Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Contraindications

Children under 18 years
Addison's disease
Anuria
Biliary obstruction
Breastfeeding
Cholestasis
Galactosaemia
Hereditary fructose intolerance
Hypercalcaemia
Hyponatraemia
Pregnancy
Refractory hypokalaemia
Renal impairment - creatinine clearance below 30 ml/minute
Severe bilateral renal artery stenosis
Severe hepatic impairment
Severe unilateral stenosis of solitary functioning kidney
Symptomatic hyperuricaemia

Precautions and Warnings

Aortic stenosis
Bilateral renal artery stenosis
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
Hepatic cirrhosis
Hepatic impairment
History of angioedema
History of asthma
History of skin cancer
Hyperaldosteronism
Hypertrophic obstructive cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Malnutrition
Mitral stenosis
Nephrotic syndrome
Peripheral vascular disease
Progressive hepatic disorder
Renal impairment
Renovascular disorder
Severe congestive cardiac failure
Severe generalised atherosclerosis
Systemic lupus erythematosus
Unilateral stenosis of solitary functioning kidney

Advise patient to protect skin if restarting following photosensitivity
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
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Diabetic control may need adjustment
Monitor blood / urinary glucose in patients suspected of latent diabetes
Monitor fluid balance
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 precipitate diabetes mellitus
May precipitate gout
Withdraw and consider hyperparathyroidism if frank hypercalcaemia develops
Discontinue before parathyroid function tests
Advise patient to seek advice at first indications of pregnancy
Discontinue if photosensitivity occurs
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

Pregnancy and Lactation

Pregnancy

Telmisartan with hydrochlorothiazide is contraindicated in pregnancy.

There are no adequate data from the use of telmisartan with hydrochlorothiazide in pregnancy women. Studies in animals have shown reproductive toxicity. 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.

Telmisartan
Telmisartan is contraindicated in pregnancy. When pregnancy is diagnosed, treatment should be immediately discontinued and if possible an alternative treatment started.

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, telmisartan 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.

Hydrochlorothiazide
Hydrochlorothiazide is not recommended for use during pregnancy.

Diuretics can reduce plasma volume and lead to a reduced perfusion of the placenta. Schaefer (2007) comments that diuretics are no longer part of the standard therapy for hypertension and oedema during pregnancy; they should only be used for particular indications. In such cases hydrochlorothiazide is the diuretic of choice. Use of hydrochlorothiazide is not an indication for interrupting pregnancy. Briggs (2011) comments that in general, diuretics are not recommended in the treatment of gestational hypertension because of the maternal hypovolaemia characteristic of the disease.

Thiazides and related diuretics may cause neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbance and hypoglycaemia. Stimulation of labour, uterine inertia and meconium staining have also been reported.

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

Telmisartan with hydrochlorothiazide is contraindicated in breastfeeding.

Alternative treatments with better established safety profiles during breastfeeding are preferable, especially when nursing a newborn or preterm infant. As this product contains two medically active ingredients these are discussed separately below.

Telmisartan
At the time of writing, there is insufficient experience concerning the use of telmisartan during breastfeeding. It is unknown is telmisartan is excreted into breast milk, however, its molecular weight would suggest that excretion into breast milk is likely. Hale (2014) comments that no paediatric concerns have been reported but telmisartan should be used with caution in early postpartum in breastfeeding mothers (especially those with premature infants). The MHRA concludes that the use of angiotensin II receptor antagonists in breastfeeding mothers is not recommended. Schaefer (2007) concludes that accidental exposure to this drug does not require weaning, and that therapy should be changed to an antihypertensive that has been better studied during breastfeeding.

Hydrochlorothiazide
Hydrochlorothiazide is excreted in small quantities into breast milk. There have been reports of thrombocytopenia in the nursing infants of mothers receiving a thiazide diuretic, however, the risk is considered low. Thiazide diuretics have been used in large quantities to suppress lactation. However, information on LactMed states that hydrochlorothiazide doses of 50 mg daily or less are acceptable during breastfeeding. Overall, 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 renal failure
Agranulocytosis
Anaemia
Angioneurotic oedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Arthrosis
Asthenia
Blood disorders
Blood glucose disturbances
Bone marrow depression
Bradycardia
Bronchitis
Changes in hepatic function
Cough
Creatine phosphokinase increased
Cystitis
Decreased appetite
Depression
Dizziness
Drowsiness
Dry mouth
Dyspnoea
Eczema
Electrolyte disturbances
Elevated triglyceride levels
Eosinophilia
Erectile dysfunction
Erythema
Fixed drug eruption
Gastro-intestinal disturbances
Glycosuria
Gout
Haemoglobin decrease
Headache
Hepatic disorders
Hypercalcaemia
Hypercholesterolaemia
Hyperkalaemia
Hypersensitivity reactions including anaphylaxis
Hyperuricaemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypotension
Hypovolaemia
Impotence
Increased sweating
Increases in hepatic enzymes
Influenza-like symptoms
Interstitial lung disease
Interstitial nephritis
Intrahepatic cholestasis
Jaundice
Leucopenia
Light-headedness
Muscle cramps
Myalgia
Narrow angle glaucoma
Necrotising vasculitis
Neutropenia
Oliguria
Pain
Pancreatitis
Paraesthesia
Pharyngitis
Photosensitivity
Pneumonitis
Postural hypotension
Pruritus
Pulmonary oedema
Pyrexia
Rash
Renal impairment
Respiratory distress syndrome
Restlessness
Sepsis
Serum creatinine increased
Sialadenitis
Sinusitis
Sleep disturbances
Somnolence
Syncope
Systemic lupus erythematosus
Tachycardia
Tendon disorder
Thirst
Thrombocytopenia
Toxic epidermal necrolysis
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vertigo
Visual disturbances
Weakness
Xanthopsia

Presentation

Oral formulations of telmisartan and hydrochlorothiazide

Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Dosage

Individual dose titration with each of the two components is recommended before changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered.

The 40 mg + 12.5 mg formulation may be administered to patients whose blood pressure is not adequately controlled by 40 mg telmisartan alone.
The 80 mg + 12.5 mg formulation may be administered to patients whose blood pressure is not adequately controlled by 80 mg telmisartan alone.
The 80 mg + 25 mg formulation may be administered to patients whose blood pressure is not adequately controlled by the 80 mg + 12.5 mg formulation.

Adults

Elderly

Patients with Hepatic Impairment

Contraindications

Children under 18 years
Addison's disease
Anuria
Biliary obstruction
Breastfeeding
Cholestasis
Galactosaemia
Hereditary fructose intolerance
Hypercalcaemia
Hyponatraemia
Pregnancy
Refractory hypokalaemia
Renal impairment - creatinine clearance below 30 ml/minute
Severe bilateral renal artery stenosis
Severe hepatic impairment
Severe unilateral stenosis of solitary functioning kidney
Symptomatic hyperuricaemia

Precautions and Warnings

Aortic stenosis
Bilateral renal artery stenosis
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
Hepatic cirrhosis
Hepatic impairment
History of angioedema
History of asthma
History of skin cancer
Hyperaldosteronism
Hypertrophic obstructive cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Malnutrition
Mitral stenosis
Nephrotic syndrome
Peripheral vascular disease
Progressive hepatic disorder
Renal impairment
Renovascular disorder
Severe congestive cardiac failure
Severe generalised atherosclerosis
Systemic lupus erythematosus
Unilateral stenosis of solitary functioning kidney

Advise patient to protect skin if restarting following photosensitivity
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
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Diabetic control may need adjustment
Monitor blood / urinary glucose in patients suspected of latent diabetes
Monitor fluid balance
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 precipitate diabetes mellitus
May precipitate gout
Withdraw and consider hyperparathyroidism if frank hypercalcaemia develops
Discontinue before parathyroid function tests
Advise patient to seek advice at first indications of pregnancy
Discontinue if photosensitivity occurs
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

Pregnancy and Lactation

Pregnancy

Telmisartan with hydrochlorothiazide is contraindicated in pregnancy.

There are no adequate data from the use of telmisartan with hydrochlorothiazide in pregnancy women. Studies in animals have shown reproductive toxicity. 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.

Telmisartan
Telmisartan is contraindicated in pregnancy. When pregnancy is diagnosed, treatment should be immediately discontinued and if possible an alternative treatment started.

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, telmisartan 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.

Hydrochlorothiazide
Hydrochlorothiazide is not recommended for use during pregnancy.

Diuretics can reduce plasma volume and lead to a reduced perfusion of the placenta. Schaefer (2007) comments that diuretics are no longer part of the standard therapy for hypertension and oedema during pregnancy; they should only be used for particular indications. In such cases hydrochlorothiazide is the diuretic of choice. Use of hydrochlorothiazide is not an indication for interrupting pregnancy. Briggs (2011) comments that in general, diuretics are not recommended in the treatment of gestational hypertension because of the maternal hypovolaemia characteristic of the disease.

Thiazides and related diuretics may cause neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbance and hypoglycaemia. Stimulation of labour, uterine inertia and meconium staining have also been reported.

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

Telmisartan with hydrochlorothiazide is contraindicated in breastfeeding.

Alternative treatments with better established safety profiles during breastfeeding are preferable, especially when nursing a newborn or preterm infant. As this product contains two medically active ingredients these are discussed separately below.

Telmisartan
At the time of writing, there is insufficient experience concerning the use of telmisartan during breastfeeding. It is unknown is telmisartan is excreted into breast milk, however, its molecular weight would suggest that excretion into breast milk is likely. Hale (2014) comments that no paediatric concerns have been reported but telmisartan should be used with caution in early postpartum in breastfeeding mothers (especially those with premature infants). The MHRA concludes that the use of angiotensin II receptor antagonists in breastfeeding mothers is not recommended. Schaefer (2007) concludes that accidental exposure to this drug does not require weaning, and that therapy should be changed to an antihypertensive that has been better studied during breastfeeding.

Hydrochlorothiazide
Hydrochlorothiazide is excreted in small quantities into breast milk. There have been reports of thrombocytopenia in the nursing infants of mothers receiving a thiazide diuretic, however, the risk is considered low. Thiazide diuretics have been used in large quantities to suppress lactation. However, information on LactMed states that hydrochlorothiazide doses of 50 mg daily or less are acceptable during breastfeeding. Overall, 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 renal failure
Agranulocytosis
Anaemia
Angioneurotic oedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Arthrosis
Asthenia
Blood disorders
Blood glucose disturbances
Bone marrow depression
Bradycardia
Bronchitis
Changes in hepatic function
Cough
Creatine phosphokinase increased
Cystitis
Decreased appetite
Depression
Dizziness
Drowsiness
Dry mouth
Dyspnoea
Eczema
Electrolyte disturbances
Elevated triglyceride levels
Eosinophilia
Erectile dysfunction
Erythema
Fixed drug eruption
Gastro-intestinal disturbances
Glycosuria
Gout
Haemoglobin decrease
Headache
Hepatic disorders
Hypercalcaemia
Hypercholesterolaemia
Hyperkalaemia
Hypersensitivity reactions including anaphylaxis
Hyperuricaemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypotension
Hypovolaemia
Impotence
Increased sweating
Increases in hepatic enzymes
Influenza-like symptoms
Interstitial lung disease
Interstitial nephritis
Intrahepatic cholestasis
Jaundice
Leucopenia
Light-headedness
Muscle cramps
Myalgia
Narrow angle glaucoma
Necrotising vasculitis
Neutropenia
Oliguria
Pain
Pancreatitis
Paraesthesia
Pharyngitis
Photosensitivity
Pneumonitis
Postural hypotension
Pruritus
Pulmonary oedema
Pyrexia
Rash
Renal impairment
Respiratory distress syndrome
Restlessness
Sepsis
Serum creatinine increased
Sialadenitis
Sinusitis
Sleep disturbances
Somnolence
Syncope
Systemic lupus erythematosus
Tachycardia
Tendon disorder
Thirst
Thrombocytopenia
Toxic epidermal necrolysis
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vertigo
Visual disturbances
Weakness
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: 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.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 18 November 2015.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press Accessed on 18 November 2015.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Actelsar HCT 40 mg/12.5 mg tablets. Actavis UK Ltd. Revised September 2014.
Summary of Product Characteristics: Actelsar HCT 80 mg/12.5 mg tablets. Actavis UK Ltd. Revised September 2014.
Summary of Product Characteristics: Actelsar HCT 80 mg/25 mg tablets. Actavis UK Ltd. Revised September 2014.

Summary of Product Characteristics: MicardisPlus 40/12.5 mg tablets. Boehringer Ingelheim Ltd. Revised September 2014.
Summary of Product Characteristics: MicardisPlus 80/12.5 mg. Boehringer Ingelheim Ltd. Revised September 2014.
Summary of Product Characteristics: MicardisPlus 80/25 mg tablets. Boehringer Ingelheim Ltd. Revised September 2014.

Summary of Product Characteristics: Tolucombi 40/12.5 mg tablets. Consilient Health Ltd. Revised May 2015.
Summary of Product Characteristics: Tolucombi 80/12.5 mg tablets. Consilient Health Ltd. Revised May 2015.
Summary of Product Characteristics: Tolucombi 80/25 mg tablets. Consilient Health Ltd. Revised May 2015.

MHRA Drug Safety Update: Breastfeeding with ACE inhibitors and angiotensin II receptor antagonists. Dated: May 2009
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: 18 November, 2015

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

National Institute for Health and Clinical excellence (NICE) clinical guidance 107: Hypertension in pregnancy. Issue date August 2010
Available at: https://publications.nice.org.uk/hypertension-in-pregnancy-cg107
Last accessed: 18 November, 2015

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
Hydrochlorothiazide. Last revised: 7 September, 2013
Last accessed: 18 November, 2015

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
Telmisartan. Last revised: 10 March, 2015
Last accessed: 18 November, 2015