Trandolapril

Registered South African indications:

• Hypertension

Should a woman become pregnant while receiving trandolapril, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine. Should a woman contemplate pregnancy, the doctor should consider alternative medication.

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other angiotensin-converting (ACE) inhibitors
• History of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs)
• Hereditary or idiopathic angioedema
• Aortic stenosis
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Severe renal function impairment (creatinine clearance less than 30ml/min)
• Concomitant use of fluoroquinolones with trandolapril in patients with moderate to severe renal impairment (creatinine clearance ≤30ml/min) and in elderly patients
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Pregnancy
• Breastfeeding
• Concomitant therapy with potassium-sparing diuretics such as spironolactone, triamterene, or amiloride
• Porphyria
• Lithium therapy: Concomitant administration with trandolapril may lead to toxic blood concentrations of lithium
• Concomitant use of trandolapril with aliskiren-containing products

Cautions

• 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: cap

Hypertension- mild to moderate

• Oral (cap): Initial: 0.5mg, dly, Titrate by doubling dose at 2-4 week intervals; Maintenance: 1-2mg, dly; Max single dose: 4mg

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If the patient response is still unsatisfactory at 4mg, combination therapy should be considered

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Left ventricular dysfunction after acute myocardial infarction

• Oral (cap): Initial: 0.5mg, dly; Maintenance dose: 4mg, dly; Max: 4mg/24hrs

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After an acute myocardial infarction, treatment can be started as early as the third day, provided that the patient is haemodynamically stable

Patients at high risk of hypotension, should be initiated on treatment under hospital supervision

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Diuretics should be stopped 2-3 days before initiating trandolapril

Not established for use in children

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Renal Impairment

• Severe (creatinine clearance less than 30ml/min): Contraindicated
• Coadministration with fluoroquinolones in patients with moderate to severe renal impairment (CrCl≤30ml/min): Contraindicated

Hepatic Impairment

• Severe: Caution; dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  The dose in elderly patients is the same as in non-elderly adults
  There is no need to reduce the dose in elderly patients with normal renal and hepatic function
  Caution should be exercised in elderly patients with concomitant use of diuretics, congestive heart failure or renal or hepatic insufficiency
  The dose should be titrated according to the need for the control of blood pressure. In these patients, therapy should be initiated at a dose of 0.5mg daily
• Coadministration with fluoroquinolones: Contraindicated

Porphyria Information

• Contraindicated

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

• Potassium-sparing diuretics
• Spironolactone
• Triamterene
• Amiloride
• Lithium
• Aliskiren-containing products
• Agents that increase serum potassium
• Diuretics
• Antihypertensive agents
• Antipsychotics
• Agents that cause leukopaenia
• Non-steroidal anti-inflammatory drugs
• Anaesthetic agents
• Alcohol
• Antacids
• Hypoglycaemic agents
• Sympathomimetics

None routine. Specific cases may require

• Renal function
• Electrolytes

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.

Capsule 0.5mg

• Mavik (Abbott) originator

Capsule 2mg 

• Mavik (Abbott) originator

COMBINATION PREPARATIONS

Trandolapril/Verapamil

Tablet  2mg/180mg

• Tarka Bilayer (Abbott) originator

Tablet 4mg/240mg

• Tarka Bilayer (Abbott) originator