Enalapril Maleate

Registered South African indications:

• Hypertension
• Heart failure
• Asymptomatic left ventricular dysfunction

Should a woman become pregnant while receiving an ACE inhibitor, the treatment must be stopped promptly and the patient switched to a different medicine. Should a woman contemplate pregnancy, the doctor should institute alternative medication.

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe renal impairment (CrCl<30ml/min)
• Porphyria
• patients who have had previous treatment with an ACE inhibitor or an angiotensin receptor blocker (ARB) that resulted in angioneurotic oedema. These patients must never again be given these medicines
• Hereditary or idiopathic angioedema
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Aortic stenosis
• Concomitant therapy with potassium-sparing diuretics such as spironolactone, triamterene, amiloride
• Lithium therapy: Concomitant administration with enalapril may lead to toxic blood concentrations of lithium

South African recommendations

• Mild to moderate renal impairment
• Hepatic impairment
• Elderly
• Collagen vascular disorders
• Left ventricular valvular and outflow tract obstruction
• Recent kidney transplantation
• Haemodialysis patients
• Surgery
• Anaesthesia
• Diabetes mellitus
• Dehydration
• Acute cardiac decompensation
• Metabolic acidosis
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Ethnic differences

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

Essential hypertension

• Oral (tab): Initial: 5-20mg, dly; Maintenance: 10-20mg, dly; adjust as needed; Max: 40mg/24hrs

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May be given in 2 divided doses if control is inadequate with a single dose

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Renovascular hypertension

• Oral (tab): Initial: 2.5-5mg; Maintenance: 5-20mg, dly; or in divided doses; as needed

Heart failure
Asymptomatic left ventricular dysfunction

• Oral (tab): Initial: 2.5mg, dly, increase gradually over 2-4weeks as needed, Maintenance: 20mg, dly or in divided doses; as needed; Max: 40mg/24hrs

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 Concomitant treatment with diuretics: The dosage of the diuretic should be reduced, or stopped, prior to initiating treatment

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Diabetic nephropathy

• Oral (tab): Initial: 5mg, 12hrly; Maintenance: 5-20mg, 12hrly

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

Essential hypertension
Renovascular hypertension

Younger than 1 month

• Not established for use

Between 1 month - 16 years

• Oral (tab): 0.1-0.5 mg/kg/day, 12-24hrs; Initial 0.08mg/kg/day, titrate up to 5mg/day; Max: 40mg/24hrs

Older than 16 years

• See adult dosage

Heart failure

Younger than 1 month

• Not established for use

Between 1 month - 16 years

• Oral(tab): 0.1-0.5 mg/kg/day, 12-24hrs; Initial 0.08mg/kg/day, titrate slowly up to 0.5mg/kg/day; Max: 40mg/24hrs

Older than 16 years

• See adult dosage

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Dose should be individualised according to patient profile and blood pressure response

Pregnancy

South African recommendations

• Contraindicated

• Pregnant women should be informed of the potential hazards to the foetus and must not take enalapril during pregnancy
• 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 enalapril should be stopped immediately and if appropriate, alternative therapy should be started
• Foetal exposure to ACE inhibitors as in enalapril during the first trimester of pregnancy has been reported to be associated with an increased risk of malformations of the cardiovascular (atrial and/or ventricular septal defect, pulmonic stenosis, patent ductus arteriosus) and central nervous system (microcephaly spins bifida) and of kidney malformations. enalapril passes through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms
• Oligohydramnios as well as hypotension, oliguria and anuria in new-borns, have been reported after administration of enalapril during the second and third trimester
• Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur

Breastfeeding

South African recommendations

• Contraindicated
• Enalapril and enalaprilat are secreted in human milk. Therefore, the use of enalapril is not recommended in women breastfeeding their babies

Fertility

South African recommendations

• No information available

South African recommendations

• Mild to moderate: Caution; dose adjustment recommended (see table below)
  The minimum maintenance dose that controls symptoms is desirable
• Severe: Contraindicated

Renal Status	Creatinine Clearance (ml/min)	Initial Dose (mg/day)
Mild	>30 - <80	5
Moderate	>10 - ≤30	2.5
Severe (dialysis patients)	≤10	2.5mg on dialysis days ++

++ Enalapril maleate is dialysable; haemodialysis patients may receive the normal dose on the day of dialysis treatment

South African recommendations

• Caution; no information available

South African recommendations

• Caution; no information available

Central Nervous System Disorders

• Dizziness
• Headache
• Syncope
• Taste alteration
• Somnolence
• Paresthesia
• Vertigo
• Depression
• Confusion
• Nervousness
• Sleep disorders
• Fatigue
• Malaise
• Aesthenia

Cardiovascular Disorders

• Chest pain
• Rhythm disturbances
• Angina pectoris
• Tachycardia
• Palpitations
• Myocardial infarction
• Cerebrovascular accident
• Hypotension 
• Flushing
• Orthostatic hypotension
• Raynaud's phenomenon

Respiratory Disorders

• Cough
• Dyspnoea
• Rhinorrhoea
• Sore throat
• Hoarseness
• Bronchospasm
• Asthma
• Pulmonary infiltrates
• Rhinitis
• Allergic alveolitis
• Eosinophilia pneumonia

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Ileus
• Pancreatitis
• Dyspepsia
• Constipation
• Anorexia
• Gastric irritation
• Dry mouth
• Peptic ulcer
• Stomatitis
• Aphthous ulcerations
• Glossitis
• Intestinal angioedema

Hepatobiliary Disorders

• Hepatic failure
• Hepatitis
• Elevations of liver enzymes
• Elevations of serum bilirubin

Genitourinary Disorders

• Renal impairment
• Renal failure
• Proteinuria
• Oliguria

Endocrine and Metabolic Disorders

• Impotence
• Gynaecomastia
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Hypoglycaemia
• Hyperkalaemia
• Increases in serum creatinine
• Increases in blood urea
• Hyponatraemia

Musculoskeletal Disorders

• Muscle cramps
• Arthralgia
• Arthritis

Skin and Subcutaneous Tissue Disorders

• Rash
• Hypersensitivity
• Angioneurotic oedema
• Diaphoresis
• Pruritus
• Urticaria
• Alopecia
• Erythema multiforme
• Stevens-Johnson syndrome
• Exfoliative dermatitis
• Toxic epidermal necrolysis
• Pemphigus
• Erythroderma
• Serositis
• Vasculitis
• Myalgia
• Myositis
• Rash
• Photosensitivity

Immune, Blood and Lymphatic System Disorders

• Anaemia 
• Neutropenia
• Decreases in haematocrit
• Thrombocytopenia
• Agranulocytosis
• Bone marrow depression
• Pancytopenia
• Lymphadenopathy
• Autoimmune diseases
• Eosinophilia
• Leucocytosis

Sensory Disorders

• Tinnitus
• Blurred vision

Others

• Fever

• Diuretics
• Lithium
• Antihypertensive agents
• Agents that increase serum potassium
• Anti-inflammatory agents
• Oestrogen
• Calcium antagonists
• Sympathomimetics
• Narcotic drugs
• Antipsychotics
• Alcohol
• Angiotensin II receptor blockers
• Aliskiren
• Anaesthetic medicinal products
• Tricyclic antidepressants 
• Non-steroidal anti-inflammatory drugs
• Selective cyclooxygenase-2 inhibitors 
• Gold
• mTOR inhibitor therapy
• Hypoglycaemic agents

None routine. Specific cases may require

• Renal function
• Serum potassium
• Full blood count

Tablet 5mg, Tablet 10mg, Tablet 20mg - EML (Primary)

Tablet 2.5mg - Non-EML

Enalapril is hydrolysed to enalaprilat which is a specific, long-acting, non-sulfhydryl angiotensin-converting enzyme inhibitor. Angiotensin-converting enzyme inhibitor is a peptidyl dipeptidase which catalyses the conversion of angiotensin I to the pressor substance angiotensin II. This results in reduced plasma renin activity and decreased aldosterone secretion. The blood pressure lowering effect of enalapril is primarily through suppression of the renin- angiotensin- aldosterone system. 

Tablet 2.5mg

• Renitec (MSD) originator

Tablet 5mg

• Alapren (Ranbaxy)
• Austell Enalapril (Austell)
• Ciplatec (Sandoz)
• Enalapril 5 Arya (Arya Pharma)
• Enalapril Ascendis (Dezzo traiding)
• Enalapril Biotech (Biotech)
• Enalapril Unicorn (Ranbaxy)
• Enap (Pharma Dynamics)
• Envas (Pharma-Q)
• HR Enalapril (Sandoz)
• Hypace (Pharmaceutical Contr)
• Pharmapress (Pharmacare)
• Renitec (MSD) originator (Discontinued: 03/04/2019)

Tablet 10mg

• Alapren (Ranbaxy)
• Austell Enalapril (Austell)
• Ciplatec (Cipla)
• Enalapril 10 Arya (Arya Pharma)
• Enalarpil Ascendis (Dezzo trading)
• Enalapril Biotech (Biotech)
• Enalapril Unicorn (Ranbaxy)
• Enap (Pharma Dynamics)
• Envas (Pharma-Q)
• Envas 10 (Pharma-Q)
• HR Enalapril (Sandoz)
• Pharmapress (Pharmacare)
• Renitec (MSD) originator (Discontinued: 03/04/2021)

Tablet 20mg

• Alapren (Ranbaxy)
• Austell Enalapril (Austell)
• Ciplatec (Cipla)
• Co-Renitec (MSD)
• Enalapril 20 Arya (Arya Pharma)
• Enalapril Biotech (Biotech)
• Enalapril Unicorn (Ranbaxy)
• Enap (Pharma Dynamics)
• HR Enalapril (Sandoz)
• Pharmapress (Pharmacare)
• Renitec (MSD) originator (Discontinued: 03/04/2019)

COMBINATION PREPARATIONS

Enalapril/ Hydrochlorothiazide

Tablet 20mg/12.5mg

• Co-renitec (MSD) originator
• Enap Co (Pharma Dynamics)
• Pharmapress Co (Pharmacare)

Enalapril/ Lercanidipine

Tablet 10mg/10mg

• Zaneril (Pharmaplan) originator

Tablet 20mg/10mg

• Zaneril (Pharmaplan) originator