Verapamil Hydrochloride

Registered South African indications:

• Hypertension - mild to moderate
• Prophylaxis of angina pectoris
• Supraventricular tachydysrrhythmia
• Prophylaxis of supraventricular relapses after electrocardioversion

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Porphyria
• Cardiogenic shock  
• Acute myocardial infarction complicated by bradycardia
• Left ventricular failure
• Second or third degree AV block (except in patients with a functioning artificial ventricular pacemaker)
• Sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker)
• Uncompensated heart failure
• Bradycardia of <50 beats/minute
• Hypotension of less than 90 mmHg systolic
• Patients with atrial flutter/fibrillation in the presence of an accessory pathway
• Wolff-Parkinson-White syndrome
• Combination with beta-blockers in patients with poor ventricular function
• Coadministration with ivabradine
• Coadministration with grapefruit juice (tab)

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment  
• Hepatic impairment
• Elderly
• Bradycardia
• First degree AV block
• Incipient cardiac failure
• Diseases in which neuromuscular transmission is affected
  - Myasthenia gravis
  - Lambert-Eaton syndrome
  - Advanced Duchenne muscular dystrophy
• Combination with beta-blockers in patients with poor ventricular function
• May impair ability to drive and operate machinery (tab, SR tab)

Forms avail. in SA and covered in this monograph:  tab, slow release tab (SR tab), inj

Supraventricular tachycardias 
Reduction of ventricular rate in atrial flutter/fibrillation

• Oral (tab): 40-120mg, 8hrly
• IV: 5-10mg over 2min as a slow injection; Repeat if needed with 5mg after of 5-10min

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The patient should be observed continuously, preferably under ECG and blood pressure control

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Hypertension - mild to moderate and renal hypertension (additional agent/s may be required)

• Oral (tab): Initial: 120mg, 12hrly; Titrate to 160mg, 12hrly if needed

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In some cases, doses of up to 480mg daily in divided doses have been used

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• Oral (SR tab): Initial: 120mg, dly; Maintenance: 240mg, dly; Max: 480mg/24hrs

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If control is not achieved after a period of 7 days, dosage may be increased to 240mg in the morning and 240mg in the evening at an interval of 12 hrs

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Do not suck or chew slow-release (SR) tablets

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Take SR tabs with, or shortly after meals

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Angina 

• Oral (tab): 80-120mg, 8hrly
• Oral (SR tab): 120-240mg, 12hrly

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Less than 120mg three times daily is unlikely to be effective in variant angina

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A small number of patients respond to a lower dose and where indicated, adjustment down to one verapamil SR tab daily could be made

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Secondary prevention of reinfarction after an acute myocardial infarction
- In patients without heart failure, and not receiving diuretics (apart from low-dose diuretics when used for indications other than heart failure), and where beta-blockers are not appropriate

• Oral (SR tab): 120mg, 8hrly; Max: 360mg/24hrs

OR

• Oral (SR tab): 240mg, in the morning; Followed by 120mg at night; Max: 360mg/24hrs

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Treatment to be initiated at least 7 days after an acute myocardial infarction

Paed. forms avail. in SA and covered in this monograph: tab, inj

Supraventricular tachycardias 
Reduction of ventricular rate in atrial flutter/fibrillation

Oral (tab)

• Younger than 2 years: 20mg, 8-12hrly
• Older than 2 years: 40-120mg, 8-12hrly

IV

• Younger than 1 year: 0.1-0.2mg/kg as slow IV; Dose range: 0.75-2mg; Repeat at intervals of 30min as needed
• Between 1-15 years: 0.1-0.3mg/kg; Dose range: 2-5mg; Repeat at intervals of 30min as needed

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Always administer under ECG monitoring

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Smaller doses may be adequate; The injection should be stopped at the onset of the desired effect 

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SR tab: Not recommended for children

Pregnancy

• Caution
• There are no adequate and well-controlled study data in pregnant women
• Although animal studies have not shown any teratogenic effects, verapamil should not be given during the first trimester of pregnancy, unless, in the clinician's judgement, it is essential for the welfare of the patient

Breastfeeding

• Caution
• Verapamil hydrochloride is excreted in human breast milk
• Limited data from oral administration has shown that the infant relative dose of verapamil is low (0.1-1% of the mother's oral dose) and that verapamil use may be compatible with breastfeeding
• Due to the potential for serious adverse reactions in nursing infants, verapamil should only be used during breastfeeding if it is essential for the welfare of the mother

Renal Impairment

• Caution; no dose adjustment recommended
  Although the pharmacokinetics of verapamil in patients with renal impairment is not affected, caution should be exercised and careful patient monitoring is recommended. Verapamil is not removed during dialysis (tab, SR tab)
  Significant renal impairment should not increase the effects of a single intravenous dose, but may prolong its duration of action (inj)

Hepatic Impairment

• Caution; dose adjustment recommended
  In cirrhosis: Reduce dose by 20% (tab)
  Reduce dose by 30% (SR tab)
  Significant hepatic impairment should not increase the effects of a single intravenous dose, but may prolong its duration of action (inj)

Elderly

• Caution; no dose adjustment recommended
  Intravenous dosage should be administered over 3mins to minimise the risk of adverse effects (inj)

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Seizures (inj)
• Paresthesia (tab, SR tab)
• Tremor (tab, SR tab)
• Extrapyramidal syndrome
  - Parkinsonism
• Nervousness (inj)
• Somnolence (inj)
• Fatigue (tab, SR tab)

Cardiovascular Disorders

• Bradycardia (inj)
• Hypotension
• Tachycardia
• Bradycardic arrhythmias (tab, SR tab)
  - Sinus bradycardia
  - Sinus arrest with asystole
  - 2nd and 3rd degree AV block
  - Bradyarrhythmia in atrial fibrillation
• Palpitations (tab, SR tab)
• Heart failure or aggravation thereof (tab, SR tab)
• Peripheral oedema (tab, SR tab)
• Decreased myocardial contractility (in)

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Constipation (tab, SR tab)
• Ileus (tab, SR tab)
• Gingival hyperplasia

Hepatobiliary Disorders

• Impaired liver function (reversible)

Genitourinary Disorders

• Gynaecomastia
• Impotence (tab, SR tab)
• Galactorrhea (tab, SR tab)

Endocrine and Metabolic Disorders

• Increased transaminases
• Increased alkaline phosphatase
• Increased prolactin (tab, SR tab)

Musculoskeletal Disorders

• Muscular weakness (tab, SR tab)
• Myalgia (tab, SR tab)
• Arthralgia (tab, SR tab)
• Dystonia (tab)

Skin and Subcutaneous Tissue Disorders

• Steven-Johnson syndrome
• Erythema
• Hyperhidrosis
• Ankle oedema (tab, SR tab)
• Quincke's oedema (tab, SR tab)
• Erythromelalgia (tab, SR tab)
• Alopecia (tab, SR tab)
• Purpura (tab, SR tab)
• Erythema multiforme (tab, SR tab)
• Flushing (tab, SR tab)

Immune System Disorders

• Allergic reactions
  - Erythema
  - Pruritis
  - Urticaria
  - Bronchospasm (inj)

Sensory Disorders

• Vertigo
• Tinnitus

• Ivabradine
• HMG CoA-reductase inhibitors
• Simvastatin
• Atorvastatin
• Lovastatin
• CYP3A4 inhibitors
• CYP3A4 inducers
• Acetylsalicylic acid
• Alpha-blockers
• Prazosin
• Terazosin
• Antiarrhythmics
• Flecainide
• Quinidine
• Anticonvulsants
• Carbamazepine
• Phenytoin
• Antidepressants
• Imipramine
• Glibenclamide
• Anti-infectives
• Rifampicin
• Erythromycin
• Clarithromycin
• Telithromycin
• Antineoplastics
• Doxorubicin (tab, SR tab)
• Barbiturates
• Phenobarbital
• Benzodiazepines and other anxiolytics
• Buspirone
• Midazolam
• Beta-blockers
• Metoprolol
• Propranolol
• Cardiac glycosides
• Digitoxin
• Digoxin
• Colchicine
• H2 receptor antagonists
• Cimetidine
• HIV antiviral agents
• Ritonavir
• Immunosuppressants
• Ciclosporin
• Everolimus
• Sirolimus
• Tacrolimus
• Inhaled anaesthetics
• Lithium
• Neuromuscular blocking agents used in anaesthesia
• Highly protein-bound agents
• Serotonin receptor agonists
• Almotriptan
• Theophylline
• Uricosurics
• Sulfinpyrazone
• Anticoagulants
• Dabigatran
• Antidiabetics
• Glibenclamide
• Antihypertensives  
• Diuretics  
• Vasodilators

Other interactions

• St John's wort
• Grapefruit juice
• Alcohol

• Blood pressure
• Heart rate
• Hepatic function
• ECG

Tablet 40mg, Tablet 240mg - EML (Hospital)

Injection - Non-EML

Verapamil, a phenylalkylamine calcium antagonist, has a balanced profile of cardiac and peripheral effects. Verapamil blocks the inward movement of calcium ions in cardiac muscle cells, in smooth muscle cells of the coronary and systemic arteries and in cells of the intracardiac conduction system. Because of its effect on the movement of calcium in the intracardiac conduction system, verapamil reduces automaticity, decreases conduction velocity and increases the refractory period. Verapamil reduces total peripheral resistance and lowers high blood pressure by vasodilation, without reflex tachycardia. Because of its use-dependent action on the voltage-operated calcium channel, the effects of verapamil are more pronounced on high than on normal blood pressure.

Tablet 40mg

• Isoptin (Abbott) originator
• Sandoz Verapamil (Sandoz)
• Verapamil 40 Oethmaan (Oethmaan Biosims)
• Vasomil (Pharmacare)
• Ravamil (Merck)

Tablet 80mg

• Sandoz Verapamil (Sandoz)
• Vasomil (Pharmacare)

Tablet 120mg

• Sandoz Verapamil HCI (Sandoz)

Tablet src 180mg

• Tarka (Abbott)

Tablet srt 240mg

• Calcicard SR (Pharma Dynamics)
• Isoptin (Abbott) originator
• Ravamil SR (Merck) originator
• Verahexal SR (Sandoz)

Injection (per 2ml) 5mg

• Isoptin (Abbott) originator
• Pharma-Q Verapamil (Pharma-Q)
• Vasomil (Pharmacare)

COMBINATION PREPARATION

Verapamil/Trandolapril

Tablet srt 180mg/2mg 

• Tarka Bilayer (Abbott) originator

Tablet srt 240mg/4mg

• Tara Bilayer (Abbott) originator