Adult: Available preparations:
Captopril 25 mg and hydrochlorothiazide 12.5 mg tab
Captopril 25 mg and hydrochlorothiazide 15 mg tab
Captopril 25 mg and hydrochlorothiazide 25 mg tab
Captopril 50 mg and hydrochlorothiazide 15 mg tab
Captopril 50 mg and hydrochlorothiazide 25 mg tab
As initial treatment or substituted for previously titrated doses of the individual components: Initially, 25 mg/15 mg once daily. Subsequent titrations may be with additional doses of individual components or as fixed combinations, if necessary. Dosage is individualised and adjusted according to patient response. Max: 150 mg captopril and 50 mg hydrochlorothiazide daily. Elderly: Initiate at the lowest possible effective dose.
Renal Impairment
Dose reduction may be necessary. Severe: Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Administration
Should be taken on an empty stomach. Take 1 hr before meals.
Contraindications
Hypersensitivity. History of angioedema related to previous ACE inhibitor treatment, hereditary or idiopathic angioneurotic oedema, anuria. Severe renal and hepatic impairment. Pregnancy. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2). Concomitant use with or within 36 hours of switching to or from sacubitril.
Special Precautions
Patient with volume and Na depletion, unstented unilateral/bilateral renal artery stenosis, aortic and mitral valve stenosis, hypertrophic cardiomyopathy with outflow obstruction, cardiogenic shock, CV disease (e.g. ischaemic heart disease, heart failure), cerebrovascular disease, collagen vascular disease, pre-diabetes or diabetes mellitus, parathyroid disease, hypercalcaemia, hypercholesterolaemia, SLE, liver cirrhosis, bronchial asthma. Patient undergoing major surgery or during anaesthesia, LDL apheresis with dextran sulfate cellulose, and desensitisation with hymenoptera venom. Black race. Elderly. Renal and hepatic impairment. Lactation.
Adverse Reactions
Significant: Symptomatic hypotension with or without syncope, intestinal angioedema, electrolyte disturbances (e.g. hyperkalaemia, hypokalaemia, hypochloraemic alkalosis, hypomagnesaemia, hyponatraemia), cough, gout, haematologic effects (e.g. neutropenia, agranulocytosis, anaemia, thrombocytopenia), photosensitivity, ocular effects (e.g. acute transient myopia, acute angle-closure glaucoma), non-melanoma skin cancer (prolonged use), SLE exacerbation or activation, proteinuria, progressive azotaemia, decreased renal Ca excretion, increased cholesterol and triglycerides, impaired glucose tolerance. Blood and lymphatic system disorders: Lymphadenopathy, pancytopenia, eosinophilia. Cardiac disorders: Tachycardia, angina pectoris, palpitations. Ear and labyrinth disorders: Vertigo. Eye disorders: Blurred vision. Gastrointestinal disorders: Nausea, vomiting, dysgeusia, abdominal pain, diarrhoea, constipation, dry mouth, peptic ulcer. General disorders and administration site conditions: Fatigue, asthenia. Investigations: Increased BUN, serum creatinine, and liver transaminases. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Rarely, myalgia, arthralgia. Nervous system disorders: Dizziness, headache, paraesthesia. Psychiatric disorders: Sleep disorders, depression. Reproductive system and breast disorders: Rarely, impotence, gynaecomastia. Respiratory, thoracic and mediastinal disorders: Dyspnoea, bronchospasm, rhinitis. Skin and subcutaneous tissue disorders: Pruritus, rash, alopecia. Rarely, erythema multiforme, pemphigoid reactions, and exfoliative dermatitis. Vascular disorders: Orthostatic hypotension. Potentially Fatal: Angioneurotic oedema associated with laryngeal oedema. Rarely, cholestatic jaundice that may progress to fulminant hepatic necrosis; anaphylactoid reactions.
PO: C (1st trimester), D (in 2nd & 3rd trimesters)
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery. Avoid or limit exposure to direct sunlight and UV light.
Monitoring Parameters
Monitor blood pressure, BUN, serum creatinine, serum electrolyte levels (e.g. Na, K); CBC with differential for the 1st 3 months of treatment and periodically thereafter. Assess skin for photosensitivity and skin cancer; signs and symptoms of angioedema; pregnancy status.
Overdosage
Symptoms: Severe hypotension, increased diuresis, electrolyte imbalance, convulsions, paresis, cardiac arrhythmias, bradycardia, coma, and renal failure. Management: Symptomatic and supportive treatment. Perform gastric lavage or administer absorbing agents within 30 minutes of ingestion. To correct hypotension, place the patient in shock position and administer volume supplementation with 0.9% NaCl IV infusion. May give atropine for bradycardia or extensive vagal reactions. Monitor and correct water, electrolyte, and acid-base balance as necessary.
Drug Interactions
May increase antihypertensive effects with other diuretics, vasodilators, and nitrates. Increased risk of lithium toxicity. May reduce antihypertensive effects with NSAIDs.
Captopril: Increased risk of hyperkalaemia with heparin, K-sparing diuretics, K supplements, or K-containing salt substitutes. May increase serum levels of digoxin. May decrease gastrointestinal absorption with antacids. May elevate serum concentrations with probenecid. May increase the hypoglycaemic effect of insulin and oral anti-diabetics. Increased risk of leucopenia with allopurinol, procainamide, and immunosuppressant agents.
Hydrochlorothiazide: Increased risk of hypokalaemia with amphotericin B, carbenoxolone, corticosteroids, corticotropin, stimulant laxatives, and agents that induce torsades de pointes (e.g. digoxin, antiarrhythmics, antipsychotics). May cause hypercalcaemia with Ca salts. May decrease absorption with colestyramine and colestipol. May increase the effects of non-depolarising muscle relaxants (e.g. tubocurarine). May increase the risk of symptomatic hyponatremia with carbamazepine. Orthostatic hypotensive effects may be potentiated by barbiturates and narcotics. Potentially Fatal: Captopril: Increased risk of hypotension, hyperkalaemia, and decreased renal function with aliskiren. Increased risk of angioedema with sacubitril. May cause anaphylactoid reactions with dextran sulfate in LDL apheresis.
Food Interaction
Captopril serum concentrations may be reduced with food. Alcohol may potentiate the orthostatic hypotensive effect of hydrochlorothiazide.
Lab Interference
May result in false-negative aldosterone/renin ratio (ARR).
Captopril: May cause false-positive results in urine acetone test.
Hydrochlorothiazide: May interfere with bentiromide test and parathyroid function test. May reduce serum iodine (protein bound) without signs of thyroid disturbance. May produce a positive analytical result in an anti-doping test.
Action
Description: Mechanism of Action: Captopril and hydrochlorothiazide both decrease blood pressure via different but complementary mechanisms, exhibiting additive effects with its combined use.
Captopril is an ACE inhibitor that prevents the conversion of angiotensin I to angiotensin II, thereby increasing plasma renin activity and reducing aldosterone secretion.
Hydrochlorothiazide, a thiazide diuretic, prevents Na reabsorption in the distal tubules leading to increased excretion of water, Na, K, and hydrogen ions. Onset: Captopril: Within 15 minutes.
Hydrochlorothiazide: Diuresis: Approx 2 hours. Duration: Hydrochlorothiazide: 6-12 hours. Pharmacokinetics: Absorption: Captopril: Rapidly absorbed from the gastrointestinal tract (60-75%). May reduce serum concentrations with food. Bioavailability: Approx 60-75%. Time to peak plasma concentration: Within 1-2 hours.
Hydrochlorothiazide: Well absorbed from the gastrointestinal tract. Bioavailability: 65-75%. Time to peak plasma concentration: Approx 1-5 hours. Distribution: Captopril: Crosses placenta and enters the breast milk. Volume of distribution: 0.71 L/kg. Plasma protein binding: 25-30%.
Hydrochlorothiazide: Crosses placenta and enters the breast milk. Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx. 40-68%. Metabolism: Captopril: Rapidly metabolised (approx 50%) into inactive disulphide.
Hydrochlorothiazide: Not metabolised. Excretion: Captopril: Mainly via urine (>95%; 40-50% as unchanged drug, 50-60% as inactive metabolites). Elimination half-life: Approx 2-3 hours.
Hydrochlorothiazide: Mainly via urine (≥61% as unchanged drug). Elimination half-life: Approx 6-15 hours.
Chemical Structure
Captopril Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 44093, Captopril. https://pubchem.ncbi.nlm.nih.gov/compound/Captopril. Accessed Sept. 28, 2022.
Hydrochlorothiazide 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.
C09BA01 - captopril and diuretics ; Belongs to the class of ACE inhibitors in combination with diuretics. Used in the treatment of cardiovascular disease.
References
Anon. Captopril and Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/05/2020.Anon. Captopril. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 11/05/2020.Anon. Captopril. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/05/2020.Anon. Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/05/2020.Buckingham R (ed). Captopril. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/05/2020.Buckingham R (ed). Hydrochlorothiazide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/05/2020.Captopril and Hydrochlorothiazide Tablet (Mylan Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 11/05/2020.Co-zidocapt 25/12.5 mg Tablets (Crescent Pharma Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 22/05/2020.Co-zidocapt 50/25 mg Tablets (Crescent Pharma Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 11/05/2020.
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