and does not result in hydrosodic retention, as evidenced by the lack of weight variation and modification of the plasma hydro-electrolyte composition.

At the cardiac level, diltiazem exerts a coronary vasodilator effect, and reduces hypertensive left ventricular hypertrophy. It does not significantly alter cardiac output.

By its bradycardizing action, moderate and decreased resistance, systemic arterial, diltiazem reduced, cardiac work.

There was no evidence of negative inotropic effect on a healthy myocardium

Diltiazem slows down the heart rate moderately and may have a depressing effect on the sinus node. It slows down atrioventricular conduction, with risk of B.A.V.

Diltiazem has no effect on conduction at the His- tian and infra-Hisian stages.

Diltiazem does not affect glycoregulation or lipid metabolism, in particular it has no adverse effect on plasma lipoproteins.

On the basis of reported adverse reactions such as (frequent) dizziness, (frequent) discomfort, ability to drive and use machines may be impaired. Nevertheless, no studies have been carried out.

This medication should never be used in case of

· Hypersensitivity to diltiazem

· Sinus dysfunction

· Atrioventricular blocks of degrees II and III not paired

· Left ventricular insufficiency with pulmonary stasis

· Severe bradycardia (less than or equal to 40 beats per min)

· Association with dantrolene by infusion (see Interactions with other medicines and other forms of interactions)

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

Diltiazem hydrochloride IS GENERALLY NOT RECOMMENDED in the following cases

· In association with

O, esmolol (in case of impaired ventricular function, left).
O beta-blockers used in cardiac insufficiency (bisoprolol, carvedilol, metoprolol, nevibolol)

O other beta-blockers.

O, triazolam.

O, ivabradine.

· In pregnant or potentially pregnant women (see section Pregnancy and breast-feeding).

·; Supervision must be exercised in patients with impaired function, left ventricular, bradycardia (risk premium), one; atrioventricular block of 1 degree; electrocardiogram (risk and increase; Exceptionally full block). On the other hand, no special precaution in case of branch block, isolated.

· In elderly patients, insufficient renal patients and patients with hepatic insufficiency, diltiazem plasma concentrations may be increased. It is recommended to be particularly attentive to contraindications and precautions of use and to monitor, attentive, especially heart rate and electrocardiogram, at the beginning of treatment. Br>

· Diltiazem may cause a drop in blood pressure and severe bradycardia, especially in elderly subjects

· In case of general anesthesia, inform the anesthesiologist of taking the drug.

· During general anesthesia, diltiazem usually results in a moderate decrease in blood pressure and systemic vascular resistances and a slight slowing of the heart rate. Vasodilatation induced by anesthetics may be potentiated by diltiazem. Their dose must be adapted to the response: hemodynamics.

· Diltiazem can be safely used in patients with chronic respiratory disorders

Calcium channel antagonists, such as diltiazem, may be associated with mood disorders, including depression.

· Like other calcium channel antagonists, diltiazem has an inhibitory effect on intestinal motility. Therefore, it should be used with caution in patients at risk of developing intestinal obstruction.


· This medicinal product contains castor oil and may cause digestive problems (mild laxative effect, diarrhea).


Drugs, Antiarrhythmics

Many antiarrhythmics are depressants of cardiac automatism, conduction and contractility.

The combination of antiarrhythmics of different classes can provide a therapeutic effect, beneficial but most often proves very delicate, requiring close clinical monitoring and ECG monitoring The combination of antiarrhythmics (Amiodarone, disopyramide, quinidinic acid, sotalol, etc.) is contraindicated.
The association with drugs having inotropic, negative, bradycardizing and / or slowing conduction properties is difficult and requires clinical monitoring and ECG monitoring. (Amiodarone, bepridil, cibenzoline, diltiazem, disopyramide, dofetilide, flecainide, hydroquinidine, ibutilide, lidocaine, mexiletine, propafenone, quinidine, sotalol, verapamil).

Medicines, bradycardisants

Many medications can cause bradycardia. These include class Ia antiarrhythmics, beta-blockers, certain class III antiarrhythmics, certain calcium antagonists, digitalis, pilocarpine, anticholinesterases, etc.
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Associations, contraindicated

+ Cisapride

Increased risk of rhythm disorders, including ventricular torsades de pointes

+ Dantrolene administered by infusion

In animals, cases of fatal ventricular fibrillation are consistently observed when verapamil and dantrolene are administered by I.V. The combination of a calcium antagonist and dantrolene is therefore potentially dangerous. However, a few patients have received the combination nifedipine and dantrolene without disadvantage

+ Dihydroergotamine

Ergotism with possibility of extremity necrosis (inhibition of hepatic alkaloid metabolism of ergot, rye).

+ Ergotamine

Ergotism with possibility of extremity necrosis (inhibition of hepatic alkaloid metabolism of ergot, rye).

+ Nifedipine

Significant increase in nifedipine concentrations due to decreased hepatic metabolism by diltiazem with risk of severe hypotension

+ Pimozide

Increased risk of rhythm disorder, ventricular, in particular of torsades de pointes.

+ Sertindole

Increased risk of rhythm disorders, including ventricular torsades de pointes

Associations deprecated

+ Beta blockers (except esmolol)

Disorders of the automatism (bradycardia, excessive, sinus stop), conduction disorders, Sino-atrial and atrio-ventricular and cardiac failure.
Such association should be made only under close clinical supervision and ECG, in particular, in the elderly or at the beginning of treatment.

+ Beta-blockers in heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)
Negative inotropic effect with risk, decompensation of cardiac insufficiency, disorders of automatism (bradycardia, sinus arrest) and disorders of sino-atrial and atrio-ventricular conduction
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+ Esmolol, in case of alteration of left ventricular function.

Disorders of the automatism (bradycardia, excessive, sinus stop), conduction disorders, Sino-atrial and atrio-ventricular and cardiac failure.
+ Ivabradine

Increased plasma concentrations of ivabradine and its adverse effects, including

Cardiac effects (sound inhibition, hepatic metabolism by diltiazem), which are added to the bradycardic effects of these molecules.
+ Triazolam

Increase in triazolam plasma levels by decreased hepatic metabolism with increased sedation

Associations that are the subject of precautions for use

+ Alfentanil

Increased depressive, respiratory effect of opioid analgesic by decreased hepatic metabolism. Adjust the dosage of the analgesic if diltiazem is used.

+ Amiodarone

Risk of bradycardia or block, atrioventricular, especially in the elderly

Clinical Surveillance and ECG.

+ Anticonvulsants inducers, enzymatic

Decreased plasma concentrations of the calcium antagonist by increased hepatic metabolism by the inducer

Clinical monitoring and adaptation of the calcium antagonist dosage regimen, during treatment by the inducer and after discontinuation

+ Atorvastatin

Increased risk of adverse effects (concentration-dependent) to type, rhabdomyolysis, decreased metabolism, hepatic cholesterol-lowering. Use lower doses of cholesterol-lowering drug or other statin not affected by this type of interaction

+ Baclofen

Increased risk of hypotension, especially orthostatic.

Blood Pressure Monitoring and Dosage Adjustment of the Antihypertensive Medication If Needed

+ Buspirone

Increased plasma concentrations of buspirone by decreased hepatic metabolism by diltiazem with increased adverse effects

Clinical monitoring and adaptation of the dosage of buspirone if necessary

+ Dronedarone

Risk of bradycardia or atrioventricular block, especially in the elderly, and a slight increase in dronedarone concentrations by decreased metabolism by the calcium channel antagonist

Begin treatment with the calcium antagonist at the recommended minimum dosages and adjust the dose according to the ECG

+ Esmolol, in case of normal left ventricular function

Disorders of the automatism (bradycardia, excessive, sinus stop), conduction disorders, Sino-atrial and atrio-ventricular and cardiac failure.
Clinical Surveillance and ECG.

+ Immunosuppressants (ciclosporin, everolimus, sirolimus, tacrolimus)

Increased blood levels of the immunosuppressant by decreasing its metabolism

Determination of blood concentrations of the immunosuppressant, control of renal function and adaptation of dosage during and after association,

+ Midazolam

Increased midazolam plasma levels by decreased metabolism, hepatic, with increased sedation

Clinical monitoring and reduction of dosage during treatment with diltiazem

+ Drugs that may, to torsades de pointes (except pimozide, cisapride) Class Ia antiarrhythmics (quinidine, hydroquinidine; disopyramide) Class III antiarrhythmic (eg amiodarone, dofetilide, ibutilide, sotalol), certain neuroleptics, phenothiazines (chlorpromazine, cyamemazine; fluphenazine levomepromazine,), benzamides, (amisulpride, sulpiride sultopride, tiapride), butyrophenones (droperidol, haloperidol), pimozide, pipamperone, pipotiazine, zuclopenthixol, other; bepridil, diphemanil, erythromycin IV, halofantrine, lumefantrine, methadone, mizolastine , Moxifloxacin, pentamidine, spiramycin IV, vincamine IV

Increased risk of rhythm disorders, including ventricular torsades de pointes

Clinical and electrocardiographic monitoring.

+ Rifampicin

Decreased plasma concentrations of the calcium antagonist by increased hepatic metabolism

Clinical monitoring and possible adaptation of calcium antagonist dosage regimen during treatment with rifampicin and after discontinuation

+ Simvastatin

Increased risk of adverse effects (dose-dependent) to rhabdomyolysis, by decreased metabolism, liver of cholesterol-lowering agent. Do not exceed the 20 mg / day dose of simvastatin or use another statin not affected by this type of interaction

Associations to be taken into account

+ Urologic alpha-blockers (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin)
Increase in hypotensive effect. Risk of increased orthostatic hypotension.

+ Amifostine

Increased risk of hypotension, especially orthostatic.

+ Antidepressants, imipraminic

Increased risk of hypotension, especially orthostatic.

+ Antihypertensive drugs, alpha-blockers

Increase in hypotensive effect. Risk increased with orthostatic hypotension.

+ Other bradycardisants

Risk of excessive bradycardia (addition, effects).

+ Clonidine, guanfacine

Disorders of automatism (disorders of atrio-ventricular conduction by addition of effects, negative on conduction).

+ Glucocorticoids (except hydrocortisone in replacement therapy) and mineralocorticoids

Decreased antihypertensive effect (hydrosodic retention of corticosteroids).

+ Neuroleptics
Increased risk of hypotension, especially orthostatic.

+ Pilocarpine

Risk of excessive bradycardia (addition, bradycardiac effects).

+ Nitrates and related derivatives

Increased risk of hypotension, especially orthostatic.

Not applicable.

The clinical picture of acute poisoning may include severe hypotension, including collapse, sinus bradycardia with or without isorhythmic dissociation and conduction disturbances, atrioventricular.
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The treatment to be undertaken in the hospital environment will include: gastric lavage, diuresis, osmotic.

Conduction disorders can benefit from a temporary electro-systolic training.

The proposed antidotes are: atropine, adrenaline, vasopressives, positive inotropic and chronotropic agents, glucagon and calcium gluconate by infusion.


Pregnancy

Studies in animals (rats, mice, rabbits) have demonstrated a teratogenic effect.


Breastfeeding

Diltiazem is found at very low concentrations in breast milk.

However, breast-feeding during treatment with diltiazem should be avoided. If the use of diltiazem is necessary, the feeding of the infant should be carried out by an alternative method.
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