Drugs List

Therapeutic Indications

Uses

Hypertension-not adequately controlled by individual components

Contraindications

Children under 18 years
Addison's disease
Anuria
Biliary obstruction
Breastfeeding
Cholestasis
Galactosaemia
Haemodialysis
Hypercalcaemia
Pregnancy
Refractory hypokalaemia
Refractory hyponatraemia
Renal artery stenosis
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Symptomatic hyperuricaemia

Precautions and Warnings

Predisposition to narrow angle glaucoma
Aortic stenosis
Atherosclerosis
Cerebral ischaemia
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
History of angioedema
History of hepatic impairment
History of skin cancer
Hyperaldosteronism
Hypertrophic obstructive cardiomyopathy
Hyponatraemia
Hypovolaemia
Kidney transplantation
Lactose intolerance
Malnutrition
Mitral stenosis
Peripheral vascular disease
Renal impairment - creatinine clearance 30-50ml/minute
Renovascular disorder
Severe cardiac dysfunction
Systemic lupus erythematosus

Correct electrolyte disorders before treatment
May decrease glucose tolerance in patients with diabetes mellitus
May exacerbate or activate systemic lupus erythematosus
Patients with primary aldosteronism may not benefit from this treatment
Switch to more suitable alternative before planned pregnancy
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
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Monitor antidiabetic drug treatment
Monitor blood / urinary glucose in patients suspected of latent diabetes
Monitor serum potassium regularly
Advise patient of increased risk of non-melanoma skin cancer
Advise patient to monitor for and report any skin changes
Excess consumption of liquorice may increase the risk of hypokalaemia
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Increases in cholesterol and triglyceride levels may be seen
May cause hyperuricaemia
May precipitate gout
Discontinue before parathyroid function tests
Advise patient to seek advice at first indications of pregnancy
Discontinue if acute respiratory distress syndrome is suspected
Discontinue if patient develops decreased visual acuity +/or ocular pain
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effects may be potentiated by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Advise patient to avoid grapefruit products
Female: Ensure adequate contraception during treatment
Advise pt. to minimise exposure to sunlight & avoid sunlamps during therapy

Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

In patients whose renal function may depend on the activity of the renin-angiotensin system (patients with severe congestive heart failure), treatment with ACE inhibitors has been associated with oliguria and/ or progressive azotaemia and in rare cases with acute renal failure and/ or death. As losartan with hydrochlorothiazide contains an angiotensin II antagonist, it cannot be excluded that the use of this medication may be associated with impairment of the renal function.

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.

Rare cases of acute respiratory toxicity including acute respiratory distress syndrome (ARDS) have been reported following treatment with hydrochlorothiazide. Symptoms can develop within minutes to hours of taking hydrochlorothiazide. If a diagnosis of ARDS is suspected, treatment should be withdrawn. This product should not be administered to a patient who has previously developed ARDS associated with hydrochlorothiazide.

Pregnancy and Lactation

Pregnancy

Losartan with hydrochlorothiazide is contraindicated in pregnancy.

Angiotensin II receptor antagonists may be associated with similar risks as ACE inhibitors. Angiotensin II receptor antagonist exposure during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).

The MHRA states that the use of angiotensin II receptor antagonists in late pregnancy has been associated with adverse effects on the foetal kidney and other congenital anomalies, therefore angiotensin II receptor antagonists should not be used at any stage during of pregnancy unless absolutely necessary and only then after the potential risks and benefits have been discussed with the patient.

Exposure to angiotensin II receptor antagonists during the first trimester has been inconclusive, however, a small increase in risk cannot be excluded and a detailed ultrasound is recommended.

If pregnancy is detected during therapy, losartan with hydrochlorothiazide should be discontinued as soon as possible and alternative treatment should be offered. Guidelines advise that women who are taking angiotensin II receptor blockers are told that there is an increased risk of congenital abnormalities if these drugs are taken during pregnancy and other antihypertensive treatments should be discussed and offered.

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

Losartan with hydrochlorothiazide is contraindicated in breastfeeding.

Schaefer (2007) suggests that accidental administration of a single dose does not require weaning, however, therapy should be changed to an antihypertensive which has been better studied in breastfeeding. The MHRA concludes that the use of angiotensin II receptor antagonists in breastfeeding mothers is not recommended. Alternative agents with more established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm baby.

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 syndrome
Agranulocytosis
Alopecia
Altered liver enzymes values
Anaemia
Anaphylactic reaction
Anaphylactoid-like reaction
Angina
Angioedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Arthritis
Asthenia
Blood glucose disturbances
Blood lipid changes
Bronchitis
Choroidal effusion
Confusion
Conjunctivitis
Cough
Decrease in haemoglobin and haematocrit
Depression
Dermatitis
Dizziness
Dry mouth
Dry skin
Dyspnoea
Ecchymosis
Electrolyte disturbances
Epistaxis
Erythema
Eye irritation
Fatigue
Fever
Flushing
Gastro-intestinal disturbances
Glycosuria
Gout
Headache
Henoch-Schonlein purpura
Hepatitis
Impaired memory
Impotence
Increase in blood urea or creatinine
Increased sweating
Interstitial nephritis
Intrahepatic cholestasis
Joint swelling
Laryngitis
Leucopenia
Liver function disturbances
Malaise
Micturition disorders
Migraine
Muscle spasm
Myalgia
Myocardial infarction
Narrow angle glaucoma
Necrotising angiitis
Nervousness
Ocular pain
Oedema
Orthostatic hypotension
Pain
Palpitations
Pancreatitis
Panic attack
Paraesthesia
Peripheral neuropathy
Pharyngitis
Photosensitivity
Pruritus
Purpura
Rash
Reduced libido
Renal failure
Rhinitis
Second and third degree AV block
Serum bilirubin increased
Sialadenitis
Sinus disorder
Sinusitis
Sleep disturbances
Somnolence
Stiffness
Stroke
Syncope
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vasculitis
Vertigo
Visual disturbances
Xanthopsia

Presentation

Oral formulations of losartan with hydrochlorothiazide.

Drugs List

Therapeutic Indications

Uses

Hypertension-not adequately controlled by individual components

Dosage

Titration with the individual components (losartan and hydrochlorothiazide) is recommended. When clinically appropriate direct change from monotherapy to the fixed combination maybe considered in patients whose blood pressure is not adequately controlled.

In general, the antihypertensive effect is attained within 3 to 4 weeks after initiation of therapy.

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
Addison's disease
Anuria
Biliary obstruction
Breastfeeding
Cholestasis
Galactosaemia
Haemodialysis
Hypercalcaemia
Pregnancy
Refractory hypokalaemia
Refractory hyponatraemia
Renal artery stenosis
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Symptomatic hyperuricaemia

Precautions and Warnings

Predisposition to narrow angle glaucoma
Aortic stenosis
Atherosclerosis
Cerebral ischaemia
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
History of angioedema
History of hepatic impairment
History of skin cancer
Hyperaldosteronism
Hypertrophic obstructive cardiomyopathy
Hyponatraemia
Hypovolaemia
Kidney transplantation
Lactose intolerance
Malnutrition
Mitral stenosis
Peripheral vascular disease
Renal impairment - creatinine clearance 30-50ml/minute
Renovascular disorder
Severe cardiac dysfunction
Systemic lupus erythematosus

Correct electrolyte disorders before treatment
May decrease glucose tolerance in patients with diabetes mellitus
May exacerbate or activate systemic lupus erythematosus
Patients with primary aldosteronism may not benefit from this treatment
Switch to more suitable alternative before planned pregnancy
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
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Monitor antidiabetic drug treatment
Monitor blood / urinary glucose in patients suspected of latent diabetes
Monitor serum potassium regularly
Advise patient of increased risk of non-melanoma skin cancer
Advise patient to monitor for and report any skin changes
Excess consumption of liquorice may increase the risk of hypokalaemia
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Increases in cholesterol and triglyceride levels may be seen
May cause hyperuricaemia
May precipitate gout
Discontinue before parathyroid function tests
Advise patient to seek advice at first indications of pregnancy
Discontinue if acute respiratory distress syndrome is suspected
Discontinue if patient develops decreased visual acuity +/or ocular pain
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effects may be potentiated by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Advise patient to avoid grapefruit products
Female: Ensure adequate contraception during treatment
Advise pt. to minimise exposure to sunlight & avoid sunlamps during therapy

Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

In patients whose renal function may depend on the activity of the renin-angiotensin system (patients with severe congestive heart failure), treatment with ACE inhibitors has been associated with oliguria and/ or progressive azotaemia and in rare cases with acute renal failure and/ or death. As losartan with hydrochlorothiazide contains an angiotensin II antagonist, it cannot be excluded that the use of this medication may be associated with impairment of the renal function.

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.

Rare cases of acute respiratory toxicity including acute respiratory distress syndrome (ARDS) have been reported following treatment with hydrochlorothiazide. Symptoms can develop within minutes to hours of taking hydrochlorothiazide. If a diagnosis of ARDS is suspected, treatment should be withdrawn. This product should not be administered to a patient who has previously developed ARDS associated with hydrochlorothiazide.

Pregnancy and Lactation

Pregnancy

Losartan with hydrochlorothiazide is contraindicated in pregnancy.

Angiotensin II receptor antagonists may be associated with similar risks as ACE inhibitors. Angiotensin II receptor antagonist exposure during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).

The MHRA states that the use of angiotensin II receptor antagonists in late pregnancy has been associated with adverse effects on the foetal kidney and other congenital anomalies, therefore angiotensin II receptor antagonists should not be used at any stage during of pregnancy unless absolutely necessary and only then after the potential risks and benefits have been discussed with the patient.

Exposure to angiotensin II receptor antagonists during the first trimester has been inconclusive, however, a small increase in risk cannot be excluded and a detailed ultrasound is recommended.

If pregnancy is detected during therapy, losartan with hydrochlorothiazide should be discontinued as soon as possible and alternative treatment should be offered. Guidelines advise that women who are taking angiotensin II receptor blockers are told that there is an increased risk of congenital abnormalities if these drugs are taken during pregnancy and other antihypertensive treatments should be discussed and offered.

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

Losartan with hydrochlorothiazide is contraindicated in breastfeeding.

Schaefer (2007) suggests that accidental administration of a single dose does not require weaning, however, therapy should be changed to an antihypertensive which has been better studied in breastfeeding. The MHRA concludes that the use of angiotensin II receptor antagonists in breastfeeding mothers is not recommended. Alternative agents with more established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm baby.

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 syndrome
Agranulocytosis
Alopecia
Altered liver enzymes values
Anaemia
Anaphylactic reaction
Anaphylactoid-like reaction
Angina
Angioedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Arthritis
Asthenia
Blood glucose disturbances
Blood lipid changes
Bronchitis
Choroidal effusion
Confusion
Conjunctivitis
Cough
Decrease in haemoglobin and haematocrit
Depression
Dermatitis
Dizziness
Dry mouth
Dry skin
Dyspnoea
Ecchymosis
Electrolyte disturbances
Epistaxis
Erythema
Eye irritation
Fatigue
Fever
Flushing
Gastro-intestinal disturbances
Glycosuria
Gout
Headache
Henoch-Schonlein purpura
Hepatitis
Impaired memory
Impotence
Increase in blood urea or creatinine
Increased sweating
Interstitial nephritis
Intrahepatic cholestasis
Joint swelling
Laryngitis
Leucopenia
Liver function disturbances
Malaise
Micturition disorders
Migraine
Muscle spasm
Myalgia
Myocardial infarction
Narrow angle glaucoma
Necrotising angiitis
Nervousness
Ocular pain
Oedema
Orthostatic hypotension
Pain
Palpitations
Pancreatitis
Panic attack
Paraesthesia
Peripheral neuropathy
Pharyngitis
Photosensitivity
Pruritus
Purpura
Rash
Reduced libido
Renal failure
Rhinitis
Second and third degree AV block
Serum bilirubin increased
Sialadenitis
Sinus disorder
Sinusitis
Sleep disturbances
Somnolence
Stiffness
Stroke
Syncope
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vasculitis
Vertigo
Visual disturbances
Xanthopsia

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: October 2016

Reference Sources

Summary of Product Characteristics: Cozaar-Comp 50/12.5 mg, 100/12.5 mg and 100/25 mg Film-coated Tablets. Merck Sharp & Dohme Ltd. Revised November 2022.

Summary of Product Characteristics: Losartan potassium/Hydrochlorothiazide 50/12.5 mg Film-coated Tablets. Actavis UK Ltd. Revised October 2015.

Summary of Product Characteristics: Losartan potassium/Hydrochlorothiazide 100/12.5 mg Film-coated Tablets. Actavis UK Ltd. Revised October 2015.

Summary of Product Characteristics: Losartan potassium/Hydrochlorothiazide 100/25 mg Film-coated Tablets. Actavis UK Ltd. Revised October 2015.

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

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