Isoptin (The solution for the on / in the)
Active material: Verapamil
When ATH: C08DA01
CCF: Kalьcievыh channel blocker
When CSF: 01.03.01
Manufacturer: ABBOTT GmbH & Co. KG (Germany)
Pharmaceutical form, composition and packaging
| Solution for / in the | 1 amp. |
| verapamil hydrochloride | 5 mg |
2 ml – ampoule (5) – packs cardboard.
2 ml – ampoule (10) – packs cardboard.
2 ml – ampoule (50) – packs cardboard.
DESCRIPTION OF ACTIVE SUBSTANCES.
Pharmacological action
Selective calcium channel blocker of class I, derivative difenilalkilamina. It has antianginalnoe, antiarrhythmic and antihypertensive action.
Antianginal effect is associated with both the direct effect on the myocardium, and the effect on peripheral hemodynamics (It lowers the tone of the peripheral arteries, PR). Blockade of calcium into the cell leads to a reduction in transformation enclosed macroergic bonds of ATP into mechanical energy, reduce myocardial contractility. It reduces myocardial oxygen demand, It has a vasodilatory, negative ino- and chronotropism.
Verapamil significantly reduces AV conduction, It prolongs the refractory period and suppresses the automaticity of sinus node. Increases the period of diastolic relaxation of the left ventricle, reduces myocardial wall tone (It is an aid for the treatment of hypertrophic obstructive cardiomyopathy). It has antiarrhythmic effect in supraventricular arrhythmias.
Pharmacokinetics
When ingestion absorbed more 90% dose. Protein binding – 90%. Metabolized in the “first pass” through the liver. The major metabolite is norverapamil, has less pronounced hypotensive activity, than unmodified verapamil.
T1/2 upon receiving a single dose of 2.8-7.4 no, when receiving repeated doses – 4.5-12 no (in connection with the saturation of the enzyme systems of the liver and an increased concentration in the blood plasma verapamil). After the on / in the initial T1/2 – about 4 m, finite – 2-5 no.
Report mostly kidneys and 9-16% through the intestine.
Testimony
Angina (voltage, stable without vasoconstriction, stable vasospastic), supraventricular tachycardia (incl. paroksizmalynaya, when WPW-syndrome, Lown-Ganong syndrome-Levine), sinus tachycardia, atrial tachyarrhythmia, auricular flutter, Atrial premature beats, arterial hypertension, hypertensive crisis (in / introduction), gipertroficheskaya obstruktivnaya cardiomyopathy, primary hypertension in the pulmonary circulation.
Dosage regimen
Individual. Inside adults – at an initial dose 40-80 mg 3 times / day. For sustained release dosage forms unit dose should be increased, and reduce the frequency of administration. For children 6-14 years – 80-360 mg / day, to 6 years – 40-60 mg / day; frequency of administration – 3-4 times / day.
If necessary, it can be administered verapamil / jet (slowly, under the control of blood pressure, Heart rate and ECG). Single dose for adults is 5-10 mg, with no effect through 20 min possible re-introduction of the same dose. Single dose for children 6-14 s is 2.5-3.5 mg, 1-5 years – 2-3 mg, to 1 year – 0.75-2 mg. For patients with severe hepatic impairment the daily dose should not exceed verapamil 120 mg.
The maximum dose: adult ingestion – 480 mg / day.
Side effect
Cardio-vascular system: bradycardia (less 50 u. / min), marked reduction in blood pressure, development or exacerbation of congestive heart failure, tachycardia; rarely – angina, until the development of myocardial infarction (especially in patients with severe obstructive coronary artery disease), arrhythmia (incl. flicker and flutter); With the rapid on / in a – AV block III degrees, asistolija, collapse.
From the central and peripheral nervous system: dizziness, headache, fainting, anxiety, lethargy, fatigue, asthenia, drowsiness, depression, extrapyramidal disorders (ataxia, mask-like face, shuffling gait, stiffness in the arms or legs, shaking hands and fingers, difficulty weight management).
From the digestive system: nausea, constipation (rarely – diarrhea), giperplaziya right (angiostaxis, soreness, puffiness), increased appetite, increase in liver transaminases and alkaline phosphatase.
Allergic reactions: itching, skin rash, facial flushing, erythema multiforme exudative (incl. Stevens-Johnson syndrome).
Other: weight gain, rarely – agranulocytosis, gynecomastia, hyperprolactinemia, galactorrhea, arthritis, transient loss of vision in the background Cmax, pulmonary edema, thrombocytopenia bessimptomnaya, peripheral edema.
Contraindications
Severe hypotension, AV-blockade II and III degrees, sinoatrialynaya blockade and SSSU (except for patients with a pacemaker), WPW-syndrome or Lown-Ganong-Levine in conjunction with flutter or atrial fibrillation (except for patients with a pacemaker), pregnancy, lactation, Hypersensitivity to verapamil.
Pregnancy and lactation
Verapamil is contraindicated in pregnancy and lactation.
Cautions
C care should be used in AV-blockade of I degree, ʙradikardii, severe aortic stenosis, chronic heart failure, with mild to moderate hypotension, myocardial infarction with left ventricular failure, hepatic and / or renal failure, in elderly patients, in children and adolescents under the age of 18 years (efficacy and safety have not been studied).
If necessary, possible combination therapy of angina and hypertension verapamil and beta-blockers. However, it should be avoided in / in the introduction of beta-blockers in the treatment with verapamil.
Effects on ability to drive vehicles and management mechanisms
After receiving the individual reactions may verapamil (drowsiness, dizziness), affecting a patient's ability to perform work, require high concentration and speed of psychomotor reactions.
Drug Interactions
While the use of antihypertensive drugs (vazodilatatorami, thiazide diuretics, ACE inhibitors) mutual strengthening of antihypertensive action.
While the use of beta-blockers, antiarrhythmics, means for inhalation anesthesia increases the risk of bradycardia, AV-blockade, severe hypotension, Heart Failure, in connection with the mutual enhancement oppressive influence on the sinoatrial node automaticity and AV-conduction, myocardial contractility and conductivity.
For parenteral administration of verapamil in patients, recently received beta-blockers, There is the risk of hypotension and asystole.
In an application with nitrates increase antianginal effect of verapamil.
In an application with amiodarone increases the negative inotropic effect, bradycardia, asequence, AV блокада.
Since verapamil inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, theoretically possible manifestations of drug interactions, caused by increasing concentrations of statins in the blood plasma. There are cases of rhabdomyolysis.
In an application with acetylsalicylic acid described cases increased bleeding time due to additive antiplatelet action.
While the use of buspirone buspirone concentration in blood plasma increases, enhances its therapeutic and side effects.
In an application described cases increasing the concentration of digitoxin in the blood plasma.
In an application with digoxin increases the concentration of digoxin in the blood plasma.
In an application with disopyramide, severe hypotension and collapse, especially in patients with cardiomyopathy or decompensated heart failure. The risk of severe manifestations of drug interactions associated, apparently, with increased negative inotropic effects.
In an application with diclofenac decreases the concentration of verapamil in plasma; with doksorubitsinom – increases the concentration of doxorubicin in the blood plasma and increases its efficiency.
In an application with imipramine imipramine increased concentration in plasma and the risk of adverse changes in the electrocardiogram. Verapamil increases the bioavailability of imipramine by reducing its clearance. ECG changes are due to an increase in the concentration of imipramine in plasma and additive inhibitory effect of verapamil and imipramine on AV-conduction.
In an application with carbamazepine increases the effects of carbamazepine and increase the risk of side effects from the central nervous system by inhibiting the metabolism of carbamazepine in the liver under the influence of verapamil.
While the use of clonidine described cases of heart failure in patients with hypertension.
In an application with lithium carbonate manifestations of drug interactions are ambiguous and unpredictable. Cases of lithium and amplification effects of neurotoxicity, reducing the concentration of lithium in the blood plasma, severe bradycardia.
Vasodilating action of alpha-blockers and calcium channel blockers may be additive or synergistic. With simultaneous use of prazosin, or terazosin and verapamil develop severe hypotension partly due to pharmacokinetic interactions: increase in Cmax and AUC values terazosin and prazosin.
With simultaneous use of rifampicin induces liver enzymes, speeding up the metabolism of verapamil, which leads to a reduction of its clinical effectiveness.
In an application increases the concentration of theophylline in the blood plasma.
While the use of tubocurarine chloride, vecuronium chloride may increase miorelaksiruyuschego action.
In an application with phenytoin, phenobarbital may significantly reduce the concentration in the blood plasma verapamil.
In an application with fluoxetine worse side effects of verapamil due to slowing down its metabolism under the influence of fluoxetine.
With simultaneous use of reduced clearance of quinidine, increases its concentration in blood plasma and increases the risk of side effects. There have been cases of arterial hypotension.
With simultaneous use of verapamil inhibits the metabolism of cyclosporine in the liver, which leads to a decrease of its excretion and increased concentrations in plasma. It is accompanied by increased immunosuppressive action, marked reduction in symptoms of nephrotoxicity.
In an application with cimetidine increases the effect of verapamil.
In an application with possible prolongation of enflurane anesthesia.
While the use of etomidate increased duration of anesthesia.
