The course of symptoms in Verapamil Hcl intoxication depends on the amount taken, the point in time at which detoxification measures are taken and myocardial contractility (age-related). The main symptoms are as follows: blood pressure fall (at times to values not detectable), shock symptoms, loss of consciousness, 1st and 2nd degree AV block (frequently as Wenckebach's phenomenon with or without escape rhythms), total AV block with total AV dissociation, escape rhythm, asystole, bradycardia up to high degree AV block and, sinus arrest, hyperglycaemia, stupor and metabolic acidosis. Fatalities have occurred as a result of overdose.
The therapeutic measures to be taken depend on the point in time at which Verapamil Hcl was taken and the type and severity of intoxication symptoms. In intoxications with large amounts of slow-release preparations, it should be noted that the release of the active drug and the absorption in the intestine may take more than 48 hours. Verapamil Hcl hydrochloride cannot be removed by haemodialysis. Depending on the time of ingestion, it should be taken into account that there may be some lumps of incompletely dissolved tablets along the entire length of the gastrointestinal tract, which function as active drug depots.
General measures to be taken: Gastric lavage with the usual precautions, even later than 12 hours after ingestion, if no gastrointestinal motility (peristaltic sounds) is detectable. Where intoxication by a modified release preparation is suspected, extensive elimination measures are indicated, such as induced vomiting, removal of the contents of the stomach and the small intestine under endoscopy, intestinal lavage, laxative, high enemas. The usual intensive resuscitation measures apply, such as extrathoracic heart massage, respiration, defibrillation and/or pacemaker therapy.
Specific measures to be taken: Elimination of cardiodepressive effects, hypotension or bradycardia. The specific antidote is calcium, e.g. 10 20ml of a 10% calcium gluconate solution administered intravenously (2.25 - 4.5mmol), repeated if necessary or given as a continuous drip infusion (e.g. 5mmol/hour).
The following measures may also be necessary: In case of 2nd or 3rd degree AV block, sinus bradycardia, asystole - atropine, isoprenaline, orciprenaline or pacemaker therapy. In case of hypotension - dopamine, dobutamine, noradrenaline (norepinephrine). If there are signs of continuing myocardial failure - dopamine, dobutamine, if necessary repeated calcium injections.
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- Hypotension (of less than 90mmHg systolic)
- Second or third degree atrioventricular block; sick sinus syndrome (except in patients with a functioning artifical pacemaker); uncompensated heart failure; marked bradycardia (less than 50 beats/minute).
- Combination with beta-blockers is contraindicated in patients with poor ventricular function.
- Wolff-Parkinson-White syndrome.
- Concomitant ingestion of grapefruit juice is contraindicated.
- Acute myocardial infarction complicated by bradycardia, marked hypotension or left ventricular failure.
- Combination with ivabradine
None known.
Immune system disorders: allergic reactions (e.g. erythema, pruritus, urticaria) are very rarely seen.
Nervous system disorders: headaches occur rarely, dizziness, paraesthesia, tremor, extrapyramidal syndrome (e.g. parkinsonism), dystonia.
Ear and labyrinth disorders: vertigo, tinnitus.
Cardiac disorders: bradycardic arrhythmias such as sinus bradycardia, sinus arrest with asystole, 2nd and 3rd degree AV block, bradyarrhythmia in atrial fibrillation, palpitations, tachycardia, development or aggravation of heart failure, hypotension.
Vascular disorders: flushing, peripheral oedema.
Gastrointestinal disorders: nausea, vomiting, constipation is not uncommon, ileus and abdominal pain/discomfort. Gingival hyperplasia may very rarely occur when the drug is administered over prolonged periods. This is fully reversible when the drug is discontinued.
Skin and subcutaneous tissue disorders: alopecia, ankle oedema, Quincke's oedema, Steven-Johnson syndrome, erythema multiforme, erythromelalgia, purpura.
Musculoskeletal and connective tissue disorders: muscular weakness, myalgia and arthralgia.
Reproductive system and breast disorders: impotence (erectile dysfunction) has been rarely reported and isolated cases of galactorrhoea. Gynaecomastia was observed on very rare occasions in elderly male patients under longer term Verapamil Hcl treatment which was fully reversible in all cases when the drug was discontinued.
General disorders and administration site conditions: fatigue.
Investigations: On very rare occasions, a reversible impairment of liver function characterised by an increase in transaminases and/or alkaline phosphatase, may occur during Verapamil Hcl treatment and is most probably a hypersensitivity reaction.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard
Not applicable.
2) For the management and prophylaxis of angina pectoris (including variant angina).
3) The treatment and prophylaxis of paroxysmal supraventricular tachycardia and the reduction of the ventricular rate in atrial fibrillation/flutter. Verapamil Hcl should not be used for atrial fibrillation/flutter in patients with Wolff-Parkinson-White syndrome.
Pharmacotherapeutic group: Selective calcium channel blockers with direct cardiac effects, phenylalkylamine derivatives.
ATC code: C08 DA01
Verapamil Hcl hydrochloride is a calcium channel blocker and is classified as a class IV anti-arrhythmic agent.
Mechanism of action
Verapamil Hcl inhibits the entry of calcium into smooth muscle cells of the systemic and coronary arteries and in the cells of cardiac muscle and the intracardiac conduction system.
Verapamil Hcl lowers peripheral vascular resistance with little or no reflex tachycardia. Its efficacy in reducing both raised systolic and diastolic blood pressure is thought to be primarily due to this mode of action.
The decrease in systemic and coronary vascular resistance and the sparing effect on intracellular oxygen consumption appear to explain the anti-anginal properties of the product.
Due to the effect on the movement of calcium in the intracardiac conduction system, Verapamil Hcl reduces automaticity, decreases conduction velocity and increases the refractory period.
Absorption
Verapamil Hcl is approximately 90% absorbed from the gastrointestinal tract.
Distribution
Verapamil Hcl acts within 1-2 hours after oral administration with a peak plasma concentration after 1-2 hours. There is considerable interindividual variation in plasma concentrations. Verapamil Hcl is about 90% bound to plasma proteins.
Biotransformation
Verapamil Hcl is subject to very considerable first-pass metabolism in the liver and the bioavailability is only about 20%. It is extensively metabolised in the liver to at least 12 metabolites of which norVerapamil Hcl has been shown to have some activity.
Elimination
Verapamil Hcl exhibits bi- or tri-phasic elimination kinetics and is reported to have a terminal plasma half-life of 2-8 hours following a single oral dose. After repeated oral doses this increases to 4.5-12 hours. About 70% of a dose is excreted by the kidneys in the form of its metabolites but about 16% is also excreted in the bile into the faeces. Less than 4% is excreted unchanged.
Pregnancy and breast-feeding
Verapamil Hcl crosses the placenta and is excreted in breast milk.
Verapamil Hcl may affect left ventricular contractility as a result of its mode of action. The effect is small and not normally important. However, cardiac failure may be aggravated or precipitated if it exists. In cases with poor ventricular function, Verapamil Hcl should therefore only be administered after appropriate therapy for cardiac failure such as digitalis, etc.
Verapamil Hcl may affect impulse conduction and should be administered with caution in patients with first degree atrioventricular block. The effects of Verapamil Hcl and beta-blockers or other drugs may be additive both in respect of conduction and contraction, therefore care should be exercised when these are administered concurrently or closely together. This is especially true when either drug is administered intravenously.
Caution should be observed in the acute stage of myocardial infarction.
Patients with atrial fibrillation/flutter and an accessory pathway (eg Wolff-Parkinson-White syndrome) may rarely develop increased conduction across the anomalous pathway and ventricular tachycardia may be precipitated.
Since Verapamil Hcl is extensively metabolised in the liver, careful dose titration of Verapamil Hcl is required in patients with liver disease. The disposition of Verapamil Hcl in patients with renal impairment has not been fully established and therefore careful patient monitoring is recommended. Verapamil Hcl is not removed during dialysis.
Depending on individual susceptibility, the patient's ability to drive or operate machines may be impaired due to feelings of drowsiness. This is particularly true in the initial stages of treatment, or when changing over from another drug. Verapamil Hcl has been shown to increase the blood levels of alcohol and slow its elimination. Therefore, the effects of alcohol may be exaggerated.
Posology
Adults:
Angina: 120mg three times daily is recommended. 80mg three times daily may be completely satisfactory in some patients with angina of effort. Less than 120mg three times daily is unlikely to be effective in variant angina.
Supraventricular tachycardias: 40-120mg three times daily depending on the severity of the condition.
Paediatric population:
A paradoxical increase in the rate of arrhythmias in children has been noted. Therefore, Verapamil Hcl should only be used under expert supervision.
Up to 2 years: 20mg 2-3 times a day.
2 years and above: 40-120mg 2-3 times a day according to age and effectiveness.
Elderly: The adult dose is recommended unless liver or renal function is impaired.
Method of Administration
For oral administration.
Not applicable.
