Candesartan + Hydrochlorothiazide


Concise Prescribing Info
Indications/Uses
Hypertension.
Dosage/Direction for Use
Adult : PO Each tab contains candesartan (mg)/hydrochlorothiazide (mg): 16/12.5, 32/12.5, 32/25: 1 tab once daily. Dosage is individualised and may be titrated according to patient condition. Max: Candesartan 32 mg and hydrochlorothiazide 50 mg.
Dosage Details
Oral
Hypertension
Adult: Available preparations:
Candesartan 16 mg and hydrochlorothiazide 12.5 mg
Candesartan 32 mg and hydrochlorothiazide 12.5 mg
Candesartan 32 mg and hydrochlorothiazide 25 mg

1 tab once daily. Dosage is individualised and may be titrated according to patient condition. Max: Candesartan 32 mg and hydrochlorothiazide 50 mg.
Renal Impairment
CrCl (mL/min) Dosage
<30 Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Administration
May be taken with or without food.
Contraindications
Hypersensitivity to candesartan, hydrochlorothiazide, or sulphonamide-derived drugs, anuria, gout, cholestasis. Severe hepatic and renal impairment (CrCl <30 mL/min) impairment. Pregnancy and lactation. Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal (GFR <60 mL/min) impairment.
Special Precautions
Patient with aortic or mitral stenosis, diabetes mellitus, obstructive hypertrophic cardiomyopathy, severe CHF, hypercalcaemia, hypercholesterolaemia, parathyroid disease, renal artery stenosis, primary hyperaldosteronism, SLE. Mild to moderate hepatic and renal impairment.
Adverse Reactions
Significant: Electrolyte disturbances (e.g. hypo- or hyperkalaemia, hyponatremia, hypomagnesaemia, hypochloraemic alkalosis), hypotension, acute transient myopia, acute angle-closure glaucoma, SLE, hypersensitivity reactions, gout, renal function deterioration, photosensitivity. Rarely, angioedema.
Blood and lymphatic system disorders: Neutropenia, leukopenia, agranulocyctosis.
Gastrointestinal disorders: Nausea, abdominal pain.
General disorders and administration site conditions: Fatigue, influenza-like symptoms.
Metabolism and nutrition disorders: Dyslipidaemia.
Musculoskeletal and connective tissue disorders: Back pain.
Nervous system disorders: Dizziness, headache.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Respiratory tract infection, pharyngitis, sinusitis, bronchitis, cough.
Skin and subcutaneous tissue disorders: Pruritus, rash, urticaria.
Patient Counseling Information
This drug may cause dizziness and weariness, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor weight, input and output, blood pressure, serum electrolytes, BUN, creatinine, renal function. Monitor for signs of angioedema, symptomatic hypotension and tachycardia.
Drug Interactions
May increase serum lithium levels and toxicity.
Candesartan: NSAIDs may reduce antihypertensive effect and result in deterioration of renal function including possible acute renal failure. K-sparing diuretics, K supplements or salt substitutes containing K may increase risk of hyperkalaemia.
Hydrochlorothiazide: Impaired absorption in the presence of anionic exchange resins e.g. with bile acid sequesterants (e.g. cholestyramine, and colestipol) resins. Potentiate the effect of nondepolarising skeletal muscle relaxants (e.g. tubocurarine). Increased electrolyte depletion, particularly hypokalaemia, when used with corticosteroids and ACTH. Reduce the excretion of cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiates their myelosuppressive effects. May enhance the hyperglycaemic effect of diazoxide. Increased bioavailability of thiazides with anticholinergic agents (e.g. atropine, biperiden). Increased risk of acute renal insufficiency with iodinated contrast media. May potentiate K loss and hypokalaemia with laxatives, amphotericin, carbenoxolone, salicylic acid. Increased risk of hyperuricaemia with ciclosporin.
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.
Food Interaction
Diminished antihypertensive effect with yohimbine. Potentiated orthostatic hypotensive effect with alcohol.
Lab Interference
May cause false-negative aldosterone/renin ratio (ARR).
Hydrochlorothiazide: May interfere with parathyroid function test and decrease serum iodine without signs of thyroid disturbances.
Action
Description: Candesartan is a prodrug of candesartan cilexetil that 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: Candesartan: 2-3 hours.
Hydrochlorothiazide: Approx 2 hours.
Duration: Candesartan: >24 hours.
Hydrochlorothiazide: 6-12 hours.
Pharmacokinetics:
Absorption: Candesartan: Rapidly and completely absorbed. Absolute bioavailability: Approx 15%. Time to peak plasma concentration: Approx 3-4 hours.
Hydrochlorothiazide: Well absorbed from the gastrointestinal tract. Bioavailability: 65-75%. Time to peak plasma concentration: Approx 1-5 hours.
Distribution: Candesartan: Volume of distribution: 0.13 L/kg. Plasma protein binding: >99%.
Hydrochlorothiazide: Crosses the placenta and enters breast milk. Volume of distribution: 3.6 to 7.8 L/kg. Plasma protein binding: Approx 40-68%.
Metabolism: Candesartan cilexetil undergoes ester hydrolysis in the gastrointestinal tract to active form candesartan; minimally metabolised in the liver via O-deethylation to inactive metabolite.
Excretion: Candesartan: Via feces (67%); urine (33%, 26% as unchanged drug). Terminal elimination half-life: Approx 5 hours.
Hydrochlorothiazide: Via urine (≥61% as unchanged drug). Elimination half-life: Approx 6-15 hours.
Chemical Structure

Chemical Structure Image
Candesartan

Source: National Center for Biotechnology Information. PubChem Database. Candesartan, CID=2541, https://pubchem.ncbi.nlm.nih.gov/compound/Candesartan (accessed on Jan. 21, 2020)


Chemical Structure Image
Hydrochlorothiazide

Source: National Center for Biotechnology Information. PubChem Database. Hydrochlorothiazide, CID=3639, https://pubchem.ncbi.nlm.nih.gov/compound/Hydrochlorothiazide (accessed on Jan. 20, 2020)

Storage
Store at 25°C. Protect from light.
ATC Classification
C09DA06 - candesartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.
References
Anon. Candesartan and Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/02/2018.

Anon. Candesartan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/02/2018.

Anon. Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/02/2018.

Anon. Thiazides General Statement. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 15/02/2018.

Buckingham R (ed). Candesartan Cilexetil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/02/2018.

Buckingham R (ed). Hydrochlorothiazide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/02/2018.

Candesartan Cilexetil and Hydrochlorothiazide (Apotex Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 09/02/2018.

Disclaimer: This information is independently developed by MIMS based on Candesartan + Hydrochlorothiazide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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