Olmesartan + Hydrochlorothiazide

Oral
Hypertension

CrCl (mL/min)	Dosage
<30	Contraindicated.
30-60	Max dose of olmesartan 20 mg once daily.

Moderate: Initially, olmesartan 10 mg once daily. Max: olmesartan 20 mg daily. Severe: Contraindicated.

May be taken with or without food.

Hypersensitivity to olmesartan, hydrochlorothiazide, or sulphonamide-derived drugs, anuria, cholestasis, biliary obstruction, refractory hypokalaemia, hypercalcaemia, hyponatremia, and symptomatic hyperuricaemia. Severe hepatic and severe renal impairment (CrCl <30 mL/min) impairment. Pregnancy and lactation. Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal (GFR <30 mL/min) impairment.

Patient with aortic/mitral stenosis, obstructive hypertrophic cardiomyopathy, diabetes mellitus, diabetic nephropathy, hypercalcaemia, hypercholesterolaemia, parathyroid disease, renal artery stenosis, SLE, intravascular volume depletion, primary aldosteronism. Mild to moderate hepatic or renal impairment.

Significant: Angioedema, electrolyte disturbance, sprue-like enteropathy, gout, hypotension, acute transient myopia, acute angle-closure glaucoma, photosensitivity, renal function deterioration, hypersensitivity.
Blood and lymphatic system disorders: Aplastic anaemia, bone marrow depression, leukopenia, thrombocytopenia.
Cardiac disorders: Palpitations.
Gastrointestinal disorders: Nausea, diarrhoea, dyspepsia, abdominal pain, vomiting.
General disorders and administration site conditions: Asthenia, chest pain, fatigue, malaise, peripheral oedema, weakness.
Infections and infestations: Sialadenitis.
Investigations: Increased creatinine phosphokinase, increased SGOT/SGPT.
Metabolism and nutrition disorders: Hypercholesterolaemia, hypertriglyceridaemia, hyperuricaemia.
Musculoskeletal and connective tissue disorders: Arthralgia, back pain, muscle spasm, myalgia, pain in extremity.
Nervous system disorders: Dizziness, headache, somnolence, postural dizziness, syncope, vertigo.
Renal and urinary disorders: Haematuria.
Reproductive system and breast disorders: Erectile dysfunction.
Respiratory, thoracic and mediastinal disorders: Upper respiratory infection, cough.
Skin and subcutaneous tissue disorders: Angioneurotic oedema, eczema, rash, urticaria.
Vascular disorders: Orthostatic hypotension.

PO: D

This drug may cause dizziness or fatigue, if affected, do not drive or operate machinery.

Monitor blood pressure, serum electrolytes, BUN, creatinine.

May increase serum lithium levels and toxicity. Reduced antihypertensive effect with NSAIDs. Enhanced hypotensive effect with other antihypertensive agents and barbiturates, narcotics or antidepressants. Increased risk of hyperkalaemia with K-sparing diuretics, K supplements, or K-containing salt substitutes. Increased risk of symptomatic hyponatremia with carbamazepine.
Olmesartan: May decrease serum concentration with colesevelam. Decreased serum concentration with antacid.
Hydrochlorothiazide: Thiazide-induced hypokalaemia or hypomagnesaemia favours the onset of digitalis-induced arrhythmia. May potentiate the effect of nondepolarising skeletal muscle relaxants (e.g. tubocurarine). May enhance the hypercalcaemic effect of fat-soluble vitamin, folate, and Fe. May increase electrolyte depletion, particularly hypokalaemia, when used with corticosteroids and ACTH, laxatives. May reduce the excretion of cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. Decreased therapeutic effect of pressor amines e.g. noradrenaline. May enhance the hyperglycaemic effect of β-blockers and diazoxide. Increased bioavailability of thiazides with anticholinergic agents (e.g. atropine, biperiden). Induced risk of lactic acidosis with metformin. May increase serum uric acid level with uricosuric medicinal products (e.g. probenecid, sulfinpyrazone, allopurinol). Increased risk of adverse effects with amantadine. Risk of haemolytic anaemia with methyldopa. Increased risk of hyperuricaemia and gout-type complications with ciclosporin. Increased risk of tetracycline-induced increase in urea with tetracycline. Enhances hypercalcaemic effect of Ca-containing medicinal products.
Potentially Fatal: Increased risk of hypotension, hyperkalaemia, and decreased renal function (e.g. acute renal failure) when concomitantly used with aliskiren especially in patients with diabetes mellitus or renal impairment.

Diminished antihypertensive effect with yohimbine. Potentiated orthostatic hypotensive effect with alcohol.

Hydrochlorothiazide: May cause false-positive analytic result with anti-doping test. May interfere with parathyroid function test and decrease serum iodine without signs of thyroid disturbances. May cause false-negative aldosterone/renin ratio (ARR).

Description:
Mechanism of Action: Olmesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to AT₁ receptors.
Hydrochlorothiazide is a diuretic acting mainly in at the beginning of the distal tubules. It increases the excretion of Na and Cl ions, and consequently of water, by reducing electrolyte reabsorption from the renal tubules.
Onset: Hydrochlorothiazide: Approx 2 hours.
Duration: Hydrochlorothiazide: 6-12 hours.
Pharmacokinetics:
Absorption: Olmesartan: Absolute bioavailability: Approx 26%. Time to peak plasma concentration: Approx 1-2 hours.
Hydrochlorothiazide: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 65-70%. Time to peak plasma concentration: Within 2-5 hours.
Distribution: Olmesartan: Volume of distribution: Approx 17 L. Plasma protein binding: 99%.
Hydrochlorothiazide: Crosses placenta and enters breast milk. Volume of distribution: 3.6-7.8L/kg. Plasma protein binding: Approx 40-68%.
Metabolism: Olmesartan: Undergoes rapid ester hydrolysis of olmesartan medoxomil to olmesartan.
Excretion: Olmesartan: Via urine (35-50%); faeces (50-65%) both as unchanged drug. Terminal elimination half-life: Approx 13 hours.
Hydrochlorothiazide: Mainly via urine (approx 70% as unchanged drug). Terminal elimination half-life: 5-15 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 158781, Olmesartan. https://pubchem.ncbi.nlm.nih.gov/compound/Olmesartan. Accessed Oct. 24, 2023.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3639, Hydrochlorothiazide. https://pubchem.ncbi.nlm.nih.gov/compound/Hydrochlorothiazide. Accessed Oct. 24, 2023.

Store between 20-25°C.

Thuốc đối kháng thụ thể angiotensin II / Thuốc lợi tiểu

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.

Anon. Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/06/2018.

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Anon. Olmesartan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/06/2018.

Buckingham R (ed). Hydrochlorothiazide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2018.

Buckingham R (ed). Olmesartan Medoxomil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2018.

Joint Formulary Committee. Olmesartan with Hydrochlorothiazide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2018.

Olmesartan Medoxomil and Hydrochlorothiazide Tablet (Torrent Pharmaceuticals Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 06/06/2018.