Alzor HCT

Olmesartan medoxomil, hydrochlorothiazide.

Each film coated tablet contains: Olmesartan Medoxomil, USP 20 mg; Hydrochlorothiazide, BP 12.5 mg.
Olmesartan medoxomil, USP 40 mg; Hydrochlorothiazide, BP 12.5 mg.

Angiotensin II Receptor Blocker/Anti-Hypertensive/Diuretic.
Pharmacology: Mechanism of Action: Olmesartan and Hydrochlorothiazide is a combination of an angiotensin II receptor antagonist, Olmesartan Medoxomil, and a thiazide diuretic, hydrochlorothiazide. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a greater degree than either component alone.
Once daily dosing with Olmesartan and Hydrochlorothiazide provides an effective and smooth reduction in blood pressure over the 24 hour dose interval.
Olmesartan Medoxomil: Olmesartan Medoxomil is an orally active, selective angiotensin II receptor (type AT1) antagonist. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system and plays a significant role in the pathophysiology of hypertension. The effects of angiotensin II include vasoconstriction, stimulation of the synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by blocking its binding to the AT1 receptor in tissues including vascular smooth muscle and the adrenal gland. The action of Olmesartan is independent of the source or route of synthesis of angiotensin II. The selective antagonism of the angiotensin II (AT1) receptors by Olmesartan results in increases in plasma renin levels and angiotensin I and II concentrations, and some decrease in plasma aldosterone concentrations.
In hypertension, Olmesartan Medoxomil causes a dose-dependent, long-lasting reduction in arterial blood pressure. There has been no evidence of first-dose hypotension, of tachyphylaxis during long-term treatment, or of rebound hypertension after abrupt cessation of therapy.
Once daily dosing with Olmesartan Medoxomil provides an effective and smooth reduction in blood pressure over the 24 hour dose interval. Once daily dosing produced similar decreases in blood pressure as twice daily dosing at the same total daily dose.
With continuous treatment, maximum reductions in blood pressure are achieved by 8 weeks after the initiation of therapy, although a substantial proportion of the blood pressure lowering effect is already observed after 2 weeks of treatment.
The effect of Olmesartan Medoxomil on mortality and morbidity is not yet known.
Hydrochlorothiazide: Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide diuretics is not fully known. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity and increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II and therefore co-administration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with thiazide diuretics.
With hydrochlorothiazide, onset of diuresis occurs at about 2 hours and peak effect occurs at about 4 hours post-dose, whilst the action persists for approximately 6-12 hours.
Epidemiological studies have shown that long-term treatment with hydrochlorothiazide monotherapy reduces the risk of cardiovascular mortality and morbidity.
Pharmacokinetics: Absorption and Distribution: Olmesartan Medoxomil is a prodrug. It is rapidly converted to the pharmacologically active metabolite, Olmesartan, by esterases in the gut mucosa and in portal blood during absorption from the gastrointestinal tract. No intact Olmesartan Medoxomil or intact side chain Medoxomil moiety have been detected in plasma or excreta. The mean absolute bioavailability of Olmesartan from a tablet formulation was 25.6%.
The mean peak plasma concentration (C_max) of Olmesartan is reached within about 2 hours after oral dosing with Olmesartan Medoxomil, and Olmesartan plasma concentrations increase approximately linearly with increasing single oral doses up to about 80 mg.
Food had minimal effect on the bioavailability of Olmesartan and therefore Olmesartan Medoxomil may be administered with or without food.
No clinically relevant gender-related differences in the pharmacokinetics of Olmesartan have been observed.
Olmesartan is highly bound to plasma protein (99.7%), but the potential for clinically significant protein binding displacement interactions between Olmesartan and other highly bound coadministered active substances is low (as confirmed by the lack of a clinically significant interaction between Olmesartan Medoxomil and warfarin). The binding of Olmesartan to blood cells is negligible. The mean volume of distribution after intravenous dosing is low (16 - 29 L).
Hydrochlorothiazide: Following oral administration of Olmesartan Medoxomil and hydrochlorothiazide in combination, the median time to peak concentrations of hydrochlorothiazide was 1.5 to 2 hours after dosing. Hydrochlorothiazide is 68% protein bound in the plasma and its apparent volume of distribution is 0.83 - 1.14 L/kg.
Biotransformation and elimination: Olmesartan Medoxomil: Total plasma clearance of Olmesartan was typically 1.3 L/h (CV, 19%) and was relatively slow compared to hepatic blood flow (ca 90 L/h). Following a single oral dose of 14C-labelled Olmesartan Medoxomil, 10 - 16% of the administered radioactivity was excreted in the urine (the vast majority within 24 hours of dose administration) and the remainder of the recovered radioactivity was excreted in the faeces. Based on the systemic availability of 25.6%, it can be calculated that absorbed Olmesartan is cleared by both renal excretion (ca 40%) and hepato-biliary excretion (ca 60%). All recovered radioactivity was identified as Olmesartan. No other significant metabolite was detected. Enterohepatic recycling of Olmesartan is minimal. Since a large proportion of Olmesartan is excreted via the biliary route, use in patients with biliary obstruction is contraindicated.
The terminal elimination half life of Olmesartan varied between 10 and 15 hours after multiple oral dosing. Steady state was reached after the first few doses and no further accumulation was evident after 14 days of repeated dosing. Renal clearance was approximately 0.5 - 0.7 L/h and was independent of dose.
Hydrochlorothiazide: Hydrochlorothiazide is not metabolised in man and is excreted almost entirely as unchanged active substance in urine. About 60% of the oral dose is eliminated as unchanged active substance within 48 hours. Renal clearance is about 250 - 300 mL/min. The terminal elimination half-life of hydrochlorothiazide is 10 - 15 hours.
Olmesartan and Hydrochlorothiazide combination: The systemic availability of hydrochlorothiazide is reduced by about 20% when co-administered with Olmesartan Medoxomil, but this modest decrease is not of any clinical relevance. The kinetics of Olmesartan are unaffected by the co-administration of hydrochlorothiazide.

For the treatment of hypertension. This fixed dose combination is not indicated for initial therapy.

Adults: The recommended starting dose of Olmesartan Medoxomil and Hydrochlorothiazide combination is 40/12.5mg once daily in patients whose blood pressure is not adequately controlled with Olmesartan monotherapy.
The recommended starting dose of Olmesartan Medoxomil and Hydrochlorothiazide combination is 20/12.5mg once daily in patients whose blood pressure is not adequately controlled with Hydrochlorothiazide monotherapy or who experience dose-limiting adverse reactions with hydrochlorothiazide.
Elderly (age 65 years or over): In elderly people the same dosage of the combination is recommended as for adults.
Renal impairment: When Olmesartan and Hydrochlorothiazide combination is used in patients with mild to moderate renal impairment (creatinine clearance of 30 - 60 mL/min) periodic monitoring of renal function is advised. Olmesartan and Hydrochlorothiazide combination is contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min).
Hepatic impairment: Olmesartan and Hydrochlorothiazide combination should be used with caution in patients with mild to moderate hepatic impairment. In patients with moderate hepatic impairment, an initial dose of 10 mg Olmesartan Medoxomil once daily is recommended and the maximum dose should not exceed 20 mg once daily. Close monitoring of blood pressure and renal function is advised in hepatically-impaired patients who are receiving diuretics and/or other antihypertensive agents. There is no experience of Olmesartan Medoxomil in patients with severe hepatic impairment.
Olmesartan and Hydrochlorothiazide combination should not be used in patients with severe hepatic impairment, cholestasis and biliary obstruction.
Pediatric population: The safety and efficacy of Olmesartan and Hydrochlorothiazide in children and adolescents below 18 years has not been established. No data are available.
Method of administration: The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed and should be taken at the same time each day.

No specific information is available on the effects or treatment of Olmesartan and Hydrochlorothiazide overdose. The patient should be closely monitored, and the treatment should be symptomatic and supportive. Management depends upon the time since ingestion and the severity of the symptoms. Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal may be useful in the treatment of overdose. Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacements given quickly.
The most likely manifestations of Olmesartan Medoxomil overdose are expected to be hypotension and tachycardia; bradycardia might also occur. Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, hypochloraemia) and dehydration resulting from excessive diuresis. The most common signs and symptoms of overdose are nausea and somnolence. Hypokalaemia may result in muscle spasm and/or accentuate cardiac arrhythmias associated with the concomitant use of digitalis glycosides or certain anti-arrhythmic medicinal products.
No information is available regarding the dialysability of Olmesartan or Hydrochlorothiazide.

Hypersensitivity to the active substances, to any of the excipients or to other sulfonamide-derived substances (since hydrochlorothiazide is a sulfonamide-derived medicinal product).
Severe renal impairment (creatinine clearance < 30 mL/min).
Refractory hypokalaemia, hypercalcaemia, hyponatraemia and symptomatic hyperuricaemia.
Severe hepatic impairment, cholestasis and biliary obstructive disorders.
2nd and 3rd trimester of pregnancy.
The concomitant use of Olmesartan and Hydrochlorothiazide combination with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m²).

Intravascular volume depletion: Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of Olmesartan and Hydrochlorothiazide combination.
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 (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with medicinal products that affect this system has been associated with acute hypotension, azotaemia, 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 and Hydrochlorothiazide combination should not be used in patients with severe renal impairment (creatinine clearance < 30 mL/min). 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 and Hydrochlorothiazide combination should be administered with caution and periodic monitoring of serum potassium, creatinine and uric acid levels is recommended. Thiazide diuretic-associated azotaemia may occur in patients with impaired renal function. If progressive renal impairment becomes evident, careful reappraisal of therapy is necessary, with consideration given to discontinuing diuretic therapy. There is no experience of the administration of Olmesartan and Hydrochlorothiazide combination in patients with a recent kidney transplantation.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended.
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Hepatic impairment: There is currently no experience of Olmesartan Medoxomil 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 care should be taken in patients with mild to moderate hepatic impairment. Use of Olmesartan and Hydrochlorothiazide in patients with severe hepatic impairment, cholestasis and biliary obstruction is contraindicated.
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 anti-hypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of Olmesartan and 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. Latent diabetes mellitus may become manifest during thiazide therapy.
Increases in cholesterol and triglyceride levels are undesirable effects known to be 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 such as nausea or vomiting.
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 and 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 and other medicinal products that may increase serum potassium levels (e.g. heparin) should be co-administered cautiously with Olmesartan and Hydrochlorothiazide.
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. 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. Dilutional hyponatraemia may occur in oedematous patients in hot weather.
Lithium: As with other medicinal products containing angiotensin II receptor antagonists and thiazide in combination, the coadministration of Olmesartan and Hydrochlorothiazide combination and lithium is not recommended.
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, and in the absence of other apparent etiologies, Olmesartan treatment should be immediately discontinued and should not be restarted. If diarrhoea does not improve during the week after the discontinuation, further specialist (e.g. a gastro-enterologist) advice should be considered.
Acute Myopia and Secondary Angle-Closure Glaucoma: Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
Non-melanoma skin cancer: An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of hydrochlorothiazide could act as a possible mechanism for NMSC.
Patients taking hydrochlorothiazide should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of hydrochlorothiazide may also need to be reconsidered in patients who have experienced previous NMSC.
Ethnic differences: As with all other angiotensin II receptor antagonists, the blood pressure lowering effect of Olmesartan Medoxomil is somewhat less in black patients than in non-black patients, possibly because of a higher prevalence of low-renin status in the black hypertensive population.
Anti-doping test: Hydrochlorothiazide contained in this medicinal product could produce a positive analytic result in an anti-doping test.
Other: In general arteriosclerosis, in patients with ischaemic heart disease or ischaemic cerebrovascular disease, there is always a risk that excessive blood pressure decrease 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.
Use in Pregnancy: Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonists therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.

Pregnancy: Given the effects of the individual components in this combination product on pregnancy, the use of Olmesartan Medoxomil and hydrochlorothiazide is not recommended during the first trimester of pregnancy. The use of Olmesartan Medoxomil and hydrochlorothiazide is contra-indicated during the 2nd and 3rd trimester of pregnancy.
Olmesartan Medoxomil: The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy. The use of angiotensin II receptor antagonists is contra-indicated during the 2nd and 3rd trimester of pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. Unless continued angiotensin receptor blocker therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.
Exposure to angiotensin II receptor antagonists therapy during the 2nd and 3rd trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).
Should exposure to angiotensin II receptor antagonists have occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.
Hydrochlorothiazide: There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient.
Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the 2nd and 3rd 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 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.
Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used.
Breast-feeding: Olmesartan Medoxomil: Because no information is available regarding the use of Olmesartan Medoxomil and hydrochlorothiazide during breast-feeding, Olmesartan Medoxomil and hydrochlorothiazide is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Hydrochlorothiazide: Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. The use of Olmesartan Medoxomil and hydrochlorothiazide combination during breast-feeding is not recommended. If Olmesartan Medoxomil and hydrochlorothiazide combination is used during breast-feeding, doses should be kept as low as possible.

The most commonly reported adverse reactions during treatment with Olmesartan and Hydrochlorothiazide are headache (2.9%), dizziness (1.9%) and fatigue (1.0%).
Hydrochlorothiazide may cause or exacerbate volume depletion which may lead to electrolyte imbalance.
Adverse reactions from Olmesartan and Hydrochlorothiazide in clinical trials, post-authorisation safety studies and spontaneous reporting are summarised in the tables as follows as well as adverse reactions from the individual components Olmesartan Medoxomil and hydrochlorothiazide based on the known safety profile of these substances.
The following terminologies have been used in order to classify the occurrence of adverse reactions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). (See Tables a and b.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Single cases of rhabdomyolysis have been reported in temporal association with the intake of angiotensin II receptor blockers.

Potential interactions related to both Olmesartan Medoxomil and hydrochlorothiazide: Concomitant use not recommended: Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors and, rarely, with angiotensin II receptor antagonists. In addition, renal clearance of lithium is reduced by thiazides and consequently the risk of lithium toxicity may be increased. Therefore use of Olmesartan and Hydrochlorothiazide and lithium in combination is not recommended. If use of the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Concomitant use requiring caution: Baclofen: Potentiation of antihypertensive effect may occur.
Non-steroidal anti-inflammatory medicinal products: NSAIDs (i.e. acetylsalicylic acid (> 3 g/day), COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of thiazide diuretics and angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly people with compromised renal function) the co-administration of angiotensin II receptor antagonists and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in elderly people. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter.
Concomitant use to be taken into account: Amifostine: Potentiation of antihypertensive effect may occur.
Other antihypertensive agents: The blood pressure lowering effect of Olmesartan and Hydrochlorothiazide can be increased by concomitant use of other antihypertensive medicinal products.
Alcohol, barbiturates, narcotics or antidepressants: Potentiation of orthostatic hypotension may occur.
Potential interactions related to Olmesartan Medoxomil: Concomitant use not recommended: ACE-inhibitors, angiotensin II receptor blockers or aliskiren: Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.
Medicinal products affecting potassium levels: Based on experience with the use of other medicinal products that affect the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase serum potassium levels (e.g. heparin, ACE inhibitors) may lead to increases in serum potassium. If medicinal products which affect potassium levels are to be prescribed in combination with Olmesartan and Hydrochlorothiazide combination, monitoring of potassium plasma levels is advised.
Bile acid sequestering agent colesevelam: Concurrent administration of the bile acid sequestering agent colesevelam hydrochloride reduces the systemic exposure and peak plasma concentration of olmesartan and reduces t½. Administration of Olmesartan medoxomil at least 4 hours prior to colesevelam hydrochloride decreased the drug interaction effect. Administering Olmesartan Medoxomil at least 4 hours before the colesevelam hydrochloride dose should be considered.
Additional information: After treatment with antacid (aluminium magnesium hydroxide), a modest reduction in bioavailability of Olmesartan was observed.
Olmesartan Medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin or the pharmacokinetics of digoxin.
Coadministration of Olmesartan Medoxomil with pravastatin had no clinically relevant effects on the pharmacokinetics of either component in healthy subjects.
Olmesartan had no clinically relevant inhibitory effects on human cytochrome P450 enzymes 1A1/2, 2A6, 2C8/9, 2C19, 2D6, 2E1 and 3A4 in vitro, and had no or minimal inducing effects on rat cytochrome P450 activities. No clinically relevant interactions between Olmesartan and medicinal products metabolised by the previously mentioned cytochrome P450 enzymes are expected.
Potential interactions related to hydrochlorothiazide: Concomitant use not recommended: Medicinal products affecting potassium levels: The potassium-depleting effect of hydrochlorothiazide may be potentiated by the coadministration of other medicinal products associated with potassium loss and hypokalaemia (e.g. other kaliuretic diuretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G sodium or salicylic acid derivatives). Such concomitant use is therefore not recommended.
Concomitant use requiring caution: Calcium salts: Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium supplements must be prescribed, serum calcium levels should be monitored and calcium dosage adjusted accordingly.
Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.
Digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia may favour the onset of digitalis-induced cardiac arrhythmias.
Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum potassium and ECG is recommended when Olmesartan and Hydrochlorothiazide is administered with medicinal products affected by serum potassium disturbances (e.g. digitalis glycosides and antiarrhythmics) and with the following torsades de pointes (ventricular tachycardia)-inducing medicinal products (including some antiarrhythmics), hypokalaemia being a predisposing factor to torsades de pointes (ventricular tachycardia): Class la antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide).
Class III antiarrythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide).
Some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol).
Others (e.g. bepridil, cisapride, diphemanil, erythromycin IV, halofantrin, mizolastin, pentamidine, sparfloxacin, terfenadine, vincamine IV).
Non-depolarizing skeletal muscle relaxants (e.g. tubocurarine): The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide.
Anticholinergic agents (e.g. atropine, biperiden): Increase of the bioavailability of thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.
Antidiabetic medicinal products (oral agents and insulin): The treatment with a thiazide may influence the glucose tolerance. Dosage adjustment of the antidiabetic medicinal product may be required.
Metformin: Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.
Beta-blockers and diazoxide: The hyperglycaemic effect of beta-blockers and diazoxide may be enhanced by thiazides.
Pressor amines (e.g. noradrenaline): The effect of pressor amines may be decreased.
Medicinal products used in the treatment of gout (e.g. probenecid, sulfinpyrazone and allopurinol): Dosage adjustment of uricosuric medicinal products may be necessary since hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary. Coadministration of a thiazide may increase the incidence of hypersensitivity reactions to allopurinol.
Amantadine: Thiazides may increase the risk of adverse effects caused by amantadine.
Cytotoxic agents (e.g. cyclophosphamide, methotrexate): Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.
Salicylates: In case of high dosages of salicylates hydrochlorothiazide may enhance the toxic effect of the salicylates on the central nervous system.
Methyldopa: There have been isolated reports of haemolytic anaemia occurring with concomitant use of hydrochlorothiazide and methyldopa.
Cyclosporine: Concomitant treatment with cyclosporine may increase the risk of hyperuricaemia and gout-type complications.
Tetracyclines: Concomitant administration of tetracyclines and thiazides increases the risk of tetracycline-induced increase in urea. This interaction is probably not applicable to doxycycline.

Store at temperatures not exceeding 30°C.

Angiotensin II Antagonists / Diuretics

C09DA08 - olmesartan medoxomil and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.

Rx