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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Elderly
Children
Adolescents
Patients with Renal Impairment
Patients with Hepatic Impairment

One tablet once daily.

20mg olmesartan medoxomil/12.5mg hydrochlorothiazide may be administered to patients whose blood pressure is not adequately controlled by the optimal monotherapy olmesartan medoxomil 20mg alone.

20mg olmesartan medoxomil/25mg hydrochlorothiazide may be administered to patients whose blood pressure is not adequately controlled by 20mg olmesartan medoxomil/12.5mg hydrochlorothiazide.

40mg olmesartan medoxomil/12.5mg hydrochlorothiazide may be administered to patients whose blood pressure is not adequately controlled by 40mg olmesartan medoxomil alone.

Precautions and Warnings

Symptomatic hypotension, especially after first dose, may occur in patients with severe sodium and/or volume depletion. This may include patients who are on high dose diuretic therapy, dietary salt restricted or suffering from diarrhoea or vomiting. Sodium and/or volume depletion should be corrected before treatment initiation.

Renal function and electrolytes should be checked before starting treatment and monitored during therapy, especially in patients post myocardial infarction or those with heart failure. Side effects (such as hyperkalaemia) are more common in patients with renal impairment- the dose may need to be reduced. A specialist should be involved if renal function is significantly reduced.

Angiotensin II receptor antagonists should be used with caution in patients with bilateral renal artery stenosis, or stenosis of the artery to a single functioning kidney.

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 olmesartan and hydrochlorothiazide includes an angiotensin II antagonist, it cannot be excluded that the use of this medication may be associated with impairment of the renal function.

Renal impairment (see Dosage, Renal Impairment). The 40/12.5mg olmesartan medoxomil/ hydrochlorothiazide presentation is contraindicated in mild - moderate renal impairment where creatinine clearance is between 30-60ml/minute.

There is no experience in patients who have received a recent kidney transplant or in patients with end-stage renal impairment (i.e. creatinine clearance below 12ml/minute).

Avoid use in patients with known or suspected renovascular disease, unless the blood pressure cannot be controlled with other drugs. Use with particular precaution in patients who have undiagnosed and clinically silent renovascular disease (including peripheral vascular disease or severe generalised atherosclerosis).

Monitor plasma potassium, particularly in the elderly, patients with renal impairment, in the presence of other conditions (fever, dehydration) which affect renal function and patients in whom potassium supplements / retaining medication is essential. Concurrent potassium-sparing diuretics, potassium supplements, salt substitutes or a diet high in potassium rich foods may lead to an increase in serum potassium.

The risk of hypokalaemia is most likely in patients with cirrhosis of the liver, patients experiencing brisk diuresis and patients who are receiving inadequate oral electrolyte intake.

Monitor creatinine and uric acid levels in patients with renal impairment.

Hepatic impairment (see Dosage, Hepatic Impairment). The 40/12.5mg olmesartan medoxomil/ hydrochlorothiazide presentation is contraindicated in moderate to severe hepatic impairment. Alterations in fluid and electrolyte balance may precipitate hepatic coma in patients with hepatic impairment or progressive liver disease.

Special caution is advised in patients suffering from aortic stenosis, mitral stenosis, and hypertrophic obstructive cardiomyopathy.

Patients with primary aldosteronism generally will not respond to olmesartan, treatment is not recommended in these patients.

Caution in diabetic patients. Adjustment of anti-diabetic medication may be required. Treatment may impair glucose tolerance due the thiazide component. Latent diabetes may be unmasked during thiazide therapy.

Thiazide therapy may result in increased cholesterol levels, increased triglyceride levels, hyperuricaemia and may precipitate gout.

Periodic measurement of serum electrolytes should be performed as thiazide therapy may cause fluid or electrolyte imbalance including hypokalaemia, hyponatraemia (particularly in oedematous patients in hot weather), hypomagnesaemia and hypochloraemic alkalosis.

Warning signs of fluid/electrolyte imbalance include dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain/cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances.

There is no evidence that olmesartan medoxomil would reduce or prevent diuretic induced hyponatraemia. Chloride deficit is generally mild and usually does not require treatment.

Thiazides should be discontinued prior to tests for parathyroid function. Thiazides may increase serum calcium levels and hypercalcaemia can be a sign of hyperparathyroidism.

Afro-Caribbean or black patients (especially those with left ventricular hypertrophy) may not benefit from this treatment.

As with other antihypertensive agents, excessive blood pressure decrease in patients with ischaemic heart disease or ischaemic cerebrovascular disease may cause a myocardial infarction or stroke.

Thiazide diuretics should also be used with caution in nephrotic syndrome, malnourishment and known or suspected renovascular disease

Hypersensitivity to hydrochlorothiazide is more likely in patients with a history of asthma.

Thiazide diuretics may cause exacerbation or activation of systemic lupus erythematosus.

Co-administration of NSAIDS may reduce the antihypertensive effect of angiotensin II receptor antagonists and thiazides, increase serum potassium and exacerbate renal impairment. Patients should be advised not to self administer NSAIDS unless on medical advice.

Co-administration of alcohol may potentiate orthostatic hypotension, patients should moderate alcohol intake.

Ability to drive or operate machinery may be affected by side effects.

Women of child bearing potential should be advised to use adequate contraception during therapy or be switched to an alternative agent. Therapy with olmesartan should be discontinued if pregnancy occurs.

Hydrochlorothiazide may cause a positive result in an anti-doping test.

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.

Contains lactose. Use with caution is patients with lactose intolerance and glucose-galactose malabsorption syndrome.

Dose dependent increased risk of non-melanoma skin cancer with exposure to increasing cumulative doses of hydrochlorothiazide.

Use with caution in patients who have had previous skin cancer.

Advise patient to monitor for and report any skin changes.

Advise patient to minimise exposure to sunlight and avoid sunlamps during therapy.

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.

Discontinue if acute respiratory distress syndrome is suspected.

Pregnancy and Lactation

Pregnancy

Olmesartan medoxomil with hydrochlorothiazide is contraindicated in pregnancy. Adequate contraception is recommended for women of childbearing potential. 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, olmesartan containing medicines 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.

Exposure of the foetus to thiazides may cause electrolyte disturbances. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia. Hydrochlorothiazide should not be used routinely for gestational oedema, gestational hypertension or pre-eclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.

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 ).

Lactation

Olmesartan medoxomil with hydrochlorothiazide is contraindicated in breastfeeding women.

Olmesartan is excreted in the milk of rats, it is unknown if it is excreted in human milk. Thiazides pass into human milk and may inhibit lactation.

Schaefer (2007) suggests that accidental administration of a single dose of olmesartan 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

Presentation

Tablets containing 20mg olmesartan medoxomil and 12.5mg hydrochlorothiazide.
Tablets containing 20mg olmesartan medoxomil and 25mg hydrochlorothiazide.
Tablets containing 40mg olmesartan medoxomil and 12.5mg hydrochlorothiazide.

Drugs List

olmesartan medoxomil 20mg and hydrochlorothiazide 12.5mg tablets

olmesartan medoxomil 20mg and hydrochlorothiazide 25mg tablets

olmesartan medoxomil 40mg and hydrochlorothiazide 12.5mg tablets

OLMETEC PLUS 20mg+12.5mg tablets

OLMETEC PLUS 20mg+25mg tablets

OLMETEC PLUS 40mg+12.5mg tablets

Therapeutic Indications

Uses

Treatment of essential hypertension in patients not adequately controlled on olmesartan medoxomil monotherapy.

Dosage

The antihypertensive effect of olmesartan medoxomil is maximal at about 8 weeks of therapy. Dose titration of the individual components is recommended.

Adults

One tablet once daily.

20mg olmesartan medoxomil/12.5mg hydrochlorothiazide may be administered to patients whose blood pressure is not adequately controlled by the optimal monotherapy olmesartan medoxomil 20mg alone.

20mg olmesartan medoxomil/25mg hydrochlorothiazide may be administered to patients whose blood pressure is not adequately controlled by 20mg olmesartan medoxomil/12.5mg hydrochlorothiazide.

40mg olmesartan medoxomil/12.5mg hydrochlorothiazide may be administered to patients whose blood pressure is not adequately controlled by 40mg olmesartan medoxomil alone.

Elderly

See adult dose.

Blood pressure should be closely monitored in this population.

Children

Not recommended in children under 18 years as safety and efficacy has not been established.

Adolescents

Not recommended in children under 18 years as safety and efficacy has not been established.

Patients with Renal Impairment

Mild-moderate renal impairment (creatinine clearance 30-60 ml/minute):
The maximum dose of olmesartan in these patients is 20mg daily. Monitor renal function periodically in these individuals. Serum potassium, creatinine and uric acid levels should be monitored periodically. Thiazide diuretic associated azotaemia may occur in patients with renal impairment. If progressive renal impairment occurs re-assess therapy and consider discontinuing treatment.

The 40mg olmesartan medoxomil/12.5mg hydrochlorothiazide presentation is contraindicated in this population.

Severe renal impairment (creatinine clearance below 30ml/minute):
Contraindicated in these patients.

Patients with Hepatic Impairment

Close monitoring of renal function and blood pressure is recommended in patients with hepatic impairment.

Moderate hepatic impairment:
An initial dose of 10mg olmesartan medoxomil once daily is recommended and the maximum dose should not exceed 20mg once daily. The 40mg olmesartan medoxomil/12.5mg hydrochlorothiazide presentation is contraindicated in this population.

Severe hepatic impairment, cholestasis & biliary obstruction:
This medication is contraindicated in this population.

Administration

To be given orally, once daily with or without food but should be taken with a glass of water.

The tablets should not be chewed and should be taken at the same time each day.

Contraindications

Severe renal impairment (creatinine clearance below 30ml/minute).
The 40/12.5mg olmesartan/hydrochlorothiazide presentation is contraindicated in patients with renal impairment whose creatinine clearance is equal to or less than 60ml/minute (see Dosage, Renal impairment).
Severe bilateral renal artery stenosis.
Severe unilateral renal artery stenosis of a solitary functioning kidney.
Refractory hypokalaemia.
Hypercalcaemia.
Hyponatraemia.
Symptomatic hyperuricaemia.
Addison's disease.
Hepatic impairment (see Dosage, Hepatic Impairment) (40/12.5mg olmesartan/hydrochlorothiazide strength is contraindicated in moderate to severe hepatic impairment, the 20/12.5mg and 20/25mg olmesartan/hydrochlorothiazide presentations are contraindicated in severe hepatic impairment).
Cholestasis.
Biliary obstructive disorders.
Pregnancy (see Pregnancy section).
Breastfeeding (see Lactation section).
Children under 18 years.
Galactosaemia.
History of acute respiratory distress syndrome due to hydrochlorothiazide.