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Intravascular-Volume Depletion: Symptomatic hypotension, especially after the 1st dose, may occur in patients who are volume and/or sodium depleted by diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of olmesartan medoxomil-hydrochlorothiazide.
Other 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 (eg, patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system has been associated with acute hypotension, azotemia, oliguria or, rarely, acute renal failure.
Renovascular Hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system.
Renal Impairment and Kidney Transplantation: Olmesartan medoxomil-hydrochlorothiazide should not be used in patients with severe renal impairment (creatinine clearance <30 mL/min) (see Contraindications). No dosage adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance is ≥30 mL/min, <60 mL/min). However, in such patients olmesartan medoxomil-hydrochlorothiazide should be administered with caution and periodic monitoring of serum potassium, creatinine and uric acid levels is recommended. Thiazide diuretic-associated azotemia may occur in patients with impaired renal function. There is no experience of the administration of olmesartan medoxomil-hydrochlorothiazide in patients with recent kidney transplantation.
Hepatic Impairment: There is currently limited experience of olmesartan medoxomil in patients with mild to moderate hepatic impairment and no experience in patients with severe hepatic impairment. Furthermore, minor alterations of fluid and electrolyte balance during thiazide therapy may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease. Therefore, use of olmesartan medoxomil-hydrochlorothiazide in patients with hepatic impairment is not recommended (see Dosage & Administration). Use of olmesartan medoxomil in patients with biliary obstruction is contraindicated (see Pharmacokinetics under Actions and Contraindications).
Aortic and Mitral Valve Stenosis, Obstructive Hypertrophic Cardiomyopathy: As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Primary Aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, the use of olmesartan medoxomil-hydrochlorothiazide is not recommended in such patients.
Metabolic and Endocrine Effects: Thiazide therapy may impair glucose tolerance. In diabetic patients dosage adjustments of insulin or oral hypoglycaemic agents may be required (see Interactions). Latent diabetes mellitus may become manifest during thiazide therapy.
Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy. Hyperuricaemia may occur or frank gout may be precipitated in some patients receiving thiazide therapy.
Electrolyte Imbalance: As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals.
Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (including hypokalaemia, hyponatraemia and hypochloraemic alkalosis). Warning signs of fluid or electrolyte imbalance are dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances eg, nausea or vomiting (see Adverse Reactions).
Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with olmesartan medoxomil may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greatest in patients with cirrhosis of the liver, in patients experiencing brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or ACTH. Conversely, due to antagonism at the angiotensin-II receptors (AT1) through the olmesartan medoxomil component of olmesartan medoxomil-hydrochlorothiazide hyperkalaemia may occur, especially in the presence of renal impairment and/or heart failure, and diabetes mellitus. Adequate monitoring of serum potassium in patients at risk is recommended. Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes should be co-administered cautiously with olmesartan medoxomil-hydrochlorothiazide (see Interactions).
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 may decrease urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia.
Lithium: As with other medicinal products containing angiotensin-II receptor antagonists and thiazide in combination, the co-administration of olmesartan medoxomil-hydrochlorothiazide and lithium is not recommended (see Interactions).
Other: As with any antihypertensive agent, excessive blood pressure decrease in patients with ischaemic heart disease or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke.
Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.
Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics.
Effects on the Ability to drive or Operate Machinery: The effect of olmesartan medoxomil-hydrochlorothiazide on the ability to drive and use machines has not been specifically studied. However, it should be born in mind that dizziness or fatigue may occasionally occur in patients taking antihypertensive therapy.
Use in pregnancy: There is no experience with the use of olmesartan medoxomil-hydrochlorothiazide in pregnant women. Studies in mice and rats using olmesartan medoxomil-hydrochlorothiazide combinations do not indicate a teratogenic effect, but foetotoxicity has been shown in rats. Thiazides cross the placental barrier and appear in cord blood. They may cause foetal electrolyte disturbances and possible other reactions that have occurred in adults. Cases of neonatal thrombocytopenia, or foetal or neonatal jaundice have been reported with maternal thiazide therapy.
Therefore, olmesartan medoxomil-hydrochlorothiazide is contraindicated during the 2nd and 3rd trimesters of pregnancy. In addition, olmesartan medoxomil-hydrochlorothiazide must not be used during the 1st trimester. If pregnancy occurs during therapy, olmesartan medoxomil-hydrochlorothiazide must be discontinued as soon as possible. (See Contraindications.)
Use in lactation: Olmesartan is excreted in the milk of lactating rats but it is not known whether olmesartan is excreted in human milk. Thiazides appear in human milk and may inhibit lactation. Mothers must not breastfeed if they are taking olmesartan medoxomil-hydrochlorothiazide. (See Contraindications.)
