Drugs List

Therapeutic Indications

Uses

Congestive cardiac failure
Prophylaxis of heart failure in asymptomatic left ventricular dysfunction
Treatment of essential hypertension

Unlicensed Uses

Diabetic nephropathy
Proteinuria in nephritis

Contraindications

Within 36 hours of discontinuing a sacubitril containing product
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal artery stenosis
Renovascular disorder

Precautions and Warnings

Children under 18 years
Desensitisation therapy
Diarrhoea
Elderly
Immunosuppression
Restricted sodium intake
Vomiting
Aortic stenosis
Atherosclerosis
Breastfeeding
Cardiogenic shock
Cerebral ischaemia
Collagen vascular disease
Dehydration
Diabetes mellitus
Galactosaemia
Glucose-galactose malabsorption syndrome
History of angioedema
Hyperkalaemia
Hypertrophic cardiomyopathy
Hyponatraemia
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Left ventricular outflow obstruction
Metabolic acidosis
Mitral stenosis
Peripheral vascular disease
Renal dialysis
Renal impairment in adult patients - creatinine clearance below 80ml/min

Anaphylactoid reactions possible with haemofiltration or LDL apheresis
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Advise ability to drive/operate machinery may be affected by side effects
Afro-Caribbean or black patients may show reduced response
Correct volume and/or salt depletion before initiating therapy
Some formulations contain lactose
Place patient in supine position if severe hypotension occurs
Resuscitation facilities must be immediately available
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Consider dose reduction if BUN and serum creatinine rise during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor antidiabetic drug treatment
Monitor blood pressure
Monitor patients with renovascular disease
Advise patients at risk of neutropenia to report any signs of infection
Higher incidence of angioedema in black patients
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Discontinue temporarily in LDL apheresis or desensitisation therapy
Advise patient to seek advice at first indications of pregnancy
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue immediately if angioedema involves face/oropharynx/larynx
Advise patient not to take NSAIDs unless advised by clinician
Alcohol may enhance side effects
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment

Pregnancy and Lactation

Pregnancy

Enalapril is contraindicated in pregnancy.

In animal studies enalapril has been shown to produce foetal growth retardation and incomplete skull ossification in pregnant rats. Enalaprilat, the active agent produced by the hydrolysis of enalapril, is known to cross the human placenta. An in vitro study using human placental lobe showed that enalaprilat crossed over to the foetal side with a mean transfer of 2.99%. Enalapril appears to be teratogenic in human when used in the 2nd and 3rd trimesters causing foetal hypocalvaria and renal defects, thought to be related to foetal hypotension and decreased renal blood flow.

ACE inhibitors are contraindicated during the second and third trimesters of pregnancy as exposure during these trimesters is known to induce human foetal toxicity (renal dysfunction, oligohydramnios, pulmonary hypoplasia, patent ductus arteriosus, delay in skull ossification, neonatal toxicity and even death). Severe and sometimes fatal anuria in the foetus and in the newborn have been observed and is thought to be caused by the compromise of the foetal renal system. Foetal renal failure resulting from in utero exposure to ACE inhibitors has been reported where dialysis has been required shortly after birth. Evidence of a risk of teratogenicity after first trimester exposure is conflicting, however, the MHRA recommends that a risk cannot be excluded. Recent data published does associate first trimester ACE inhibitor exposure with congenital CNS and cardiovascular defects. Unless treatment with an ACE inhibitor is considered absolutely essential, women who are planning to become pregnant should be switched to an alternative drug with an established safety record. If exposure has occurred in the first trimester a detailed ultrasound diagnosis is advisable. Exposure to an ACE inhibitor during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy. In cases involving long term prenatal therapy in the second and/ or third trimesters, the foetus should be monitored for the potential development of oligohydramnios, and foetal growth should be assessed with detailed ultrasound scans (Schaefer, 2007).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use enalapril with caution in breastfeeding.

May be considered during breastfeeding of older infants.

Enalapril is excreted at low levels in breast milk. The amounts ingested by the infant are small and would not be expected to cause any adverse effects.

The MHRA has stated that although ACE inhibitors are not generally recommended for use by breastfeeding mothers they are not absolutely contraindicated and may be prescribed if treatment is considered essential. The MHRA state that ACE inhibitors should not be used by breastfeeding mothers in the first few weeks after delivery because of possible profound neonatal hypotension particularly in preterm infants. If ACE inhibitor therapy is considered essential for the mother the use of captopril, enalapril or quinapril may be considered when the infant is older. The infant should be carefully followed up for signs of hypotension should ACE inhibitor treatment be deemed necessary.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Accelerated erythrocyte sedimentation
Agranulocytosis
Allergic alveolitis
Alopecia
Anaemia
Angina pectoris
Angioneurotic oedema
Anorexia
Arthralgia
Arthritis
Asthenia
Asthma
Autoimmune disorders
Blood urea increased
Blurred vision
Bone marrow depression
Bronchospasm
Cardiac arrhythmias
Cerebrovascular accident
Chest pain
Cholestasis
Confusion
Cough
Decrease in haematocrit
Decrease in haemoglobin
Depression
Diaphoresis
Dizziness
Dream abnormalities
Dry mouth
Dyspnoea
Eosinophilia
Eosinophilic pneumonia
Erythema multiforme
Erythroderma
Exfoliative dermatitis
Fever
Flushing
Gastro-intestinal symptoms
Glossitis
Gynaecomastia
Headache
Hepatic failure
Hepatic necrosis
Hepatitis
Hoarseness
Hyperkalaemia
Hypersensitivity reactions
Hypoglycaemia
Hyponatraemia
Hypotension
Ileus
Impotence
Inappropriate secretion of antidiuretic hormone
Increases in hepatic enzymes
Insomnia
Intestinal angioedema
Leukocytosis
Lymphadenopathy
Malaise
Muscle cramps
Myalgia
Myocardial infarction
Myositis
Nervousness
Neutropenia
Oliguria
Orthostatic hypotension
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Pemphigus
Peptic ulceration
Photosensitivity
Positive ANA titre
Proteinuria
Pruritus
Pulmonary infiltrates
Raynaud's phenomenon
Renal failure
Rhinitis
Rhinorrhoea
Serositis
Serum bilirubin increased
Serum creatinine increased
Sleep disturbances
Somnolence
Sore throat
Stevens-Johnson syndrome
Stomatitis
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Urticaria
Vasculitis
Vertigo

Presentation

Oral formulations of enalapril

Drugs List

Therapeutic Indications

Uses

Congestive cardiac failure
Prophylaxis of heart failure in asymptomatic left ventricular dysfunction
Treatment of essential hypertension

Unlicensed Uses

Diabetic nephropathy
Proteinuria in nephritis

Dosage

Adults

Children

Neonates

Patients with Renal Impairment

Contraindications

Within 36 hours of discontinuing a sacubitril containing product
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal artery stenosis
Renovascular disorder

Precautions and Warnings

Children under 18 years
Desensitisation therapy
Diarrhoea
Elderly
Immunosuppression
Restricted sodium intake
Vomiting
Aortic stenosis
Atherosclerosis
Breastfeeding
Cardiogenic shock
Cerebral ischaemia
Collagen vascular disease
Dehydration
Diabetes mellitus
Galactosaemia
Glucose-galactose malabsorption syndrome
History of angioedema
Hyperkalaemia
Hypertrophic cardiomyopathy
Hyponatraemia
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Left ventricular outflow obstruction
Metabolic acidosis
Mitral stenosis
Peripheral vascular disease
Renal dialysis
Renal impairment in adult patients - creatinine clearance below 80ml/min

Anaphylactoid reactions possible with haemofiltration or LDL apheresis
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Advise ability to drive/operate machinery may be affected by side effects
Afro-Caribbean or black patients may show reduced response
Correct volume and/or salt depletion before initiating therapy
Some formulations contain lactose
Place patient in supine position if severe hypotension occurs
Resuscitation facilities must be immediately available
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Consider dose reduction if BUN and serum creatinine rise during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor antidiabetic drug treatment
Monitor blood pressure
Monitor patients with renovascular disease
Advise patients at risk of neutropenia to report any signs of infection
Higher incidence of angioedema in black patients
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Discontinue temporarily in LDL apheresis or desensitisation therapy
Advise patient to seek advice at first indications of pregnancy
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue immediately if angioedema involves face/oropharynx/larynx
Advise patient not to take NSAIDs unless advised by clinician
Alcohol may enhance side effects
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment

Pregnancy and Lactation

Pregnancy

Enalapril is contraindicated in pregnancy.

In animal studies enalapril has been shown to produce foetal growth retardation and incomplete skull ossification in pregnant rats. Enalaprilat, the active agent produced by the hydrolysis of enalapril, is known to cross the human placenta. An in vitro study using human placental lobe showed that enalaprilat crossed over to the foetal side with a mean transfer of 2.99%. Enalapril appears to be teratogenic in human when used in the 2nd and 3rd trimesters causing foetal hypocalvaria and renal defects, thought to be related to foetal hypotension and decreased renal blood flow.

ACE inhibitors are contraindicated during the second and third trimesters of pregnancy as exposure during these trimesters is known to induce human foetal toxicity (renal dysfunction, oligohydramnios, pulmonary hypoplasia, patent ductus arteriosus, delay in skull ossification, neonatal toxicity and even death). Severe and sometimes fatal anuria in the foetus and in the newborn have been observed and is thought to be caused by the compromise of the foetal renal system. Foetal renal failure resulting from in utero exposure to ACE inhibitors has been reported where dialysis has been required shortly after birth. Evidence of a risk of teratogenicity after first trimester exposure is conflicting, however, the MHRA recommends that a risk cannot be excluded. Recent data published does associate first trimester ACE inhibitor exposure with congenital CNS and cardiovascular defects. Unless treatment with an ACE inhibitor is considered absolutely essential, women who are planning to become pregnant should be switched to an alternative drug with an established safety record. If exposure has occurred in the first trimester a detailed ultrasound diagnosis is advisable. Exposure to an ACE inhibitor during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy. In cases involving long term prenatal therapy in the second and/ or third trimesters, the foetus should be monitored for the potential development of oligohydramnios, and foetal growth should be assessed with detailed ultrasound scans (Schaefer, 2007).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use enalapril with caution in breastfeeding.

May be considered during breastfeeding of older infants.

Enalapril is excreted at low levels in breast milk. The amounts ingested by the infant are small and would not be expected to cause any adverse effects.

The MHRA has stated that although ACE inhibitors are not generally recommended for use by breastfeeding mothers they are not absolutely contraindicated and may be prescribed if treatment is considered essential. The MHRA state that ACE inhibitors should not be used by breastfeeding mothers in the first few weeks after delivery because of possible profound neonatal hypotension particularly in preterm infants. If ACE inhibitor therapy is considered essential for the mother the use of captopril, enalapril or quinapril may be considered when the infant is older. The infant should be carefully followed up for signs of hypotension should ACE inhibitor treatment be deemed necessary.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Accelerated erythrocyte sedimentation
Agranulocytosis
Allergic alveolitis
Alopecia
Anaemia
Angina pectoris
Angioneurotic oedema
Anorexia
Arthralgia
Arthritis
Asthenia
Asthma
Autoimmune disorders
Blood urea increased
Blurred vision
Bone marrow depression
Bronchospasm
Cardiac arrhythmias
Cerebrovascular accident
Chest pain
Cholestasis
Confusion
Cough
Decrease in haematocrit
Decrease in haemoglobin
Depression
Diaphoresis
Dizziness
Dream abnormalities
Dry mouth
Dyspnoea
Eosinophilia
Eosinophilic pneumonia
Erythema multiforme
Erythroderma
Exfoliative dermatitis
Fever
Flushing
Gastro-intestinal symptoms
Glossitis
Gynaecomastia
Headache
Hepatic failure
Hepatic necrosis
Hepatitis
Hoarseness
Hyperkalaemia
Hypersensitivity reactions
Hypoglycaemia
Hyponatraemia
Hypotension
Ileus
Impotence
Inappropriate secretion of antidiuretic hormone
Increases in hepatic enzymes
Insomnia
Intestinal angioedema
Leukocytosis
Lymphadenopathy
Malaise
Muscle cramps
Myalgia
Myocardial infarction
Myositis
Nervousness
Neutropenia
Oliguria
Orthostatic hypotension
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Pemphigus
Peptic ulceration
Photosensitivity
Positive ANA titre
Proteinuria
Pruritus
Pulmonary infiltrates
Raynaud's phenomenon
Renal failure
Rhinitis
Rhinorrhoea
Serositis
Serum bilirubin increased
Serum creatinine increased
Sleep disturbances
Somnolence
Sore throat
Stevens-Johnson syndrome
Stomatitis
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Urticaria
Vasculitis
Vertigo

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: November 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press Accessed 10 November 2015

Summary of Product Characteristics: Innovace Tablets. Merck Sharp & Dohme Ltd. Revised August 2015.

Summary of Product Characteristics: Enalapril 2.5mg Tablets. Aurobindo Pharma - Milpharm Ltd. Revised December 2020.
Summary of Product Characteristics: Enalapril 5mg Tablets. Aurobindo Pharma - Milpharm Ltd. Revised December 2020.
Summary of Product Characteristics: Enalapril 10mg Tablets. Aurobindo Pharma - Milpharm Ltd. Revised December 2020.
Summary of Product Characteristics: Enalapril 20mg Tablets. Aurobindo Pharma - Milpharm Ltd. Revised December 2020.

MHRA Drug Safety Update: Volume 2, Issue 10, May 2009.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: 10 November, 2015

MHRA Drug Safety Update: Volume 1, Issue 5, December 2007
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON2033216
Last accessed: 10 November, 2015

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 29 June 2017.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Enalapril Last revised: 10 March, 2015
Last accessed: 10 November, 2015