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
Breastfeeding
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Kidney transplantation
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Symptomatic hyperuricaemia

Precautions and Warnings

Desensitisation therapy
Females of childbearing potential
History of allergies including anaphylaxis
Immunosuppression
Aortic stenosis
Asthma
Atherosclerosis
Cardiac failure
Cerebral ischaemia
Collagen vascular disease
Diabetes mellitus
Electrolyte imbalance
Gout
Hepatic cirrhosis
Hepatic impairment
History of angioedema
History of skin cancer
Hyperaldosteronism
Hyperkalaemia
Hypertrophic cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Left ventricular outflow obstruction
Malnutrition
Mitral stenosis
Nephrotic syndrome
Peripheral vascular disease
Progressive hepatic disorder
Renal artery stenosis
Renal impairment - creatinine clearance 30-80ml/minute
Renovascular disorder
Severe renin-dependent hypertension
Systemic lupus erythematosus

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaesthetist should be made aware patient is taking this medication
Advise ability to drive/operate machinery may be affected by side effects
Afro-Caribbean or black patients may show reduced response
Exclude renovascular disorder before treatment
Indigestion remedies should not be taken at the same time
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 patients with existing or tendency towards diabetes mellitus
Monitor patients with renovascular disease
Advise patient of increased risk of non-melanoma skin cancer
Advise patient to monitor for and report any skin changes
Advise patient to report symptoms of infection immediately
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
May affect results of some laboratory 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 laryngeal stridor/angioedema of face/tongue or glottis
Discontinue if symptoms of acute angle closure glaucoma occur
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

First dose hypotension: Very rapid falls in blood pressure may occur especially in patients taking high doses of diuretics, on a low salt diet, on dialysis, dehydrated, have diarrhoea/vomiting, have severe renin-dependant hypertension and with heart failure. First dose hypotension is rarely seen in uncomplicated hypertensive patients but is more likely in the presence of fluid or electrolyte imbalance (e.g. hypovolaemia, hyponatraemia, hypochloraemic alkalosis, hypomagnesaemia or hypokalaemia). Initiation of treatment and dose adjustment should be carefully monitored.

If hypotension occurs, place the patient in the supine position and if necessary administer IV infusion of normal saline. A transient hypotensive response is not a contraindication to further doses. Following restoration of effective blood volume and pressure, reinstitution of therapy at reduced dosage may be possible or either of the components may be used appropriately alone.

In patients with ischaemic heart disease or cerebrovascular disease, severe hypotension may result in a myocardial infarction or cerebrovascular event.

Some hypertensive patients (with no apparent pre-existing renal disease), have developed minor and transient increases in serum urea and creatinine levels when lisinopril has been given concomitantly with a diuretic. If this occurs, the combination should be discontinued. Reinstitution of therapy at reduced dosages may be possible, or either component can be used alone.

Patients with bilateral renal artery stenosis and unilateral renal artery stenosis in the single kidney may experience increases in blood urea nitrogen and serum creatinine. Treatment in these patients should be under medical supervision with low doses and careful dose titration. Monitor renal function especially in the first few weeks of treatment.

Lisinopril/hydrochlorothiazide is not indicated in dialysis for renal failure. There has been a high incidence of anaphylactoid reactions in patients dialysed with high flux membranes and treated with an ACE inhibitor. If dialysis is to be performed for other indications, a different membrane or a different class of antihypertensive to ACE inhibitors should be used.

Thiazides may precipitate hyperuricaemia and/or gout. Lisinopril may increase urinary uric acid and therefore may attenuate the hyperuricaemic effect of hydrochlorothiazide.

Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia. There is an increased risk of hypomagnesaemia in hepatic cirrhosis.

Intestinal angioedema has been reported in patients taking ACE inhibitors. This should be taken into consideration when diagnosing abdominal pain.

Antacids may decrease the bioavailability of lisinopril with hydrochlorothiazide.

Dose dependent increased risk of non-melanoma skin cancer with exposure to increasing cumulative doses of hydrochlorothiazide.

Hydrochlorothiazide has been associated with an idiosyncratic reaction resulting in choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma. Symptoms can occur within hours to weeks of the drug initiation, these include acute onset of decreased visual activity or ocular pain.

If intraocular pressure remains uncontrolled, consider prompt medical or surgical treatment. Risk factors for developing acute closure glaucoma may include a history of sulfonamide or penicillin allergy.

Pregnancy and Lactation

Pregnancy

Lisinopril with hydrochlorothiazide is contraindicated during pregnancy.

The manufacturer does not recommend using lisinopril with hydrochlorothiazide during pregnancy. If pregnancy occurs during treatment, this product must be discontinued immediately and an alternative antihypertensive with greater experience in pregnancy should be considered. As this product contains two medically active ingredients these are discussed separately below.

Lisinopril
The exposure to ACE inhibitors during the second and third trimesters of pregnancy is known to induce human foetotoxicity and neonatal toxicity. The risk of teratogenicity due to the exposure during the first trimester cannot be excluded. An ultrasound check of renal function and the skull would be recommended in case of an exposure to ACE inhibitors in the last two trimesters of the pregnancy.

Infants whose mothers have taken ACE inhibitors should be closely monitored for hypotension and renal function.

Hydrochlorothiazide
Hydrochlorothiazide crosses the placenta. There is limited experience with hydrochlorothiazide use during pregnancy, especially during the first trimester. In the second and third trimesters of the pregnancy, hydrochlorothiazide may cause foetal and neonatal adverse effects.

Lactation

Lisinopril with hydrochlorothiazide is contraindicated during breastfeeding.

The manufacturer states that the use of lisinopril with hydrochlorothiazide is not recommended during breastfeeding and alternative treatments with better established safety profiles during breastfeeding are preferable, especially whilst nursing a newborn or preterm infant. Large doses of thiazide diuretics may suppress milk production. Hydrochlorothiazide can pass into breast milk in small amounts. The effect on exposed infants to lisinopril and hydrochlorothiazide is unknown.

Side Effects

Accelerated erythrocyte sedimentation
ACE inhibitor hypersensitivity complex
Acute myopia
Acute renal failure
Allergic alveolitis
Alopecia
Altered liver function tests
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Anuria
Arthralgia
Arthritis
Asthenia
Autoimmune disorders
Blood dyscrasias
Blood glucose disturbances
Blurred vision (transient)
Bone marrow depression
Bronchospasm
Cerebrovascular accident
Chest discomfort
Choroidal effusion
Confusion
Cough
Decrease in haematocrit
Decreased appetite
Depressive symptoms
Diaphoresis
Dizziness
Dry mouth
Fatigue
Fever
Fluctuating serum potassium levels
Gastro-intestinal symptoms
Glaucoma (closed angle)
Glycosuria
Gout
Gynaecomastia
Headache
Hepatic failure
Hepatitis
Hypercalcaemia
Hyperglycaemia
Hypersensitivity reactions
Hyperuricaemia
Hypochloraemic alkalosis
Hypomagnesaemia
Hyponatraemia
Hypotension
Impotence
Inappropriate secretion of antidiuretic hormone
Increase in antinuclear antibodies (ANA)
Increase in blood urea nitrogen
Increase in plasma cholesterol
Increase in plasma triglyceride concentration
Interstitial nephritis
Intrahepatic cholestasis
Jaundice
Light-headedness
Lupus erythematosus-like syndrome
Lymphadenopathy
Mood changes
Muscle disorders
Myocardial infarction
Necrotising angiitis
Olfactory senses altered
Oliguria
Orthostatic hypotension
Palpitations
Pancreatitis
Paraesthesia
Pemphigus
Photosensitivity
Pneumonitis
Pruritus
Psoriasis
Pulmonary oedema
Raynaud's phenomenon
Renal impairment
Respiratory distress
Restlessness
Rhinitis
Serum bilirubin increased
Serum creatinine increased
Sialadenitis
Sinusitis
Skin reactions
Sleep disturbances
Stevens-Johnson syndrome
Syncope
Tachycardia
Taste disturbances
Toxic epidermal necrolysis
Uraemia
Urticaria
Vasculitis
Vertigo
Xanthopsia

Presentation

Oral formulations of lisinopril and hydrochlorothiazide.

Drugs List

Therapeutic Indications

Uses

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

Dosage

Patients should be stabilised on the individual components in the same proportions before commencing treatment with the lisinopril/hydrochlorothiazide combination product.

Adults

Patients with Renal Impairment

Additional Dosage Information

Contraindications

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

Precautions and Warnings

Desensitisation therapy
Females of childbearing potential
History of allergies including anaphylaxis
Immunosuppression
Aortic stenosis
Asthma
Atherosclerosis
Cardiac failure
Cerebral ischaemia
Collagen vascular disease
Diabetes mellitus
Electrolyte imbalance
Gout
Hepatic cirrhosis
Hepatic impairment
History of angioedema
History of skin cancer
Hyperaldosteronism
Hyperkalaemia
Hypertrophic cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Left ventricular outflow obstruction
Malnutrition
Mitral stenosis
Nephrotic syndrome
Peripheral vascular disease
Progressive hepatic disorder
Renal artery stenosis
Renal impairment - creatinine clearance 30-80ml/minute
Renovascular disorder
Severe renin-dependent hypertension
Systemic lupus erythematosus

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaesthetist should be made aware patient is taking this medication
Advise ability to drive/operate machinery may be affected by side effects
Afro-Caribbean or black patients may show reduced response
Exclude renovascular disorder before treatment
Indigestion remedies should not be taken at the same time
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 patients with existing or tendency towards diabetes mellitus
Monitor patients with renovascular disease
Advise patient of increased risk of non-melanoma skin cancer
Advise patient to monitor for and report any skin changes
Advise patient to report symptoms of infection immediately
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
May affect results of some laboratory 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 laryngeal stridor/angioedema of face/tongue or glottis
Discontinue if symptoms of acute angle closure glaucoma occur
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

First dose hypotension: Very rapid falls in blood pressure may occur especially in patients taking high doses of diuretics, on a low salt diet, on dialysis, dehydrated, have diarrhoea/vomiting, have severe renin-dependant hypertension and with heart failure. First dose hypotension is rarely seen in uncomplicated hypertensive patients but is more likely in the presence of fluid or electrolyte imbalance (e.g. hypovolaemia, hyponatraemia, hypochloraemic alkalosis, hypomagnesaemia or hypokalaemia). Initiation of treatment and dose adjustment should be carefully monitored.

If hypotension occurs, place the patient in the supine position and if necessary administer IV infusion of normal saline. A transient hypotensive response is not a contraindication to further doses. Following restoration of effective blood volume and pressure, reinstitution of therapy at reduced dosage may be possible or either of the components may be used appropriately alone.

In patients with ischaemic heart disease or cerebrovascular disease, severe hypotension may result in a myocardial infarction or cerebrovascular event.

Some hypertensive patients (with no apparent pre-existing renal disease), have developed minor and transient increases in serum urea and creatinine levels when lisinopril has been given concomitantly with a diuretic. If this occurs, the combination should be discontinued. Reinstitution of therapy at reduced dosages may be possible, or either component can be used alone.

Patients with bilateral renal artery stenosis and unilateral renal artery stenosis in the single kidney may experience increases in blood urea nitrogen and serum creatinine. Treatment in these patients should be under medical supervision with low doses and careful dose titration. Monitor renal function especially in the first few weeks of treatment.

Lisinopril/hydrochlorothiazide is not indicated in dialysis for renal failure. There has been a high incidence of anaphylactoid reactions in patients dialysed with high flux membranes and treated with an ACE inhibitor. If dialysis is to be performed for other indications, a different membrane or a different class of antihypertensive to ACE inhibitors should be used.

Thiazides may precipitate hyperuricaemia and/or gout. Lisinopril may increase urinary uric acid and therefore may attenuate the hyperuricaemic effect of hydrochlorothiazide.

Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia. There is an increased risk of hypomagnesaemia in hepatic cirrhosis.

Intestinal angioedema has been reported in patients taking ACE inhibitors. This should be taken into consideration when diagnosing abdominal pain.

Antacids may decrease the bioavailability of lisinopril with hydrochlorothiazide.

Dose dependent increased risk of non-melanoma skin cancer with exposure to increasing cumulative doses of hydrochlorothiazide.

Hydrochlorothiazide has been associated with an idiosyncratic reaction resulting in choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma. Symptoms can occur within hours to weeks of the drug initiation, these include acute onset of decreased visual activity or ocular pain.

If intraocular pressure remains uncontrolled, consider prompt medical or surgical treatment. Risk factors for developing acute closure glaucoma may include a history of sulfonamide or penicillin allergy.

Pregnancy and Lactation

Pregnancy

Lisinopril with hydrochlorothiazide is contraindicated during pregnancy.

The manufacturer does not recommend using lisinopril with hydrochlorothiazide during pregnancy. If pregnancy occurs during treatment, this product must be discontinued immediately and an alternative antihypertensive with greater experience in pregnancy should be considered. As this product contains two medically active ingredients these are discussed separately below.

Lisinopril
The exposure to ACE inhibitors during the second and third trimesters of pregnancy is known to induce human foetotoxicity and neonatal toxicity. The risk of teratogenicity due to the exposure during the first trimester cannot be excluded. An ultrasound check of renal function and the skull would be recommended in case of an exposure to ACE inhibitors in the last two trimesters of the pregnancy.

Infants whose mothers have taken ACE inhibitors should be closely monitored for hypotension and renal function.

Hydrochlorothiazide
Hydrochlorothiazide crosses the placenta. There is limited experience with hydrochlorothiazide use during pregnancy, especially during the first trimester. In the second and third trimesters of the pregnancy, hydrochlorothiazide may cause foetal and neonatal adverse effects.

Lactation

Lisinopril with hydrochlorothiazide is contraindicated during breastfeeding.

The manufacturer states that the use of lisinopril with hydrochlorothiazide is not recommended during breastfeeding and alternative treatments with better established safety profiles during breastfeeding are preferable, especially whilst nursing a newborn or preterm infant. Large doses of thiazide diuretics may suppress milk production. Hydrochlorothiazide can pass into breast milk in small amounts. The effect on exposed infants to lisinopril and hydrochlorothiazide is unknown.

Side Effects

Accelerated erythrocyte sedimentation
ACE inhibitor hypersensitivity complex
Acute myopia
Acute renal failure
Allergic alveolitis
Alopecia
Altered liver function tests
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Anuria
Arthralgia
Arthritis
Asthenia
Autoimmune disorders
Blood dyscrasias
Blood glucose disturbances
Blurred vision (transient)
Bone marrow depression
Bronchospasm
Cerebrovascular accident
Chest discomfort
Choroidal effusion
Confusion
Cough
Decrease in haematocrit
Decreased appetite
Depressive symptoms
Diaphoresis
Dizziness
Dry mouth
Fatigue
Fever
Fluctuating serum potassium levels
Gastro-intestinal symptoms
Glaucoma (closed angle)
Glycosuria
Gout
Gynaecomastia
Headache
Hepatic failure
Hepatitis
Hypercalcaemia
Hyperglycaemia
Hypersensitivity reactions
Hyperuricaemia
Hypochloraemic alkalosis
Hypomagnesaemia
Hyponatraemia
Hypotension
Impotence
Inappropriate secretion of antidiuretic hormone
Increase in antinuclear antibodies (ANA)
Increase in blood urea nitrogen
Increase in plasma cholesterol
Increase in plasma triglyceride concentration
Interstitial nephritis
Intrahepatic cholestasis
Jaundice
Light-headedness
Lupus erythematosus-like syndrome
Lymphadenopathy
Mood changes
Muscle disorders
Myocardial infarction
Necrotising angiitis
Olfactory senses altered
Oliguria
Orthostatic hypotension
Palpitations
Pancreatitis
Paraesthesia
Pemphigus
Photosensitivity
Pneumonitis
Pruritus
Psoriasis
Pulmonary oedema
Raynaud's phenomenon
Renal impairment
Respiratory distress
Restlessness
Rhinitis
Serum bilirubin increased
Serum creatinine increased
Sialadenitis
Sinusitis
Skin reactions
Sleep disturbances
Stevens-Johnson syndrome
Syncope
Tachycardia
Taste disturbances
Toxic epidermal necrolysis
Uraemia
Urticaria
Vasculitis
Vertigo
Xanthopsia

Effects on Laboratory Tests

The hydrochlorothiazide component could produce a positive analytic result in an anti-doping test.

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: July 2020.

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Lisoretic 10mg/12.5mg Tablets. Bristol Laboratories Ltd. Revised September 2020.

Summary of Product Characteristics: Lisoretic 20mg/12.5mg Tablets. Bristol Laboratories Ltd. Revised September 2020.

Summary of Product Characteristics: Zestoretic 10. AstraZeneca UK Ltd. Revised February 2020.

Summary of Product Characteristics: Zestoretic 20. AstraZeneca UK Ltd. Revised February 2020.

Nice Evidence Services.
Available at: www.nice.org
Last accessed: 25 June 2020.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922
Hydrochlorothiazide. Last Revised: 31 October 2018.
Last accessed: 06 July 2020.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922
Lisinopril. Last Revised: 28 February 2019.
Last accessed: 06 July 2020.