Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Contraindications

Children under 18 years
Breastfeeding
Pregnancy
Severe bilateral renal artery stenosis
Severe hepatic impairment
Severe unilateral stenosis of solitary functioning kidney

Precautions and Warnings

Patients over 75 years
Aortic stenosis
Bilateral renal artery stenosis
End stage renal disease
Hepatic impairment
Hypertrophic obstructive cardiomyopathy
Hyponatraemia
Hypovolaemia
Mitral stenosis
Peripheral vascular disease
Renovascular disorder
Severe congestive cardiac failure
Severe generalised atherosclerosis
Severe renal impairment
Unilateral stenosis of solitary functioning kidney

Consider reducing initial dose in hepatic impairment
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
Advise patient that first dose hypotension may occur
Afro-Caribbean or black patients may show reduced response
Correct volume and/or salt depletion before initiating therapy
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Monitor serum potassium regularly
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Advise patient to seek advice at first indications of pregnancy
Consider reducing initial dose in the elderly
Advise patient not to take NSAIDs unless advised by clinician
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment

In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. 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 azilsartan medoxomil is an angiotensin II antagonist, it cannot be excluded that the use of this medication may be associated with impairment of the renal function.

Pregnancy and Lactation

Pregnancy

Azilsartan medoxomil 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, azilsartan medoxomil 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

Azilsartan medoxomil 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

Angioedema
Blood urea increased
Creatine phosphokinase increased
Decrease in haematocrit
Diarrhoea
Dizziness
Fatigue
Haemoglobin decrease
Hyperkalaemia
Hypotension
Malaise
Muscle spasm
Nausea
Peripheral oedema
Pruritus
Rash
Serum creatinine increased

Presentation

Oral formulations of azilsartan medoxomil (as potassium)

Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Dosage

Adults

Elderly

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Pregnancy
Severe bilateral renal artery stenosis
Severe hepatic impairment
Severe unilateral stenosis of solitary functioning kidney

Precautions and Warnings

Patients over 75 years
Aortic stenosis
Bilateral renal artery stenosis
End stage renal disease
Hepatic impairment
Hypertrophic obstructive cardiomyopathy
Hyponatraemia
Hypovolaemia
Mitral stenosis
Peripheral vascular disease
Renovascular disorder
Severe congestive cardiac failure
Severe generalised atherosclerosis
Severe renal impairment
Unilateral stenosis of solitary functioning kidney

Consider reducing initial dose in hepatic impairment
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
Advise patient that first dose hypotension may occur
Afro-Caribbean or black patients may show reduced response
Correct volume and/or salt depletion before initiating therapy
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Monitor serum potassium regularly
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Advise patient to seek advice at first indications of pregnancy
Consider reducing initial dose in the elderly
Advise patient not to take NSAIDs unless advised by clinician
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment

In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. 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 azilsartan medoxomil is an angiotensin II antagonist, it cannot be excluded that the use of this medication may be associated with impairment of the renal function.

Pregnancy and Lactation

Pregnancy

Azilsartan medoxomil 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, azilsartan medoxomil 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

Azilsartan medoxomil 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

Angioedema
Blood urea increased
Creatine phosphokinase increased
Decrease in haematocrit
Diarrhoea
Dizziness
Fatigue
Haemoglobin decrease
Hyperkalaemia
Hypotension
Malaise
Muscle spasm
Nausea
Peripheral oedema
Pruritus
Rash
Serum creatinine increased

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: June 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.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 15 June 2015.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press Accessed on 15 June 2015.

Summary of Product Characteristics: Edarbi tablets. Takeda UK Ltd. Revised September 2014.

MHRA Drug Safety Update May 2009
Available at: https://www.mhra.gov.uk
Last accessed: 15 June, 2015

National Institute for Health and Clinical excellence (NICE) clinical guidance 107: Hypertension in pregnancy. Issue date August 2010
Available at: https://guidance.nice.org.uk/CG107
Last accessed: 15 June, 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
Azilsartan Last revised: 10 March, 2015
Last accessed: 15 June, 2015