Isoptin tablets instructions for use. Isoptin for the treatment of arterial hypertension in the form of tablets and solution. Who should not be treated with a calcium channel blocker
Various medicines are used to treat high blood pressure. One of them is the drug "Isoptin". It helps in lowering blood pressure and stabilizing the heart rate. How to take the drug for hypertension?
Isoptin is produced in two dosage forms - in tablets of 40 and 80 mg of the active substance and in the form of an injection solution, which contains 5 mg of the active ingredient.
Verapamil acts as the main element that has a therapeutic effect. In addition to it, the composition of the drug contains excipients.
Pharmacodynamics and pharmacokinetics
The drug is absorbed through the intestines. The active element of the tablets reaches its highest concentration 1.5 hours after ingestion. The half-life of the substance is from 3 to 7 hours.
The drug is excreted from the body mainly through the organs of the urinary system, in a minimal part - through the intestines. A large concentration of the active substance leaves on the first day, after 5 days all components are removed completely.
pharmachologic effect
"Isoptin SR240" has a hypotensive effect, normalizes the work of the heart and blood vessels. The active substance of the drug effectively eliminates cardiac spasms. It also reduces the resistance of blood vessels, which leads to a decrease in blood pressure.
The medication helps in restoring the heart rhythm if the patient has atrial fibrillation and other diseases that disrupt the rhythm. Also, the active component inhibits the conduction of an electrical impulse in the atrioventricular node. It also allows you to normalize the rhythm of the heart.
Thanks to Isoptin tablets - the heart rhythm returns to normal
Indications for use
The drug, depending on the form, has its own indications for use. Isoptin tablets are used in the presence of such pathologies as:
- Hypertension.
- Tachycardia.
- Cardiac ischemia.
- Angina.
- Atrial flutter, in which tachyarrhythmia is observed.
In the form of an injection solution, the agent is used if the patient has supraventricular tachyarrhythmia. In this case, the drug is prescribed to normalize sinus rhythm, control the frequency of ventricular contractions.
Method of application and dosage
The tablet must be taken with meals. The pill should be swallowed completely, without chewing, and washed down with plenty of water or other drink.
Instructions for use prescribes standard dosages for patients. But the attending physician must select the dose individually for each patient, taking into account his condition.
Use during pregnancy and lactation
When carrying a baby, taking "Isoptin" is prohibited. Only in extreme cases is it possible to prescribe a remedy in the last stages of pregnancy. In this case, the doctor must compare the possible harm and benefit of using the drug, both for the expectant mother and for the fetus.
When breastfeeding, the medicine is prohibited. If you can not do without medication, you will have to give up breastfeeding.
Elderly and children's age
Elderly patients "Isoptin" can be taken, but only with caution. The attending physician should adjust the dose depending on the patient's condition.
Children under the age of 18 are not recommended to use the medication.
Admission for pathological processes in the liver and kidneys
The use of "Isoptin" for violations in the activity of the kidneys and liver is not prohibited, but it is important to carry out treatment with extreme caution. It is recommended to start therapy with the lowest dosage - approximately 0.04 g. When prescribing a medicine, the doctor must take into account how severe the damage to these organs is.
Side effects
Negative reactions of the body when taking "Isoptin SR240" in patients are not uncommon. There are a lot of them, so patients should adhere to the prescriptions of the attending doctor as much as possible, do not violate the dosage and treatment regimen.
Antihypertensive medicine may cause the following side effects:
- Violations in the work of the heart and blood vessels. This may be AV blockade, termination of the sinus node, a sharp decrease in blood pressure, rapid heartbeat, tissue swelling, exacerbation of heart failure.
- Failure in the activity of the gastrointestinal tract. Patients develop nausea, vomiting, stool disorders, pain in the abdomen, intestinal obstruction, bleeding gums.
- Disorder of the nervous system. Patients often note that when taking pills they experience headaches, trembling fingers.
- Attacks of dizziness.
- Noise or ringing in the ears.
- Skin rashes that may be accompanied by itching, burning, redness.
- Violation of the functioning of the reproductive and reproductive systems, both in men and women.
- Deterioration of the musculoskeletal system. Patients complain of pain and weakness in the muscles.
- Weakening of the immune system, development of hypersensitivity.
If the side effects are disturbing too often, you need to inform the doctor about it. He will adjust the dose or even replace it with another drug.
Contraindications
Like almost any other medication, "Isoptin SR 240" has its own restrictions on use, in the presence of which the doctor cannot prescribe treatment for them. Contraindications include the following:
- Individual intolerance to the active or additional element of the drug.
- Cardiogenic shock.
- High weakness of the sinus node.
- Atrioventricular block, occurring in the second or third degree.
- Heart failure.
- Atrial flutter.
- Carrying a baby.
- Breastfeeding an infant.
- Children's age, when the child is not yet 18 years old.
There are also conditions in which the use of "Isoptin" is not prohibited, but with it it is important to exercise maximum caution. This list includes the following violations:
- Bradycardia.
- Acute myocardial infarction.
- Malfunction of the left ventricle.
- Insufficiency of the kidneys and liver.
- Pathological processes affecting neuromuscular transmission.
- Elderly age.
To identify contraindications before prescribing a medication, the doctor must conduct an examination.
special instructions
Receiving "Isoptin" can adversely affect the general condition of the patient, causing drowsiness, weakness, bouts of dizziness. In this regard, it is not recommended during treatment to work with dangerous mechanisms, drive a vehicle and perform other activities that require maximum concentration and high speed of psychomotor reactions.
Interaction with other drugs
"Isoptin" is able to come into contact with other medicines, causing different effects. This is important to consider when prescribing and taking medication. When contacting a doctor, the patient must tell what drugs he is still taking.
"Isoptin" interacts with the following means:
- Other drugs that lower blood pressure. Together with them, the patient's blood pressure may decrease to critical levels. Therefore, you should not take Isoptin and drugs such as ACE inhibitors, diuretics, vasodilators at the same time.
- Beta-blockers, antiarrhythmic drugs. Joint reception with these types of drugs leads to severe hypotension, the development of heart failure, bradycardia.
- Nitrates. Together with them, the antianginal effect of Isoptin is enhanced.
- Aliskiren. Simultaneous reception leads to an increase in the likelihood of side effects
- Dantrolene. If you combine it and Isoptin, the risk of developing ventricular fibrillation will increase, in which the death of a person often occurs.
- Carbamazepine. With this substance, there is an increase in the therapeutic effect, an increase in the likelihood of adverse reactions of the body.
- Rifampicin. Simultaneous use with this agent can lead to an acceleration of the activity of liver enzymes. This will cause the rapid removal of the active component of "Isoptin" from the body, which will negatively affect the effectiveness of the drug.
- Sertindole. Combination with this substance turns into malfunctions of the ventricles, heart rhythm disturbances.
- Cimetidine. With him, the action of "Isoptin" is enhanced.
These interactions must be taken into account in the treatment of hypertension.
Overdose
When taking a large concentration of the drug in humans, an overdose occurs. It is fraught with the following manifestations:
- Excessive decrease in blood pressure.
- Increase in blood glucose.
- Brief cardiac arrest.
- Vomiting, nausea.
- Loss of consciousness.
In case of an overdose, you should call an ambulance as soon as possible. Treatment is carried out by gastric lavage and symptomatic therapy in stationary conditions.
Price and analogues
The cost of "Isoptin" is optimal, the drug is available to all patients. For a package containing 100 tablets, you will need to pay about 350 rubles. The concentration of the active ingredient in such a pack will be 80 mg.
If, for any reason, the patient does not want or cannot take Isoptin, the attending physician may replace it with an analogue. You can use medicines with the same active ingredient and with a different element, but with a similar therapeutic effect.
Absolute analogues include such drugs as Verapamil, Veracard, Finoptin. Means with a similar effect - Amlodak, Kaveril, Lekoptin. These lists include drugs, both Russian and foreign.
Instructions for use:
Isoptin is a drug with antihypertensive, antiarrhythmic and antianginal effects.
Release form and composition
Isoptin is produced in the following dosage forms:
- Film-coated tablets: white, biconvex, round; 40 mg each - with the inscription "40" on one side and an engraving in the form of a triangle on the other; 80 mg each - with the inscription "ISOPTIN 80" on one side and the risk for dividing and the inscription "KNOLL" on the other (tablets of 40 and 80 mg: 10 pcs. in blisters, 2 or 10 blisters in a carton box; 20 pieces in blisters, 1 or 5 blisters in a carton box; tablets of 80 mg: 25 pieces in blisters, 4 blisters in a carton box);
- Solution for intravenous administration: colorless, transparent (2 ml in colorless glass ampoules, 5, 10 or 50 ampoules in trays or blisters, 1 blister or tray in a cardboard box).
The composition of 1 tablet includes:
- Active substance: verapamil - 40 or 80 mg (in the form of hydrochloride);
- Auxiliary components (40/80 mg, respectively): calcium hydrophosphate dihydrate - 70/140 mg; microcrystalline cellulose - 23/46 mg; colloidal silicon dioxide - 0.7 / 1.4 mg; croscarmellose sodium - 1.8 / 3.6 mg; magnesium stearate - 1.5 / 3 mg.
The composition of the film shell (40/80 mg, respectively): sodium lauryl sulfate - 0.1 / 0.1 mg; hypromellose 3 MPa - 1.7 / 2 mg; talc - 4 / 4.5 mg; macrogol 6000 - 2 / 2.3 mg; titanium dioxide - 1 / 1.1 mg.
The composition of 1 ampoule includes:
- Active substance: verapamil - 5 mg (in the form of hydrochloride);
- Auxiliary components: hydrochloric acid 36% - to bring the pH; sodium chloride - 17 mg; water for injection - up to 2 ml.
Indications for use
Isoptin in the form of tablets is prescribed for the treatment of the following diseases:
- Arterial hypertension;
- Paroxysmal supraventricular tachycardia;
- Ischemic heart disease, including unstable angina, chronic stable angina (classic exertional angina), Prinzmetal's angina (angina pectoris caused by vasospasm);
- Atrial fibrillation / flutter, which is accompanied by tachyarrhythmia (except Lown-Ganong-Levin syndrome (LGL) and Wolff-Parkinson-White (WPW)).
The drug in the form of a solution for intravenous administration is used in the treatment of supraventricular tachyarrhythmias. Isoptin is prescribed for the following indications:
- Restoration of sinus rhythm in paroxysmal supraventricular tachycardia, including conditions that are associated with the presence of additional pathways (Lown-Ganong-Levin and Wolff-Parkinson-White syndromes);
- Control of the frequency of ventricular contractions during atrial fibrillation and flutter (tachyarrhythmic variant), except when the atrial fibrillation or flutter is associated with the presence of additional pathways (Lown-Ganong-Levin and Wolff-Parkinson-White syndromes).
Contraindications
- AV block II-III degree (except for patients with an artificial pacemaker);
- Syndrome of weakness of the sinus node ("bradycardia-tachycardia" syndrome, except for patients with an artificial pacemaker);
- Atrial fibrillation / flutter in the presence of additional pathways (Lown-Ganong-Levin and Wolff-Parkinson-White syndrome);
- Age up to 18 years (efficacy and safety of the drug for this age group of patients have not been established);
- Hypersensitivity to the components of the drug.
Additional contraindications to taking Isoptin in the form of tablets are:
- Chronic heart failure;
- Acute myocardial infarction, complicated by severe arterial hypotension, bradycardia and left ventricular failure;
- Cardiogenic shock;
- Simultaneous reception with colchicine.
Intravenous administration of Isoptin is contraindicated in the presence of the following diseases/conditions:
- Arterial hypotension or cardiogenic shock (except caused by arrhythmia);
- Morgagni-Adams-Stokes syndrome;
- Sinoauricular blockade;
- Ventricular tachycardia with wide QRS complexes (more than 0.12 seconds);
- Chronic heart failure stage IIB-III (except for those caused by supraventricular tachycardia, which is to be treated with verapamil);
- Preliminary use of disopyramide (within 48 hours);
- Simultaneous intravenous administration of beta-blockers;
- Pregnancy and lactation.
Isoptin in all formulations should be used with caution in bradycardia and first degree AV block.
Inside the drug is prescribed with caution in severe functional disorders of the kidneys and liver, arterial hypotension, diseases related to neuromuscular transmission, including Lambert-Eaton syndrome, myasthenia gravis and Duchenne muscular dystrophy.
Intravenous administration is recommended with caution in elderly patients, as well as in the following diseases: heart failure, severe aortic stenosis, myocardial infarction with left ventricular failure, mild or moderate arterial hypotension, renal and / or liver failure.
Method of application and dosage
Isoptin in the form of tablets is taken orally, swallowed whole (can not be chewed or dissolved) and washed down with water. It is preferable to take the drug during or immediately after a meal.
The scheme of Isoptin application is determined individually, taking into account the severity of the disease and the clinical picture.
For all recommended indications, the average daily dose is 240-480 mg. With prolonged therapy, a daily dose of 480 mg should not be exceeded. The maximum daily dose of Isoptin should be taken only in a hospital setting.
The initial single dose is 40-80 mg, the frequency of administration is 3-4 times a day.
Patients with functional disorders of the liver are recommended to start therapy with a single dose of 40 mg. Multiplicity of reception - 2-3 times a day. In the future, the doctor selects the dose individually.
Isoptin in the form of a solution for injection can only be administered intravenously.
The introduction must be carried out slowly with continuous monitoring of the ECG and blood pressure for at least 2 minutes (in elderly patients - 3 minutes, which reduces the risk of adverse effects).
The initial dose is 5-10 mg (0.075-0.15 mg / kg of body weight). With an inadequate response to the first injection after 30 minutes, you can enter a second dose (10 mg).
Side effects
During therapy, the development of disorders from some body systems is possible:
- Digestive system: pain and discomfort in the abdomen, vomiting, nausea, constipation, intestinal obstruction; in some cases - a transient increase in the blood plasma activity of hepatic transaminases and alkaline phosphatase; rarely - gum hyperplasia (soreness, bleeding, swelling), increased appetite, diarrhea;
- Cardiovascular system: severe bradycardia, reddening of the face, atrioventricular blockade, marked decrease in blood pressure, the appearance of symptoms of heart failure when using high doses of the drug, especially in predisposed patients; palpitations, tachycardia, sinus arrest; rarely - arrhythmia (including flutter and ventricular fibrillation), angina pectoris up to the development of myocardial infarction (especially in patients with severe obstructive lesions of the coronary arteries), bradycardia;
- Nervous system: general weakness, anxiety, depression, drowsiness, extrapyramidal disorders (stiffness of the legs or arms, ataxia, shuffling gait, mask-like face, difficulty swallowing, trembling of the hands and fingers), headache, dizziness, convulsions during drug administration, tremor , paresthesia; in rare cases - lethargy, increased nervous excitability, fatigue;
- Allergic reactions: erythema multiforme exudative, flushing of the skin of the face, skin rash, itching, Stevens-Johnson syndrome, bronchospasm;
- Other: weight gain; very rarely - arthritis, agranulocytosis, transient blindness at the peak of drug concentration in the blood, asymptomatic thrombocytopenia, pulmonary edema, development of peripheral edema, fatigue, hyperprolactinemia, gynecomastia, impotence, galactorrhea, muscle weakness, increased sweating, joint pain, myalgia.
Most of the listed side effects are typical for all dosage forms of Isoptin.
special instructions
It is impossible to abruptly cancel the reception of Isoptin. The dose is recommended to be reduced gradually until the complete withdrawal of therapy.
Intravenous administration of Isoptin can cause a transient decrease in blood pressure, which is usually not clinically manifested, but may be accompanied by the development of dizziness.
Circulatory insufficiency (except severe or caused by arrhythmia) before starting therapy with Isoptin should be compensated with diuretics and cardiac glycosides. In patients with severe and moderate heart failure, acute progression of circulatory failure may occur during therapy.
The solution does not contain antimicrobial or bacteriostatic agents and is intended for simultaneous intravenous administration.
Isoptin remains stable for at least 24 hours (when stored at temperatures up to 25 ° C in a place protected from light) in most large volume parenteral solutions. After taking a portion of the contents of any volume, the unused solution should be destroyed immediately.
It is not recommended to dilute Isoptin with sodium lactate solutions in plastic bags made of polyvinyl chloride to avoid stability problems. Avoid mixing Isoptin solutions with amphotericin B, albumin, hydralazine hydrochloride or trimethoprim and sulfamethoxazole.
Verapamil hydrochloride precipitates in any solution with a pH greater than 6.
Isoptin, depending on individual characteristics, can change the reaction rate, disrupting the ability to drive a car and perform work that requires increased attention.
drug interaction
With the simultaneous use of Isoptin with inhibitors of the CYP3A4 isoenzyme, an increase in the concentration of verapamil in the blood plasma is observed, with inducers of the CYP3A4 isoenzyme - a decrease in its concentration (the interaction should be taken into account with the simultaneous use of such agents).
With the simultaneous use of Isoptin with certain drugs, undesirable effects may occur (C ss - the average equilibrium concentration of the substance in the blood plasma, C max - the maximum concentration of the substance in the blood plasma, AUC - the area under the pharmacokinetic curve "concentration-time", T1 / 2 - half-life):
- Prazosin: an increase in its C max , T 1/2 prazosin does not change;
- Terazosin: increase in its AUC and C max ;
- Quinidine: decrease in its clearance;
- Theophylline: decrease in its systemic clearance;
- Carbamazepine: increase in its AUC in patients with sustained partial epilepsy;
- Imipramine: increase in its AUC; on the concentration of the active metabolite of imipramine - desipramine, Isoptin does not affect;
- Glibenclamide: an increase in its C max and AUC;
- Clarithromycin, erythromycin, telithromycin: an increase in the concentration of verapamil is possible;
- Rifampicin: decrease in AUC, C max and oral bioavailability of verapamil;
- Doxorubicin: an increase in its AUC and C max in patients with small cell lung cancer;
- Phenobarbital: increased clearance of verapamil;
- Buspirone, midazolam: an increase in their AUC and C max;
- Metoprolol, propranolol: an increase in their AUC and C max in patients with angina pectoris;
- Digitoxin: a decrease in its total and extrarenal clearance;
- Digoxin: an increase in its C max , AUC and C ss ;
- Cimetidine: an increase in the AUC of the R-enantiomer and S-enantiomer of verapamil with a corresponding decrease in the clearance of R- and S-verapamil;
- Cyclosporine: increase in its AUC, C ss , C max ;
- Sirolimus, tacrolimus, lovastatin: their concentration may increase;
- Atorvastatin: possible increase in its concentration and AUC;
- Simvastatin, almotriptan: increase in their AUC and C max ;
- Sulfinpyrazone: an increase in the clearance of verapamil and a decrease in its bioavailability;
- St. John's Wort perforatum: a decrease in the AUC of the R-enantiomer and S-enantiomer of verapamil with a corresponding decrease in C max ;
- Grapefruit juice: an increase in AUC and C max of the R-enantiomer and S-enantiomer of verapamil (renal clearance and T 1/2 do not change);
- Terazosin, prazosin: additive hypotensive effect;
- Diuretics, antihypertensives, vasodilators: increased hypotensive effect;
- Ritonavir and other antiviral agents for the treatment of HIV infection: inhibition of the metabolism of verapamil is possible, which can lead to an increase in its concentration in the blood plasma (with simultaneous use of the dose of Isoptin should be reduced);
- Quinidine: may increase the hypotensive effect; in patients with hypertrophic obstructive cardiomyopathy, pulmonary edema may develop;
- Carbamazepine: increase in its concentration in blood plasma; possible development of adverse reactions characteristic of carbamazepine (headache, diplopia, dizziness or ataxia);
- Lithium: increasing its neurotoxicity;
- Rifampicin, sulfinpyrazone: it is possible to reduce the hypotensive effect of verapamil;
- Muscle relaxants: their effect may be enhanced;
- Acetylsalicylic acid: increased bleeding;
- Colchicine: a significant increase in its concentration in the blood is possible;
- Ethanol (alcohol): an increase in its concentration in blood plasma;
- Beta-blockers, antiarrhythmics: mutual enhancement of cardiovascular effects (more significant decrease in heart rate, more pronounced AV blockade, increased arterial hypotension and the development of symptoms of heart failure).
Patients taking Isoptin, treatment with lipid-lowering agents - HMG-CoA reductase inhibitors (lovastatin, simvastatin, atorvastatin) should be started with the lowest possible doses, which are gradually increased with continued therapy. If it is necessary to use Isoptin in patients already receiving HMG-CoA reductase inhibitors, it is necessary to consider the possibility of reducing the dose of statins and re-titrating the dose, taking into account the concentration in serum cholesterol. Fluvastatin, rosuvastatin and pravastatin are not metabolized by the action of the CYP3A4 isoenzyme, so their interaction with verapamil is the least likely.
Composition and form of release
1 ampoule with 2 ml of injection solution contains verapamil hydrochloride 5 mg; in a box of 5 or 50 pcs.
1 coated tablet - 40 and 80 mg; in a blister 20 pcs., in a box of 5 blisters.
pharmachologic effect
pharmachologic effect- hypotensive, antiarrhythmic, antianginal.It inhibits the transmembrane flow of calcium ions in the cells of the myocardium and vascular smooth muscles (causes vasodilation), reduces peripheral vascular resistance without a reflex increase in heart rate, reduces myocardial contractility.
Indications for Isoptin ®
Arterial hypertension, ischemic heart disease, atrial fibrillation (paroxysmal supraventricular tachycardia).
Contraindications
Cardiogenic shock, acute complicated myocardial infarction, severe conduction disorders, sick sinus syndrome.
Use during pregnancy and lactation
With caution, especially in the first trimester.
Side effects
Myocardial rhythm and conduction disturbances, heart failure, hypotension, edema, myalgia, arthralgia, allergic reactions, etc.
Interaction
Increases the effects (including side effects) of beta-blockers. Increases hypotension when co-administered with other antihypertensive drugs.
Dosage and administration
Tablets: inside - 40-80 mg 3-4 times a day after meals; maintenance dose can be used for a long period.
Injection: in / in, under the control of ECG and blood pressure, either slowly (within 2 minutes) at an initial dose of 5 mg (if ineffective - again 5 mg after 5-10 minutes), or drip (to maintain the effect) - 5-10 mg / h in saline, glucose solution or other solutions with a pH less than 6.5, the total dose is 100 mg / day.
Storage conditions of the drug Isoptin ®
At a temperature not higher than 25 °C.Keep out of the reach of children.
Shelf life of Isoptin ®
5 years.Do not use after the expiry date stated on the packaging.
Synonyms of nosological groups
| Category ICD-10 | Synonyms of diseases according to ICD-10 |
|---|---|
| I10 Essential (primary) hypertension | arterial hypertension |
| Arterial hypertension | |
| arterial hypertension | |
| Sudden increase in blood pressure | |
| Hypertensive state | |
| Hypertensive crises | |
| hypertension | |
| Arterial hypertension | |
| Hypertension, malignant | |
| Essential hypertension | |
| Hypertonic disease | |
| Hypertensive crises | |
| Hypertensive crisis | |
| Hypertension | |
| malignant hypertension | |
| Malignant hypertension | |
| Isolated systolic hypertension | |
| Hypertensive crisis | |
| Primary arterial hypertension | |
| Essential arterial hypertension | |
| Essential arterial hypertension | |
| Essential hypertension | |
| Essential hypertension | |
| I15 Secondary hypertension | arterial hypertension |
| Arterial hypertension | |
| Arterial hypertension of the crisis course | |
| Arterial hypertension complicated by diabetes mellitus | |
| arterial hypertension | |
| Vasorenal hypertension | |
| Sudden increase in blood pressure | |
| Hypertensive circulatory disorders | |
| Hypertensive state | |
| Hypertensive crises | |
| hypertension | |
| Arterial hypertension | |
| Hypertension, malignant | |
| Symptomatic hypertension | |
| Hypertensive crises | |
| Hypertensive crisis | |
| Hypertension | |
| malignant hypertension | |
| Malignant hypertension | |
| Hypertensive crisis | |
| Exacerbation of hypertension | |
| Renal hypertension | |
| Renovascular hypertension | |
| Renovascular hypertension | |
| Symptomatic arterial hypertension | |
| Transient arterial hypertension | |
| I20 Angina pectoris [angina pectoris] | Heberden's disease |
| Angina pectoris | |
| An attack of angina pectoris | |
| Recurrent angina | |
| Spontaneous angina | |
| stable angina | |
| Angina Syndrome X | |
| angina pectoris | |
| Angina (attack) | |
| angina pectoris | |
| rest angina | |
| Angina pectoris progressive | |
| Mixed angina | |
| Angina spontaneous | |
| Stable angina | |
| Chronic stable angina | |
| I21 Acute myocardial infarction | left ventricular infarction |
| Myocardial infarction without Q wave | |
| Myocardial infarction in the acute period | |
| Myocardial infarction non-transmural (subendocardial) | |
| acute myocardial infarction | |
| Myocardial infarction with and without pathological Q wave | |
| Myocardial infarction transmural | |
| Myocardial infarction complicated by cardiogenic shock | |
| Non-transmural myocardial infarction | |
| Acute phase of myocardial infarction | |
| Acute myocardial infarction | |
| Subacute stage of myocardial infarction | |
| Subacute period of myocardial infarction | |
| subendocardial myocardial infarction | |
| Thrombosis of the coronary artery(s) | |
| Threatening myocardial infarction | |
| I25 Chronic ischemic heart disease | Ischemic heart disease against the background of hypercholesterolemia |
| Chronic ischemic heart disease | |
| Myocardial ischemia in arteriosclerosis | |
| Recurrent myocardial ischemia | |
| coronary heart disease | |
| Stable coronary artery disease | |
| Percutaneous transluminal angioplasty | |
| I47.1 Supraventricular tachycardia | Supraventricular paroxysmal tachycardia |
| Supraventricular tachyarrhythmia | |
| Supraventricular tachycardia | |
| Supraventricular arrhythmias | |
| Supraventricular paroxysmal tachycardia | |
| Supraventricular tachyarrhythmias | |
| Supraventricular tachycardia | |
| Neurogenic sinus tachycardia | |
| orthodromic tachycardias | |
| Paroxysmal supraventricular tachycardia | |
| Paroxysm of supraventricular tachycardia | |
| Paroxysm of supraventricular tachycardia in WPW syndrome | |
| Paroxysm of atrial tachycardia | |
| Paroxysmal supraventricular tachyarrhythmia | |
| Paroxysmal supraventricular tachycardia | |
| Polytopic atrial tachycardia | |
| Atrial arrhythmia | |
| Atrial true tachycardia | |
| Atrial tachycardia | |
| Atrial tachycardia with AV block | |
| Reperfusion arrhythmia | |
| Berzold-Yarish reflex | |
| Recurrent sustained supraventricular paroxysmal tachycardia | |
| Symptomatic ventricular tachycardias | |
| Wolff-Parkinson-White Syndrome | |
| Sinus tachycardia | |
| Supraventricular paroxysmal tachycardia | |
| Supraventricular extrasystole | |
| Supraventricular arrhythmias | |
| Tachycardia from the AV junction | |
| Supraventricular tachycardia | |
| Tachycardia orthodromic | |
| Sinus tachycardia | |
| Nodal tachycardia | |
| Chaotic polytopic atrial tachycardia | |
| I49.4 Other and unspecified premature depolarization | Extrasystolic arrhythmia |
| Extrasystole | |
| Extrasystole, unspecified | |
| I49.9 Cardiac arrhythmia, unspecified | AV reciprocal tachycardia |
| AV nodal reciprocal tachycardia | |
| Antidromic reciprocal tachycardia | |
| Arrhythmias | |
| Arrhythmia | |
| Heart arythmy | |
| Arrhythmia due to hypokalemia | |
| Ventricular arrhythmia | |
| Ventricular tachyarrhythmia | |
| High ventricular rate | |
| Atrial tachysystolic arrhythmia | |
| Heart rhythm disorder | |
| Heart rhythm disorders | |
| Heart rhythm disorders | |
| Paroxysmal supraventricular arrhythmia | |
| Paroxysmal supraventricular arrhythmia | |
| Paroxysmal supraventricular tachycardia | |
| Paroxysmal arrhythmia | |
| Paroxysmal atrioventricular rhythm | |
| Precordial pathological pulsation | |
| Cardiac arrhythmias | |
| Supraventricular tachyarrhythmia | |
| Supraventricular tachycardia | |
| Supraventricular arrhythmias | |
| tachyarrhythmia | |
| Extrasystolic arrhythmia | |
| R07.2 Pain in the region of the heart | Pain syndrome in myocardial infarction |
| Pain in cardiac patients | |
| Cardialgia | |
| Cardialgia on the background of dyshormonal myocardial dystrophy | |
| Cardiac syndrome | |
| Cardioneurosis | |
| Myocardial ischemic pain | |
| Neuroses of the heart | |
| Pericardial pain | |
| Pseudoangina pectoris | |
| Functional cardialgia |
Composition and form of release of the drug
Film-coated tablets white, round, biconvex, engraved with "ISOPTIN 80" on one side and "KNOLL" above the score line on the other.
Excipients: calcium hydrophosphate dihydrate - 140 mg, microcrystalline cellulose - 46 mg, colloidal silicon dioxide - 1.4 mg, croscarmellose sodium - 3.6 mg, magnesium stearate - 3 mg.
The composition of the film shell: hypromellose 3 MPa - 2 mg, sodium lauryl sulfate - 0.1 mg, macrogol 6000 - 2.3 mg, talc - 4.5 mg, titanium dioxide - 1.1 mg.
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
20 pcs. - blisters (1) - packs of cardboard.
20 pcs. - blisters (5) - packs of cardboard.
25 pcs. - blisters (4) - packs of cardboard.
pharmachologic effect
Selective class I, diphenylalkylamine derivative. It has antianginal, antiarrhythmic and antihypertensive effects.
The antianginal effect is associated both with a direct effect on the myocardium and with an effect on peripheral hemodynamics (reduces the tone of peripheral arteries, OPSS). The blockade of calcium entry into the cell leads to a decrease in the transformation of energy contained in macroergic bonds of ATP into mechanical work, and a decrease in myocardial contractility. Reduces myocardial oxygen demand, has a vasodilating, negative foreign and chronotropic effect. Increases the period of diastolic relaxation of the left ventricle, reduces the tone of the myocardial wall.
A decrease in peripheral vascular resistance may also be due to the antihypertensive effect of verapamil.
Verapamil significantly reduces AV conduction, prolongs the refractory period and suppresses the automatism of the sinus node. It has an antiarrhythmic effect in supraventricular arrhythmias.
Pharmacokinetics
When taken orally, more than 90% of the dose is absorbed. Protein binding - 90%. It is metabolized during the "first pass" through the liver. The main metabolite is norverapamil, which has less pronounced hypotensive activity than unchanged verapamil.
T 1 / 2 when taking a single dose is 2.8-7.4 hours, when taking repeated doses - 4.5-12 hours (due to saturation of the liver enzyme systems and an increase in the concentration of verapamil in the blood). After intravenous administration, the initial T 1/2 is about 4 minutes, the final one is 2-5 hours.
It is excreted mainly by the kidneys and 9-16% through the intestines.
Indications
Treatment and prevention of coronary artery disease: chronic stable angina (angina), unstable angina, vasospastic angina (Prinzmetal's angina / variant angina).
Treatment and prevention of rhythm disturbances: paroxysmal supraventricular tachycardia, chronic form of atrial flutter and fibrillation (tachyarrhythmic variant), supraventricular extrasystole.
Arterial hypertension. Hypertensive crisis.
Hypertrophic cardiomyopathy.
Contraindications
Cardiogenic shock, heart failure, pronounced violation of the contractile function of the left ventricle, severe arterial hypotension (systolic blood pressure less than 90 mm Hg), bradycardia; SSSU, sinoatrial blockade, AV block II and III degree (except for patients with a pacemaker); flutter and atrial fibrillation in combination with WPW syndrome or Lown-Ganong-Levin syndrome (except for patients with a pacemaker); simultaneous reception with colchicine, dantrolene, aliskiren, sertindole; pregnancy, lactation (breastfeeding); hypersensitivity to verapamil.
Dosage
Individual. Inside adults - at an initial dose of 40-80 mg 3 times / day. For dosage forms of prolonged action, a single dose should be increased, and the frequency of administration should be reduced. Children aged 6-14 years - 80-360 mg / day, up to 6 years - 40-60 mg / day; reception frequency - 3-4 times / day.
If necessary, verapamil can be administered intravenously (slowly, under the control of blood pressure, heart rate and ECG). A single dose for adults is 5-10 mg, if there is no effect after 20 minutes, repeated administration at the same dose is possible. A single dose for children aged 6-14 years is 2.5-3.5 mg, 1-5 years - 2-3 mg, up to 1 year - 0.75-2 mg. For patients with severely impaired liver function, the daily dose of verapamil should not exceed 120 mg.
Maximum daily dose for adults when taken orally is 480 mg.
Side effects
From the side of the cardiovascular system: bradycardia (less than 50 beats / min), a pronounced decrease in blood pressure, the development or aggravation of heart failure, tachycardia; rarely - angina pectoris, up to the development of myocardial infarction (especially in patients with severe obstructive lesions of the coronary arteries), arrhythmia (including flicker and ventricular flutter); with rapid on / in the introduction - AV blockade of the III degree, asystole, collapse.
From the side of the central nervous system and peripheral nervous system: dizziness, headache, fainting, anxiety, lethargy, fatigue, asthenia, drowsiness, depression, extrapyramidal disorders (ataxia, mask-like face, shuffling gait, stiffness of the arms or legs, trembling of the hands and fingers, difficulty swallowing).
From the digestive system: nausea, constipation (rarely - diarrhea), gingival hyperplasia (bleeding, soreness, swelling), increased appetite, increased activity of hepatic transaminases and alkaline phosphatase.
Allergic reactions: skin itching, skin rash, flushing of the skin of the face, erythema multiforme exudative (including Stevens-Johnson syndrome).
Other: weight gain, very rarely - agranulocytosis, gynecomastia, hyperprolactinemia, galactorrhea, arthritis, transient loss of vision against the background of maximum plasma concentration (with intravenous administration), pulmonary edema, asymptomatic thrombocytopenia, peripheral edema.
drug interaction
With simultaneous use with (vasodilators, thiazide diuretics, ACE inhibitors), there is a mutual enhancement of the antihypertensive effect.
With simultaneous use with beta-blockers, antiarrhythmic drugs, inhalation anesthesia, the risk of developing bradycardia, AV blockade, severe arterial hypotension, heart failure increases, due to the mutual strengthening of the inhibitory effect on the automatism of the sinoatrial node and AV conduction, contractility and conduction myocardium.
With parenteral administration of verapamil to patients who have recently received, there is a risk of developing arterial hypotension and asystole.
With simultaneous use with nitrates, the antianginal effect of verapamil is enhanced.
With simultaneous use with aliskiren, its concentration in plasma increases and the risk of side effects increases.
With simultaneous use with amiodarone, the negative inotropic effect, bradycardia, conduction disturbance, and AV blockade increase.
Since verapamil inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, drug interactions are theoretically possible due to an increase in plasma concentrations of statins. Cases of rhabdomyolysis have been described.
With simultaneous use with described cases of increased bleeding time due to additive antiplatelet action.
With simultaneous use with buspirone, the concentration of buspirone in the blood plasma increases, its therapeutic and side effects increase.
With the simultaneous administration of verapamil and dantrolene (in / in) in experimental studies in animals, ventricular fibrillation with a fatal outcome was observed. This combination is potentially dangerous.
With simultaneous use with digoxin, cases of an increase in the concentration of digitoxin in the blood plasma are described.
With simultaneous use with digoxin, the concentration of digoxin in the blood plasma increases.
With simultaneous use with disopyramide, severe arterial hypotension and collapse are possible, especially in patients with cardiomyopathy or decompensated heart failure. The risk of developing severe manifestations of drug interactions is apparently associated with increased negative inotropic action.
With simultaneous use with diclofenac, the concentration of verapamil in the blood plasma decreases; with doxorubicin - the concentration of doxorubicin in the blood plasma increases and its effectiveness increases.
With simultaneous use with imipramine, the concentration of imipramine in the blood plasma increases and there is a risk of developing unwanted changes on the ECG. Verapamil increases the bioavailability of imipramine by reducing its clearance. Changes in the ECG are due to an increase in the concentration of imipramine in the blood plasma and the additive inhibitory effect of verapamil and imipramine on AV conduction.
With simultaneous use with carbamazepine, the effect of carbamazepine increases and the risk of side effects from the central nervous system increases due to inhibition of the metabolism of carbamazepine in the liver under the influence of verapamil.
With simultaneous use with clonidine, cases of cardiac arrest in patients with arterial hypertension have been described.
Increases the plasma concentration of colchicine (a substrate of the CYP3A isoenzyme and P-glycoprotein).
With simultaneous use with lithium carbonate, the manifestations of drug interactions are ambiguous and unpredictable. Cases of increased effects of lithium and the development of neurotoxicity, a decrease in the concentration of lithium in the blood plasma, and severe bradycardia are described.
The vasodilatory effects of alpha-blockers and calcium channel blockers may be additive or synergistic. With the simultaneous use of terazosin or prazosin and verapamil, the development of severe arterial hypotension is partly due to pharmacokinetic interaction: an increase in C max and AUC of terazosin and prazosin.
With simultaneous use, rifampicin induces the activity of liver enzymes, accelerating the metabolism of verapamil, which leads to a decrease in its clinical effectiveness.
With simultaneous use with sertindole, the risk of developing ventricular arrhythmias, especially ventricular arrhythmia of the "pirouette" type, increases.
With simultaneous use, the concentration of theophylline in the blood plasma increases.
With simultaneous use with tubocurarine chloride, vecuronium chloride, it is possible to increase the muscle relaxant effect.
With simultaneous use with phenytoin, phenobarbital, a significant decrease in the concentration of verapamil in the blood plasma is possible.
With simultaneous use with fluoxetine, the side effects of verapamil increase due to a slowdown in its metabolism under the influence of fluoxetine.
With simultaneous use, the clearance of quinidine decreases, its concentration in the blood plasma increases and the risk of side effects increases. Cases of development of arterial hypotension were observed.
With simultaneous use, verapamil inhibits the metabolism of cyclosporine in the liver, which leads to a decrease in its excretion and an increase in plasma concentration. This is accompanied by an increase in the immunosuppressive effect, a decrease in the manifestations of nephrotoxicity was noted.
With simultaneous use with cimetidine, the effects of verapamil are enhanced.
With simultaneous use with enflurane, prolongation of anesthesia is possible.
With simultaneous use with etomidate, the duration of anesthesia increases.
special instructions
Caution should be used with AV blockade of the I degree, bradycardia, severe aortic stenosis, chronic heart failure, with mild or moderate arterial hypotension, in the acute phase of myocardial infarction, obstructive hypertrophic cardiomyopathy, with hepatic and / or renal failure, in elderly patients age, in children and adolescents under the age of 18 years (efficacy and safety of use have not been studied).
If necessary, combined therapy of angina pectoris and arterial hypertension with verapamil and beta-blockers is possible. However, intravenous administration of beta-blockers should be avoided while using verapamil.
Influence on the ability to drive vehicles and control mechanisms
After taking verapamil, individual reactions (drowsiness, dizziness) are possible, affecting the patient's ability to perform work that requires a high concentration of attention and speed of psychomotor reactions.
Pregnancy and lactation
Verapamil is contraindicated during pregnancy and lactation.
Application in childhood
Caution should be used in children and adolescents under the age of 18 years (efficacy and safety have not been studied).
For impaired renal function
Caution should be used in renal failure.
For impaired liver function
Caution should be used in liver failure.
Use in the elderly
Caution should be used in elderly patients.
Compound
active ingredient: 1 tablet contains verapamil hydrochloride 40 mg or 80 mg; excipients: calcium hydrogen phosphate dihydrate, cellulose
microcrystalline, anhydrous colloidal silicon dioxide, sodium croscarmellose, magnesium stearate, hypromelose, sodium lauryl sulfate, macrogol 6000, talc, titanium dioxide (E 171).
Description
white biconvex film-coated tablets, marked “40” on one side and the company's trademark on the other;
white biconvex film-coated tablets, on the one hand it is indicated “Isoptin 80”, on the other - the trademark of the company above the risks.
pharmachologic effect
Verapamil blocks the transmembrane flow of calcium ions into cardiomyocytes and vascular smooth muscle cells. It directly reduces myocardial oxygen demand by influencing energy-consuming metabolic processes in myocardial cells and indirectly reduces afterload. By blocking the calcium channels of the smooth muscle cells of the coronary arteries, blood flow to the myocardium increases, even in post-stenotic areas, and the spasm of the coronary arteries is relieved. The antihypertensive efficacy of verapamil is due to a decrease in peripheral vascular resistance without an increase in heart rate as a reflex response. Undesirable changes in the physiological values of blood pressure are not observed. Verapamil has a pronounced antiarrhythmic effect, especially in supraventricular arrhythmia. It delays the conduction of the impulse in the atrioventricular node, as a result of which, depending on the type of arrhythmia, the sinus rhythm resumes and / or the ventricular rate normalizes. The normal level of heart rate does not change or decreases slightly.
Pharmacokinetics
Verapamil is rapidly and almost completely absorbed in the small intestine. The degree of absorption is more than 90%. The average absolute bioavailability in healthy people after a single dose of the drug is 22%, which is explained by extensive first-pass hepatic metabolism. Bioavailability increases 2-fold after multiple doses.
Peak plasma concentrations are reached 1 to 2 hours after taking the immediate release tablets. The elimination half-life is 3-7 hours for a single dose and 4.5-12 hours for a course. Plasma protein binding - 90%. Verapamil is almost completely metabolized, resulting in the formation of various metabolites. Among these metabolites, only norverapamil is pharmacologically active (which has been established in experiments on dogs). Verapamil and its metabolites are excreted mainly by the kidneys, only 3-4% is excreted unchanged. About 50% of the administered dose is excreted within 24 hours, 70% is excreted within 5 days. Up to 16% of the drug is excreted in the faeces. Recent data suggest that there is no difference in the pharmacokinetics of verapamil in people with healthy kidneys and in patients with end-stage renal disease. The elimination half-life is increased in cirrhotic patients due to the low clearance and large volume of distribution.
Indications for use
Ischemic heart disease, including: stable angina pectoris;
Unstable angina (progressive angina, rest angina),
Vasospastic angina (variant angina, Prinzmetal's angina),
Postinfarction angina in patients without heart failure, unless P-blockers are indicated.
Arrhythmias: paroxysmal supraventricular tachycardia; atrial flutter/fibrillation with rapid atrioventricular conduction (with the exception of Wolff-Parkinson-White syndrome (WPW).
Arterial hypertension.
Contraindications
Cardiogenic shock.
Acute myocardial infarction with complications (bradycardia, hypotension, left ventricular failure).
II and III degree atrioventricular blockade (except for patients who are implanted with an artificial pacemaker) and sinoatrial blockade.
Sick sinus syndrome (except for patients who are implanted with an artificial pacemaker). ,
Known hypersensitivity to verapamil or to any other component of the drug.
Congestive heart failure.
Atrial fibrillation / flutter in the presence of additional pathways (WPW-syndrome and LGL-syndrome).
During treatment with Isoptin, do not use simultaneously intravenously (3-adrenergic blockers (with the exception of intensive care).
Pregnancy and lactation
The drug should not be taken in the first and second trimesters of pregnancy. Reception in the third trimester of pregnancy - only in case of emergency, when the result exceeds the risk to the mother and child. Verapamil penetrates through the placenta and is determined in cord blood.
The biologically active substance passes into breast milk. Limited oral human data suggest that the neonatal dose of verapamil is low (0.1-1% of the maternal dose), so verapamil use may be compatible with breastfeeding. Taking into account the risk of serious adverse reactions in newborns who are breast-fed, verapamil should be used during breast-feeding only if absolutely necessary for the mother.
Dosage and administration
Doses are selected individually for each patient. The drug should be taken without sucking or chewing with a sufficient amount of liquid (for example, 1 glass of water, in no case grapefruit juice), preferably during or immediately after a meal.
Adults and adolescents weighing over 50 kg:
Ischemic heart disease, paroxysmal supraventricular tachycardia, atrial flutter/fibrillation
Children of senior preschool age up to 6 years, only with heart rhythm disturbances: the recommended dosage is in the range of 80-120 mg per day, divided into 2-3 single doses.
Children 6-14 years old, only for cardiac arrhythmias: the recommended dosage is 80-360 mg per day divided into 2-4 single doses.
Liver dysfunction
In patients with impaired liver function, depending on the severity, the effect of verapamil hydrochloride is enhanced and prolonged due to the slowing down of the disintegration of the drug. Therefore, in such cases, the dosage should be set with extreme caution and start with small doses (for example, for patients with impaired liver function, first 40 mg 2-3 times a day, respectively, 80-120 mg per day).
Do not take the drug while lying down.
Verapamil hydrochloride should not be administered to patients with myocardial infarction within 7 days after the event.
After prolonged therapy, the drug should be discontinued, gradually reducing the dose.
The duration of treatment is determined by the doctor individually and depends on the patient's condition and the course of the disease.
Side effect
The following adverse reactions have been reported in post-marketing use of verapamil or in phase IV clinical trials. Given the impossibility of accurately counting patients in the post-marketing use of the drug, adverse reactions are presented without calculating their frequency, but classified by organ systems. Cardiovascular disorders: 1st, 2nd, or 3rd degree AV block, sinus bradycardia, sinus arrest, peripheral edema, palpitations, increased heart rate (tachycardia), hypotension, flushing, may develop or worsen cardiac failure. Gastrointestinal disorders: the occurrence of nausea, vomiting, constipation, pain, abdominal discomfort, intestinal obstruction, gum hyperplasia (gingivitis and bleeding).
Neurological disorders: headache, extrapyramidal disorders, dizziness, paresthesia, tremor may occur.
Disturbances from the organ of hearing and the vestibular apparatus: dizziness, ringing in the ears.
Changes in the skin and subcutaneous tissues: angioedema, Stevens-Johnson syndrome, erythema multiforme, maculopapular rash, alopecia, erythromelalgia, urticaria, itching, hemorrhages in the skin or mucous membranes (purpura) were observed.
Reproductive system and mammary gland disorders: erectile dysfunction, gynecomastia, galactorrhea.
Musculoskeletal and connective tissue disorders: myalgia, arthralgia, muscle weakness.
Immune system disorders: hypersensitivity.
General disorders: fatigue.
Investigations: increased levels of liver enzymes and serum prolactin levels.
There has been a single post-marketing report of paralysis (tetraparesis) associated with the combined use of verapamil and colchicine. This may be due to the penetration of colchicine through the blood-brain barrier as a result of inhibition of CYP3A4 and P-gp by verapamil. The combined use of colchicine and verapamil is not recommended.
Overdose
Symptoms of poisoning with an overdose of verapamil depend on the amount of the drug taken, the time when detoxification measures were taken, and the age of the patient. The following symptoms predominate: a significant decrease in blood pressure, cardiac arrhythmias (bradycardia, borderline rhythms with atrioventricular dissociation and high-degree atrioventricular block), which can lead to shock and cardiac arrest, impaired consciousness to a coma, stupor, hyperglycemia, hypokalemia, metabolic acidosis , hypoxia, cardiogenic shock with pulmonary edema, renal dysfunction and convulsions. Therapeutic measures aimed at removing a substance from the body and restoring the stability of the cardiovascular system. General measures: gastric lavage is recommended even if more than 12 hours have passed since taking the drug and the motility of the gastrointestinal tract is not determined (no bowel sounds). General resuscitation measures include chest compressions, artificial respiration, defibrillation, and pacing. Hemodialysis is not indicated. It is possible to use hemofiltration and plasmapheresis (calcium antagonists bind well to plasma proteins). Special measures: elimination of cardiodepressive influences, arterial hypotension and bradycardia. Calcium is a specific antidote: 10-20 ml of a 10% solution of calcium gluconate (2.25-4.5 mmol) is injected intravenously. If necessary, you can repeat the introduction or conduct an additional drip infusion (for example, 5 mmol / hour). Additional measures: for AV block II and III degree, sinus bradycardia, cardiac arrest, atropine, isoprenaline, orciprenaline, or pacing are used. In the case of arterial hypotension as a result of cardiogenic shock and arterial vasodilation, dopamine (up to 25 mcg / kg per minute), dobutamine (up to 15 mcg / kg per minute) or norepinephrine are used. Serum calcium concentrations should be within the upper limit of normal or slightly above normal. In connection with vasodilation in the early stages, the introduction of replacement fluid (Ringer's solution or saline) is carried out.
Interaction with other drugs
Verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil is an inhibitor of CYP3A4 and P-glycoprotein (P-gp) enzymes. Clinically important interactions have been reported with CYP3A4 inhibitors, which were accompanied by an increase in plasma levels of verapamil, while CYP3A4 inducers caused a decrease in plasma levels of verapamil hydrochloride, so monitoring for interactions with other drugs is necessary.
Antiarrhythmic drugs, /3-blockers: mutual enhancement of the cardiovascular action (atrioventricular blockade of a high degree, a significant decrease in heart rate, the appearance of heart failure, a significant decrease in blood pressure).
Quinidine: decreased oral clearance of quinidine (-35%). Can develop
arterial hypotension, and in patients with hypertrophic obstructive cardiomyopathy - pulmonary edema.
Flecainidin: Minimal effect on plasma clearance of flecainidin (<~10%); не влияет на клиренс верапамила в плазме крови.
Metoprolol: an increase in metoprolol AUC (-32.5%) and Cmax (-41%) in patients with angina pectoris.
Propranolol: increased propranolol AUC (-65%) and C max (-94%) in patients with angina pectoris.
Antihypertensive drugs, diuretics, vasodilators: increased hypotensive effect. Prazosin, terazosin: additional hypotensive effect (prazosin: increase in Cmax of prazosin (-40%) without effect on the half-life; terazosin: increase in AUC of terazosin (-24%) and Cmax (~25%)).
Antiviral (HIV) agents: Plasma concentrations of verapamil may be increased. Assign with caution or it may be necessary to reduce the dose of verapamil.
Carbamazepine: increased levels of carbamazepine, increased neurotoxic side effects of carbamazepine - diplopia, headache, ataxia, dizziness. Increased AUC of carbamazepine (-46%) in patients with refractory partial epilepsy.
Lithium: increased neurotoxicity of lithium.
Antimicrobials:
Clarithromycin, erythromycin, telithromycin: May increase verapamil levels. Rifampicin: may reduce the hypotensive effect. Decreased AUC of verapamil (-97%), Cmax (~94%), bioavailability after oral administration (-92%).
Colichicine: Co-administration with verapamil is not recommended due to increased colchicine exposure. I
Sulfinpyrazone: increased oral clearance of verapamil by 3 times, bioavailability by 60%. May reduce the hypotensive effect.
Neuromuscular blockers: possible increased action due to verapamil hydrochloride. Acetylsalicylic acid: increased possibility of bleeding.
Ethanol: increased plasma ethanol levels.
HMG-CoA reductase inhibitors: Treatment with HMG-CoA reductase inhibitors (simvastatin, atorvastatin, lovastatin) in patients taking verapamil should be started at the lowest possible dose and gradually increased. If a patient already taking verapamil needs to be prescribed an HMG-CoA reductase inhibitor, the necessary reduction in the dose of statins should be considered and the dosage should be adjusted according to the concentration of cholesterol in the blood plasma.
Atorvastatin: May increase atorvastatin levels. Atorvastatin increases the AUC of verapamil by approximately 42.8%.
Lovastatin: An increase in lovastatin levels is possible.
Simvastatin: an increase in AUC of simvastatin by approximately 2.6 times, Cmax of simvastatin - by 4.6 times.
Fluvastatin, pravastatin and rosuvastatin are not metabolized by cytochrome CYP3A4 and do not interact with verapamil.
Digoxin: in healthy people, C max of digoxin increases by 45-53%, C ss - by 42%, AUC - by 52%.
Digitoxin: Decrease in digitoxin clearance (-27%) and extrarenal clearance (-29%).
Cimetidine: AUC of R- (-25%) and S-verapamil (-40%) increases with a corresponding decrease in the clearance of R- and S-verapamil.
Antidiabetic drugs (glyburide): C max glyburide increases by approximately 28%, AUC - by 26%.
Theophylline: decrease in oral and systemic clearance by approximately 20%, in smokers by 11%.
Imipramine: Increased AUC (-15%) without affecting the active metabolite desipramine. Doxorubicin: with the simultaneous use of doxorubicin and verapamil (orally), AUC (-89%) and Cmax of doxorubicin in plasma (-61%) increase in patients with small cell lung cancer. In patients in the stage of a progressive tumor, there are no significant changes in the pharmacokinetics of doxorubicin with simultaneous intravenous use of verapamil.
Phenobarbital: Increases oral clearance of verapamil by 5 times.
Buspirone: increase in AUC and Cmax by 3-4 times.
Midazolam: an increase in AUC by 3 times and C max - by 2 times.
Almotriptan: an increase in AUC by 20%, C max - by 24%. .
Sulfinpyrazone ". increase in oral clearance of verapamil by 3 times, bioavailability - by 60%.
Immunological preparations:
Cyclosporine: increase in AUC, C max Css by approximately 45%.
Everolimus, sirolimus, tacrolimus: levels of these drugs may increase. Grapefruit juice: AUC of R- (-49%) and S-verapamil (-37%) increases, Cmax of R- (-75%) and S-verapamil (-51%) increases without changing the half-life and renal clearance.
St. John's Wort perforatum: AUC R- (-78%) and S-verapamil (-80%) decreases with a corresponding decrease in C max.
Application features
When using verapamil and determining its dose, special attention should be paid to patients:
With AV block I degree;
With arterial hypotension (systolic blood pressure< 90 мм рт. ст.);
With bradycardia (heart rate less than 50 beats per minute);
With severe liver failure;
With disorders of neuromuscular conduction (myasthenia (Myasthenia gravis), Eaton-Lamberg syndrome, progressive Duchenne muscular dystrophy).
Although data from validated comparative studies have shown that renal insufficiency does not affect the pharmacokinetics of verapamil in patients with end-stage renal disease, there have been several reports indicating that verapamil in patients with renal insufficiency should be used with caution and under close supervision. Verapamil cannot be removed by hemodialysis.
40 mg: 20 tablets in a blister, 5 blisters in a carton or 25 tablets in a blister, 4 blisters in a carton;
80 mg: 20 tablets in a blister, 5 blisters in a cardboard box.
Storage conditions
Keep out of the reach of children at a temperature not exceeding 25°C.