ISOPTIN

What it is

ISOPTIN is a medicine containing verapamil hydrochloride. It is available as ISOPTIN SR (modified release) tablets containing 180 mg or 240 mg of verapamil hydrochloride, and as ISOPTIN immediate release tablets containing 40 mg or 80 mg of verapamil hydrochloride. Verapamil is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist) which exerts its pharmacologic effects by modulating the influx of ionic calcium across the cell membrane of the arterial smooth muscle as well as in conductile and contractile myocardial cells.

Approved indications

ISOPTIN SR is indicated for the management of hypertension and angina pectoris. ISOPTIN immediate release is indicated for: — Hypertension — Angina of effort — Angina at rest — Vasospastic angina (including Prinzmetal's variant angina) — Tachyarrhythmias including paroxysmal supra-ventricular tachycardia — Atrial fibrillation with rapid ventricular response — Atrial flutter with rapid ventricular response

Dosing overview

**ISOPTIN SR (modified release)** The usual daily dose in clinical trials has been 240 mg given by mouth once daily in the morning. Some patients may respond to initial therapy of one 180 mg tablet once daily. However, initial doses of 120 mg (½ 240 mg tablet) a day may be warranted in patients who may have an increased response to verapamil (e.g. elderly, small people). For angina pectoris, the usual dose is one 240 mg tablet once daily. In patients with an increased response to verapamil (e.g. the elderly, people with low body weight) an initial dose of one 180 mg tablet may be more appropriate. Depending on individual response, the dosage can be increased to a total of 480 mg daily, given in two divided doses. **ISOPTIN immediate release** The usual starting dose is one 80 mg tablet two or three times a day. The maintenance dose may be adjusted to 160 mg two or three times a day. Paediatric dose range is 40 to 360 mg per day in two or three divided daily doses according to age and response.

Key safety warnings

**Heart failure** Verapamil has a negative inotropic effect which, in most patients, is compensated by its afterload reduction properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary oedema. Verapamil should be avoided in patients with severe left ventricular dysfunction (e.g. ejection fraction less than 30%, pulmonary wedge pressure above 20 mmHg, or severe symptoms of cardiac failure) and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. **Hypotension** Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. **Liver function** Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear even in the face of continued verapamil treatment. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent. **Atrioventricular conduction** Verapamil affects the AV and SA nodes and prolongs AV conduction time. Development of second- or third-degree AV block or unifascicular, bifascicular or trifascicular bundle branch block requires discontinuation of subsequent doses of verapamil and institution of appropriate therapy, if needed.

Contraindications

Verapamil is contraindicated in severe left ventricular dysfunction, hypotension (less than 90 mmHg systolic pressure) or cardiogenic shock, sick sinus syndrome (except in patients with a functioning artificial pacemaker), and second- or third-degree AV block (except in patients with a functioning artificial pacemaker). Verapamil is contraindicated in patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). These patients are at risk to develop ventricular tachyarrhythmia including ventricular fibrillation if verapamil is administered. Verapamil is contraindicated in heart failure with reduced ejection fraction of less than 35%, and/or pulmonary wedge pressure above 20 mmHg. Verapamil is contraindicated in patients concomitantly administered ivabradine, in simultaneous initiation of treatment with dabigatran etexilate and oral verapamil, and in treatment initiation with oral verapamil in patients following major orthopaedic surgery who are already treated with dabigatran etexilate. Verapamil is contraindicated in patients with known hypersensitivity to verapamil hydrochloride or any of the inactive ingredients.

PBS listing

The 80 mg tablet is listed on the PBS with 2 items. The restriction type is unrestricted and restricted. The ex-manufacturer price is A$9.04.

Regulatory history

ISOPTIN SR 240 mg was first registered on the Australian Register of Therapeutic Goods on 8 October 1991. ISOPTIN SR 180 mg was registered on 4 December 1995. ISOPTIN 80 mg immediate release was registered on 25 March 1999.