Verapamil (HCl)

Verapamil is an oral and parenteral calcium-channel blocking (CCB) agent. Verapamil (HCl) is useful for the treatment of angina, hypertension, and for supraventricular tachyarrhythmias. Verapamil is considered a class IV antiarrhythmic agent and Verapamil (HCl) is more effective than digoxin for controlling ventricular rate in patients with atrial fibrillation. Verapamil was synthesized in 1962 and, in 1981, became the first calcium channel blocker to be approved by the FDA. Verapamil inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. It exerts its activity at the membrane surface of arterial smooth muscle cells and within conductile and contractile tissue in the myocardium, but the serum calcium levels remain unchanged.

Verapamil (HCl) is primarily indicated in conditions like Angina, Cardiac arrhythmia, Hypertension, Ischemic heart disease, Paroxysmal tachyarrhythmias, Supraventricular arrhythmias, Supraventricular tachycardia, and can also be given in adjunctive therapy as an alternative drug of choice in Cardiomyopathy, Migraine, Psychosis, Pulmonary hypertension.

Verapamil (HCl) is contraindicated in conditions like Congestive Heart failure, Bradycardia, Platelet dysfunction, Cardiogenic shock, Symptomatic hypotension, Sick sinus syndrome.

Serious adverse reactions are uncommon when verapamil HCl therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. In clinical trials involving 285 hypertensive patients on verapamil hydrochloride extended-release capsules for greater than 1 week the following adverse reactions were reported in greater than 1.0% of the patients: In clinical trials of other formulations of verapamil HCl (N = 4,954) the following reactions have occurred at rates greater than 1.0%: In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or atrial flutter, ventricular rate below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients. The following reactions, reported in 1.0% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope. Digestive System: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia. Hemic and Lymphatic: ecchymosis or bruising. Nervous System: cerebrovascular accident, confusion, equilibrium disorders, extrapyramidal symptoms insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence. Respiratory: dyspnea. Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, maculae, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme. Special Senses: blurred vision, tinnitus. Urogenital: gynecomastia, impotence, increased urination, spotty menstruation.

Verapamil should be used with caution in patients with liver or kidney impairment. Consider decrease in dose of calcium channel blockers and monitor drug response in cirrhosis patients.

Drug should not be given to patients suffering from Liver Malfunction. If prescribing authority justifies the benefits of the drug against the possible damages he/she should reevaluate them and consult the reference material and previous studies.

40 to 120 mg (80 (80)) 8 hourly PO — Scraped Dose — There is no specific antidote for verapamil overdosage; treatment should be supportive. Delayed pharmacodynamic consequences may occur with extended-release formulations, and patients should be observed for at least 48 hours, preferably under continuous hospital care. Reported effects include hypotension, bradycardia, cardiac conduction defects, arrhythmias, hyperglycemia, and decreased mental status. In addition, there have been literature reports of non-cardiogenic pulmonary edema in patients taking large overdoses of verapamil (up to approximately 9 g). In acute overdosage, gastrointestinal decontamination with cathartics and whole bowel irrigation should be considered. Calcium, inotropes (i.e., isoproterenol, dopamine, and glucagon), atropine, vasopressors (i.e., norepinephrine, and epinephrine), and cardiac pacing have been used with variable results to reverse hypotension and myocardial depression. In a few reported cases, overdose with calcium channel blockers that was initially refractory to atropine became more responsive to this treatment when the patients received large doses (close to 1 g/hour for more than 24 hours) of calcium chloride. Calcium chloride is preferred to calcium gluconate since it provides 3 times more calcium per volume. Asystole should be handled by the usual measures including cardiopulmonary resuscitation. Verapamil cannot be removed by hemodialysis.

2 to 3 mg/kg (2.5 (2.5)) 8 hourly Oral — -

2 to 3 mg/kg (2.5 (2.5)) 8 hourly Oral —

Verapamil (HCl) is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAcebutololVerapamil may enhance the hypotensive effect of Acebutolol. Bradycardia and signs of heart failure have also been reported. Verapamil may decrease the metabolism, via CYP isoenzymes, of Acebutolol.ModerateManagement Though usually safe and effective during concomitant use, monitor for increased evidence of bradycardia, hypotension, or signs of heart failure during concomitant use of beta-blockers and nondihydropyridine calcium channel blockers. Ophthalmic beta-blockers are likely of little concern. Though usually safe and effective during concomitant use, monitor for increased evidence of bradycardia, hypotension, or signs of heart failure during concomitant use of Acebutolol and Verapamil. Ophthalmic beta-blockers are likely of little concern.Afatinibmay increase the level of fatinib use alternative or reduced doseAlcoholPlasma alcohol concentration possibly increased by verapamil.Alcuronium (Cl)AldesleukinEnhanced hypotensive effect when aldesleukin given with Calcium-channel antagonists (e.g verapamil).AlprostadilEnhanced hypotensive effects when alprostadil given with Calcium-channel blockers (e.g Verapamil)Amiodarone (HCl)Verapamil may enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported.MajorMonitor increased therapeutic effects, and potential signs of toxicity (eg, bradycardia, sinus arrest, and decreased cardiac output) of verapamil.AmobarbitalBarbiturates reduces hypotensive effects of Verapamil.MajorAtenololVerapamil may enhance the hypotensive effect of Atenolol.Bradycardia and signs of heart failure have also been reported.Verapamil may decrease the metabolism, via CYP isoenzymes, of Atenolol.ModerateThough usually safe and effective during concomitant use, monitor bradycardia, hypotension, or signs of heart failure during concomitant use of Atenolol and Verapamil. Ophthalmic beta-blockers are of little concern. It is recommended that atenolol should not be administered IV within 24 hourrs of discontinuing Verapamil.Atracurium (Besylate)Betaxolol (HCl)Severe hypotension when and heart failure when beta blockers (e.g Betaxolol) given with Verapamil.MajorBisoprolol (Fumarate)Severe hypotension and heart failure when beta-blockers given with Verapamil.Buspirone (HCl)CalciferolCalciumCarbamazepineEffects of Carbamazepine enhanced by Verapamil MajorCarteolol (HCl)CarvedilolChloroquineChlorpheniramine (Maleate)It increases effects of chlotpheniramine. as it is is a CYP3A4 inhibitorCilostazoleClonidine (HCl)Coadministration causes complete AV block or profound hypotension.MinorClosely monitored the blood pressure of patient.Cyclosporin AVerapamil inhibit the CYP450 3A4 hepatic metabolism of cyclosporine and increased the risk of nephrotoxicity.ModerateCyclosporine level and renal function must be monitored.DabigatranVerapamil increases Cmax and AUC of Dabigatran.Dantrolene (Na)DiazepamDigitoxinDigoxinVerapamil [Calcium Channel Blocker (Nondihydropyridine)] may enhance the AV-blocking effect of Digoxin. Verapamil may decrease the metabolism of Digoxin by decreasing its renal and extra renal clearance and hence increases digoxin levels. MajorIf Verapamil and Digoxin are used together to control the supraventricular tachyarrhythmia, the dosage of each drug may have to be reduced. patients should be closely monitored for clinical and laboratory evidence of digoxin safety while taking verapamil and evaluated for under digitialisation when verapamil is discontinued.DisopyramideDisopyramideBoth work additively producing negative inotropic effects,hypotension and collapse especially in conduction defects.ModerateDisopyramide must not be administered less than 48 hours before or 24 hours after verapamil.Distigmine (Br)EsmololEtomidateFlecainide (Acetate)HalothaneHalothaneIndacaterolStrong inhibitors of CYP3A4 may increase levels of indacaterolmonitor closelyIohexolLithiumMeglumineMetipranololInfrequent reports of VERAPAMIL HYDROCHLORIDE increasing the NEGATIVE INOTROPIC effect of METIPRANOLOL [EYE]. ModerateMetoprolol (Tartrate)MidazolamNeostigmineNitrendipineMay increase the levels/effects of nitrendipine.NitroprussideShould not be use concurrently without doctor or pharmacist approval.OxcarbazepineVerapamil produced a decrease of 20% of the plasma levels of Oxcarbazepine.Oxprenolol (HCl)ParegoricThe concomitant administration of agents with hypotensive effects and psychotherapeutic agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics), narcotic analgesics, alcohol, or muscle relaxants may additively increase hypotensive and/or central nervous system depressant effects.ModerateDuring concomitant use of these drugs, patients should be monitored for hypotension and excessive or prolonged CNS depression. Ambulatory patients should be made aware of the possibility of additive effects (e.g., drowsiness, dizziness, lightheadedness, confusion, orthostasis, fainting) and be cautioned about driving, operating machinery, or performing other hazardous tasks, and to arise slowly from a sitting or lying position. Patients should also be advised to notify their doctor if they experience excessive side effects that interfere with their normal activities, or dizziness and fainting.PenbutololPhenobarbitonePindololPractololPramipexoleVerapamil (HCl) decrease the clearance of pramipexole by ~20%.Propranolol (HCl)Pyridostigmine (Br)coadministration with ca channel blockers such as verapamil may produce an enhance muscle block.manage with EdrophoniumQuinidineRanolazineDiltiazem (180–360 mg daily) and verapamil (120 mg three times daily) increase ranolazine steady-state plasma concentrations about 2-foldLimit the dose of ranolazine to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products.RifampicinRifampicinRocuronium (Br)Ropivacaine (HCl Monohydrate)TerazosinHypotensive effect of verapamil and terazosin may be additive.Verapamil may inhibit the hepatic metabolism of terazosin.ModerateClosely monitor te hemodynamic response especially during the first week of therapy.TheophyllineVecuronium (Br)VORICONAZOLEVoriconazole may increase the serum concentration of verapamil by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects Vortioxetineincreases toxicity of vortioxetineuse alternative These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

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