Verapamil/ Trandolapril

Registered South African indications:

• Hypertension

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Verapamil
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product 
• 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 less than 50 beats/minute 
• Hypotension of less than 90 mmHg systolic 
• Patients with atrial flutter/fibrillation in the presence of an accessory pathway 

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment  
• Hepatic impairment 
• Bradycardia 
• First degree AV block 
• Diseases in which neuromuscular transmission is affected
• Acute stage of myocardial infarction

Trandolapril
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Pregnancy
• History of angioedema related to angiotension-converting enzyme inhibitor use
• History of angioedema associated with prior admin. of angiotensin converting enzyme inhibitor
• Hereditary or idiopathic angioedema
• Coadministration with aliskiren containing agents in patients with diabetes mellitus or renal impairment

Cautions

• Breastfeeding
• Severe renal impairment
• Severe hepatic impairment
• Elderly
• Angina pectoris
• Cerebrovascular disorders
• Prior diuretic therapy
• Fluid and salt depletion 
• Aortic stenosis or obstructed outflow from the left ventricle
• Risk factors for hyperkalaemia
• Diabetes mellitus
• Cardiac failure
• Renal artery stenosis
• Renovascular hypertension
• Recent kidney transplant
• Collagen vascular disease
• Desensitization with hymenoptera vemon
• Lipodensity lipoprotein aphoresis
• Dialysis with high-flux membranes
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Hypertension

Verapamil/ Trandolapril
180/2 (mg)
240/4 (mg)

• Oral (tab): 1 tab, dly

Do not cut/crush/chew

Take with some water

Not established for use in children

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• FDA Pregnancy Category D (Trandolapril)

Breastfeeding

• Caution; not recommended (Verapamil, Trandolapril)

Renal Impairment

• Severe: Caution; dose adjustment recommended (Trandolapril)

Hepatic Impairment

• Severe: Caution; dose adjustment recommended (Trandolapril)

Elderly

• Caution; no dose adjustment recommended (Trandolapril)

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warning

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Verapamil
Central Nervous System Disorders

• Dizziness
• Headache
• Nervousness
• Somnolence
• Paresthesia
• Tremor
• Extrapyramidal syndrome

Cardiovascular Disorders

• Bradycardia  
• Hypotension
• Tachycardia
• Decreased myocardial contractility
• Second and third block
• Asystole
• Flushing
• Peripheral oedema
• Palpitations

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Gingival hyperplasia
• Constipation

Genitourinary Disorders

• Gynaecomastia
• Impotence
• Galactorrhea

Musculoskeletal Disorders

• Muscular weakness
• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Steven-Johnson syndrome
• Erythema
• Hyperhidrosis
• Ankle oedema
• Quincke's oedema
• Erythromelalgia
• Alopecia
• Purpura

Immune System Disorders

• Allergic reactions

Sensory Disorders

• Vertigo
• Tinnitus

Trandolapril
Central Nervous System Disorders

• Headache
• Dizziness
• Myoclonus
• Paresthesia
• Migraine
• Dysgeusia
• Transient ischemic attack
• Cerebral haemorrhage
• Balance disorder
• Insomnia
• Somnolence
• Hallucination
• Depression
• Sleep difficulties
• Anxiety
• Agitation
• Apathy
• Asthenia

Cardiovascular Disorders

• Palpitations
• Myocardial infarction
• Myocardial ischemia
• Angina pectoris
• Cardiac failure
• Ventricular tachycardia
• Tachycardia
• Bradycardia
• Atrioventricular block
• Cardiac arrest
• Arrhythmia
• Abnormal ECG
• Arterial hypotension
• Hypertension
• Angiopathy
• Orthostatic hypotension
• Peripheral vascular disorder
• Varicose vein
• Cerebrovascular infarction
• Syncope
• Chest pain
• Oedema 
• Congenital arterial malformation

Respiratory Disorders

• Cough
• Upper respiratory tract inflammation
• Rhinorrhoea
• Epistaxis
• Pharyngeal inflammation
• Throat irritation
• Productive cough
• Respiratory disorder
• Dyspnoea
• Bronchitis
• Bronchospasm

Gastrointestinal Disorders

• Nausea and vomiting
• Gastrointestinal pain
• Gastrointestinal disorder
• Diarrhoea
• Obstipation
• Hematemesis
• Abdominal pain
• Dyspepsia
• Gastritis
• Flatulence
• Mouth dryness
• Ileus
• Pancreatitis

Hepatobiliary Disorders

• Hepatitis
• Hyperbilirubinemia
• Jaundice
• Increased transaminases

Genitourinary Disorders

• Functional renal insufficiency
• Azotemia
• Polyuria
• Pollakiuria
• Proteinuria
• Decreased libido

Endocrine and Metabolic Disorders

• Erectile dysfunction
• Hyperglycemia
• Hyponatremia
• Hypercholesterolemia
• Hyperlipidemia
• Hyperuricemia
• Gout
• Anorexia
• Increased appetite
• Enzyme abnormality
• Hyperkalaemia
• Increases in serum urea
• Increases in serum creatinine
• Increased liver enzymes
• Increased alkaline phosphatase
• Increased lactate dehydrogenase

Musculoskeletal Disorders

• Back pain
• Muscle spasms
• Pain in extremity
• Arthralgia
• Bone pain
• Osteoarthritis
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Skin rash
• Angioedema
• Psoriasis
• Tendency to sweat
• Eczema
• Acne
• Dry skin
• Hot flushes
• Ichthyosis
• Skin disorder
• Urticaria
• Alopecia
• Steven's Johnson syndrome
• Toxic epidermal necrolysis

Immune, Blood and Lymphatic System Disorders

• Upper respiratory tract infection
• Urinary tract infection, pharyngitis
• Anaemia
• Platelet disorder
• White blood cell disorder
• Leukopoenia
• Agranulocytosis
• Pancytopenia
• Decreased platelet count
• Decreased haemoglobin
• Decreased haematocrit 
• Allergic reactions including pruritus and skin rash
• Fever

Sensory Disorders

• Vertigo
• Tinnitus
• Blepharitis
• Conjunctival oedema
• Visual impairment
• Eye disorder

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Verapamil

• CYP3A4 enzyme 
• P-glycoprotein  
• HMG CoA reductase inhibitor  
• Ivabradine 
• St. John's Wort 
• Grapefruit juice 

Trandolapril

• Agents that increase serum potassium
• Lithium
• Diuretics
• Antihypertensive agents
• Antipsychotics
• Agents that cause leukopaenia
• Non-steroidal anti-inflammatory drugs
• Anaesthetic agents
• Alcohol
• Antacids
• Hypoglycaemic agents
• Sympathomimetics

• Vital signs

Specific cases may require

• Renal function
• Electrolytes

Verapamil
Verapamil is a calcium antagonist. It inhibits the entry 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. 

Trandolapril
Trandolaprilat, the active metabolite of trandolapril, inhibits angiotensin-I-converting enzyme activity. It inhibits conversion of relatively inactive angiotensin I to active angiotensin II. Angioitensin II is a potent vasoconstrictor and stimulates the release of aldosterone. Decreased angiotensin II levels causes decreased vasopressor activity and reduced aldosterone secretion, which decreases blood pressure. Angiotensin-converting enzyme inhibition may also inhibit the breakdown of bradykinin. 

COMBINATION PREPARATION

Verapamil/ Trandolapril

Tablet SRT 180mg/2mg 

• Tarka Bilayer (Abbott) originator

Tablet SRT 240mg/4mg

• Tarka Bilayer (Abbott) originator