VERAPAMIL
Interaction
When used concomitantly with carbamazepine in patients with persistent partial epilepsy due to inhibition of carbamazepine metabolism in the liver, verapamil increases its effect (risk of side effects from the central nervous system, such as diplopia, headache, ataxia and dizziness).
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 concentrations. This is accompanied by an increased immunosuppressive effect.
With simultaneous use, verapamil increases the concentration of theophylline (due to decreased clearance).
With simultaneous use of verapamil with quinidine, the concentration of quinidine in the blood plasma increases (risk of a pronounced decrease in blood pressure, especially in patients with IHSS).
With simultaneous use, verapamil increases the concentration of ethanol in the blood plasma and prolongs its effect.
Since verapamil inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, drug interactions due to increased plasma concentrations of statins (rhabdomyolysis) are possible.
With simultaneous use, verapamil increases the plasma concentration of almotriptan and glibenclamide.
With simultaneous use, verapamil increases the plasma concentrations of sirolimus and tacrolimus.
With simultaneous use, verapamil increases the concentration of cardiac glycosides (requires careful monitoring and reduction in the dose of glycosides).
With simultaneous use, verapamil increases the concentration of metoprolol and propranolol in patients with angina pectoris.
With simultaneous use, verapamil increases the plasma concentration of colchicine (a substrate for the CYP3A isoenzyme and P-glycoprotein).
With simultaneous use of verapamil with doxorubicin, the concentration of doxorubicin in the blood plasma increases and its effectiveness increases.
With simultaneous use of verapamil with imipramine, the concentration of imipramine in the blood plasma increases (the risk of developing undesirable changes due to the additive inhibitory effect of verapamil and imipramine on AV conduction). Does not affect the concentration of the active metabolite, desipramine.
Verapamil increases the concentration of prazosin and terazosin when used simultaneously (risk of developing severe arterial hypotension).
When verapamil is used simultaneously with buspirone or midazolam, their concentration in the blood plasma increases (risk of increased side effects).
CYP3A4 inhibitors (including erythromycin, human immunodeficiency virus protease inhibitors), telithromycin increase plasma concentrations of verapamil.
Grapefruit juice increases plasma concentrations of the R- and S-isomers of verapamil. Cimetidine either does not change or reduces the clearance of verapamil (the effects of verapamil may be enhanced).
Rifampin can significantly reduce the bioavailability (up to 92%) as well as the plasma concentration of verapamil, which leads to a decrease in its clinical effectiveness.
Phenobarbital increases the clearance of verapamil by 5 times.
Sulfinpyrazone increases the clearance of verapamil by approximately 3 times and reduces bioavailability by up to 60%.
St. John's wort preparations reduce the concentration of the R- and S-isomer of verapamil in the blood plasma.
With the simultaneous use of verapamil with inhalational anesthetics, the risk of developing bradycardia, AV block, and heart failure increases. The combination of verapamil with beta-blockers can lead to an increased negative inotropic effect, an increased risk of developing AV conduction disorders, bradycardia (the use of verapamil and beta-blockers must be carried out at intervals of several hours).
Prazosin and other alpha-blockers, as well as other antihypertensive drugs (angiotensin-converting enzyme inhibitors, vasodilators, diuretics, beta-blockers) enhance the hypotensive effect of verapamil.
With the simultaneous use of verapamil with disopyramide and flecainide, severe arterial hypotension and collapse, including death, are possible. The risk of developing severe manifestations of drug interactions is associated with increased negative inotropic effects. Disopyramide and flecainide should not be administered within 48 hours before or 24 hours after verapamil.
Verapamil increases the risk of neurotoxic effects of lithium preparations.
Verapamil enhances the effect of peripheral muscle relaxants (may require a change in dosage regimen).
With the simultaneous use of verapamil with acetylsalicylic acid, cases of increased bleeding time have been described.
Verapamil, 40 mg, film-coated tablets, 50 pcs.
When used simultaneously:
- increases the AUC (area under the concentration-time curve) of carbamazepine in patients with persistent partial epilepsy (risk of side effects such as diplopia, headache, ataxia and dizziness).
- increases AUC, Css (clearance) and Cmax (maximum drug concentration) of cyclosporine.
— increases the AUC and Cmax of glibenclamide.
- increases the concentration of sirolimus and tacrolimus.
— significantly increases the AUC and Cmax of buspirone and midazolam.
- increases the concentration of theophylline (due to decreased clearance), ethanol (and prolongs its effect), the concentration of quinidine (risk of a pronounced decrease in blood pressure).
- may increase concentrations of atorvastatin and lovastatin.
— significantly increases the AUC and Cmax of simvastatin.
— increases the AUC and Cmax of almotriptan.
- increases the concentration of cardiac glycosides (requires careful monitoring and reduction in the dose of glycosides).
- increases the AUC and Cmax of metoprolol and propranolol in patients with angina pectoris.
- increases the plasma concentration of colchicine (a substrate for CYP 3 A and p-glycoprotein).
— when taken orally, it significantly increases the AUC and Cmax of doxorubicin.
- slightly increases the AUC of imipramine; does not affect the concentration of the active metabolite, desipramine.
— increases the Cmax of prazosin and terazosin and the AUC of terazosin.
- CYP3A inhibitors (including erythromycin, ritonavir and other antiviral HIV drugs), teligomycin increase plasma concentrations of verapamil.
- grapefruit juice increases the AUC and Cmax of the R - and S - isomer of verapamil.
- cimetidine increases the bioavailability of verapamil by almost 40–50% (due to a decrease in hepatic metabolism), and therefore, it may be necessary to reduce the dose of the latter.
- Rifampicin can significantly reduce the bioavailability (up to 92%), as well as the AUC and Cmax of verapamil.
- phenobarbital increases the clearance of verapamil by 5 times.
- sulfinpyrazone increases the clearance of verapamil by approximately 3 times and reduces bioavailability (60%).
- preparations of St. John's wort reduce the AUC R - and S - isomer of verapamil and, accordingly, C max.
- when used simultaneously with inhalational anesthetics, the risk of developing bradycardia, atrioventricular block, and heart failure increases.
- combination with beta-blockers can lead to an increased negative inotropic effect, increasing the risk of developing atrioventricular conduction disorders, bradycardia (administration of verapamil and beta-blockers must be carried out at intervals of several hours).
- prazosin and other alpha-blockers, as well as other antihypertensive drugs (ATP inhibitors, vasodilators, diuretics, beta-blockers) enhance the hypotensive effect.
- disopyramide and flecainide should not be administered within 48 hours or 24 hours after the use of verapamil (the sum of the negative inotropic effect, including death).
- increases the risk of the neurotoxic effect of lithium preparations.
- enhances the effect of peripheral muscle relaxants (a change in dosage regimen may be required)
- with simultaneous use with acetylsalicylic acid (ASA), a slightly greater increase in bleeding time was observed than with the use of ASA alone.
- carbamazepine and lithium increase the risk of neurotoxic effects.
Overdose symptoms, interactions
Accidentally exceeding the recommended volume of Verapamil leads to a slow heartbeat, a drop in blood pressure, asystole, etc. Therapeutic measures include:
- gastric lavage and use of sorbents;
- administration of Atropine, Calcium Gluconate into a vein - in case of impaired conductivity;
- prescribing alpha-adrenergic agonists to normalize blood pressure levels.
In some cases, an artificial pacemaker is used.
The instructions indicate the following therapeutic nuances:
- combination with Cyclosporine, Theophylline, Quinidine, Caramazepine increases their concentration;
- the inclusion of lithium preparations leads to increased neurotoxic effects;
- Cimetidine, Rifampicin reduce the bioavailability of verapamil;
- inhalation anesthetics and beta-blockers - provoke the development of heart failure and bradycardia.
Verapamil can enhance the effect of muscle relaxants.
Verapamil therapy
The instructions include the exact dosage of the drug and the specifics of its administration. The standards depend on the type of tablet:
- With a standard duration of action - before meals from 40 to 80 mg, three times a day for registered angina or increased heart rate. For hypertension, the daily dose is divided into two procedures and is 480 mg. For children under five years of age, no more than 60 mg of medication is allowed per day.
- With prolonged action - for hypertension, 240 mg in the morning, therapy begins with a dosage of 120 mg, which is gradually increased. The dose is increased after 14 days, the maximum volume of the drug does not exceed 480 mg (taken in 2 doses, observing a twelve-hour break).
An intravenous solution is used to suppress the symptoms of a hypertensive crisis. From 5 to 10 ml of Verapamil is injected in a stream. A similar amount is used for paroxysmal pathologies; in the absence of the expected result, the procedure is duplicated.
Maintenance therapy involves the use of the drug in conjunction with sodium chloride or dextrose. When treating children under 5 years of age, the dosage does not exceed 3 mg.
Adverse reactions
The drug can become a source of non-standard responses in the body. Veramil provokes:
- slowing of cardiac activity;
- cephalgia with dizziness;
- dyspeptic disorders;
- facial hyperemia;
- weight gain.
Less commonly, the medication leads to the appearance of:
- digestive disorders, gum tissue hyperplasia;
- lethargy, nervousness, fatigue;
- skin rash, obsessive itching;
- gynecomastia, arthritis, galactorrhea.
The drug causes the development of pulmonary and peripheral edema.
Prescription of Verapamil
The abstract advises the use of the medication:
- with supravenricular and sinus tachycardia;
- stable angina pectoris and pathology with supraventricular rhythm disturbances;
- atrial fibrillation;
- hypertensive crisis;
- supraventricular extrasystole;
- hypertension.
Verapamil is contraindicated in patients:
- with a pronounced slow heartbeat;
- disorders of the left ventricle;
- intolerance to the component composition;
- low blood pressure levels.
The drug is not prescribed to pregnant and nursing mothers. Particular caution is needed during therapeutic procedures in patients with bradycardia, sinoatrial, atrioventricular block, chronic heart, renal, and liver failure. Doctor's supervision is required in old age.
Manufacturer's instructions
Clinical studies have not shown sufficient information about the effect of the drug on the body of pregnant women. The use of the drug is allowed after assessing the real risk to the health of the fetus and the benefits to the maternal body.
Verapamil is used:
- when there is a threat of spontaneous abortion;
- placental insufficiency;
- nephropathy.
The drug is prescribed by the obstetrician-gynecologist leading the pregnancy strictly according to indications. Self-medication is unacceptable and can provoke any results.
