Thiazide diuretic
Hydrochlorothiazide is a diuretic used to treat high blood pressure and swelling (oedema) associated with heart failure, liver or kidney disease. It is effective and well tolerated, but requires monitoring of electrolytes and blood sugar.
Also known as: HCTZ
Corticosteroid + thiazide: additive hypokalaemia and hyperglycaemia.
Both drugs cause renal potassium loss: hydrochlorothiazide (the exchange of sodium for potassium in the distal tubule can cause hypokalaemia and hypomagnesaemia, with a risk of ventricular arrhythmias and of potentiating digitalis toxicity) and dexamethasone (the label lists, among the fluid and electrolyte disturbances, sodium and fluid retention, potassium loss and hypokalaemic alkalosis). The hydrochlorothiazide label explicitly states that hypokalaemia may develop "during concomitant use of corticosteroid or ACTH" and that corticosteroids cause "intensified electrolyte depletion, particularly hypokalemia". The combination is common in practice (e.g. asthma/COPD with a corticosteroid + hypertension with a thiazide), but requires vigilance: monitor serum potassium (and magnesium), especially in the elderly, cirrhotics and digitalised patients, and replace potassium when indicated.
Dexamethasone + hydrochlorothiazide: additive potassium loss (hypokalaemia). Monitor potassium and replace if needed.
Both promote potassium loss and raised blood glucose.
Potassium, blood glucose and blood pressure.
Weakness, cramps, polyuria, glycaemic decompensation.
Monitor potassium and blood glucose; adjust therapy if needed.
DailyMed (FDA) — approved Dexamethasone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cbd9005-7df2-47ee-adb3-7244c1c69bc3 ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Thiazide-induced hypokalaemia raises the risk of torsades with sotalol.
Sotalol prolongs the QT interval (class III) and the risk of torsades de pointes rises as serum potassium and magnesium fall. Hydrochlorothiazide depletes these electrolytes and creates the electrophysiological environment for potentially fatal polymorphic ventricular arrhythmias. The combination is common in hypertensive and cardiac patients, which demands discipline: keep serum potassium at least at 4.0 mEq/L, correct hypomagnesaemia, monitor the ECG (QT) and electrolytes during treatment and avoid other QT-prolonging drugs.
Thiazide + sotalol: diuretic-induced hypokalaemia (and hypomagnesaemia) increases the risk of torsades de pointes. Correct electrolytes before and during treatment and monitor the QT.
The thiazide depletes potassium and amplifies sotalol's QT prolongation.
Potassium, magnesium, ECG (QT).
Ventricular arrhythmia or syncope.
Monitor potassium and ECG; correct the hypokalaemia first.
DailyMed (FDA) — approved Sotalol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9a36d95c-6e93-4e57-befe-b5274f359244 ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
No clinically relevant interaction. The combination is sometimes used intentionally for synergistic diuresis with less hypokalaemia.
Spironolactone (potassium-sparing diuretic) and hydrochlorothiazide (thiazide) have complementary mechanisms in the renal tubule: the thiazide increases sodium and potassium excretion, while spironolactone antagonises aldosterone and retains potassium. The combination is sometimes used intentionally to potentiate diuresis and natriuresis with less hypokalaemia than the thiazide alone. There is no clinically relevant adverse interaction, but the electrolyte balance must be monitored: the main risks are hyperkalaemia in patients with renal impairment or potassium supplements, and hyponatraemia in the elderly.
No clinically relevant interaction. The combination is sometimes used intentionally for synergistic diuresis with less hypokalaemia.
DailyMed/FDA (NIH/NLM) — approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73564b3d-8ede-4008-b75c-1277153b5bb6 ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565
Calcitriol + thiazide: risk of hypercalcaemia (reduced renal calcium excretion).
Thiazides decrease renal calcium excretion (hydrochlorothiazide increases tubular calcium reabsorption) and the hydrochlorothiazide label documents hypercalcaemia and hypophosphataemia in patients on prolonged thiazide therapy, with parathyroid changes; the calcitriol label explicitly states that "thiazides induce hypercalcaemia by reducing urinary calcium excretion" and that there are reports of hypercalcaemia when thiazides are given concomitantly with calcitriol, recommending caution. The combination thus adds up the two hypercalcaemic mechanisms. Monitor serum calcium (and the calcium x phosphorus product), especially at initiation or dose adjustment; watch for hypercalcaemia signs (weakness, headache, nausea, vomiting, constipation, polyuria) and reduce/stop calcitriol or calcium supplements if needed.
Calcitriol + hydrochlorothiazide: thiazides reduce renal calcium excretion and can potentiate calcitriol-induced hypercalcaemia. Monitor serum calcium.
Thiazides reduce urinary calcium excretion, adding to the hypercalcaemic effect of calcitriol.
Serum calcium and renal function periodically.
Polyuria, constipation, confusion, renal stones.
Monitor serum calcium, especially in the first weeks and in renal impairment.
DailyMed (FDA) — approved Calcitriol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8465337c-86ca-ea9d-e053-2991aa0ab167 ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Corticosteroid + thiazide: additive hypokalaemia and hyperglycaemia.
Hydrochlorothiazide can cause hypokalaemia, and the label explicitly states that hypokalaemia may develop during concomitant use of corticosteroids or ACTH, with intensified electrolyte depletion, particularly potassium. Prednisolone, in turn, causes potassium loss and hypokalaemic alkalosis (listed as fluid and electrolyte disturbances in the label). The combination adds up the risk of hypokalaemia, which can provoke ventricular arrhythmias or sensitise the heart to the toxic effects of digitalis. Monitor serum electrolytes, especially potassium, and consider potassium supplementation.
Hydrochlorothiazide + prednisolone: additive risk of hypokalaemia. Monitor potassium and consider supplementation.
Both promote potassium loss and raised blood glucose.
Potassium, blood glucose and blood pressure.
Weakness, cramps, polyuria, glycaemic decompensation.
Monitor potassium and blood glucose; adjust therapy if needed.
DailyMed (FDA) — approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Thiazide + calcium: risk of hypercalcaemia (thiazide reduces renal calcium excretion).
Thiazides (hydrochlorothiazide) increase tubular calcium reabsorption and reduce its urinary excretion, raising serum calcium. In patients taking calcium supplements (carbonate) and vitamin D, the combination can cause hypercalcaemia — the Prontuário Terapêutico even records thiazides as contraindicated in hypercalcaemia by this mechanism. Monitor serum calcium in patients on calcium supplementation starting a thiazide, and consider reducing the calcium dose; the interaction can, however, be used favourably in renal stone disease due to hypercalciuria.
Thiazide + calcium: the thiazide reduces renal calcium excretion — risk of hypercalcaemia.
Hydrochlorothiazide reduces renal calcium elimination; with calcium supplements hypercalcaemia may occur.
Serum calcium and hypercalcaemia symptoms.
Polyuria, constipation, weakness, confusion.
Monitor serum calcium in patients on chronic supplementation.
DailyMed (FDA) — approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 ; approved Calcium carbonate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=348d3dfa-6a52-4583-96e3-83c4bf2df45b — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Thiazide + vitamin D3: additive hypercalcaemia.
Hydrochlorothiazide reduces renal calcium excretion and vitamin D3 increases intestinal calcium absorption; together the two effects add up and can cause hypercalcaemia, especially in patients with renal impairment, prolonged immobilisation or additional calcium supplementation. The risk is particularly relevant when starting vitamin D in patients already on thiazides, or when increasing the dose. Monitor serum calcium (and urinary calcium) after starting or adjusting vitamin D in patients on thiazides, and reduce supplementation if serum calcium rises.
Thiazide + vitamin D3: additive hypercalcaemia. Monitor serum calcium.
The thiazide reduces calcium excretion and vitamin D increases its absorption; together they raise serum calcium.
Serum calcium.
Polyuria, constipation, weakness.
Monitor serum calcium during prolonged supplementation.
DailyMed (FDA) — approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining Lithium with Hydrochlorothiazide increases serum Lithium concentrations, with a risk of toxicity.
Thiazides such as hydrochlorothiazide reduce renal lithium clearance: diuretic-induced sodium loss decreases lithium elimination and markedly increases the risk of toxicity. The hydrochlorothiazide label states that lithium generally should not be given with diuretics and refers to the lithium package insert; the lithium label confirms that diuretic-induced sodium loss can reduce lithium clearance and raise lithium levels. If the combination is unavoidable, reduce the lithium dose, monitor lithium levels frequently and watch for signs of toxicity (tremor, confusion, ataxia, dysarthria); ensure adequate sodium intake.
Hydrochlorothiazide + lithium: thiazides reduce renal lithium clearance and greatly increase the risk of toxicity. Avoid; if unavoidable, monitor lithium levels.
Thiazide diuretics reduce the renal excretion of Lithium (increased tubular reabsorption), raising its serum levels.
Frequent Lithium levels and electrolyte/creatinine checks.
Signs of Lithium toxicity (confusion, tremor, vomiting, seizures) require discontinuation and urgent evaluation.
Avoid the combination whenever possible; if needed, closely monitor Lithium levels and renal function.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Enhanced hypotensive effect. The combination may cause symptomatic hypotension in the first weeks, especially with prior volume depletion.
The combination of an ACE inhibitor with a thiazide is a well-established fixed combination for hypertension, with an approximately additive antihypertensive effect (the enalapril label states the blood pressure effects are "approximately additive" with thiazide diuretics) and a benefit in reducing thiazide-induced hypokalaemia. The risks to watch: (1) first-dose hypotension — in patients with volume/sodium depletion from the diuretic, the enalapril label recommends correcting the depletion or reducing the initial dose; (2) renal function — hypovolaemia can raise creatinine; (3) electrolytes — the balance between thiazide hypokalaemia and the ACE inhibitor hyperkalaemic tendency (the thiazide label states it may be used in patients in whom hyperkalaemia cannot be risked, including patients taking ACE inhibitors). Monitor BP, creatinine and potassium after initiation/adjustment; start with low doses in the elderly and in volume-depleted patients.
Enalapril + hydrochlorothiazide: additive antihypertensive effect (common fixed combination). Watch for first-dose hypotension, renal function and potassium.
The thiazide lowers circulating volume and the ACE inhibitor lowers peripheral resistance — the synergistic effect lowers BP more sharply.
BP in week 1; creatinine and electrolytes (K+, Na+) at 2 weeks.
Dizziness, syncope, cramps, intense thirst — possible signs of hypotension or hyponatraemia.
Start at low doses. Monitor BP and renal function in the first 2 weeks.
DailyMed/FDA (NIH/NLM) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565
Liquorice causes pseudoaldosteronism with hypokalaemia, adding to thiazide-induced potassium depletion.
Avoid excessive liquorice intake; monitor serum potassium.
EMC-UK (MHRA) — approved Hydrochlorothiazide SmPC: https://www.medicines.org.uk/emc/product/11721/smpc
Thiazides reduce renal calcium excretion; high-dose calcium supplements may cause hypercalcaemia.
Monitor serum calcium in patients taking high-dose calcium supplements.
EMC-UK (MHRA) — approved Hydrochlorothiazide SmPC: https://www.medicines.org.uk/emc/product/11721/smpc
Hydrochlorothiazide is contraindicated in anuria because of the risk of drug accumulation.
Do not use in patients with anuria.
EMC-UK (MHRA) — approved Hydrochlorothiazide SmPC: https://www.medicines.org.uk/emc/product/11721/smpc
Hydrochlorothiazide crosses the placenta; data in pregnancy do not indicate teratogenicity, but it may cause placental hypoperfusion.
Avoid as an antihypertensive in pregnancy; use only if the benefit outweighs the risk.
Hydrochlorothiazide is excreted into breast milk in small amounts; use with caution.
In women of childbearing age, chronic diuretic therapy should be reviewed before conception.
EMC-UK (MHRA) — approved Hydrochlorothiazide SmPC: https://www.medicines.org.uk/emc/product/11721/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Thiazide diuretic. Acts on the distal renal tubular mechanism of electrolyte reabsorption; increases excretion of sodium and chloride in approximately equivalent amounts, with some loss of potassium and bicarbonate. Diuresis begins within 2 hours, peaks in about 4 hours and lasts 6 to 12 hours. The mechanism of the antihypertensive effect is unknown.
It inhibits the sodium-chloride cotransporter in the distal convoluted tubule, increasing the excretion of sodium, chloride and water; natriuresis is accompanied by loss of potassium and bicarbonate, increased urinary magnesium excretion and decreased calcium excretion. It increases uric acid and blood glucose.
Well absorbed orally; diuresis begins within 2 hours and peaks in about 4 hours. Cholestyramine and colestipol resins reduce absorption by up to 85% and 43%, respectively.
It is not metabolised; it is eliminated rapidly by the kidney, with at least 61% of the oral dose eliminated unchanged within 24 hours. It crosses the placenta but not the blood-brain barrier; it is excreted in breast milk. Hypokalaemia and hypomagnesaemia can sensitise the heart to digitalis toxicity.
Plasma half-life of 5.6 to 14.8 hours (when plasma levels are followed for at least 24 hours). Cumulative effects may develop in patients with severe renal impairment.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
