Olmesartan with amlodipine and hydrochlorothiazide oral
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of olmesartan with amlodipine and hydrochlorothiazide.
Essential hypertension when stabilised on same ingreds.in same proportions
Patients should be controlled on stable doses of olmesartan medoxomil, amlodipine and hydrochlorothiazide taken at the same time as a dual component (olmesartan and amlodipine or olmesartan medoxomil and hydrochlorothiazide) and a single component formulation (amlodipine or hydrochlorothiazide).
The dose of olmesartan with amlodipine and hydrochlorothiazide has to be based on the doses of the individual components of the combination at the time of switching.
One tablet daily.
Olmesartan with amlodipine and hydrochlorothiazide 20 mg/5 mg/12.5 mg may be administered in patients whose blood pressure is not adequately controlled on olmesartan 20 mg and amlodipine 5 mg taken as a dual-component combination.
Olmesartan with amlodipine and hydrochlorothiazide 40 mg/5 mg/12.5 mg may be administered in patients whose blood pressure is not adequately controlled on olmesartan 40 mg and amlodipine 5 mg taken as a dual-component combination or in patients whose blood pressure is not adequately controlled on olmesartan with amlodipine and hydrochlorothiazide 20 mg/5 mg/12.5 mg.
Olmesartan with amlodipine and hydrochlorothiazide 40 mg/5 mg/25 mg may be administered in patients whose blood pressure is not adequately controlled on olmesartan with amlodipine and hydrochlorothiazide 40 mg/5 mg/12.5 mg.
Olmesartan with amlodipine and hydrochlorothiazide 40 mg/10 mg/12.5 mg may be administered in patients whose blood pressure is not adequately controlled on olmesartan 40 mg and amlodipine 10 mg taken as a dual-component combination or in patients whose blood pressure is not adequately controlled on olmesartan with amlodipine and hydrochlorothiazide 40 mg/5 mg/12.5 mg.
Olmesartan with amlodipine and hydrochlorothiazide 40 mg/10 mg/25 mg may be administered in patients whose blood pressure is not adequately controlled on olmesartan with amlodipine and hydrochlorothiazide 40 mg/10 mg/12.5 mg or 40 mg/5 mg/25 mg.
(See Dosage; Adult).
Use with caution particularly at the maximum dose of 40 mg olmesartan with 10 mg amlodipine and 25 mg hydrochlorothiazide. Blood pressure should be monitored more frequency than in adult patients. Lower initial doses may be appropriate.
An increase of the dosage should take place with care in elderly patients.
Patients with Renal Impairment
Mild to moderate renal impairment (creatinine clearance 30 to 60 ml/minute)
Maximum dose is 20 mg olmesartan with 5 mg amlodipine and 12.5 mg hydrochlorothiazide once daily. Lower initial doses may be appropriate.
Potassium and creatinine levels in patients with moderate renal impairment should be closely monitored.
There is no experience of 40 mg olmesartan in these patients.
Patients with Hepatic Impairment
Mild to moderate hepatic impairment
Patients with moderate hepatic impairment should not receive more than 20 mg olmesartan with 5 mg amlodipine and 12.5 mg hydrochlorothiazide once daily.
Close monitoring of blood pressure and renal function is advised.
A dose reduction may be required as in these patients as amlodipine has a prolonged half life.
Additional Dosage Information
A step-wise titration of the dosage of the individual components is recommended before changing to the triple-component combination may be considered.
Children under 18 years
Cardiac failure within 1 month of a myocardial infarction
History of acute respiratory distress syndrome due to hydrochlorothiazide
Left ventricular outflow obstruction
Renal impairment - creatinine clearance below 30 ml/minute
Severe bilateral renal artery stenosis
Severe hepatic impairment
Severe unilateral stenosis of solitary functioning kidney
Precautions and Warnings
Vascular tone dependent on renin-angiotensin system
Bilateral renal artery stenosis
History of asthma
History of skin cancer
Hypertrophic obstructive cardiomyopathy
Ischaemic heart disease
Mild hepatic impairment
New York Heart Association class III failure
New York Heart Association class IV failure
Peripheral vascular disease
Renal impairment - creatinine clearance 30-60ml/minute
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
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
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
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Diabetic control may need adjustment
Monitor fluid and electrolyte status
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
May precipitate diabetes mellitus
May precipitate gout
Discontinue before parathyroid function tests
Abrupt withdrawal may be associated with exacerbation of angina
Discontinue & do not restart if sprue-like enteropathy confirmed by biopsy
Discontinue if acute respiratory distress syndrome is suspected
Discontinue if photosensitivity occurs
Discontinue or reduce dose if renal impairment worsens
Pregnancy confirmed: Discontinue this medication
Reduce dose in elderly
Advise patient not to take NSAIDs unless advised by clinician
Advise patient to avoid aluminium / magnesium hydroxide containing antacids
Hypotensive effects may be potentiated by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Grapefruit prod increase dihydropyridine Ca channel blocker bioavailability
Female: Ensure adequate contraception during treatment
Advise pt. to minimise exposure to sunlight & avoid sunlamps during therapy
Dilutional hyponatraemia may occur in oedematous patients in hot weather.
Use with caution with patients with acute porphyria due to the amlodipine component.
Rare cases of acute respiratory toxicity including acute respiratory distress syndrome (ARDS) have been reported following treatment with hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours of taking hydrochlorothiazide.
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
Olmesartan medoxomil with amlodipine and hydrochlorothiazide should be avoided during the first trimester of pregnancy and is contraindicated during the second and third trimesters. Olmesartan has a greater risk profile than amlodipine or hydrochlorothiazide so the recommendations regarding olmesartan should be followed for the combination product.
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, olmesartan 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.
Some dihydropyridine compounds have been found to be teratogenic in animals. However, amlodipine was found not to be teratogenic or embryotoxic in rats and rabbits up to 8 and 23 times, respectively, the maximum human dose based on BSA (MRHD) during their respective periods of major organogenesis. Effects on reproduction in animals were found at high dosages (including delayed parturition, difficult labour and impaired foetal and pup survival) (Briggs, 2011). There is no adequate data for the use of amlodipine in pregnant women. The molecular weight of amlodipine is low enough that passage to the foetus should be expected. Calcium channel blockers may inhibit labour (Schaefer,2007). In the first trimester, calcium antagonists are considered to be second-line therapy. Manufacturers advise amlodipine should not be administered during pregnancy or to women of childbearing potential unless effective contraception is used unless clearly needed. Schaefer (2007) suggests that if exposure to amlodipine has occurred during the first trimester, a detailed ultrasound diagnosis is advisable. Overall exposure to a calcium antagonist during pregnancy is not an indication for either invasive diagnostic procedures or termination of 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 14-17 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 ).
Licensed in pregnancy? - No, contraindicated
Known human teratogen? - Yes
Effects on foetus - Foetal toxic effects include; anuria, oligohydramnios, foetal hypocalvaria, intrauterine growth retardation (IUGR), prematurity and patent ductus arteriosus.
Other information - If pregnancy occurs during treatment, olmesartan must be discontinued immediately and an alternative antihypertensive with greater experience in pregnancy should be considered.
Olmesartan with amlodipine and hydrochlorothiazide is contraindicated during breastfeeding.
There is no information available for the use of olmesartan with amlodipine and hydrochlorothiazide during breastfeeding. Alternative treatments with better established safety profiles are preferred, especially whilst nursing a newborn or preterm infant.
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.
There is no adequate data for the use of amlodipine in breastfeeding. Hale (2010) comments that because most calcium channel blockers readily transfer into milk, that the same should be assumed for this drug. The molecular weight of amlodipine is low enough that excretion into breast milk should be expected. No paediatric concerns have been reported but the infant should be observed for bradycardia or hypotension upon prolonged use. Guidelines from NICE recommend that women who still need antihypertensive treatment in the postnatal period are told that there is insufficient evidence on the safety in babies receiving breast milk of amlodipine. Some manufacturers advise patients to stop breast feeding during treatment with amlodipine as it is not known whether amlodipine is excreted in breast milk. Schaefer (2007) comments that individual doses of amlodipine do not require limitation of breastfeeding, but therapy should be changed. An alternative drug may be preferred.
Hydrochlorothiazide is excreted in breast milk. Hale (2011) reports no paediatric concerns have been reported via the milk.
Schaefer (2007) concludes that during breastfeeding, diuretics should not normally be prescribed for treating hypertonia. However, when such a drug is urgently needed, moderately dosed treatment with hydrochlorothiazide can be undertaken, with attention to the side effects. Single doses of indapamide do not require limitation of breastfeeding, but therapy should be changed.
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
Considered suitable or recommended by manufacturer? - No
Drug substance licensed in infants? - No.
Acute renal failure
Acute respiratory distress syndrome
Bone marrow depression
Decrease in haemoglobin and haematocrit
Fluctuating serum potassium levels
Hypersensitivity reactions including anaphylaxis
Increase in blood urea or creatinine
Increases in hepatic enzymes
Toxic epidermal necrolysis
Upper respiratory tract infection
Urinary tract infections
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 ).
Last Full Review Date: June 2013
British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.
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.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Sevikar HCT. Daiichi Sankyo UK Ltd. Revised July 2022.
Drug Safety Update: ACE inhibitors and angiotensin II receptor antagonists: Recommendations on use during breastfeeding. Volume 2. Issue 10. May 2009. MHRA.
Available at: https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: June 12, 2013
National Institute for Health and Care Excellence (NICE) clinical guidance 107: Hypertension in pregnancy. Issue date August 2010
Available at: https://guidance.nice.org.uk/CG107
Last accessed: June 12, 2013
MHRA Drug Safety Update November 2018
Available at: https://www.mhra.gov.uk
Last accessed: 08 January 2019
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
Amlodipine. Last revised: October 2, 2012.
Hydrochlorothiazide. Last revised: January 24, 2013.
Olmesartan. Last revised: September 29, 2009.
Last accessed: June 12, 2013
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