Verapamil 240 mg 20 pcs extended-release film-coated tablets

pharmachologic effect

Calcium channel blocker. Inhibits the transmembrane flow of calcium ions into smooth muscle cells of the myocardium and blood vessels. It has antianginal, antiarrhythmic and antihypertensive effects.

The antianginal effect is associated with a direct effect on the myocardium and an effect on peripheral hemodynamics (reduces the tone of peripheral arteries, peripheral arterial resistance). Blockade of the entry of calcium ions into the cell leads to a decrease in the transformation of energy contained in macroergic bonds of ATP into mechanical work and to a decrease in myocardial contractility.

The antihypertensive effect of the drug is due to a decrease in peripheral vascular resistance without a reflex increase in heart rate. Blood pressure begins to decrease immediately on the first day of treatment, and this effect persists with long-term therapy. The drug Isoptin SR 240 is used for the treatment of all types of arterial hypertension: for monotherapy of mild or moderate arterial hypertension, in combination with other antihypertensive drugs, especially diuretics and (according to recent observations) ACE inhibitors. The drug has a vasodilating, negative ino- and chronotropic effect .

The drug has a pronounced antiarrhythmic effect, especially effective for supraventricular arrhythmia. It delays the conduction of the impulse in the AV node, as a result of which sinus rhythm is restored and/or heart rate is normalized, depending on the type of arrhythmia. Normal heart rate does not change or decreases slightly.

Indications for use

Indications for use of the tablet form are:

• Treatment and prevention of angina pectoris;
• Arterial hypertension is a steadily increasing blood pressure indicator;
• Cardiac arrhythmia and tachycardia.

Injections:

• For high blood pressure, if the problem occurs frequently.
• To reduce the volume of coronary blood flow.
• Heart rhythm disturbances due to myocardial ischemia.

Hypertension is the main indication for taking Verapamil

Pharmacokinetics

Suction

When taken orally, it is quickly and almost completely absorbed in the small intestine. The degree of absorption is 90-92%. The average systemic bioavailability in healthy volunteers after a single dose of the drug is 22%. Studies in patients with atrial fibrillation or angina showed mean bioavailability levels of 35% and 24% after a single oral and IV dose, respectively. With repeated administration of the drug, bioavailability increases almost 2 times compared with a single dose (this effect is probably due to partial saturation of liver enzyme systems and/or a transient increase in blood circulation in the liver after a single dose of verapamil).

Distribution

In case of coronary artery disease and arterial hypertension, no correlation was found between the therapeutic effect and the concentration of the drug in the blood plasma; there is only a definite relationship between plasma drug levels and the effect on the PR interval.

After administration of a prolonged-release dosage form, the plasma concentration curve of verapamil stretches and becomes flatter than with the administration of normal-release dosage forms.

Plasma protein binding is 90%.

Penetrates the placental barrier; concentrations found in umbilical vein plasma were 20–92% of maternal plasma concentrations.

It is excreted in breast milk, but when used in therapeutic doses, its concentrations are so low that a clinical effect in newborns is unlikely.

Metabolism

Verapamil undergoes a first-pass effect through the liver. Almost completely metabolized. The main metabolite is norverapamil, which has pharmacological activity; other metabolites are largely inactive.

Removal

T1/2 ranges from 3 to 7 hours after a single oral dose. With repeated doses, T1/2 of verapamil can increase almost 2 times compared to a single dose.

Verapamil and its metabolites are excreted primarily through the kidneys (3-4% unchanged). Within 24 hours, 50% of the administered dose is excreted, within 48 hours - 55-60%, within 5 days - 70%. Up to 16% is excreted in feces.

Dosage regimen

The average daily dose of the drug is 240-360 mg. For long-term treatment, the daily dose should not exceed 480 mg; a temporary dose increase above this level is possible.

For ischemic heart disease (chronic stable angina; angina caused by vasospasm /Prinzmetal's angina, variant/), Isoptin SR 240 is prescribed in a daily dose of 240-480 mg (1/2-1 tablet 2 times a day with an interval of 12 hours).

For arterial hypertension (mild or moderate), Isoptin SR 240 is prescribed 240 mg (1 tablet) 1 time per day in the morning. If a slow decrease in blood pressure is preferred, then treatment should begin with a dose of 120 mg (1/2 tablet of Isoptin CP 240) once a day in the morning. If necessary, an additional 1/2-1 tablet is prescribed in the evening with an interval between doses of about 12 hours. If necessary, the dose should be increased every 2 weeks of treatment.

For paroxysmal supraventricular tachycardia, atrial fibrillation/flutter, accompanied by tachyarrhythmia, Isoptin SR 240 is prescribed 120-240 mg (1/2-1 tablet) 2 times a day with an interval of 12 hours.

In case of liver dysfunction, the effect of the drug is enhanced and becomes longer lasting as a result of the slow metabolism of verapamil, which depends on the severity of liver dysfunction. In such cases, the dose should be set with extreme caution; treatment should begin with taking the drug in lower doses (i.e., patients with liver cirrhosis are prescribed the drug Isoptin 40 mg 2-3 times a day).

The tablets should be taken during meals or immediately after meals, swallowed whole and washed down with water.

The duration of use is not limited.

Instructions for use for blood pressure and hypertension

To determine the amount of the drug and the duration of treatment, you must consult a doctor.

Tablet form

Adults and adolescents (weight at least 50 kg) should take Verapamil three times a day, 40-80 mg for 7 days. If there is no change in blood pressure, the dosage should be slowly increased to 120-160 mg.

The maximum amount of the drug per day should not exceed 480 mg. In case of liver disorders, the daily dosage is reduced to 120.

If the patient suffered a myocardial infarction at least a week ago, it is necessary to refrain from using the drug.

The tablets should be taken orally during or after meals.

Injections

Verapamil can be used in ampoules by injection intravenously or in a dropper. To do this, the contents of the ampoule are poured into a 5% glucose solution or physiological solution (0.9% sodium chloride), no more than 10 mg per hour.

The dosage for adults is 2-4 ml, no more than 100 mg daily. If there is no decrease in pressure, the amount of the drug must be increased.

Children are given a one-time injection of 5 mg of verapamil.

The drug is not used intramuscularly.

Solution for injection Verapamil

Side effect

From the cardiovascular system: sometimes (when taken in high doses or in the presence of cardiovascular disorders) - arrhythmia due to bradycardia (sinus bradycardia, sinoatrial block, AV block I, II or III degree or bradyarrhythmia with atrial fibrillation), arterial hypotension, palpitations, tachycardia, development or worsening of symptoms of heart failure.

From the central nervous system and peripheral nervous system: rarely - headache, dizziness, drowsiness, increased fatigue, increased nervousness, tremor, paresthesia.

From the digestive system: often - constipation; rarely - nausea, vomiting, intestinal obstruction, pain or discomfort in the abdomen; a reversible increase in liver transaminase and/or alkaline phosphatase levels has been described; in extremely rare cases, during long-term treatment - gum hyperplasia, which is completely reversible after discontinuation of the drug.

From the musculoskeletal system: in very rare cases - myalgia and arthralgia.

Allergic reactions: rarely - exanthema, urticaria, angioedema, Stevens-Johnson syndrome.

From the endocrine system: reversible increase in prolactin levels; rarely (in elderly patients with long-term therapy) - gynecomastia, completely reversible after discontinuation of the drug; in some cases - galactorrhea, impotence.

Other: rarely - swelling of the legs, erythromelalgia, hot flashes.

Contraindications to the use of the drug ISOPTIN SR 240

Absolute contraindications:

• cardiogenic shock;
• complicated acute myocardial infarction (bradycardia, severe arterial hypotension, left ventricular failure);
• AV block II or III degree;
• SSSS (bradycardia-tachycardia syndrome);
• sinoatrial block.

Relative contraindications:

• AV block of the first degree;
• bradycardia (less than 50 beats/min);
• arterial hypotension (systolic blood pressure less than 90 mm Hg);
• atrial fibrillation/flutter with WPW syndrome (risk of ventricular tachycardia);
• heart failure (if necessary, cardiac glycosides are prescribed before starting treatment with Isoptin CP 240).

Verapamil

Acute myocardial infarction

The drug should be used with caution in patients with acute myocardial infarction complicated by bradycardia, a marked decrease in blood pressure, or left ventricular dysfunction.

Heart block/Atrioventricular block I degree/Bradycardia/Asystole

Verapamil affects the AV and SA nodes and slows AV conduction. The drug should be used with caution, since the development of 2nd or 3rd degree AV block (see section “Contraindications”) or single-bundle, double-bundle or triple-bundle block requires discontinuation of verapamil and appropriate therapy if necessary.

Verapamil affects the AV and SA nodes and in rare cases can cause the development of second or third degree AV block, bradycardia and, in extreme cases, asystole. These events are most likely to occur in patients with sick sinus syndrome, which is more common in older patients.

Asystole in patients without sinus node weakness is usually brief (a few seconds or less) with spontaneous restoration of atrioventricular or normal sinus rhythm. If sinus rhythm is not restored in a timely manner, appropriate treatment should be prescribed immediately.

When treating hypertension, the patient's blood pressure should be monitored at regular intervals.

Caution should be exercised in patients with: wide complex ventricular tachycardia, bradycardia less than 50 beats/min, systolic blood pressure less than 90 mmHg. Art., atrial fibrillation/flutter, concurrent preexcitation syndrome, e.g. Wolff-Parkinson-White syndrome (risk of induction of ventricular tachycardia), intravenous beta-blockers should not be administered in patients concomitantly taking extended-release verapamil (except in intensive care units ).

If acute cardiovascular side effects occur, treat as for overdose (see section "Overdose").

Colchicine.

During post-marketing use of verapamil, a single case of paralysis (tetraparesis) associated with the combined use of verapamil and colchicine was reported. This could be due to the penetration of colchicine through the blood-brain barrier due to the suppression of the activity of the CYP3A4 isoenzyme and P-glycoprotein under the influence of verapamil. Combined use is not recommended (see “Interaction with other drugs”).

Digoxin.

In case of simultaneous use of verapamil with digoxin, the dose of digoxin should be reduced (see section “Interaction with other drugs”).

Heart failure.

Patients with heart failure and a left ventricular ejection fraction greater than 35% should achieve a stable condition before starting verapamil and receive appropriate therapy thereafter.

Arterial hypotension.

Intravenous administration of verapamil hydrochloride often causes a decrease in blood pressure below baseline values, usually short-term and asymptomatic, but may be accompanied by dizziness.

HMG-CoA reductase inhibitors (statins).

See section "Interaction with other drugs".

Diseases affecting neuromuscular transmission.

Verapamil should be used with caution in patients with diseases affecting neuromuscular transmission (myasthenia gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy). Respiratory arrest was reported in one patient with progressive muscular dystrophy after administration of verapamil.

Renal dysfunction.

Although renal impairment does not affect the pharmacokinetic parameters of verapamil, as found in comparative studies in patients with end-stage renal disease, caution and close monitoring should still be exercised when using verapamil in such patients. Verapamil is not excreted during hemodialysis.

Liver dysfunction.

Verapamil should be used with caution in patients with severe hepatic impairment.

The drug contains lactose. It should not be taken by patients with rare hereditary diseases: galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Impact on the ability to drive vehicles and machinery

The drug may affect the speed of psychomotor reactions due to its antihypertensive effect and as a result of individual sensitivity. During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

This is especially important at the beginning of treatment, when increasing the dose or when switching from therapy with another drug.

Overdose

Symptoms of poisoning resulting from an overdose of Isoptin CP 240 depend on the amount of the drug taken, the time of detoxification measures and the contractility of the myocardium, which depends on age. Fatal cases resulting from overdose have been reported.

Symptoms: fall in blood pressure (in some cases to levels that cannot be measured), shock, loss of consciousness, 1st or 2nd degree AV block, often as Wenckebach periods with or without escape rhythm, complete AV block with complete AV dissociation , escape rhythm, cardiac arrest; sinus bradycardia, sinus node arrest.

In case of an overdose of Isoptin CP 240, it must be borne in mind that the active substance is released and absorbed from the intestine within 48 hours after taking the drug orally. Depending on the time of taking the drug, individual conglomerates of swollen tablet residues, acting as active depots, will be located throughout the gastrointestinal tract.

Treatment: measures aimed at removing the drug are indicated (for example, induce vomiting, rinse the stomach and intestines in combination with endoscopic examination, prescribe laxatives, emetics). If there is no motility of the stomach and intestines (signs of peristalsis during auscultation), then it is advisable to perform gastric lavage even 12 hours after taking the drug orally. Common emergency resuscitation measures include chest compressions, artificial respiration, and electrical stimulation of the heart.

Effects associated with depression of cardiac function, arterial hypotension and bradycardia should be excluded.

Calcium is a specific antidote: 10-30 ml of a 10% calcium gluconate solution is administered as an intravenous infusion (2.25-4.5 mmol), if necessary, re-introduced or as a slow drip infusion (5 mmol/h).

In the case of AV blockade of the second or third degree, sinus bradycardia, cardiac arrest, administration of atropine, isoprenaline, orciprenaline, and cardiac stimulation are indicated.

In case of arterial hypotension, dopamine, dobutamine, and norepinephrine (norepinephrine) are administered.

In case of persistent signs of myocardial failure, dopamine, dobutamine are administered, and, if necessary, additional calcium is administered.

Isoptin (Verapamil) Prolong. table 120mg No. 30

Pharmacological action: Isoptin is an antianginal drug related to calcium channel blockers (the active ingredient is verapamil hydrochloride). Reduces blood pressure, is used for arrhythmias, and has an antianginal effect. Under the influence of the drug, the transmembrane flow of calcium ions into the smooth myocytes of blood vessels and the heart is blocked. The effect of lowering blood pressure is associated with a decrease in peripheral vascular resistance, and there is no effect of increasing heart rate in the form of a reflex reaction. The antianginal effect of Isoptin is associated with a direct effect on myocardial cells, and is also realized through a decrease in the tone of the peripheral parts of the vascular system (reduction in the total precardiac load). Inhibition of the entry of calcium ions into myocytes causes a decrease in the conversion of the ATP-associated energy potential of macroergic bonds into mechanical work, which leads to a decrease in the contractility of the heart muscle. Isoptin is used for the treatment of supraventricular arrhythmias due to its ability to delay the conduction of nerve impulses through the atrioventricular node, suppression of sinoatrial conduction and increase the refractory state interval in the atrioventricular formation. This causes the heart rate to normalize or restore physiological sinus rhythm. The final effects of Isoptin on atrioventricular conduction depend on the type of arrhythmia - when taking the drug against the background of normal heart contractions, the frequency remains normal or decreases slightly. Isoptin is classified as a group 4 antiarrhythmic drug with a dose-dependent effect. Thus, Isoptin causes negative chronotropic, negative isotropic and vasodilating effects. It also leads to a decrease in platelet aggregation properties and a diuretic (natriuretic) effect by reducing sodium reabsorption in the kidney tubules. Absorption occurs in the small intestine quickly and completely by approximately 90-92%, regardless of the parallel consumption of food. Bioavailability was studied in healthy volunteers and averaged 22%; significant fluctuations in bioavailability (from 10 to 35%) are associated with the rapid removal of verapamil from the systemic circulation after passing through the liver. In a study of patients taking Isoptin against the background of angina and atrial fibrillation, it was shown that the median levels of bioavailability for them with bolus administration were 24% and 35% for internal administration of a single dose of the drug. It was also found that the bioavailability of Isoptin increases more than 2 times in case of repeated administration of the drug. This is associated with a temporary increase in liver blood circulation after a single dose of the drug and partial saturation of liver enzymes. There is no correlation between the content of Isoptin in the blood serum and the therapeutic effect in patients with coronary heart disease or arterial hypertension. Some relationship was found between the concentration of the drug in the blood serum and the effect on the electrocardiographic QR interval. Subject to first pass through liver tissue. Metabolism occurs in hepatocytes, and almost all verapamil taken or administered undergoes biotransformation. The main metabolite is norverapamil, which has pharmacological activity comparable to that of verapamil, 10-20%. The remaining metabolites are almost all inactive. Affinity for plasma proteins reaches 90%. It passes well through placental tissue, reaching the umbilical vessels in amounts up to 20-29% of the dose taken. Cmax of the main metabolite of Isoptin is achieved 6 hours after consuming one dose of the drug. The half-life ranges from 2.5 to 7.5 hours in the case of a single dose and from 4.5 to 12 hours after repeated administration, which is associated with an increase in the content of verapamil in the blood plasma and sufficient saturation of liver enzymes. After bolus administration, the initial half-life reaches 4 minutes, and the final half-life after 2-5 hours. Stable parameters of therapeutic concentration in the blood are observed 4 days after the start of repeated oral doses. It is also eliminated through breast milk, but therapeutic doses of verapamil in milk have been shown to be too low to cause any clinical effects in a nursing infant. The half-life is 3-7 hours (in the case of a single internal dose). The half-life increases by 2 times or more with regular repeated use. Most of the active substance and its metabolites are eliminated by the kidneys, with approximately 3-5% of verapamil excreted unchanged, about 16% eliminated by the intestines (with feces). Long-acting isoptin The peculiarity of long-acting isoptin is that the curve of verapamil content in the blood has a flatter shape and is significantly extended over time, which does not happen when using a dosage form with a standard release of the active substance. Within 24 hours after consuming long-acting Isoptin, half of the administered dosage is eliminated, over the next 24 hours - up to 60%, after 5 days - approximately 70%. Features of pharmacokinetics in case of renal failure There is an increase in the half-life and bioavailability of the active substance. No particular differences in pharmacokinetics were detected at different degrees of severity of renal failure (including terminal stages). Features of pharmacokinetics in cases of impaired liver function The half-life and bioavailability of the active substance Isoptin increase in patients with significant impairment of liver function. However, the pharmacokinetics of verapamil are unchanged in compensated liver failure. Indications for use: • Mild or moderate arterial hypertension in the form of monotherapy; • severe arterial hypertension as part of combination treatment; • Prinzmetal's angina (angiospastic); • atrial flutter and fibrillation, which is accompanied by tachyarrhythmia (excluding cases of Wolff-Parkinson-White syndrome); • exertional angina (stable); • paroxysmal supraventricular tachycardia. Method of administration: Isoptin tablets Prescribed orally. 40-80 mg 3-4 times a day, preferably after eating. An effective maintenance dosage can be prescribed over a long period of time. Isoptin - injection solution Administered intravenously slowly over no less than 2 minutes, exclusively under the supervision of a physician, monitoring ECG and blood pressure. Patients who received the drug for angina pectoris should switch to the tablet form of Isoptin as quickly as possible. For adults weighing more than 50 kg, it is recommended to use a dose of 5 mg of the drug (2 ml of Isoptin - solution for injection). If necessary, a repeat dose is administered 5-10 minutes after injection (2 ml - 5 mg verapamil hydrochloride hydrochloride). Further treatment, if necessary, is carried out using intravenous drip administration of 5-10 mg of the drug. To do this, the required amount of Isoptin solution is dissolved in an isotonic solution of sodium chloride or 5% glucose with a pH level of less than 6.5. The average daily dose for intravenous administration is no more than 100 mg. Isoptin solution should absolutely not be administered to patients taking beta blockers (except for resuscitation measures). In pediatric practice, before administering Isoptin, it is necessary to carry out digitalization. Before the age of 1 year, verapamil hydrochloride is used strictly for health reasons, if no other alternative treatment can be prescribed. In rare cases, after intravenous use of the drug in newborns and infants, severe hemodynamic disturbances developed, and deaths were reported. Dosage for newborns – 0.75-1 mg of Isoptin (corresponds to 0.3-0.4 ml of solution). Dosage for children under 1 year of age is 0.75-2 mg of Isoptin (0.3-0.8 ml of solution). Dosage for children from 1 year to 5 years – 2-3 mg (0.8-1.2 ml of solution). Dosage for children from 6 years to 14 years – 2.5-5 mg (1-2 ml). The administration of Isoptin solution to children is stopped immediately after the onset of the effect. Isoptin SR The average daily dosage ranges from 240 to 360 mg. It is better to take the tablets immediately after meals or during meals, without chewing and with water. It is not recommended to increase the average daily dosage if the drug is prescribed for a long time (more than 480 mg), although it is possible to increase the dosage of Isoptin above this maximum level for a short time. Coronary heart disease For all forms of angina (both Prinzmetal and exertional angina), Isoptin CP240 is recommended from 240 to 480 mg, with the daily dose divided into morning and evening doses (half or 1 whole tablet with an interval of 12 hours). Arterial hypertension For mild or moderate hypertension, 1 tablet (240 mg) in the morning is recommended. If the patient needs to reduce blood pressure at a slow pace, it is better to first use half the recommended dose (120 mg), and if this regimen is ineffective, take an additional half tablet (120 mg) in the evening. The interval between dosages should be at least 12 hours. Every 14 days of therapy, the grid dosage can be increased to the optimal one. Arrhythmias Prescribe 120-240 mg 2 times a day with an interval of 12 hours (half or 1 tablet). Dosage regimen for patients with liver failure Prescribe with caution. It is recommended to start taking Isoptin CP240 with low dosages. For example, for liver cirrhosis, the starting dosage is 40 mg 2-3 times a day. Side effects: From the cardiovascular system: when prescribed in high doses or in case of disorders in the cardiovascular system, heart rhythm disturbances may sometimes develop due to bradycardia (sinoatrial block, sinus bradycardia, bradyarrhythmia with atrial fibrillation, atrioventricular block II or III degrees). Tachycardia, arterial hypotension, palpitations, increased or signs of heart failure are also possible. If the intravenous form of Isoptin is administered very quickly, asystole, transverse complete heart block, and collapse may occur. From the digestive system: rarely - intestinal obstruction, nausea, discomfort and pain in the abdomen, vomiting; often - constipation; the literature describes a transient reversible increase in the values ​​of liver transaminases, as well as alkaline phosphatase; Rare cases of gum hyperplasia have been reported, which completely disappear after discontinuation of Isoptin. From the central and peripheral nervous system: rarely - excessive fatigue, headache, drowsiness, dizziness, tremor, increased or onset of nervousness, paresthesia. From the endocrine glands: hyperprolactemia; rare (in elderly patients, gynecomastia is rarely possible, which disappears completely after discontinuation of Isoptin. Isolated cases of impotence and galactorrhea have been recorded. Hyperergic reactions: rarely - urticaria, exanthema, Stevens-Johnson syndrome, angioedema. From the musculoskeletal system: pain in the joints and/or muscles (in some cases). Others: swelling of the legs in the lower legs, hot flashes, erythromelalgia (rarely). Contraindications: Relative contraindications: • 1st degree of atrioventricular block; • heart rate less than 50 beats per minute; • atrial flutter or fibrillation, which is accompanied by Wolf-Parkinson-White syndrome (since in this case the risk of ventricular tachycardia is high); • systolic pressure less than 90 mm Hg; • heart failure (if it is necessary for a patient with heart failure to prescribe Isoptin, up to taking it, the patient must receive cardiac glycosides); Absolute contraindications: • Tachycardia-bradycardia syndrome (weakness of the sinus node); • cardiogenic shock; • 2 or 3 degree atrioventricular block; • acute complicated myocardial infarction (significant hypotension, bradycardia, left ventricular failure); • blockade of the sinoatrial node. Pregnancy: Taking Isoptin and Isoptin CP240 is not recommended for pregnant women. It is allowed to prescribe the drug after assessing the ratio of “probable risk and benefit from the expected therapeutic effect.” If Isoptin needs to be taken by a lactating woman, stop breastfeeding. Interaction with other drugs: The active substance Isoptin (based on in vitro experiments) is metabolized with the participation of isoenzymes CYP1A2, CYP2C9, CYP3A4 CYP2C8, and CYP2C18 cytochrome P450. A clinically significant interaction was noted when verapamil hydrochloride was combined with CYP3A4 inhibitors - with this combination, an increase in the concentration of verapamil hydrochloride in the blood was observed. Inducers of this isoenzyme reduce the concentration of verapamil in the blood. The most significant interactions among commonly prescribed drugs were the following. Increases the maximum plasma concentration of prazosin by approximately 40% without affecting its half-life. Increase in AUC parameters by 24% for terazosin and increase in its maximum plasma concentration by 25%. Verapamil minimally changes the clearance of flecainide (about 10%), flecainide does not affect the clearance of verapamil hydrochloride. A decrease in systemic clearance was found by 20% for theophylline and by 35% for quinidine, with the rate for theophylline in smokers being 11%. Verapamil increases the AUC of imipramine by 15%, carbamazepine by 46% (with stable partial epilepsy), glyburide by 26%, buspirone, midazolam by 3 times, metoprolol by 32.5%, propranolol by 65%, digoxin - by 52%, cyclosporine, simvastatin - 3 times, almotriptan - by 20%. Verapamil does not change the concentration of the active metabolite of imipramine, desipramine. When rifampicin is taken in combination with verapamil, the AUC of verapamil hydrochloride decreases by 97%. An increase in the concentration of verapamil is possible when combined with telithromycin, erythromycin, a decrease is possible when combined with St. John's wort. With parallel administration of doxorubicin, a decrease in the half-life of doxorubicin by approximately 27%, as well as its maximum concentration, is detected, and in patients with progressive tumors, Isoptin does not affect the clearance or level of doxorubicin. In patients suffering from lung cancer (small cell variant only), Isoptin reduces both the concentration and half-life of doxirubicin. The clearance of Isoptin increases when taken with phenobarbital (5 times), sulfinpyrazone (3 times). When taking verapamil hydrochloride, the extrarenal and total (by 29 and 27%, respectively) clearance of digitoxin decreases. When taking cimetidine, the AUC for the S- and R-enantiomers of verapamil increases (by 40 and 25%, respectively), and the clearance of S- and R-verapamil decreases. An increase in the blood levels of tacrolimus, sirolimus, lovastatin, and atorvastatin was detected. Verapamil enhances the effect of antihypertensive drugs of other groups (for example, diuretics, vasodilators). A mutual increase in the effect on the cardiovascular system is possible when combined with beta-blockers and other antiarrhythmic drugs. This may be accompanied by the appearance of signs of cardiovascular failure and progression of arterial hypotension. An additive hypotensive effect is observed when combined with terazosin and prazosin. Antiviral drugs (for example, ritonavir) inhibit the biotransformation of verapamil hydrochloride, which causes an increase in its content in the blood. Such combinations require a reduction in the dosage of verapamil. In some cases, the combination of quinidine with verapamil in patients with obstructive hypertrophic cardiomyopathy caused pulmonary edema. The toxicity of carbamazepine increases while taking verapamil hydrochloride, and side effects often appear (dizziness, ataxia, headache, diplopia). The neurotoxicity of lithium increases when taken concomitantly with verapamil hydrochloride. Effectiveness in lowering blood pressure is reduced when combined with sulfinpyrazone and rifampicin. The effects of muscle relaxants are enhanced by Isoptin. It was found that bleeding while taking acetylsalicylic acid increases if verapamil hydrochloride is taken in parallel. If you consume ethanol while taking Isoptin, increased levels of ethanol will be recorded in the blood. If it is necessary to combine verapamil hydrochloride and lovastatin, simvastatin and other HMG-CoA reductase inhibitors, the lowest dosage of the latter is chosen, gradually increasing it. If verapamil is prescribed against the background of the use of GMG-CoA reductase inhibitors, then it is better to reduce their dosage. So far, there is no data on the interaction of atorvastatin and hydrochloride of verapamil, however, taking into account some pharmacological studies, tactics of reducing the dosage of the Hypolypidemic agent should be followed in this case. It is least likely to interact with isoptin of right -handed, fluvastatin and rosuvastatin, since they are not metabolized with the participation of the CYP3A4 isoenzyme. An overdose: with an overdose of isoptin, a sharp drop in blood pressure is possible even to numbers that cannot be measured with a tonometer, loss of consciousness, shock, complete atrioventricular blockade, complete dissociation of the atrioventricular node, attrioventricular blockade of the 1-2 degrees in the form of a wreatinbach without slipping rhythm or with its slip , stop the sinus node, bradycardia of sinus origin. Flying cases with cardiac arrest are also described. Signs of overdose depend on the amount of dosage adopted, the beginning of therapeutic measures for detoxification, on the age -related ability of the contractile activity of the myocardium. With an overdose of the prolonged form of isoptin, it should be borne in mind that the hydrochloride of the verapamil is released and absorbed from the digestive canal during the first day after the internal administration. Separate swollen particles tablets can be located along the entire length of the intestine and thereby be a depot from which verapamil will be constantly released. Therapeutic measures: rapid elimination of verapamil from the intestines (vomiting initiation, gastric lavage, vomiting and laxatives, washing of the intestines with an endoscope). With an overdose of the prolonged dosage form of isoptin, the gastric lavage and intestines is advisable even 12 hours after the dose. Urgen resuscitation measures are carried out if necessary (artificial respiration, indirect heart massage, myocardial electrical stimulation). Specific antidote - calcium (gluconate). 10-30 ml of calcium gluconate is administered 10% intravenously (approximately 2.25-4.5 mmol). If necessary, the administration of gluconate calcium can be repeated by drip infusion at a speed of 5 mmol/hour. In case of bradycardia of sinus origin, atrioventricular blockade of 1-2 degrees, cardiac arrest is necessary to prescribe isoprenaline, atropine, orciprenaline, electrical stimulation of the heart. With deep arterial hypotension, probamine, norepinephrine (norepinephrine), dopamine are used. Dobutamin or dopamine is also necessary in the case of stable symptoms of heart failure (in combination with calcium). Release form: isoptin solution isoptin - in ampoules of 2 ml (5 mg of verapamil hydrochloride). There are 50 ampoules in the box. 40 tablets; 80 mg. In packaging 20; 100 pcs. Isoptin CP240 prolonged tablets of 240 mg. The tablets are light green, with transverse risks on both sides, capsul-shaped, on one side of the tablet-two symbols of the "delta" (δ). In the blister - 10; 15 pieces. In 1 package (cardboard pack) 2; 3; 5; 10 blisters. Storage conditions: a prescription drug. Store no more than 3 years at a temperature of not more than 25 degrees Celsius. Keep away from children. See also the list of analogues of the drug isoptin. Composition: isopine CP240 Active substance: hydrochloride verapamil 240 mg in 1 tablet. Excipients: gypromellose, povidon, cellulose microcrystallic, talc, sodium alginate, purified water, macrogol 400, magnesium stearate, titanium dioxide, macrogol 6000, indigotine, yellow chinolin, mountain glycole wax. Isoptin - a solution for injection Active substance: hydrochloride isopine 5 mg in 1 ampoule (2 ml). Excipients: chloristoric acid (36%), lead for injection, sodium chloride. Isoptin tablets Active substance: Verapamil hydrochloride 40 or 80 mg. Excipients: magnesium stearate, microcrystalline cellulose. Pharmacological group: Antiarrhythmic drugs cardiovascular drugs. Medicines used for violations of excitability and automatism of the heart. Class 4 Active substance: Verapamil additionally: if arterial hypertension is expressed significantly, then the product must be combined with antihypertensive drugs (angiotensinoproding factor inhibitors, diuretics). The reaction to isoptin can vary in different people, which should be taken into account if it is necessary to work with dangerous units and machine management. The probable moments in the development of reduced psychomotor reactions can be the initial stages of treatment, transfer to isoptin from another drug, in case of simultaneous use with alcohol -containing drinks or drugs.

Drug interactions

In vitro studies indicate that verapamil hydrochloride is metabolized with the participation of isoenzymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. A clinically significant interaction was observed with concomitant use of CYP3A4 inhibitors, which caused an increase in plasma levels of verapamil, while CYP3A4 inducers decreased its plasma concentration. Accordingly, when using such agents simultaneously, the possibility of interaction should be taken into account.

In patients with advanced neoplasms, verapamil does not affect the level or clearance of doxorubicin. In patients with small cell lung cancer, verapamil reduced T1/2 and Cmax of doxorubicin.

With the simultaneous use of the drug Isoptin CP 240 with antiarrhythmic drugs, beta-blockers, a mutual enhancement of effects on the cardiovascular system is possible (the appearance of AV blockade, a decrease in heart rate, increased arterial hypotension, the development of heart failure).

Isoptin CP 240 enhances the hypotensive effect of other antihypertensive drugs (including diuretics, vasodilators).

With simultaneous use of the drug Isoptin CP 240 with prazosin, terazosin, an additive hypotensive effect is observed.

Ritonavir and antiviral drugs may inhibit the metabolism of verapamil, resulting in increased plasma concentrations. In this regard, the dose of Isoptin CP 240 should be reduced.

With simultaneous use of the drug Isoptin SR 240 with quinidine - hypotension; in patients with hypertrophic obstructive cardiomyopathy, pulmonary edema may develop.

With the simultaneous use of the drug Isoptin SR 240 with carbamazepine, an increase in the level of carbamazepine in plasma and an increase in its neurotoxicity are observed. Adverse reactions characteristic of carbamazepine, such as diplopia, headache, ataxia or dizziness, are possible.

Isoptin CP 240, when used simultaneously, increases the neurotoxicity of lithium.

The hypotensive effect of Isoptin CP 240 may be reduced when used simultaneously with rifampicin and sulfinpyrazone.

When used simultaneously with the drug Isoptin SR 240, the effect of muscle relaxants may be enhanced.

When used simultaneously with acetylsalicylic acid, an increase in bleeding is observed.

With the simultaneous use of ethanol with the drug Isoptin CP 240, the level of ethanol in plasma increases.

Concomitant use with Isoptin CP 240 may lead to an increase in plasma concentrations of simvastatin or lovastatin.

In patients receiving verapamil, treatment with HMG-CoA reductase inhibitors (simvastatin, lovastatin) should be started with the lowest possible doses, which are then increased. If it is necessary to prescribe verapamil to patients already receiving HMG-CoA reductase inhibitors, their doses should be reconsidered and reduced according to the concentration of cholesterol in the blood serum. Similar tactics should be followed when concomitantly prescribing verapamil with atorvastatin (although there is no clinical data confirming the interaction of verapamil and atorvastatin), since pharmacokinetic studies are clearly known to confirm that verapamil had a similar effect on the level of atorvastatin.

Fluvastatin, pravastatin and rosuvastatin are not metabolized by CYP3A4 isoenzymes, so their interaction with verapamil is least likely.

Interaction with other drugs and alcohol

Grapefruit juice increases the release of Verapamil into the blood plasma. It is prohibited to drink the drug with the juice of this fruit.

When drinking alcohol, the removal of Verapamil from the body slows down.

It is forbidden to take tablets with grapefruit juice.