Triamterene + Hydrochlorothiazide

May be taken with or without food.

Hypersensitivity to triamterene, hydrochlorothiazide or other sulfonamide-derived drugs. Hyperkalaemia (≥5.5 mEq/L), anuria, acute and chronic renal insufficiency. Severe renal impairment. Concomitant use with other K-sparing agents (e.g. spironolactone, amiloride), K-containing salt substitutes, or K supplements (except in severe cases of hypokalaemia).

Patient with history of gout or family history of predisposition to gout, prediabetes or diabetes mellitus, moderate or high cholesterol concentrations, hypercalcaemia, kidney stones, parathyroid disease, SLE, history of allergy or bronchial asthma. Severely ill patient. Postoperative period after bariatric surgery. Not indicated for initial treatment of hypertension or oedema except in patients in whom development of hypokalaemia cannot be risked. Avoid electrolyte and acid/base imbalances that may lead to hepatic encephalopathy or coma particularly in patients with progressive or severe liver disease. Hepatic and mild to moderate renal impairment. Elderly. Pregnancy and lactation.

Significant: Electrolyte disturbances (e.g. hypokalaemia, hypochloraemic alkalosis, hyponatraemia), dehydration, hyperuricaemia or gout (increased risk with doses ≥25 mg), azotaemia (particularly in patients with renal disease), increased cholesterol and triglyceride levels, decreased renal Ca excretion, altered glycaemic control, hypersensitivity reactions, ocular effects (e.g. acute transient myopia, acute angle-closure glaucoma), photosensitivity, non-melanoma skin cancer (prolonged use [≤3 years]), exacerbation or activation of SLE.
Blood and lymphatic system disorders: Leucopenia, thrombocytopenia, megaloblastic anaemia, purpuric disease.
Cardiac disorders: Arrhythmia.
Eye disorders: Xanthopsia, transient blurred vision.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, abdominal pain, gastric irritation, appetite disturbance, taste alteration, dry mouth, pancreatitis.
General disorders and administration site conditions: Weakness, fatigue.
Hepatobiliary disorders: Jaundice.
Immune system disorders: Anaphylaxis.
Infections and infestations: Sialadenitis.
Investigations: Liver enzyme abnormalities, elevated BUN and serum creatinine.
Metabolism and nutrition disorders: Hyperglycaemia, anorexia.
Musculoskeletal and connective tissue disorders: Muscle cramps.
Nervous system disorders: Headache, dizziness, paraesthesia, vertigo.
Renal and urinary disorders: Glycosuria, interstitial nephritis, acute renal failure, nephrolithiasis.
Reproductive system and breast disorders: Impotence.
Skin and subcutaneous tissue disorders: Rash, urticaria.
Vascular disorders: Orthostatic hypotension.
Potentially Fatal: Hyperkalaemia.

PO: C

Avoid prolonged exposure to sunlight and UV rays; wear sunscreen or protective clothing when going outdoors.

Monitor serum electrolytes (e.g. serum K), BUN, creatinine (periodically); blood pressure, LFTs. Monitor for precipitation of hepatic coma (particularly in patients with hepatic impairment). Assess for signs and symptoms of hyperkalaemia.

Symptoms: Electrolyte imbalance (e.g. hyperkalaemia), polyuria, nausea, vomiting, weakness, lassitude, fever, flushed face, hyperactive deep tendon reflexes, hypotension. Management: Symptomatic and supportive treatment. Induce emesis or gastric lavage. May be given with pressor agents (e.g. norepinephrine) for hypotension. Monitor serum electrolyte concentrations and fluid balance. Supportive measures may be instituted to maintain hydration, electrolyte balance; respiratory, CV, and renal function as required. Dialysis may be of some benefit.

Increased risk of renal failure with NSAIDs (e.g. indometacin). May increase the risk of severe hyponatraemia with chlorpropramide. May decrease the excretion of lithium and increase the risk of lithium toxicity.
Triamterene: Increased risk of hyperkalaemia with ACE inhibitors.
Hydrochlorothiazide: May reduce arterial responsiveness to norepinephrine. Additive effect with other antihypertensive drugs (e.g. ACE inhibitors). Increased risk of hypokalaemia with corticosteroids, ACTH, or amphotericin B. May increase neuromuscular-blocking effect of nondepolarising skeletal muscle relaxants (e.g. tubocurarine).
Potentially Fatal: Enhanced hyperkalaemic effect with other K-sparing diuretics (e.g. spironolactone, amiloride), K supplements, K salts or K-containing salt substitutes.

Hydrochlorothiazide: May increase the orthostatic hypotensive effect with alcohol.

Triamterene: May interfere with the fluorometric assay of quinidine.
Hydrochlorothiazide: May interfere with parathyroid function tests. May reduce serum protein-bound iodine levels without signs of thyroid disturbance.

Description:
Mechanism of Action: Triamterene and hydrochlorothiazide exerts its diuretic and antihypertensive effect mainly through the hydrochlorothiazide component. In addition, triamterene decreases the excessive K depletion associated with hydrochlorothiazide.
Triamterene, a weak diuretic, acts directly on the distal renal tubule. It inhibits sodium reabsorption and decreases potassium and hydrogen excretion.
Hydrochlorothiazide is a thiazide diuretic and an antihypertensive agent. It inhibits Na reabsorption in the distal tubules, thereby causing an increased excretion of water, sodium, potassium and hydrogen ions.

Onset: Triamterene: Diuresis: 2-4 hours.
Hydrochlorothiazide: Diuresis: Approx 2 hours.
Duration: Triamterene: Diuresis: 7-9 hours.
Hydrochlorothiazide: 6-12 hours.
Pharmacokinetics:
Absorption: Triamterene: Rapidly absorbed from the gastrointestinal tract, but the degree of absorption may vary in different patients. Bioavailability: Approx 50%. Time to peak plasma concentration: Approx 3 hours.
Hydrochlorothiazide: Well absorbed from the gastrointestinal tract. Bioavailability: 65-75%. Food decreases the rate and extent of absorption. Time to peak plasma concentration: Approx 1-5 hours.
Distribution: Triamterene: Crosses the placenta. Plasma protein binding: Approx 67%.
Hydrochlorothiazide: Crosses the placenta and enters breast milk. Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-68%.
Metabolism: Triamterene: Extensively metabolised by CYPA12 isoenzyme to 6-p-hydroxytriamterene and its sulfate conjugate.
Excretion: Triamterene: Via urine (21-<50%; mainly as metabolites). Plasma half-life: Approx 2 hours.
Hydrochlorothiazide: Via urine (≥61% as unchanged drug). Elimination half-life: Approx 6-15 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5546, Triamterene. https://pubchem.ncbi.nlm.nih.gov/compound/Triamterene. Accessed Mar. 22, 2024.

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.

Thuốc lợi tiểu / Thuốc trị tăng huyết áp khác

C03EA01 - hydrochlorothiazide and potassium-sparing agents ; Belongs to the class of low-ceiling diuretics in combination with potassium-sparing agents. Used as diuretics.

Anon. Hydrochlorothiazide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 19/07/2024.

Anon. Triamterene. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 19/07/2024.

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Hydrochlorothiazide. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 18/06/2024.

Joint Formulary Committee. Hydrochlorothiazide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 18/06/2024.

Joint Formulary Committee. Triamterene. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 18/06/2024.

Triamterene and Hydrochlorothiazide Capsule (Sandoz Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 18/06/2024.

Triamterene and Hydrochlorothiazide Tablet (NuCare Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 18/06/2024.

Triamterene. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 18/06/2024.