Drugs List

Therapeutic Indications

Uses

Mild to moderate hypertension when stabilised on same ingreds./proportions

Contraindications

Children under 18 years
Within 36 hours of discontinuing a sacubitril containing product
Addison's disease
Anuria
Cardiogenic shock
Galactosaemia
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal artery stenosis
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Symptomatic hyperuricaemia

Precautions and Warnings

Desensitisation therapy
Immunosuppression
Patients over 70 years
Predisposition to narrow angle glaucoma
Aortic stenosis
Atherosclerosis
Breastfeeding
Cerebral ischaemia
Collagen vascular disease
Decompensated cardiac failure
Diabetes mellitus
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatic impairment
History of skin cancer
Hyperkalaemia
Hypertrophic cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Left ventricular outflow obstruction
Malnutrition
Metabolic acidosis
Mitral stenosis
Nephrotic syndrome
Peripheral vascular disease
Progressive hepatic disorder
Renal impairment - creatinine clearance 30-80ml/minute
Renovascular disorder
Systemic lupus erythematosus

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaesthetist should be made aware patient is taking this medication
Anaphylactoid reactions possible with haemofiltration or LDL apheresis
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Patients with primary aldosteronism may not benefit from this treatment
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
Contains lactose
Place patient in supine position if severe hypotension occurs
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 blood urea
Monitor closely patient with a history of congestive cardiac failure
Monitor patients with existing or tendency towards diabetes mellitus
Monitor patients with renovascular disease
Monitor serum creatinine
Monitor serum magnesium in hepatic cirrhosis
Monitor serum potassium regularly
Advise patient of increased risk of non-melanoma skin cancer
Advise patient to monitor for and report any skin changes
Advise patients at risk of neutropenia to report any signs of infection
Excess consumption of liquorice may increase the risk of hypokalaemia
Higher incidence of angioedema in black patients
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
May cause anaphylactic / anaphylactoid reactions
May precipitate gout
Withdraw and consider hyperparathyroidism if frank hypercalcaemia develops
Discontinue before parathyroid function tests
Withdraw before apheresis
Withdraw before desensitisation
Advise patient to seek advice at first indications of pregnancy
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if patient develops decreased visual acuity +/or ocular pain
Discontinue immediately if angioedema involves face/oropharynx/larynx
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment
Advise pt. to minimise exposure to sunlight & avoid sunlamps during therapy

Enalapril with hydrochlorothiazide should not be administered with aliskiren containing products in patients with diabetes or renal impairment (GFR less than 60 ml/minute/1.73 metres squared).

An idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute closed angle glaucoma may occur. Symptoms including acute onset of decreased visual acuity or ocular pain may occur within hours to weeks of initiation of this product and can lead to permanent vision loss. If symptoms occur treatment should be discontinued and prompt medical or surgical treatments should be considered if the intraocular pressure remains uncontrolled.

Pregnancy and Lactation

Pregnancy

Enalapril maleate with hydrochlorothiazide tablets are contraindicated during pregnancy.

If pregnancy is diagnosed, the MHRA recommend treatment with ACE inhibitors be stopped immediately, and, if appropriate, alternative therapy started. Schaefer suggests that exposure to an ACE inhibitor during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy. Unless treatment with an ACE inhibitor is considered absolutely essential, the MHRA recommend women who are planning to become pregnant should be switched to an alternative drug with an established safety record.

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, limb contractures, intrauterine growth retardation, prematurity, persistent 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. The primary means for removal of enalapril is renal so the impairment of this system in newborns prevents its elimination, resulting in prolonged hypotension. Newborn renal function and blood pressure should be closely monitored. If oligohydramnios occurs, stopping enalapril may resolve the problem but may not improve infant outcome because of irreversible foetal damage (Briggs, 2011).

Evidence of a risk of teratogenicity after first trimester exposure is conflicting, however, the MHRA states that a risk cannot be excluded and do not recommend enalapril in the first trimester. Although this is contrary to previous findings, recent data published does associate first trimester ACE inhibitor exposure with congenital CNS and cardiovascular defects. 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 manufacturer also recommends that ultrasound scans should be used to check renal function and skull. Similarly, if exposure occurs in the first trimester a detailed ultrasound diagnosis is advisable. Briggs (2011) recommends the close monitoring of newborn renal function and blood pressure.

Enalaprilat, the active agent produced by the hydrolysis of enalapril, is known to cross the human placenta. Hydrochlorothiazide is also known to cross the placenta.

Diuretics are no longer part of standard therapy for hypertension during pregnancy. The hypovolaemia characteristic of gestational hypertension would be adversely affected by hydrochlorothiazide. This could lead to a decrease in placental perfusion. Other risks to the foetus or newborn include bone marrow depression, hypoglycaemia, thrombocytopenia, hyponatraemia, hypokalaemia, growth retardation, foeto-placental ischaemia with the attendant risk of foetal hypotrophy, jaundice and death from maternal complications. Prolonged labour has also been described as the result of inhibition of smooth muscle action. Thiazide diuretics may also cause electrolyte disturbances, stimulation of labour and meconium staining.

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 14-17 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

Enalapril maleate with hydrochlorothiazide tablets may be considered during breastfeeding of older infants.

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. The infant should be carefully followed up for signs of hypotension should ACE inhibitor treatment be deemed necessary. Schaefer states that ACE inhibitors can be used during breastfeeding when the first choice antihypertensives are not effective or not indicated. Schaefer suggests watching for oedema and a possible increase in infant weight as indicators of disturbed kidney function.

LactMed recommends that enalapril may be administered to breastfeeding mothers because the drug gives very low levels in the infant with no apparent effects.

Hydrochlorothiazide is excreted in small quantities into breast milk. Thiazide diuretics have been used in large quantities to suppress lactation. There have been reports of thrombocytopenia in the nursing infants of mothers receiving a thiazide diuretic, however, the risk is considered low by Briggs (2011) and Hale (2010). Hydrochlorothiazide is considered safe while breastfeeding.

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

Acute respiratory distress
Agranulocytosis
Allergic alveolitis
Alopecia
Anaphylactoid reaction
Angina pectoris
Angioedema
Anorexia
Aplastic anaemia
Arrhythmias
Arthralgia
Arthritis
Asthenia
Asthma
Autoimmune disorders
Blood glucose disturbances
Blood lipid changes
Blurred vision
Bone marrow depression
Changes in erythrocyte sedimentation rate
Chest pain
Cholestasis
Choroidal effusion
Confusion
Cough
Decrease in haemoglobin and haematocrit
Depression
Diaphoresis
Dizziness
Dry mouth
Dyspnoea
Electrolyte disturbances
Elevation of liver enzymes
Eosinophilia
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fever
Flushing
Gastro-intestinal symptoms
Glossitis
Gout
Gynaecomastia
Haemolytic anaemia
Headache
Hepatic failure
Hepatitis
Hypersensitivity reactions
Hypotension
Ileus
Impotence
Inappropriate secretion of antidiuretic hormone
Increase in antinuclear antibodies (ANA)
Increase in blood urea or creatinine
Interstitial nephritis
Leucocytosis
Leucopenia
Lymphadenopathy
Malaise
Muscle cramps
Myalgia
Myocardial infarction
Myositis
Narrow angle glaucoma
Nervousness
Neutropenia
Ocular pain
Oliguria
Palpitations
Pancreatitis
Paraesthesia
Pemphigus
Peptic ulceration
Photosensitivity
Pneumonitis
Proteinuria
Pulmonary infiltrates
Pulmonary oedema
Purpura
Raynaud's phenomenon
Reduced libido
Renal failure
Renal impairment
Rhinitis
Rhinorrhoea
Serositis
Serum bilirubin increased
Sleep disturbances
Somnolence
Sore throat
Stevens-Johnson syndrome
Stomatitis
Syncope
Systemic lupus erythematosus
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Vertigo

Presentation

Oral formulations containing enalapril maleate and hydrochlorothiazide

Drugs List

Therapeutic Indications

Uses

Mild to moderate hypertension when stabilised on same ingreds./proportions

Dosage

The dosage should be determined primarily by the required dosage of the enalapril component of the formulation.

Adults

Elderly

Patients with Renal Impairment

Contraindications

Children under 18 years
Within 36 hours of discontinuing a sacubitril containing product
Addison's disease
Anuria
Cardiogenic shock
Galactosaemia
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal artery stenosis
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Symptomatic hyperuricaemia

Precautions and Warnings

Desensitisation therapy
Immunosuppression
Patients over 70 years
Predisposition to narrow angle glaucoma
Aortic stenosis
Atherosclerosis
Breastfeeding
Cerebral ischaemia
Collagen vascular disease
Decompensated cardiac failure
Diabetes mellitus
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatic impairment
History of skin cancer
Hyperkalaemia
Hypertrophic cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Left ventricular outflow obstruction
Malnutrition
Metabolic acidosis
Mitral stenosis
Nephrotic syndrome
Peripheral vascular disease
Progressive hepatic disorder
Renal impairment - creatinine clearance 30-80ml/minute
Renovascular disorder
Systemic lupus erythematosus

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaesthetist should be made aware patient is taking this medication
Anaphylactoid reactions possible with haemofiltration or LDL apheresis
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Patients with primary aldosteronism may not benefit from this treatment
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
Contains lactose
Place patient in supine position if severe hypotension occurs
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 blood urea
Monitor closely patient with a history of congestive cardiac failure
Monitor patients with existing or tendency towards diabetes mellitus
Monitor patients with renovascular disease
Monitor serum creatinine
Monitor serum magnesium in hepatic cirrhosis
Monitor serum potassium regularly
Advise patient of increased risk of non-melanoma skin cancer
Advise patient to monitor for and report any skin changes
Advise patients at risk of neutropenia to report any signs of infection
Excess consumption of liquorice may increase the risk of hypokalaemia
Higher incidence of angioedema in black patients
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
May cause anaphylactic / anaphylactoid reactions
May precipitate gout
Withdraw and consider hyperparathyroidism if frank hypercalcaemia develops
Discontinue before parathyroid function tests
Withdraw before apheresis
Withdraw before desensitisation
Advise patient to seek advice at first indications of pregnancy
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if patient develops decreased visual acuity +/or ocular pain
Discontinue immediately if angioedema involves face/oropharynx/larynx
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment
Advise pt. to minimise exposure to sunlight & avoid sunlamps during therapy

Enalapril with hydrochlorothiazide should not be administered with aliskiren containing products in patients with diabetes or renal impairment (GFR less than 60 ml/minute/1.73 metres squared).

An idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute closed angle glaucoma may occur. Symptoms including acute onset of decreased visual acuity or ocular pain may occur within hours to weeks of initiation of this product and can lead to permanent vision loss. If symptoms occur treatment should be discontinued and prompt medical or surgical treatments should be considered if the intraocular pressure remains uncontrolled.

Pregnancy and Lactation

Pregnancy

Enalapril maleate with hydrochlorothiazide tablets are contraindicated during pregnancy.

If pregnancy is diagnosed, the MHRA recommend treatment with ACE inhibitors be stopped immediately, and, if appropriate, alternative therapy started. Schaefer suggests that exposure to an ACE inhibitor during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy. Unless treatment with an ACE inhibitor is considered absolutely essential, the MHRA recommend women who are planning to become pregnant should be switched to an alternative drug with an established safety record.

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, limb contractures, intrauterine growth retardation, prematurity, persistent 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. The primary means for removal of enalapril is renal so the impairment of this system in newborns prevents its elimination, resulting in prolonged hypotension. Newborn renal function and blood pressure should be closely monitored. If oligohydramnios occurs, stopping enalapril may resolve the problem but may not improve infant outcome because of irreversible foetal damage (Briggs, 2011).

Evidence of a risk of teratogenicity after first trimester exposure is conflicting, however, the MHRA states that a risk cannot be excluded and do not recommend enalapril in the first trimester. Although this is contrary to previous findings, recent data published does associate first trimester ACE inhibitor exposure with congenital CNS and cardiovascular defects. 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 manufacturer also recommends that ultrasound scans should be used to check renal function and skull. Similarly, if exposure occurs in the first trimester a detailed ultrasound diagnosis is advisable. Briggs (2011) recommends the close monitoring of newborn renal function and blood pressure.

Enalaprilat, the active agent produced by the hydrolysis of enalapril, is known to cross the human placenta. Hydrochlorothiazide is also known to cross the placenta.

Diuretics are no longer part of standard therapy for hypertension during pregnancy. The hypovolaemia characteristic of gestational hypertension would be adversely affected by hydrochlorothiazide. This could lead to a decrease in placental perfusion. Other risks to the foetus or newborn include bone marrow depression, hypoglycaemia, thrombocytopenia, hyponatraemia, hypokalaemia, growth retardation, foeto-placental ischaemia with the attendant risk of foetal hypotrophy, jaundice and death from maternal complications. Prolonged labour has also been described as the result of inhibition of smooth muscle action. Thiazide diuretics may also cause electrolyte disturbances, stimulation of labour and meconium staining.

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 14-17 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

Enalapril maleate with hydrochlorothiazide tablets may be considered during breastfeeding of older infants.

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. The infant should be carefully followed up for signs of hypotension should ACE inhibitor treatment be deemed necessary. Schaefer states that ACE inhibitors can be used during breastfeeding when the first choice antihypertensives are not effective or not indicated. Schaefer suggests watching for oedema and a possible increase in infant weight as indicators of disturbed kidney function.

LactMed recommends that enalapril may be administered to breastfeeding mothers because the drug gives very low levels in the infant with no apparent effects.

Hydrochlorothiazide is excreted in small quantities into breast milk. Thiazide diuretics have been used in large quantities to suppress lactation. There have been reports of thrombocytopenia in the nursing infants of mothers receiving a thiazide diuretic, however, the risk is considered low by Briggs (2011) and Hale (2010). Hydrochlorothiazide is considered safe while breastfeeding.

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

Acute respiratory distress
Agranulocytosis
Allergic alveolitis
Alopecia
Anaphylactoid reaction
Angina pectoris
Angioedema
Anorexia
Aplastic anaemia
Arrhythmias
Arthralgia
Arthritis
Asthenia
Asthma
Autoimmune disorders
Blood glucose disturbances
Blood lipid changes
Blurred vision
Bone marrow depression
Changes in erythrocyte sedimentation rate
Chest pain
Cholestasis
Choroidal effusion
Confusion
Cough
Decrease in haemoglobin and haematocrit
Depression
Diaphoresis
Dizziness
Dry mouth
Dyspnoea
Electrolyte disturbances
Elevation of liver enzymes
Eosinophilia
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fever
Flushing
Gastro-intestinal symptoms
Glossitis
Gout
Gynaecomastia
Haemolytic anaemia
Headache
Hepatic failure
Hepatitis
Hypersensitivity reactions
Hypotension
Ileus
Impotence
Inappropriate secretion of antidiuretic hormone
Increase in antinuclear antibodies (ANA)
Increase in blood urea or creatinine
Interstitial nephritis
Leucocytosis
Leucopenia
Lymphadenopathy
Malaise
Muscle cramps
Myalgia
Myocardial infarction
Myositis
Narrow angle glaucoma
Nervousness
Neutropenia
Ocular pain
Oliguria
Palpitations
Pancreatitis
Paraesthesia
Pemphigus
Peptic ulceration
Photosensitivity
Pneumonitis
Proteinuria
Pulmonary infiltrates
Pulmonary oedema
Purpura
Raynaud's phenomenon
Reduced libido
Renal failure
Renal impairment
Rhinitis
Rhinorrhoea
Serositis
Serum bilirubin increased
Sleep disturbances
Somnolence
Sore throat
Stevens-Johnson syndrome
Stomatitis
Syncope
Systemic lupus erythematosus
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
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: March 2013

Reference Sources

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.

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

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: January 11, 2010.
Last accessed: March 6, 2013.

Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Hydrochlorothiazide, Last revised: January 24, 2013.
Last accessed: March 6, 2013.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

MHRA Drug Safety Update: Volume 2, Issue 10, May 2009.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: February 22, 2011.

MHRA Drug Safety Update: Volume 1, Issue 5, December 2007
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON2033216
Last accessed: February 22, 2011.

MHRA Drug Safety Update November 2018
Available at: https://www.mhra.gov.uk
Last accessed: 08 January 2019.

NHS National Institute for Health and Clinical Excellence, Hypertension in pregnancy. The management of hypertensive disorders during pregnancy, published August 2010 (last modified January 2011).
https://www.nice.org.uk/nicemedia/live/13098/50418/50418.pdf
Last accessed: March 6, 2013.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 September 2022.

Summary of Product Characteristics: Enalapril maleate/ Hydrochlorothiazide 20/12.5mg Tablets. Sandoz Limited. Revised February 2012.

Summary of Product Characteristics: Innozide tablets. Merck Sharp & Dohme Ltd. Revised March 2022.