Captopril

Registered South African indications:

• Hypertension
• Congestive heart failure
• Myocardial infarction

Contraindication

• Hypersensitivity to the active ingredient or any of its excipients
• History of angioedema associated with previous angiotensin-converting enzyme inhibitor therapy
• Second and third trimester of pregnancy
• Angioneurotic oedema
• Coadministration use with aliskiren-containing products in patients with diabetes or renal impairment

Caution

• First trimester of pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Hypertensive patients who are volume and/or sodium depleted
• Cardiac failure
• Renal artery stenosis
• Aortic and mitral valve stenosis/ Obstructive hypertrophic cardiomyopahy
• Diabetes mellitus
• Collagen vascular disease
• Surgery
• Anaesthesia
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption  
• May impair ability to drive and operate machinery 
• Ethnic differences

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

Hypertension- mild to moderate

• Oral (tab): Initial: 25mg, 8-12hrly; Titrate at intervals of 2 weeks; Maintenance: 25-50mg, 8-12hrly; Max dose: 150mg/24hrs

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A once daily dosing regimen may be appropriate when other antihypertensive medication is added

Dose adjustment recommended in coadministration with a diuretic

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Congestive heart failure

• Oral (tab): 6.25-12.5mg, 8-12hrly; Titrate at intervals of 2 weeks; Maintenance: 25mg, 8-12hrly; Max dose: 150mg/24hrs

Left ventricular dysfunction following myocardial infarction

• Oral (tab): Short term treatment: Initial: 6.25mg test dose immediately, 12.5mg after 2 hours, and 25mg after 12hrs; Maintenance: 50mg, 12hrly for 4 weeks  

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Patient must be haemodynamically stable before initiation

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• Oral (tab): Chronic treatment: 6.25mg immediately, then 12.5mg, 8hrly for 48hrs; then 25-50mg, 8hrly

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In cases where captopril treatment is not initiated in first 24hrs, it is suggested treatment should be started between 3-16 days post myocardial infarction once haemodynamically stable and residual ischaemia is managed

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Take medication 1 hour before meals

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For insulin dependent diabetic nephropathy a reduced daily dose is recommended

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

Hypertension

• Oral (tab): Initial: 0.1mg/kg/dose, 8hrly; Max: 2mg/kg/dose

Dilated cardiomyopathy in persistent cardiac failure

• Oral (tab): Initial: 0.5mg/kg/day, 8hrly for 24-48hrs; Titrate by 0.5mg/kg/24hrs every 24-48hrs; Mainterance: 3-5mg/kg/day

Heart failure

• Oral (tab): Initial: 0.5mg/kg/day, 8hrly for 24-48hrs; Titrate by 0.5mg/kg/day every 24-48hrs; Maintenance: 3-5mg/kg/24hrs; Duration as long as needed to control cardiac failure

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Only give once stable and maintaining blood pressure

If younger than 1 year; Max: 4mg/kg/day

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Heart failure in neonates

• Oral (tab): 0.01-0.05mg/kg/dose, 8-12hrly; Duration: as long as needed to control heart failure

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Consider in persistent heart failure where left sided outflow obstruction has been excluded, other measures have failed and only after consultation with a paediatrician or paediatric cardiologist

Administer 1 hour before feeding

Adjust dose and interval based on response

Pregnancy

• Caution; first trimester
• Contraindicated; second and third trimester
• The use of ACE inhibitors is not recommended during the first trimester of pregnancy. The use of ACE inhibitors is contra-indicated during the 2nd and 3rd trimester of pregnancy. Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy
• When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started. Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension

Breastfeeding

• Caution
• Limited pharmacokinetic data demonstrate very low concentrations in breast milk. Although these concentrations seem to be clinically irrelevant, the use of captopril in breastfeeding is not recommended for pre-term infants and for the first few weeks after delivery, because of the hypothetical risk of cardiovascular and renal effects and because there is not enough clinical experience. In the case of an older infant, the use of captopril tablets in a breastfeeding mother may be considered if this treatment is necessary for the mother and the child is observed for any adverse effect

Renal Impairment

• Caution; dose adjustment recommended

eGFR (ml/min)	Dose
≥30- 89	Administer 75% of the normal dose 12hrly
<30	Administer 50% of the normal dose every 24hrs
Haemodialysis	Administer after haemodialysis on dialysis days

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Consider initiating therapy with a lower starting dose

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Taste impairment 
• Dizziness
• Paraesthesia
• Headache 
• Drowsiness
• Cerebrovascular incidents
• Syncope
• Sleep disorders
• Confusion
• Depression
• Fatigue
• Malaise

Cardiovascular Disorders

• Tachycardia
• Tachyarrhythmia
• Angina pectoris
• Palpitations
• Cardiac arrest
• Cardiogenic shock
• Hypotension 
• Raynaud syndrome

Respiratory Disorders

• Dry, irritating, non-productive cough
• Dyspnea
• Bronchospasms
• Rhinitis
• Allergic alveolitis
• Eosinophilic pneumonia

Gastrointestinal Disorders

• Nausea and vomiting
• Loss of taste
• Abdominal pain
• Dry mouth
• Diarrhoea
• Constipation
• Gastric irritations
• Weight loss
• Loss of appetite
• Stomatitis
• Mouth ulcers
• Glossitis
• Peptic ulcer
• Pancreatitis

Hepatobiliary Disorders

• Elevation of liver enzymes and bilirubin
• Impaired hepatic function
• Cholestasis 
• Hepatitis including necrosis

Genitourinary Disorders

• Renal failure
• Polyuria
• Oliguria
• Urinary frequency
• Nephrotic syndrome
• Proteinuria

Endocrine and Metabolic Disorders

• Anorexia
• Hyperkalaemia
• Hypoglycaemia 
• Impotence
• Gynaecomastia

Immune, Blood and Lymphatic disorders

• Neutropenia
• Agranulocytosis
• Pancytopenia 
• Anaemia 
• Thrombocytopenia
• Lymphadenopathy
• Eosinophilia
• Auto-immune diseases and/or positive ANA-titres
• Anaphylaxis

Musculoskeletal Disorders

• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Pruritus with or without a rash
• Rash
• Alopecia
• Angioedema 
• Urticaria
• Stevens Johnson syndrome
• Erythema multiforme
• Photosensitivity
• Erythroderma
• Pemphigoid reactions
• Exfoliative dermatitis

Sensory Disorders

• Blurred vision

Others

• Fever
• Flush
• Pallor

• Aliskiren-containing products in patients with diabetes or renal impairment
• Lithium
• Allopurinol
• Procainamide
• Cytostatics  
• Immunosuppressive agents
• Diuretics
• Potassium sparing diuretics
• Potassium supplements
• Antihypertensive agents
• Non-steroidal anti-inflammatory drugs
• Clonidine
• Probenecid
• Tricyclic antidepressants
• Antipsychotics
• Sympathomimetics
• Antidiabetics

None routine. Specific cases may require

• White blood cell count and differential counts
• Renal function
• Proteinuria
• Serum potassium
• Bilirubin
• Antinuclear antibody
• Erythrocyte sedimentation rate

• Captopril dose should be individualised according to the patient's profile and blood pressure response
• The recommended maximum daily dose is 150 mg per 24 hours

Capotopril is a highly specific, competitive inhibitor of angiotensin-I converting enzyme. It inhibits the conversion of angiotensin I to angiotensin II; resulting in reduced levels of angiotensin II. This causes an increase in plasma renin activity and a reduction in aldosterone secretion.

Tablet 12.5mg

• Captohexal (Sandoz)

Tablet 25mg

• Adco Captomax (Adcock)
• Bio Captopril (Biotech)
• Capace (Pharmacare)
• Captohexal (Sandoz)
• Mylan Captopril (Mylan)
• Sandoz Captopril (Sandoz)
• Zapto (Litha)

Tablet 50mg

• Adco Captomax (Adcock)
• Bio-Captopril (Biotech)
• Mylan Captopril (Mylan)
• Sandoz Captopril (Sandoz)
• Zapto (Litha)

COMBINATION PREPARATIONS

Captopril/ Hydrochlorothiazide

Tablet 25mg/12.5mg

• Captoretic hs (Sandoz)

Captopril/ Hydrochlorothiazide

Tablet 50mg/25mg

• Captoretic (Sandoz)
• Zapto Co (Pharmacare)