Isoptinum

Isoptinum – drug with hypotensive, antiarrhytmic and anti-anginal action.

Form of release and structure

Isoptinum is released in the following dosage forms:

• Tablets, film coated: white, biconvex, round; on 40 mg – with a text "40" on one of the parties and an engraving in the form of a triangle on another; on 80 mg – with a text of "ISOPTIN 80" on one of the parties both risky for division and a text "KNOLL on another (tablets on 40 and 80 mg: on 10 pieces in blisters, on 2 or 10 blisters in a cardboard pack; on 20 pieces in blisters, on 1 or 5 blisters in a cardboard pack; tablets on 80 mg: on 25 pieces in blisters, on 4 blisters in a cardboard pack);
• Solution for intravenous administration: colourless, transparent (on 2 ml in colourless glass ampoules, on 5, 10 or 50 ampoules in pallets or blisters, on 1 blister or the pallet in a cardboard pack).

Is a part of 1 tablet:

• Active agent: verapamil – 40 or 80 mg (in the form of a hydrochloride);
• Auxiliary components (40/80 mg respectively): a calcium hydrophosphate dihydrate – 70/140 mg; microcrystallic cellulose – 23/46 mg; colloid silicon dioxide – 0,7/1,4 mg; croscarmellose sodium – 1,8/3,6 mg; magnesium stearate – 1,5/3 mg.

Structure of a film cover (40/80 mg respectively): sodium lauryl sulfate – 0,1/0,1 mg; a gipromelloza of 3 MPas – 1,7/2 mg; talc – 4/4,5 mg; macrogoal of 6000 - 2/2,3 mg; titanium dioxide – 1/1,1 mg.

Is a part of 1 ampoule:

• Active agent: verapamil – 5 mg (in the form of a hydrochloride);
• Auxiliary components: Acidum hydrochloricum of 36% – before finishing pH; sodium chloride – 17 mg; water for injections – to 2 ml.

Indications to use

Isoptinum in the form of tablets is appointed for treatment of the following diseases:

• Arterial hypertension;
• Bouveret's supraventricular disease;
• Coronary heart disease, including unstable stenocardia, chronic stable stenocardia (a classical angina of exertion), Printsmetal's stenocardia (stenocardia which is caused by a vasospasm);
• Blinking/atrial flutter which is followed by a tachyarrhythmia (except a syndrome of Launa-Ganonga-Levina (LGL) and Wolf-Parkinson-Whyte (WPW)).

Drug in the form of solution for intravenous administration is used at treatment of supraventricular tachyarrhythmias. Isoptinum is appointed at the following indications:

• Recovery of a sinoatrial rate at Bouveret's supraventricular disease, including states which are connected with existence of additional conduction paths (syndromes of Launa-Ganonga-Levina and Wolf-Parkinson-Whyte);
• Control of frequency of reductions of ventricles during the blinking and an atrial flutter (takhiaritmichesky option), except cases when blinking or an atrial flutter is connected with existence of additional conduction paths (syndromes of Launa-Ganonga-Levina and Wolf-Parkinson-Whyte).

Contraindications

• AV blockade of the II-III degree (except patients with an artificial pacemaker);
• Sick sinus syndrome (a syndrome of "bradycardia tachycardia", except patients with an artificial pacemaker);
• Blinking/atrial flutter in the presence of additional ways of carrying out (a syndrome of Launa-Ganonga-Levina and Wolf-Parkinson-Whyte);
• Age up to 18 years (efficiency and safety of use of drug for this age group of patients are not established);
• Hypersensitivity to drug components.

Additional contraindications to reception of Isoptinum in the form of tablets are:

• Chronic heart failure;
• The acute myocardial infarction complicated by the expressed arterial hypotension, bradycardia and a left ventricular failure;
• Cardiogenic shock;
• Concomitant use with colchicine.

Intravenous administration of Isoptinum is contraindicated in the presence of the following diseases / states:

• Arterial hypotension or cardiogenic shock (except caused by arrhythmia);
• Morganyi-Adams-Stokes's syndrome;
• Sinoauricular block;
• Ventricular tachycardia with the wide QRS complexes (more than 0,12 seconds);
• Chronic heart failure of IIB-III of a stage (except the caused supraventricular tachycardia which is subject to treatment by verapamil);
• Preliminary use of Disopyramidum (within 48 hours);
• Simultaneous intravenous administration of beta adrenoblockers;
• Pregnancy and period of a lactation.

Isoptinum in all medicinal headlights should be applied with care at bradycardia and AV blockade of the I degree.

Inside drug is appointed with care at the expressed functional disturbances of kidneys and a liver, arterial hypotension, diseases concerning neuromuscular transfer including a syndrome of Lambera-Eton, a myasthenia of gravis and muscular dystrophy of Dyushenn.

Intravenous administration is recommended to be carried out with care at patients of advanced age, and also at the following diseases: heart failure, a heavy stenosis of the mouth of an aorta, a myocardial infarction with a left ventricular failure, slight or moderate arterial hypotension, a renal and/or liver failure.

Route of administration and dosage

Isoptinum in the form of tablets is accepted inside, swallowing entirely (it is impossible to chew or rassasyvat) and washing down with water. It is more preferable to accept drug in time or right after meal.

The scheme of use of Isoptinum is defined individually with disease severity and a clinical picture.

For all recommended indications the average daily dose makes 240-480 mg. At long therapy it is not necessary to exceed a daily dose of 480 mg. In the maximum daily dose Isoptinum should be accepted only in the conditions of a hospital.

Initial single dose – 40-80 mg, frequency rate of reception – 3-4 times a day.

Patients with functional disturbances of a liver therapy are recommended to begin 40 mg with a single dose. Frequency rate of reception – 2-3 times a day. Further the doctor selects a dose individually.

Isoptinum in the form of solution for injections can be entered only intravenously.

Introduction needs to be carried out slowly at continuous control of an ECG and arterial pressure for, at least, 2 minutes (at elderly patients – 3 minutes that reduces risk of development of undesirable effects).

Initial dose – 5-10 mg (0,075-0,15 mg/kg of body weight). At the inadequate response to the first introduction in 30 minutes it is possible to enter a repeated dose (10 mg).

Side effects

During therapy development of disturbances from some systems of an organism is possible:

• Alimentary system: pain and feeling of discomfort in a stomach, vomiting, nausea, lock, intestinal impassability; in some cases – tranzitorny increase in a blood plasma of activity of hepatic transaminases and an alkaline phosphatase; seldom – a hyperplasia of gums (morbidity, bleeding, puffiness), increase in appetite, diarrhea;
• Cardiovascular system: the expressed bradycardia, face reddening, an atrioventricular block, the expressed lowering of arterial pressure, emergence of symptoms of heart failure at use of high doses of drug, especially at predisposed patients; heartbeat, tachycardia, stop of a sinus node; seldom – arrhythmia (including trembling and ventricular fibrillation), stenocardia up to development of a myocardial infarction (especially at patients with crushing obstructive defeat of coronary arteries), bradycardia;
• Nervous system: the general weakness, uneasiness, a depression, drowsiness, extrapyramidal disturbances (rigidity of legs or hands, the ataxy shuffling gait, a mask-like face, swallowing difficulty, trembling of brushes and fingers of hands), a headache, dizziness, spasms during administration of drug, a tremor, paresthesias; in rare instances – block, the increased nervous irritability, fatigue;
• Allergic reactions: multiformny exudative erythema, dermahemia of the person, skin rash, itch, Stephens-Johnson's syndrome, bronchospasm;
• Others: increase in body weight; very seldom – arthritis, an agranulocytosis, a tranzitorny blindness at the peak of concentration of drug in blood, asymptomatic thrombocytopenia, a fluid lungs, development of peripheral hypostases, fatigue, a giperprolaktinemiya, a gynecomastia, impotence, a galactorrhoea, muscular weakness, the increased sweating, joint pains, mialgiya.

The majority of the listed side effects are characteristic of all dosage forms of Isoptinum.

Special instructions

Sharply it is impossible to cancel reception of Isoptinum. The dose is recommended to be reduced gradually to full cancellation of therapy.

Intravenous administration of Isoptinum can cause passing lowering of arterial pressure which usually clinically is not shown, but can be followed by development of dizziness.

The circulatory unefficiency (except heavy or caused by arrhythmia) prior to therapy by Isoptinum needs to be compensated by diuretics and cardiac glycosides. At patients with heavy and moderate heart failure during therapy acute progressing of a circulatory unefficiency can be observed.

Solution does not support antimicrobic or bacteriostatic agents and is intended for simultaneous intravenous administration.

Isoptinum keeps stability at least for 24 hours (at its storage at a temperature up to 25 °C in the place protected from light) in the majority of parenteral solutions of large volume. After a fence of a portion of contents of any volume, unused solution should be destroyed immediately.

To avoid disturbance of stability it is not recommended to part Isoptinum with lactate sodium solutions in plastic packages from polyvinylchloride. It is necessary to avoid mixing of solutions of Isoptinum with Amphotericinum In, albumine, a gidralazin a hydrochloride or Trimethoprimum and sulfamethoxazole.

Verapamil the hydrochloride pretsipitirut in any solutions with рН more than 6.

Isoptinum, depending on specific features, can change speed of response, breaking ability to driving and performance of work, requiring special attention.

Medicinal interaction

At simultaneous use of Isoptinum with inhibitors of an isoenzyme CYP3A4 increase in concentration of verapamil in a blood plasma, with CYP3A4 isoenzyme inductors – decrease in its concentration is observed (interaction should be considered at simultaneous use of similar means).

At simultaneous use of Isoptinum with some medicines there can be undesirable effects (_Css – average equilibrium concentration of substance in a blood plasma, _Cmax – the maximum concentration of substance in a blood plasma, AUC – the area under a pharmacokinetic curve "concentration time", T1/2 – an elimination half-life):

• Prazozinum: increase in its _Cmax, _T1/2 of Prazozinum does not change;
• Terazozin: increase in its AUC and _Cmax;
• Quinidine: reduction of its clearance;
• Theophylline: reduction of its system clearance;
• Carbamazepine: increase in its AUC at patients with steady partial epilepsy;
• Imipraminum: increase in its AUC; on concentration of an active metabolite of Imipraminum – desipramine, Isoptinum of influence does not render;
• Glibenclamidum: increase in its _Cmax and AUC;
• Klaritromitsin, erythromycin, телитромицин: increase in concentration of verapamil is possible;
• Rifampicin: reduction of AUC, _Cmax and bioavailability of verapamil at intake;
• Doxorubicine: increase in its AUC and _Cmax at patients with small-celled cancer of a lung;
• Phenobarbital: increase in clearance of verapamil;
• Buspiron, midazolam: increase in their AUC and _Cmax;
• Metoprolol, propranolol: increase in their AUC and _Cmax at patients with stenocardia;
• Digitoxin: reduction of its general and extrarenal clearance;
• Digoxin: increase in its _Cmax, AUC and _Css;
• Cimetidinum: increase in AUC R-enantiomera and S-enantiomera of verapamil with the corresponding decrease in clearance of R-and S-verapamil;
• Cyclosporine: increase in its AUC, _Css, _Cmax;
• Sirolimus, такролимус, ловастатин: increase in their concentration is possible;
• Atorvastatin: increase in its concentration and AUC is possible;
• Simvastatin, алмотриптан: increase in their AUC and _Cmax;
• Sulfinpyrazonum: increase in clearance of verapamil and decrease in its bioavailability;
• The St. John's Wort which is made a hole: reduction of AUC R-enantiomera and S-enantiomera of verapamil with the corresponding decrease _{in Cmax};
• Grapefruit juice: increase in AUC and _{Cmax R-enantiomera} and S-enantiomera of verapamil (the renal clearance and _T1/2 do not change);
• Terazozin, Prazozinum: the additive hypotensive action;
• Diuretics, antihypertensives, vazodilatator: strengthening of hypotensive effect;
• Ritonavir and other antiviral means for treatment of HIV infection: the verapamil metabolism inhibition is possible that can lead to increase in its concentration in a blood plasma (at simultaneous use of a dose of Isoptinum it is necessary to lower);
• Quinidine: strengthening of hypotensive action is possible; at patients with a hypertrophic subaortic stenosis edematization of lungs is possible;
• Carbamazepine: increase in its concentration in a blood plasma; development of the side reactions inherent to carbamazepine (a headache, a diplopia, dizziness or an ataxy) is possible;
• Lithium: increase in its neurotoxicity;
• Rifampicin, Sulfinpyrazonum: reduction of hypotensive effect of verapamil is possible;
• Muscle relaxants: strengthening of their effect is possible;
• Acetylsalicylic acid: increase in bleeding;
• Colchicine: perhaps significant increase in its concentration in blood;
• Ethanol (alcohol): increase in its concentration in a blood plasma;
• Beta adrenoblockers, antiarrhytmic means: mutual strengthening of cardiovascular effects (more considerable urezheniye of heart rate, more expressed AV blockade, strengthening of arterial hypotension and development of symptoms of heart failure).

To the patient accepting Isoptinum, treatment by hypolipidemic means – with GMG-KOA-reduktazy inhibitors (lovastatiny, simvastatiny, atorvastatiny), it is necessary to begin with perhaps lower doses which at therapy continuation gradually increase. If it is necessary to apply Isoptinum at the patients who are already receiving GMG-KOA-reduktazy inhibitors it is necessary to consider the possibility of reduction of a dose of statines and repeated titration of a dose, considering concentration in cholesterol blood serum. Fluvastatin, розувастатин and правастатин under the influence of an isoenzyme of CYP3A4 are not metabolized therefore their interaction with verapamil is least probable.

Terms and storage conditions

To store in the place, unavailable to children, at a temperature: tablets – 15-25 °C, solution for intravenous administration – to 25 °C.

Period of validity – 5 years.