Isoptin

When our blood pressure rises and other heart problems occur that cause a deterioration in our general condition, we seek help from medications that have a positive effect on the cardiovascular system. "Isoptin" is one of those cardiac medications that normalize the functioning of the heart and blood vessels.

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Indications Isoptin

The indications for the use of Isoptin also differ slightly when considered in relation to what is prescribed by the doctor: taking tablets or injections.

For example, the prescription of tablets is justified in the following situations:

• diagnosed with arterial hypertension (stably high blood pressure),
• in case of hypertensive crisis,
• thickening of the wall of one of the heart ventricles (diagnosis: hypertrophic cardiomyopathy),
• for the treatment of cardiac ischemia (vasospastic, chronic stable and unstable angina),
• in case of heart rhythm disturbances: sudden attacks of rapid heartbeat (paroxysmal supraventricular tachycardia (PVT), which is one of the types of arrhythmia), tachyarrhythmic form of atrial fibrillation (atrial fibrillation and flutter), the appearance of additional defective heart contractions (supraventricular extrasystole).

"Isoptin" in the form of an injection solution is used as monotherapy for mild forms of hypertension and as part of complex treatment for its severe, complicated manifestations, for angiospastic angina (against the background of vascular spasm) and angina of effort. But most often it is used to treat supraventricular tachyarrhythmias, when it is necessary to restore normal heart rhythm in PNT, as well as to correct the heart rate in atrial fibrillation of the tachyarrhythmic type (with the exception of Wolff-Parkinson-White and Lown-Ganong-Levine syndromes).

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Release form

The following dosage forms of the drug "Isoptin" can be found on sale:

Ordinary tablets 40 mg (white, film-coated, round, convex on both sides, with the number 40 engraved on one side and a triangle sign on the other). The tablets are placed in blisters:

• 10 pieces each (there are either 2 or 10 blisters in a package),
• 20 pieces each (the package contains either 1 or 5 blisters).

Ordinary tablets 80 mg (white, film-coated, round, convex on both sides, engraved with the inscription "ISOPTIN 80" on one side, "KNOOL" on the other and a score line for dividing the tablet into 2 parts). The tablets are packaged in blisters:

• 10 pieces each (there are either 2 or 10 blisters in a package),
• 20 pieces each (either 1 or 5 blisters in a package),
• 25 pieces each (4 blisters in a package).

SR240 prolonged-release (long-acting) tablets 240 mg (light green, oblong, capsule-like, with 2 identical triangles engraved on one side, score lines on both sides). Tablets in blisters:

• 10 pieces (2,3,5 or 10 blisters in a package),
• 15 pieces (2,3,5 or 10 blisters in a package),
• 20 pieces (in a package of 2, 3.5 or 10 blisters).

Solution for intravenous administration in glass colorless ampoules of 2 ml (transparent liquid without a specific color). The ampoules are placed in transparent trays of 5, 10 and 50 pieces. Each tray is packed in a separate box made of thin cardboard.

The main active ingredient of the drug "Isoptin" is verapamil, presented in the form of hydrochloride. It is known to many by the drug of the same name.

The composition of Isoptin has certain differences depending on the form of the drug. Thus, tablets can contain 40, 80 or 240 mg of the main active ingredient plus auxiliary substances present in the tablet or its shell.

Excipients in Isoptin tablets:

• pyrogenic or colloidal silicon dioxide as an adsorbent,
• dicalcium phosphate dihydrate as a light source of calcium,
• croscarmellose sodium as a leavening agent,
• microcrystalline cellulose for cleansing the body,
• magnesium stearate to give the tablets a uniform consistency.

In turn, the film coating of the tablets consists of talc, hypromellose 3 MPa, sodium lauryl sulfate, macrogol and titanium dioxide.

An ampoule of Isoptin solution, in addition to verapamil hydrochloride in the amount of 5 mg, contains: NaCl and hydrochloric acid (HCl) with a concentration of 36%, diluted with water for injection.

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Pharmacodynamics

"Isoptin" belongs to a group of antianginal drugs called calcium antagonists. These drugs help reduce the need of the main heart muscle for oxygen, provide a vasodilatory effect on the coronary arteries and protection against overloading them and the heart muscle with calcium. The drug is able to limit the flow of calcium ions through the membrane into the muscle tissue of the heart and blood vessels.

Having a vasodilatory effect, it helps to reduce blood pressure by reducing the resistance of peripheral vessels without increasing the heart rate (a common reflex reaction). The antianginal effect of the drug "Isoptin" in the treatment of angina is based on its relaxing effect on cardiomyocytes (muscle cells that make up the heart wall), as well as on reducing the tone of peripheral vessels, due to which the load on the atria is reduced. Reduction in the flow of calcium ions into myocytes leads to inhibition of the conversion of energy into work, and therefore to a slowdown in the heart rate.

The use of Isoptin in the treatment of supraventricular tachyarrhythmias is justified due to its ability to delay the passage of nerve impulses through the atrioventricular node, block the conductivity of the sinoatrial node and reduce the duration of the refractory period in the atrioventricular plexus. In this way, an optimal heart rate is achieved and normal (sinus) heart rhythm is restored.

The drug has a selective effect and belongs to the group of dose-dependent drugs. If the disease proceeds with the preservation of normal heart rate indicators, then taking the drug will not affect them in any way, and if the heart rate decreases, then insignificantly.

In addition to the antianginal and vasodilating (relaxation of vascular muscles) effects, the drug has a diuretic effect.

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Pharmacokinetics

The active substance of the drug "Isoptin" is absorbed in the intestine by almost 90%, and its absorption does not depend on food intake. The bioavailability of the drug ranges from 10 to 35% both when taking tablets orally and when infusing the solution intravenously.

In cases of coronary heart disease and hypertension, there is no relationship between the content of verapamil in the patient's blood and the resulting therapeutic effect.

The drug is metabolized in the parenchymal cells of the liver, where it undergoes almost complete biotransformation. It is able to pass through the placental tissues relatively easily, since about 25% of the drug is found in the vessels of the umbilicus.

The only active metabolite of Isoptin is norverapamil. Its maximum concentration in the blood is observed 6 hours after taking 1 dose of the drug. The half-life indicators can vary significantly (2.5-7.5 hours with a single dose and 4.5-12 hours with repeated administration). When using a solution for intravenous injections, the half-life of the drug can range from 4 minutes to 5 hours.

The therapeutic concentration of the drug in the blood is observed on the 5th day after repeated administration of the drug.

"Isoptin" is able to penetrate and be excreted from the body together with breast milk, but its content there is so small that it does not cause undesirable symptoms in the infant. The half-life in this case will be about 3-7 hours, but with repeated administration it can increase to 14 hours.

The majority of the drug "Isoptin" and its metabolites are excreted through the kidneys and only 16% is eliminated through the intestines.

In the case of prolonged-release tablets, the drug is eliminated from the body more slowly. 50% of the administered dose of the drug is eliminated from the body during the first day. On the second day, 60% of the drug is eliminated, and on the 5th day, 70% of the drug is eliminated.

In patients with renal failure and severe forms of liver failure, an increase in the half-life and an increase in bioavailability are observed.

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Dosing and administration

To help your heart do its hard work and not cause other troubles, you need to listen carefully to your doctor's recommendations regarding taking medications. Advice from girlfriends and neighbors will do if we are talking about a recipe for a delicious cake or roast, but not about taking any other medications, especially cardiac ones. When it comes to our "motor", strict intake of cardiac medications regarding the dose and method of administration is the key to not only effective but also safe treatment.

"Isoptin" is a drug that improves heart function, which means that everything said above applies to it in full.

So, how to take the drug correctly, so that having cured one, not to cripple the other. The instructions for the drug indicate that it is advisable to combine the intake of "Isoptin" in tablets with food, or take the drug immediately after eating. At the same time, the tablet form of the drug is not intended for resorption or crushing when taken. Tablets (regular and prolonged action) should be swallowed whole, washed down with water in sufficient quantity (usually take half a glass of water). This ensures a gentle effect on the gastric mucosa, and creates optimal conditions for the absorption of this dosage form.

The tablets are taken orally, i.e. through the mouth. They are not used for any other purposes. The dosage depends on the patient's age and, of course, on the diagnosis.

Adult patients: the initial daily dose for angina pectoris, atrial fibrillation and hypertension, depending on the severity of the pathology and the body's response, ranges from 120 to 240 mg. In case of hypertension, the dosage (according to the attending physician's instructions) can be increased to 480 mg, and in case of cardiomyopathy, temporarily even to 720 mg per day. The recommended frequency of administration is 3 times a day.

The effective dose for prolonged-release tablets ranges from 240 to 360 mg. Long-term use of the drug does not allow increasing the dose above 480 mg per day, except for a short time.

If the patient has liver dysfunction, it is recommended to take tablets with a minimum dosage. The daily dose with 2-3 times intake will be 80-120 mg.

The solution "Isoptin" can be used only for intravenous injections. Slow administration of the drug is indicated, for at least 2 minutes. In this case, it is necessary to monitor blood pressure and heart rate. In elderly patients, the drug should be administered even more slowly (at least 3 minutes).

The effective initial dose is calculated based on the ratio: 0.075 to 0.15 mg of the drug in solution per 1 kg of the patient's weight. Usually, this is 2-4 ml (1-2 ampoules or 5-10 mg of verapamil hydrochloride). If the expected result does not occur within half an hour, it is time to make another injection with a dosage of 10 ml of the drug.

The duration of the therapeutic course is determined individually by the attending physician.

Children: the dosage depends on the age of the little patient. Despite the fact that Isoptin can be used even for the treatment of newborns, doctors prefer to resort to this practice extremely rarely, if there are no other treatment options at the moment, in order to avoid possible serious consequences (there have been isolated cases of a child's death after an injection). The dosage for newborns is from 0.75 to 1 mg (for babies up to 12 months - up to 2 mg), which in terms of solution will be 0.3-0.4 (0.3-0.8) ml.

The effective dose of Isoptin for children over one year old (up to 5 years) is 2-3 mg (in the form of a solution - 0.8-1.2 ml), for children over 5 years old (up to 14 years) - from 2.5 to 5 mg (in the form of a solution - from 1 to 2 ml).

Before using the drug "Isoptin" in children, it is advisable to take a course of drugs based on digitalis or its derivatives, which will help reduce the symptoms of heart failure and shorten the course of treatment with "Isoptin".

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Use Isoptin during pregnancy

The use of the drug "Isoptin" during pregnancy and breastfeeding is considered unsafe due to the lack of proven data on its effect on the course of pregnancy and the health of the fetus. Theoretically, the drug is considered quite safe, so if the risk from using the drug is presumably less than the expected benefit, it can be prescribed in tablet form during pregnancy as prescribed by a doctor. But breastfeeding will have to be stopped during therapy with the drug.

Contraindications

"Isoptin", like most cardiac drugs, has quite a few contraindications for use, which must be taken into account in order to avoid sad, and sometimes tragic, consequences.

General contraindications for all forms of the drug are:

• disruption of the conduction of nerve impulses from the atria to the ventricles (atrioventricular block 2 and 3 degrees), if it is not controlled by a special pacemaker,
• weakness of the pacemaker, as the sinus node is called, with alternating episodes of tachycardia and bradycardia,
• atrial fibrillation in the presence of additional conduction pathways in the heart, which is typical for Wolff-Parkinson-White and Lown-Ganong-Levine syndromes,
• intolerance to individual components of the drug.

The drug is also not used to treat patients under 18 years of age. This is due to insufficient information about the effect of Isoptin on children's bodies.

It is considered undesirable to prescribe the drug to patients with 1 degree atrioventricular block, as well as to those whose heart rate is less than 50 beats per minute. If the patient's upper pressure indicator is below 90 mm Hg, he will also have to choose another drug.

Taking tablets is also contraindicated:

• in acute myocardial infarction against the background of greatly reduced blood pressure and pulse, complicated by left ventricular dysfunction,
• severe cases of left ventricular failure (cardiogenic shock),
• during therapy with Colchicine, used to treat gout.

Contraindications for using the drug in solution form:

• persistently low blood pressure (hypotension),
• cardiogenic shock, if it does not arise as a result of a disturbance in heart rhythm,
• fainting caused by a sudden, acute disturbance of heart rhythm (Morgagni-Adams-Stokes syndrome),
• slowing or complete cessation of impulse transmission from the sinus node to the atria (sinoauricular block),
• increased heart rate due to rapid work of the heart ventricles (ventricular tachycardia),
• chronic heart failure, unless its cause is supraventricular tachycardia,
• periods of pregnancy and breastfeeding,

Isoptin injections are not given within 2 days after the end of Disopyramide therapy. Simultaneous administration of Isoptin and beta-blockers is also not practiced.

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Side effects Isoptin

It is possible that even correct drug administration, depending on the individual characteristics of the patient's body and its reaction to a certain drug, may be accompanied by symptoms not related to the main purpose of the drug. We are talking about side effects of drugs, which can be positive (useful), but most often the situation is exactly the opposite.

So, taking Izodinit may be accompanied by some unpleasant symptoms that occur with varying frequency.

The gastrointestinal tract may react to the drug by causing some digestive problems. Most often, patients taking Isoptin experience stool disorders in the form of constipation, nausea, and much less often diarrhea. Some note an increase in appetite, while others experience noticeable swelling of the gums while taking the drug, which subsequently begin to hurt and bleed, and others complain of intestinal obstruction. If the patient has certain liver disorders, an increase in the level of enzymes in the blood (liver transaminase and alkaline phosphatase) may be observed.

Some undesirable disorders can also be observed in the work of the cardiovascular system. The most common of them are bradycardia (pulse less than 50 beats per minute) or, on the contrary, increased heart rate at rest (tachycardia), a fairly strong decrease in pressure (hypotension), and increased symptoms of heart failure. But the appearance or increase of signs of angina pectoris occurs rarely, although sometimes such a condition against the background of severe damage to the coronary arteries can be accompanied by myocardial infarction. Cases of heart rhythm disorders, including ventricular fibrillation/flutter (arrhythmia), are also far from common.

It was noted above that intravenous injections should be administered slowly, otherwise the following life-threatening conditions may occur: complete cessation of impulses from the atrium to the ventricles (3rd degree AV block), a strong decrease in pressure with the development of acute vascular insufficiency (collapse), cardiac arrest (asystole).

The central and peripheral nervous systems may react to taking Isonidin with headaches, dizziness, and short-term loss of consciousness (fainting). Some patients report increased fatigue, slow reactions, and drowsiness, while in others taking the drug may cause depressive states with increased anxiety. Also, in some cases, tremors of the hands and arms, impaired swallowing function, kinetic disturbances in the upper and lower extremities, shuffling gait, etc. are observed.

Among the reactions of the immune system, one can single out such allergic manifestations as skin rashes, itching, redness of the skin, and the development of Stevens-Johnson syndrome.

Other side effects of the drug include weight gain, pulmonary and limb edema, increased platelet levels (thrombocytopenia), decreased white blood cell levels (agranulocytosis), enlarged breasts (gynecomastia) and discharge from them (galactorrhea), increased prolactin hormone levels (hyperprolactinemia), and joint pathologies.

When large doses of the drug are administered intravenously, temporary loss of vision may occur as they accumulate in the blood plasma.

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Overdose

In principle, therapy with large doses of the drug "Isoptin" should be carried out in a hospital setting under the supervision of the attending physician, which in most cases excludes an overdose of the drug. If for some reason this does happen, you must immediately take all necessary measures to remove particles of the drug from the body as soon as possible.

How can you tell if you have an overdose? Most likely, based on the following signs:

• a very strong drop in blood pressure readings, up to critical levels,
• complete loss of consciousness while taking the drug,
• state of shock,
• the appearance of symptoms of 1st or 2nd degree AV block of the heart, and sometimes even the onset of complete block (3rd degree) is possible,
• the appearance of signs of ventricular tachycardia,
• sinus bradycardia with a pulse rate below 55 beats per minute.

Sometimes, when taking Isoptin in large doses (especially when administered intravenously), cases of cardiac arrest were observed. And it was not always possible to save the patients.

The severity of overdose symptoms depends on the dose of the drug taken by the patient, the patient's age, the timeliness and completeness of first aid, which consists of stopping the process of intoxication of the body.

If everything points to an overdose of Isoptin tablets, the first step is to remove the drug from the gastrointestinal tract. For this purpose, vomiting can be induced in the patient (by mechanical action on the root of the tongue or by taking emetics), gastric lavage and bowel emptying (enemas, laxatives). In case of critically weak intestinal motility and in case of using prolonged-release tablets, gastric lavage is relevant even within 12 hours after taking the drug.

If a prolonged form of the drug was used in the treatment of diseases, it should be taken into account that its effect may be felt within the next 2 days, during which time particles of the tablets will be released in the intestines, where they are absorbed and transported into the blood. Individual particles of the drug can be located along the entire gastrointestinal tract, creating additional foci of poisoning, which cannot be removed by regular gastric lavage.

In case of cardiac arrest, standard resuscitation measures are carried out (direct and indirect cardiac massage, artificial respiration).

A specific antidote to verapramil is calcium gluconate, a 10% solution of which is administered by injection in a volume of 10 to 30 ml. Repeated administration of calcium is carried out by drip (injection rate of 5 mmol per hour).

Cardiac arrest, AV block, sinus bradycardia in addition to cardiac electrical stimulation require the administration of the following drugs: Isoprenaline, Orciprenaline, and atropine drugs.

In case of a strong decrease in blood pressure, "Dopamine", "Dobutamine", "Norepinephrine" are used. If there are persistent symptoms of myocardial insufficiency, the first two drugs in combination with calcium intake will be useful.

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Interactions with other drugs

The cardiac drug Isoptin has the property of reacting with many medications, therefore, the use of any other drug during therapy with Isoptin should be reported to the attending physician in order to avoid unpleasant and dangerous consequences, including an overdose of verapramil.

Thus, the simultaneous use of Isoptin and drugs that lower blood pressure leads to the fact that the effect of both drugs is significantly enhanced, which can lead to a sharp drop in blood pressure.

The probability of developing various complications in the form of a drop in heart rate and blood pressure, the development of atrioventricular block or heart failure increases if Isoptin is taken together with beta-blockers, antiarrhythmic drugs, and inhalation anesthetics. This is due to the increased inhibitory effect of the drugs on the conductivity and function of the sinus node and cardiac myocardium.

"Isoptin" when taken simultaneously with certain drugs (antihypertensive drugs aliskiren ("Rasilez"), tranquilizers based on buspirone ("Spitomin", "Buspirone"), cardiac glycoside "Digoxin", antitumor antibiotic "Doxorubicin", gout treatment "Colchicine", bronchodilator "Theophylline" and antiarrhythmic drug "Quinidine") can increase their concentration in the blood plasma, enhancing their effect and provoking the development of side effects. Most often, an excessive drop in pressure or the development of AV block is observed.

An increase in the concentration of drugs in the blood under the influence of Isoptin is also observed when taken simultaneously with the alpha-adrenergic blockers Prazosin and Terazosin, the immunosuppressant Cyclosporine, the anticonvulsant Carmazepine, the antiepileptic drug Valproic acid and muscle relaxants.

It is possible that the blood levels of the active substance of the sedative drug "Midazolam" and ethanol may increase with simultaneous therapy with these drugs and "Isoptin".

The simultaneous use of Isoptin with the antiarrhythmic drugs Amidaron and Desopyramide provokes a significant decrease in the force of heart contractions, causing bradycardia and collapse, decreased conduction of impulses in the heart, and AV blocks of varying degrees.

Concomitant therapy with Isoptin and the antiarrhythmic drug Flecainide may negatively affect the contractility of the main heart muscle and slow down AV conduction.

"Isoptin" may interact with some statins (atorvastatin, lovastatin, simvastatin), since it suppresses the action of the CYP3A4 isoenzyme, which is involved in the metabolism of the above statins. In this case, the level of statins in the blood plasma increases, which can lead to the destruction of muscle tissue cells.

When veraptamil preparations are administered intravenously to patients undergoing beta-blocker treatment, there is a high risk of a severe drop in blood pressure and cardiac arrest.

An increase in the antianginal effect of Isoptin is observed against the background of parallel administration of nitrates used to treat cardiac ischemia.

Taking acetylsalicylic acid while taking Isoptin increases the risk of various bleedings.

The combination of Isoptin with the muscle relaxant Dantrolene is also considered potentially dangerous, since their interaction can cause the patient’s death associated with the development of ventricular fibrillation.

Nonsteroidal anti-inflammatory drugs (Diclofenac), the anti-tuberculosis drug Rifampicin, barbiturates (Phenytoin, Phenobarbital) and nicotine can reduce the content of verapamil in the blood, largely due to the acceleration of its metabolism in the liver and rapid elimination from the body. In this regard, all the beneficial effects of Isoptin are noticeably weakened.

But the antiulcer drug Cimetidine, on the contrary, enhances the action of verapamil, which is part of the Isoptin tablets. But it has no effect on the kinetic characteristics of Isoptin when administered intravenously.

The results of the interaction of Isoptin and the antidepressant Imipramine (Melipramine) are visible on the cardiogram in the form of indicators indicating a decrease in atrioventricular conduction.

It is not advisable to carry out simultaneous therapy with the antiherpetic drug Clonidine (Clonidine), since there is a risk of cardiac arrest.

It is difficult to predict the results of drug interactions with lithium preparations (lithium carbonate). Such dangerous situations as the development of severe bradycardia and disruption of the structure and functions of the nervous system (neurotoxicity) are possible. Sometimes a decrease in the lithium content in the blood is observed, which negatively affects the mental health of the patient.

Taking the neuroleptic "Sertindole" ("Serdolect") during therapy with "Isoptin" increases the likelihood of developing ventricular heart rhythm disturbances.

"Isoptin" is able to enhance the muscle relaxant effect of tubocurarine and vecuronium chlorides.

Estrogens and sympathomimetics may significantly reduce the hypotensive effect of Isoptin.

The use of anesthetics (Enflurane, Etomidate) during treatment with Isoptin should be done with caution, since the latter can prolong the effect of anesthesia, significantly inhibiting the activity of the cardiovascular system.

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Storage conditions

The storage conditions for various forms of the drug provide for maintaining its effectiveness for the specified time at a temperature not exceeding 25 degrees. Keep out of reach of children.

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Special instructions

It is not prohibited to use Isoptin and alpha-blockers during combined therapy of angina and hypertension. However, in this case, intravenous administration of alpha-blockers is not allowed.

The drug may cause individual reactions of drowsiness and dizziness, which will negatively affect the performance of work that requires increased attention.

When taking Isoptin, you should refrain from smoking and drinking alcohol.

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Shelf life

The solution and tablets "Isoptin" can be stored for no more than 5 years. The shelf life of the prolonged-release drug is 36 months (3 years).

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