Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Mild to moderate hypertension. Angina pectoris.

Adult Dosage

For oral administration only. The capsules should be swallowed whole and not chewed.

The bioequivalence of Univer to other prolonged release verapamil formulations may not have been evaluated. As such, this product should not be directly substituted for other non-identical formulations of verapamil and vice-versa.

Mild to moderate hypertension: Initial dose in adult patients new to verapamil therapy should be 120 mg once daily. This can be increased to 240 mg once daily which is the normal maintenance dosage. The dose may be further increased to a maximum of 480 mg once daily if required.

Angina: The usual adult dose is 360 mg once daily. Dosage may be increased to a maximum of 480 mg daily if required.

Hepatic impairment: Verapamil is extensively metabolised in the liver and for those patients with impaired liver function, the dose should be reduced and carefully titrated.

Renal impairment: About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Verapamil should be prescribed cautiously when renal function is impaired. Careful patient monitoring is recommended.

Child Dosage

Elderly Dosage

Elderly patients show enhanced bioavailability of verapamil and therapeutic control may be achieved with lower doses in this patient population.

Contra Indications

Acute myocardial infarction with complications such as bradycardia, hypotension, left ventricular decompensation or congestive heart failure.

• Second or third degree atrioventricular block without pacemaker.
• Sick sinus syndrome, sino-atrial block, or severe sinus bradycardia (except in patients with functioning artificial ventricular pacemaker).
• Uncompensated cardiac failure.
• Atrial flutter or atrial fibrillation associated with an accessory pathway (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndrome).
• Porphyria.
• Hypotension (systolic pressure <90 mm Hg) or cardiogenic shock.
• Intravenous dantrolene.
• Known hypersensitivity to any of the ingredients.
• Concomitant ingestion of grapefruit juice.

Special Precautions

Special care should be taken in hypotension (see section 4.3), especially in acute myocardial infarction as this is a condition where atrioventricular conduction defects may develop and contractility may be impaired.

Use with caution in patients with first degree atrioventricular block or bradycardia.

Left ventricular contractility may be affected and although the effect is small, cardiac failure may be precipitated or aggravated. Hence incipient cardiac failure should be controlled using appropriate therapy before verapamil is given.

Caution should be exercised in treatment with HMG CoA reductase inhibitors (e.g., simvastatin, atorvastatin or lovastatin) for patients taking verapamil. These patients should be started at the lowest possible dose of verapamil and titrated upwards. If verapamil treatment is to be added to patients already taking an HMG CoA reductase inhibitor (e.g., simvastatin, atorvastatin or lovastatin), refer to advice in the respective statin product information.

Verapamil is extensively metabolised in the liver and special care should be taken in cases where liver damage exists, as plasma levels of verapamil may be increased.

There have been reports of calcium-channel blockers exacerbating muscle weakness in patients with myasthenia gravis. Verapamil should be used with caution in the presence of diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy).

Verapamil is not removed during dialysis.

Owing to the presence of sucrose, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Interactions

In vitro metabolic studies indicate that verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil has been shown to be an inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride while inducers of CYP3A4 have caused a lowering of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions.

Concomitant use contra-indicated

Dantrolene: the association of this muscle relaxant given intravenously and verapamil is potentially dangerous (can cause fatal ventricular fibrillation in animals) and is contraindicated.

Intravenous beta-blockers should not be given to patients under treatment with verapamil.

Other relevant interactions

Acetylsalicylic acid

Concomitant use of verapamil with aspirin may increase the risk of bleeding

Alcohol

Alcohol: an increase in blood alcohol and slowed elimination has been reported.

Alpha blockers

Verapamil may increase the plasma concentrations of prazosin and terazosin which may have an additive hypotensive effect.

Antiarrhythmics

Verapamil may slightly decrease the plasma clearance of flecainide whereas flecainide has no effect on the verapamil plasma clearance. Verapamil may increase the plasma concentrations of quinidine. Pulmonary oedema may occur in patients with hypertrophic cardiomyopathy The combination of verapamil and antiarrhythmic agents may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).

Anticonvulsants

Verapamil may increase the plasma concentrations of carbamazepine. This may produce side effects such as diplopia, headache, ataxia or dizziness. Verapamil may also increase the plasma concentrations of phenytoin.

Antidepressants

Verapamil may increase the plasma concentrations of imipramine.

Antidiabetics

Verapamil may increase the plasma concentrations of glibenclamide (glyburide).

Antihypertensives, diuretics, vasodilators

Potentiation of the hypotensive effect.

Anti-infectives

Rifampicin may reduce the plasma concentrations of verapamil which may produce a reduced blood pressure lowering effect. Ketoconozole, erythromycin, clarithromycin and telithromycin may increase the plasma concentrations of verapamil.

Antineoplastics

Verapamil may increase the plasma concentrations of doxorubicin.

Barbiturates

Phenobarbital may reduce the plasma concentrations of verapamil.

Benzodiazepines and other anxiolytics

Verapamil may increase the plasma concentrations of buspirone and midazolam.

Beta blockers

Verapamil may increase the plasma concentrations of metoprolol and propranolol which may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).

A period between stopping beta-blocking therapy and starting therapy with this product may be advisable. Concomitant use of verapamil and beta-blockers or antiarrhythmics, if necessary, should only be administered to patients in a closely monitored clinical setting.

The effects of verapamil may be additive to other hypotensive agents.

Cardiac glycosides

Verapamil may increase the plasma concentrations of digitoxin and digoxin. Verapamil has been shown to increase the serum concentration of digoxin and caution should be exercised with regard to digitalis toxicity. The digitalis level should be determined and the glycoside dose reduced, if required.

Colchicine

Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (P-gp). Verapamil is known to inhibit CYP3A and Pgp. When verapamil and colchicine are administered together, inhibition of P-gp and/or CYP3A by verapamil may lead to increased exposure to colchicine. Combined use is not recommended.

H₂ Receptor antagonists

Cimetidine may increase the plasma concentrations of verapamil.

HIV antiviral agents

Due to the metabolic inhibitory potential of some of the HIV antiviral agents, such as ritonavir, plasma concentrations of verapamil may increase. Caution should be used or dose of verapamil may be decreased.

Immunosuppressants

Verapamil may increase the plasma concentrations of ciclosporin, everolimus, sirolimus and tacrolimus.

Inhaled anaesthetics

When used concomitantly, inhalation anaesthetics and calcium antagonists, such as verapamil hydrochloride, should each be titrated carefully to avoid additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).

Lipid lowering agents

Verapamil may increase the plasma concentrations of atorvastatin, lovastatin and simvastatin. Treatment with HMG CoA reductase inhibitors (e.g., simvastatin, atorvastatin or lovastatin) in a patient taking verapamil should be started at the lowest possible dose and titrated upwards. If verapamil treatment is to be added to patients already taking an HMG CoA reductase inhibitor (e.g., simvastatin, atorvastatin or lovastatin), consider a reduction in the statin dose and retitrate against serum cholesterol concentrations. Atorvastatin has been shown to increase verapamil levels. Although there is no direct in vivo clinical evidence, there is strong potential for verapamil to significantly affect atorvastatin pharmacokinetics in a similar manner to simvastatin or lovastatin. Consider using caution when atorvastatin and verapamil are concomitantly administered. Fluvastatin, pravastatin and rosuvastatin are not metabolized by CYP3A4 and are less likely to interact with verapamil.

Lithium

Serum levels of lithium may be reduced. However, there may be increased sensitivity to lithium causing enhanced neurotoxicity. Lithium can enhance neuromuscular block during anaesthesia and hence verapamil with lithium may potentiate the neuromuscular blocking effect.

Neuromuscular blocking agents employed in anaesthesia

The effects may be potentiated.

Serotonin receptor agonists

Verapamil may increase the plasma concentrations of almotriptan.

Theophylline

Verapamil may increase the plasma concentrations of theophylline.

Uricosurics

Sulfinpyrazone may reduce the plasma concentrations of verapamil which may produce a reduced blood pressure lowering effect.

Other

St. John's Wort may reduce the plasma concentrations of verapamil, whereas grapefruit juice may increase the plasma concentrations of verapamil.

Adverse Reactions

Occasionally, particularly in high doses or with prior myocardial damage, cardiovascular effects may be larger than desired giving rise to bradycardic arrhythmias, such as sinus bradycardia, second and third degree atrioventricular block, bradyarrhythmia in atrial fibrillation, transient asystole, hypotension, heart failure.

Constipation may occur. Headaches, dizziness, fatigue and ankle oedema are uncommon. Very infrequently nausea, vomiting, flushing and allergic reactions have been observed. Reversible impairment of liver function has been rarely reported and is most likely a hypersensitivity reaction.

There have been rare reports of gynaecomastia, gingival hyperplasia, erythromelalgia, paraesthesia and elevated prolactin levels.

Manufacturer

Drug Availability

Updated