Candesartan + Hydrochlorothiazide

Oral
Hypertension

Mild to moderate: Dose titration of candesartan (an initial dose of 4 mg may be considered) is recommended before treatment with this combination. Severe: Contraindicated.

Mild to moderate: Dose titration of candesartan (an initial dose of 4 mg may be considered) is recommended before treatment with this combination. Severe: Contraindicated.

May be taken with or without food.

Hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs. Anuria, cholestasis, refractory hypokalaemia and hypercalcaemia, gout. Severe hepatic and renal impairment. Pregnancy and lactation. Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²).

Patient with intravascular volume and/or Na depletion, heart failure, aortic or mitral valve stenosis, obstructive hypertrophic cardiomyopathy, ischaemic heart disease, atherosclerotic cerebrovascular disease, diabetes mellitus, SLE, history of NMSC. Not recommended in patients with primary hyperaldosteronism. Patients undergoing anaesthesia and surgery. Mild to moderate hepatic and renal impairment.

Significant: Symptomatic hypotension, changes in renal function including acute renal failure, electrolyte imbalance (e.g. hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia and hypochloraemic alkalosis), acute transient myopia, acute angle-closure glaucoma, non-melanoma skin cancer (NMSC), photosensitivity reactions. Rarely, severe cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS).
Cardiac disorders: Tachycardia or bradycardia, palpitation, extrasystoles.
Ear and labyrinth disorders: Tinnitus, vertigo.
Eye disorders: Conjunctivitis.
Gastrointestinal disorders: Abdominal pain, diarrhoea, dyspepsia, gastritis, gastroenteritis, nausea, vomiting.
General disorders and administration site conditions: Back pain, influenza-like symptoms, fatigue, pain, peripheral oedema, asthenia.
Hepatobiliary disorders: Abnormal hepatic function.
Investigations: Increased BUN, creatinine phosphokinase, cholesterol, triglyceride and transaminase levels; abnormal ECG.
Metabolism and nutrition disorders: Hyperglycaemia, hyperuricaemia.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, arthrosis, arthritis, leg cramps, sciatica.
Nervous system disorders: Dizziness, headache, paraesthesia, hypoaesthesia.
Psychiatric disorders: Depression, insomnia, anxiety.
Renal and urinary disorders: UTI, haematuria, cystitis, glycosuria.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, bronchitis, sinusitis, pharyngitis, cough, rhinitis, dyspnoea, epistaxis.
Skin and subcutaneous tissue disorders: Eczema, increased sweating, pruritus, dermatitis, rash.

PO: D

This drug may cause dizziness or weariness, if affected, do not drive or operate machinery. Apply sunscreen when going outdoors and avoid excessive exposure to sunlight and UV light.

Monitor serum electrolytes (e.g. Na, K) and renal function (e.g. BUN, creatinine) periodically; blood pressure, heart rate.

Symptoms: Candesartan: Symptomatic hypotension and dizziness. Hydrochlorothiazide: Acute loss of fluid and electrolytes; dizziness, hypotension, thirst, tachycardia, ventricular arrhythmias, sedation, impaired consciousness, and muscle cramps. Management: Symptomatic treatment. Induction of vomiting or gastric lavage may be considered. Monitor vital signs. Place the patient in a supine position with the legs elevated. If insufficient, plasma volume can be increased by infusion of isotonic NaCl solution. Check and correct serum electrolyte and acid balance needed. Sympathomimetic medicinal products may be administered.

Increased risk of renal impairment with NSAIDs. May increase the serum levels of lithium. Enhanced hypotensive effect with other antihypertensives.
Candesartan: Concomitant use with K sparing diuretics, K supplements, K-containing salt substitutes or other drugs that raise serum K levels may increase the risk of hyperkalaemia.
Hydrochlorothiazide: Potentiation of orthostatic hypotensive effect with barbiturates or narcotics. May diminish the therapeutic effect of antidiabetic agents. May enhance the hyperglycaemic effect of diazoxide. Reduced absorption with colestyramine or colestipol. May enhance the effects of nondepolarising skeletal muscle relaxants (e.g. tubocurarine). May decrease the arterial responsiveness to norepinephrine. Concomitant use with steroids or adrenocorticotropic hormone (ACTH), other kaliuretic diuretics, laxatives, amphotericin B, carbenoxolone, penicillin G Na, and salicylic acid derivatives may lead to hypokalaemia. May potentiate the myelosuppressive effects of cytotoxic drugs (e.g. cyclophosphamide, methotrexate). May increase the risk of hyperuricaemia and gout-type complications with ciclosporin. May increase the risk of cardiotoxic effects of digitalis glycosides and antiarrhythmics. Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of hydrochlorothiazide. May increase the risk of adverse reactions caused by amantadine.
Potentially Fatal: Concomitant use with aliskiren increases the risk of hypotension, hyperkalaemia and changes in renal function (including acute renal failure) in patients with diabetes mellitus or renal impairment (GFR<60mL/min/1.73 m²).

Potentiation of orthostatic hypotensive effect with alcohol.

May interfere with parathyroid function tests and may reduce serum iodine without signs of thyroid impairment. May cause false-negative aldosterone/renin ratio (ARR).

Description:
Mechanism of Action: 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 at the beginning of the distal tubules. It increases the excretion of Na 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. Bioavailability: 15%. Time to peak plasma concentration: 3-4 hours.
Hydrochlorothiazide: Rapidly and 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: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-68%.
Metabolism: Candesartan cilexetil undergoes ester hydrolysis in the gastrointestinal tract to the active form candesartan. Candesartan undergoes minimal metabolism in the liver via O-deethylation to an inactive metabolite.
Excretion: Candesartan: Mainly via faeces (approx 67%); urine (approx 33%, approx 26% as unchanged drug). Elimination half-life: 5-9 hours (dose-dependent).
Hydrochlorothiazide: Via urine (≥61% as unchanged drug). Elimination half-life: 5.6-14.8 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2541, Candesartan. https://pubchem.ncbi.nlm.nih.gov/compound/2541. Accessed Aug. 25, 2022.

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. Protect from light.

Angiotensin II Antagonists / Diuretics

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.

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