Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Contraindications

Children under 18 years
Biliary obstruction
Breastfeeding
Galactosaemia
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Elderly
Vascular tone dependent on renin-angiotensin system
Aortic stenosis
Cerebrovascular disorder
Dehydration
Diabetes mellitus
Electrolyte depletion
Glucose-galactose malabsorption syndrome
History of angioedema
Hyperkalaemia
Hypertrophic obstructive cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Metabolic acidosis
Mitral stenosis
Moderate hepatic impairment
Peripheral vascular disease
Renal artery stenosis
Renal impairment
Renovascular disorder
Severe cardiac failure
Severe generalised atherosclerosis

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
Contains lactose
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
Discontinue & do not restart if sprue-like enteropathy confirmed by biopsy
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

Intravascular volume depletion
Patients who have previously undergone diuretic therapy, dietary salt restrictions or suffered from diarrhoea or vomiting may be volume and/or sodium depleted. In order to reduce symptomatic hypotension (especially following the first dose), this volume depletion should be corrected before starting treatment with olmesartan.

Conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system, using drugs that act upon this system may lead to acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. These adverse effects may occur with angiotensin II receptor antagonists. Such patients include those with severe congestive heart failure or underlying renal disease, including renal artery stenosis.

Renovascular hypotension
Patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are at an increased risk of severe hypotension and renal impairment when treated with drugs that affect the renin-angiotensin-aldosterone system.

Hyperkalaemia
Drugs which affect the renin-angiotensin-aldosterone system may cause hyperkalaemia, which could be fatal. The risk is increased in elderly patients, in patients with renal impairment, in patients with diabetes mellitus and in patients receiving concomitant treatment with other medicinal products that affect potassium levels.

Additional risk factors for hyperkalaemia include dehydration, acute cardiac decompensation, metabolic acidosis, worsening renal function, sudden worsening renal condition (e.g. infection) and cellular lysis (e.g. acute limb ischaemia, rhabdomyolysis, extended trauma).

It is advisable to assess the benefit risk ratio when administering more than one medical product that acts upon the renin-angiotensin-aldosterone system concomitantly as this may increase the risk of hyperkalaemia. If dual blockade of the renin-angiotensin-aldosterone system is considered necessary it should be done under close medical supervision, with regular monitoring of renal function, electrolytes and blood pressure.

Sprue-like enteropathy
In very rare cases severe chronic diarrhoea with substantial weight loss has been reported in patients taking olmesartan few months to years after drug initiation, possibly caused by a localized delayed hypersensitivity reaction. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with olmesartan, exclude other etiologies. Consider discontinuation of olmesartan in cases where no other etiology is identified. In cases where symptoms disappear and sprue-like enteropathy is confirmed by biopsy, treatment with olmesartan should not be restarted.

Pregnancy and Lactation

Pregnancy

Olmesartan is contraindicated during pregnancy.

Epidemiological studies assessing the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy have not been conclusive; therefore a small increase in risk cannot be excluded for angiotensin II antagonists. Patients planning pregnancy should be changed to an alternative anti-hypertensive treatment (which has an established safety profile for use in pregnancy) unless continued angiotensin receptor blocker therapy is considered essential. Treatment with angiotensin II antagonists should be stopped when pregnancy is diagnosed and, if possible, alternative therapy should be considered. Exposure during the second and third trimesters to angiotensin II antagonists is known to cause human foetotoxicity, including decreased renal function, oligohydramnios and skull ossification retardation. Neonatal toxicity including renal failure, hypotension and hyperkalaemia has also occurred.

An ultrasound check of renal function and skull to exclude oligohydramnios is recommended should exposure to angiotensin II antagonists have occurred past 20 weeks. It is also advisable to closely observe infants whose mothers have taken angiotensin II antagonists for renal impairment and hypotension (Schaefer, 2015).

The antihypertensive mechanism of olmesartan and ACE inhibitors are closely related. Consequently, olmesartan may cause foetal and neonatal toxicity similar to that seen with ACE inhibitors. Such foetal toxic effects may include patent ductus arteriosus, prematurity, intrauterine growth restriction, foetal hypocalvaria, and anuria. Anuria-associated oligohydramnios may cause limb contractures, craniofacial deformations and pulmonary hypoplasia. A newborn exposed to olmesartan in utero may experience severe anuria and hypotension that is resistant to both volume expansion and pressor agents (Briggs, 2015).
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

Olmesartan is contraindicated during breastfeeding.

Olmesartan is excreted in the milk of lactating rats, it is unknown if it is excreted in human milk.

The molecular weight of olmesartan is low enough that excretion in breast milk should be expected (Briggs, 2015).

Schaefer (2015) 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. LactMed agrees that due to the lack of available information, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

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

Abdominal pain
Acute renal failure
Allergic dermatitis
Anaphylactic reaction
Angina pectoris
Angioedema
Arthritis
Asthenia
Back pain
Blood urea increased
Bronchitis
Chest pain
Cough
Creatine phosphokinase increased
Diarrhoea
Dizziness
Dyspepsia
Epistaxis
Exanthema
Facial oedema
Fatigue
Gastro-enteritis
Haematuria
Headache
Hyperkalaemia
Hypertriglyceridaemia
Hyperuricaemia
Hypotension
Increase in creatinine
Increases in hepatic enzymes
Influenza-like symptoms
Lethargy
Malaise
Muscle spasm
Musculoskeletal pain
Myalgia
Nausea
Pain
Peripheral oedema
Pharyngitis
Pruritus
Rash
Renal impairment
Rhabdomyolysis
Rhinitis
Skeletal pain
Sprue-like enteropathy
Thrombocytopenia
Urinary tract infections
Urticaria
Vertigo
Vomiting

Presentation

Oral formulations containing olmesartan medoxomil

Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Dosage

Adults

Elderly

Patients with Renal Impairment

Patients with Hepatic Impairment

Contraindications

Children under 18 years
Biliary obstruction
Breastfeeding
Galactosaemia
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Elderly
Vascular tone dependent on renin-angiotensin system
Aortic stenosis
Cerebrovascular disorder
Dehydration
Diabetes mellitus
Electrolyte depletion
Glucose-galactose malabsorption syndrome
History of angioedema
Hyperkalaemia
Hypertrophic obstructive cardiomyopathy
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Metabolic acidosis
Mitral stenosis
Moderate hepatic impairment
Peripheral vascular disease
Renal artery stenosis
Renal impairment
Renovascular disorder
Severe cardiac failure
Severe generalised atherosclerosis

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
Contains lactose
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
Discontinue & do not restart if sprue-like enteropathy confirmed by biopsy
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

Intravascular volume depletion
Patients who have previously undergone diuretic therapy, dietary salt restrictions or suffered from diarrhoea or vomiting may be volume and/or sodium depleted. In order to reduce symptomatic hypotension (especially following the first dose), this volume depletion should be corrected before starting treatment with olmesartan.

Conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system, using drugs that act upon this system may lead to acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. These adverse effects may occur with angiotensin II receptor antagonists. Such patients include those with severe congestive heart failure or underlying renal disease, including renal artery stenosis.

Renovascular hypotension
Patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are at an increased risk of severe hypotension and renal impairment when treated with drugs that affect the renin-angiotensin-aldosterone system.

Hyperkalaemia
Drugs which affect the renin-angiotensin-aldosterone system may cause hyperkalaemia, which could be fatal. The risk is increased in elderly patients, in patients with renal impairment, in patients with diabetes mellitus and in patients receiving concomitant treatment with other medicinal products that affect potassium levels.

Additional risk factors for hyperkalaemia include dehydration, acute cardiac decompensation, metabolic acidosis, worsening renal function, sudden worsening renal condition (e.g. infection) and cellular lysis (e.g. acute limb ischaemia, rhabdomyolysis, extended trauma).

It is advisable to assess the benefit risk ratio when administering more than one medical product that acts upon the renin-angiotensin-aldosterone system concomitantly as this may increase the risk of hyperkalaemia. If dual blockade of the renin-angiotensin-aldosterone system is considered necessary it should be done under close medical supervision, with regular monitoring of renal function, electrolytes and blood pressure.

Sprue-like enteropathy
In very rare cases severe chronic diarrhoea with substantial weight loss has been reported in patients taking olmesartan few months to years after drug initiation, possibly caused by a localized delayed hypersensitivity reaction. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with olmesartan, exclude other etiologies. Consider discontinuation of olmesartan in cases where no other etiology is identified. In cases where symptoms disappear and sprue-like enteropathy is confirmed by biopsy, treatment with olmesartan should not be restarted.

Pregnancy and Lactation

Pregnancy

Olmesartan is contraindicated during pregnancy.

Epidemiological studies assessing the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy have not been conclusive; therefore a small increase in risk cannot be excluded for angiotensin II antagonists. Patients planning pregnancy should be changed to an alternative anti-hypertensive treatment (which has an established safety profile for use in pregnancy) unless continued angiotensin receptor blocker therapy is considered essential. Treatment with angiotensin II antagonists should be stopped when pregnancy is diagnosed and, if possible, alternative therapy should be considered. Exposure during the second and third trimesters to angiotensin II antagonists is known to cause human foetotoxicity, including decreased renal function, oligohydramnios and skull ossification retardation. Neonatal toxicity including renal failure, hypotension and hyperkalaemia has also occurred.

An ultrasound check of renal function and skull to exclude oligohydramnios is recommended should exposure to angiotensin II antagonists have occurred past 20 weeks. It is also advisable to closely observe infants whose mothers have taken angiotensin II antagonists for renal impairment and hypotension (Schaefer, 2015).

The antihypertensive mechanism of olmesartan and ACE inhibitors are closely related. Consequently, olmesartan may cause foetal and neonatal toxicity similar to that seen with ACE inhibitors. Such foetal toxic effects may include patent ductus arteriosus, prematurity, intrauterine growth restriction, foetal hypocalvaria, and anuria. Anuria-associated oligohydramnios may cause limb contractures, craniofacial deformations and pulmonary hypoplasia. A newborn exposed to olmesartan in utero may experience severe anuria and hypotension that is resistant to both volume expansion and pressor agents (Briggs, 2015).
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

Olmesartan is contraindicated during breastfeeding.

Olmesartan is excreted in the milk of lactating rats, it is unknown if it is excreted in human milk.

The molecular weight of olmesartan is low enough that excretion in breast milk should be expected (Briggs, 2015).

Schaefer (2015) 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. LactMed agrees that due to the lack of available information, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

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

Abdominal pain
Acute renal failure
Allergic dermatitis
Anaphylactic reaction
Angina pectoris
Angioedema
Arthritis
Asthenia
Back pain
Blood urea increased
Bronchitis
Chest pain
Cough
Creatine phosphokinase increased
Diarrhoea
Dizziness
Dyspepsia
Epistaxis
Exanthema
Facial oedema
Fatigue
Gastro-enteritis
Haematuria
Headache
Hyperkalaemia
Hypertriglyceridaemia
Hyperuricaemia
Hypotension
Increase in creatinine
Increases in hepatic enzymes
Influenza-like symptoms
Lethargy
Malaise
Muscle spasm
Musculoskeletal pain
Myalgia
Nausea
Pain
Peripheral oedema
Pharyngitis
Pruritus
Rash
Renal impairment
Rhabdomyolysis
Rhinitis
Skeletal pain
Sprue-like enteropathy
Thrombocytopenia
Urinary tract infections
Urticaria
Vertigo
Vomiting

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: January 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Joint Formulary Committee. British National Formulary. 72nd ed. London: BMJ Group and Pharmaceutical Press; 2016.

Summary of Product Characteristics: OLMETEC film-coated tablets. Daiichi-Sankyo UK Ltd. Revised February 2016.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

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
Olmesartan. Last revised: March 10, 2015
Last accessed: January 18, 2017