Adult: As adjunctive treatment: Usual dose: 500-1,000 mg once daily or bid via slow IV inj or via IV infusion; dose may also be given on alternate days or on 3-5 days weekly. Dose is individualised based on patient response.
Oral Hypertension
Adult: As monotherapy or adjunct to other antihypertensive agents: Initially, 500-1,000 mg daily as a single dose or in 2 divided doses. Dose may be adjusted according to blood pressure response. Max: 2,000 mg daily in divided doses. Child: Infants <6 months Up to 30 mg/kg daily in 2 divided doses; 6 months to 12 years 10-20 mg/kg daily in 1-2 divided doses. Max: <2 years 375 mg daily; 2-12 years 1,000 mg daily.
Oral Oedema
Adult: As adjunctive treatment: Usual dose: 500-1,000 mg once daily or bid; dose may also be given on alternate days or on 3-5 days weekly. Dose is individualised based on patient response. Child: Infants <6 months Up to 30 mg/kg daily in 2 divided doses; 6 months to 12 years 10-20 mg/kg daily in 1-2 divided doses. Max: <2 years 375 mg daily; 2-12 years 1,000 mg daily.
Administration
Should be taken with food.
Reconstitution
IV: Reconstitute vial labelled as 500 mg with 18 mL of sterile water for inj to provide a solution of 28 mg/mL. May be further diluted with NaCl 0.9% and dextrose 5% solutions.
Incompatibility
IV: Incompatible with injectable preparations of the following: Chlorpromazine hydrochloride, amikacin sulfate, hydralazine hydrochloride, insulin, levorphanol tartrate, norepinephrine bitartrate, methadone hydrochloride, morphine sulfate, prochlorperazine mesylate, promethazine hydrochloride, polymyxin B sulfate, streptomycin sulfate, tetracycline hydrochloride, vancomycin hydrochloride. Avoid concurrent administration with whole blood or its derivatives.
Contraindications
Hypersensitivity to sulfonamide-derived drugs. Anuria.
Special Precautions
Patient with gout or familial predisposition to gout, prediabetes or diabetes mellitus, moderate or high cholesterol levels, hypercalcaemia, hypokalaemia. Patient undergoing surgery. Post-sympathectomy patient. Avoid use for treatment of hypertension in patients with primary adrenal insufficiency (Addison disease). Avoid extravasation (IV). Hepatic and severe renal impairment. Neonates and children. Pregnancy and lactation.
Adverse Reactions
Significant: Exacerbation or activation of SLE; hypersensitivity reactions, photosensitivity, electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia, hypercalcaemia, hyponatraemia, hypochloraemic alkalosis), hyperuricaemia or acute gout, hyperglycaemia, increased cholesterol and triglyceride levels, orthostatic hypotension. Blood and lymphatic system disorders: Agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopenia, thrombocytopenia. Ear and labyrinth disorders: Vertigo. Eye disorders: Blurred vision, xanthopsia. Gastrointestinal disorders: Pancreatitis, diarrhoea, gastric irritation, nausea, vomiting, abdominal cramping, constipation, sialoadenitis. General disorders and administration site conditions: Weakness, fever. Hepatobiliary disorders: Jaundice. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Muscle spasm. Nervous system disorders: Dizziness, paraesthesia, headache. Psychiatric disorders: Restlessness. Renal and urinary disorders: Interstitial nephritis, renal failure, renal dysfunction, glycosuria; haematuria (IV). Reproductive system and breast disorders: Impotence. Respiratory, thoracic and mediastinal disorders: Pneumonitis, pulmonary oedema, respiratory distress. Skin and subcutaneous tissue disorders: Alopecia, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria. Vascular disorders: Necrotising angiitis.
Avoid excessive exposure to sunlight or UV light, apply sunscreen or wear protective clothing when going outdoors.
Monitoring Parameters
Monitor serum electrolytes (periodically), renal function, blood pressure, and fluid status (intake and output, oedema, and weight).
Overdosage
Symptoms: Hypokalaemia, hypochloraemia, hyponatraemia, and dehydration resulting from excessive diuresis. Management: Symptomatic and supportive treatment. Correct dehydration, electrolyte imbalance, hypotension, and hepatic coma using established procedures. If needed, may give oxygen or artificial respiration for respiratory impairment.
Drug Interactions
May reduce the renal clearance of lithium, which may increase the risk of lithium toxicity. Potentiation of orthostatic hypotension with barbiturates or narcotics. May reduce the therapeutic effect of antidiabetic agents. Additive or potentiated effect with other antihypertensive agents. Reduced absorption from the gastrointestinal tract with colestyramine and colestipol. May reduce the response to pressor amines. Increased electrolyte depletion (particularly hypokalaemia) with corticosteroids and ACTH. Reduced diuretic and antihypertensive effects with NSAID. May enhance the effect of nondepolarising skeletal muscle relaxants (e.g. tubocurarine).
Food Interaction
May increase the extent of absorption with food. Alcohol may increase the risk of orthostatic hypotension.
Lab Interference
May interfere with parathyroid function tests.
Action
Description: Mechanism of Action: Chlorothiazide is a thiazide diuretic that inhibits the reabsorption of Na and chloride ions in the distal tubules causing increased excretion of Na, chloride, and water. The exact mechanism for its antihypertensive effect is unknown; however, the excretion of urinary Na by the kidneys is needed to achieve blood pressure reduction. Onset: Diuresis: Within 2 hours (oral); 15 minutes (IV). Duration: Diuresis: Approx 6-12 hours (oral); 2 hours (IV). Pharmacokinetics: Absorption: Incompletely and variably absorbed from the gastrointestinal tract. Food may increase the extent of absorption. Distribution: Crosses the placenta; enters breast milk (small amounts). Metabolism: Not metabolised. Excretion: Via urine (10-15% as unchanged drug [oral]; 96% as unchanged drug [IV]). Elimination half-life: 45-120 minutes.
Chemical Structure
Chlorothiazide Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2720, Chlorothiazide. https://pubchem.ncbi.nlm.nih.gov/compound/Chlorothiazide. Accessed Nov. 22, 2023.
Storage
Oral susp: Store between 15-30°C. Protect from freezing. IV inj: Store intact vials between 2-25°C.
C03AA04 - chlorothiazide ; Belongs to the class of low-ceiling thiazide diuretics.
References
Anon. Chlorothiazide (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 16/11/2023.Anon. Chlorothiazide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 26/09/2023.Anon. Chlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 26/09/2023.Buckingham R (ed). Chlorothiazide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/09/2023.Chlorothiazide Sodium Injection (Akorn). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 26/09/2023.Chlorothiazide Sodium Injection, Powder, Lyophilized, for Solution (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 26/09/2023.Chlorothiazide. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 26/09/2023.Diuril Suspension (Salix Pharmaceuticals, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 13/11/2023.Paediatric Formulary Committee. Chlorothiazide. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 16/11/2023.
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