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Logo ISOPTIN Injection solution
SCHEDULING STATUS
S3

PROPRIETARY NAME
(and dosage form):

ISOPTIN Injection solution

COMPOSITION
1 ampoule contains 5 mg of verapamil hydrochloride per 2 mL.

PHARMACOLOGICAL CLASSIFICATION
7.1.4 Vasodilators - coronary and other medicines used in angina pectoris

PHARMACOLOGICAL ACTION
Coronary and anti-arrhythmic agent.
Isoptin is characterised by a number of pharmacological effects on the heart and circulation. These are the expression of its calcium-antagonising and anti-arrhythmic properties.
The calcium-antagonising effect is due to inhibition of calcium influx across the cell membrane. As a result of the reduction in the amounts of free calcium ions available in the muscle cell, there is a falling-off in the activity of the calcium-dependent myosin-ATPase. This leads to a decrease in the turnover of high-energy phosphates (a reduction in energy metabolism) and hence to a diminution in the oxygen requirements of the myocardium.
The increase in coronary blood flow is due to coronary vasodilation. This too, like the fall in peripheral resistance, is due to a calcium-antagonising effect on the plain muscle of the vessel walls, thereby leading to a diminution in vascular tone.
The fall in the peripheral resistance reduces the pressure work of the heart and thus relieves the demands on the heart. There is consequently a further reduction in myocardial oxygen consumption.
The anti-arrhythmic effects are chiefly due to an increase in the refractory period of the AV node (while the duration of the action potential and rate of conduction within the atria and ventricles remain unchanged).
Sympathetic control of the heart is maintained in the presence of Isoptin, since the compound does not block the adrenergic beta receptors. In the usual therapeutic doses, Isoptin does not exert a negative inotropic effect, i.e. it does not reduce the stroke volume or the cardiac minute volume.

INDICATIONS
Acute and chronic coronary insufficiency
Tachyarrhythmias, such as paroxysmal supraventricular tachycardia
Continuous arrhythmia due to atrial fibrillation
Atrial flutter with rapid ventricular response
Extrasystoles
For the prophylaxis and/or therapy of ectopic arrhythmias (predominantly ventricular extrasystoles) in halothane anaesthesia and in the application of adrenaline in halothane anaesthesia, respectively.
Prophylaxis and treatment of the cardiovascular side effects of betasympathomimetic agents, which are used to inhibit premature labour pains.
Hypertensive crises.

CONTRA-INDICATIONS
Absolute
Contraindications:
  1. Cardiogenic shock
  2. Recent myocardial infarction (acute stage)
  3. Complete AV block
  4. Overt heart failure (where heart failure is present, full compensation with cardiac glycosides must be achieved before the administration of Isoptin)
    N B (2) The intravenous administration of Isoptin may be considered in the management of critical emergency cases of tachyarrhythmias complicating acute myocardial infarction. The decision here must be made by the physician.
Relative
Contraindications:
  1. Partial AV block
  2. Left bundle branch block
  3. Marked bradycardia
  4. Hypotension
    NB (4) This excludes conditions where the hypotension - the fall in the stroke volume - results from the tachycardia per se. Normalization or reduction of the heart rate with Isoptin may, in such cases, lead to a rise in blood pressure.

DOSAGE AND DIRECTIONS FOR USE
Intravenous injection - For the treatment of acute angina pectoris, tachyarrhythmias and hypertensive crises one ampoule of Isoptin may be injected slowly intravenously with continuous observation of the patient.
In cases of paroxysmal tachyarrhythmias and hypertensive crises, a second ampoule may be applied, if necessary, about 5-10 minutes later in the same way as the first injection.
In general, higher doses are not required in the usual clinical indications.
Intravenous infusion - In cases of pronounced recidivity or prolonged critical increase in blood pressure it has proved useful to continue with slow drip infusion after the first injection.
For the infusion patients receive 5-10 mg per hour contained in saline, glucose solution, levulose solution or similar solutions, until an average total dose of 25 to 100 mg per day is reached.

Dosage in Children
Newborn                        0,75-1 mg (= 0.3-0,4 mL)
Infants                        0,75-2 mg (= 0,3-0,8 mL)
Children aged 1 - 5 years 2 - 3 mg (= 0,8-1,2 mL)
Children aged 6 - 14 years 2,5-5 mg (=1,0-2,0 mL)
In many cases smaller doses then those mentioned above are sufficient. The injection should be given only until onset of the effect.
The intravenous injection should be made slowly with continuous observation of the patient and under electrocardiographic control. If necessary, the same dose may be repeated after 5 - 10 minutes.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
As is the case with all anti-arrhythmic agents which inhibit AV conduction, the intravenous administration of Isoptin may on rare occasions cause an undesirably marked blocking effect, ie an AV block which, in extreme cases, may result in asystole. The asystole is normally of short duration, and cardiac action returns spontaneously after a few seconds, usually in the form of sinus rhythm. If, as rarely happens, this is not the case, the measures described in the next section should be carried out.
The danger of precipitating ventricular fibrillation is exceedingly small. Should this complication (which basically may happen in the course of any antiarrhythmic treatment) appear following the adminislralion of Isoptin, the measures mentioned below should be performed. Following the intravenous injection of Isoptin, the fall in the peripheral resistance may lead to a slight and transient decrease in blood pressure. This does not generally result in any interference with haemodynamics, but may, however, on rare occasions result in critical hypotension, where the heart is no longer able to increase the cardiac minute volume to maintain adequate blood pressure. In accordance with present views on the use of drugs in pregnant women prescription of Isoptin should be carefully evaluated during the first 3 months of pregnancy.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Where acute complications follow the intravenous injection of Isoptin (asystole, total AV block or ventricular fibrillation), the usual emergency measures should be applied cardiac massage and mouth-to-mouth, or artificial respiration, and the intravenous or, if necessary intracardiac injection of orciprenaline (Alupent® *) or adrenaline. In the event of ventricular asystole, one or two thumps with the clenched fist against the sternum will in many cases restore regular cardiac contractions. Special treatment when the diagnosis has been established: electrical stimulation in cases of asystole, electric defibrillation or an attempt at medical treatment with procainamide in cases of ventricular fibrillation. In the case of a critical decrease in blood pressure as a result of inadequate myocardial compensation the intravenous injection of orciprenaline or strophanthin is recommended.
* Manufacturer: C. H. Boehringer Sohn. Ingelheim-On-Rhine

IDENTIFICATION
Clear colourless solution in colourless ampoules.

PRESENTATION
5 and 30 ampoules of 2 mL (5 mg Isoptin hydrochloride/2 mL)
Other forms of Isoptin 75 (blister) and 500 (glass bottle) dragées of Isoptin 40 mg.
  50 and 250 dragées of Isoptin 80 mg (glass bottles).
  50 and 250 dragées of Isoptin 120 mg (glass bottles).

STORAGE DIRECTIONS
Store in room temperature.

REFERENCE NUMBER
H 647 (Act 101/1965)

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Knoll Pharmaceuticals South Africa (Pty.) Ltd.,
P.O. Box 3030, Halfway House 1685
Rep. of South Africa

DATE OF PUBLICATION
7/10/74

Manufacture by
KNOLL AG - D 6700 Ludwigshafen - Germany                Knoll logo

                                24185 055 - 17 - 5201 (1567) - 2/1                141 U [O]

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