A triple-drug, fixed-dose combination (FDC) antihypertensive therapy containing an angiotensin II receptor blocker (ARB), a dihydropyridine calcium channel blocker (CCB), and a thiazide diuretic. This combination provides synergistic blood pressure lowering through complementary mechanisms, targeting the renin-angiotensin-aldosterone system (RAAS), vascular smooth muscle calcium channels, and sodium/fluid balance. It is indicated for patients whose hypertension is not adequately controlled on dual therapy. The FDC improves compliance by reducing pill burden.
Adult: One tablet once daily. Dose may be titrated after 2-4 weeks based on response. Maximum: One tablet of this strength per day.
Note: Can be taken with or without food. Administer at the same time each day, preferably in the morning to avoid nocturia from diuretic effect. Swallow whole with a glass of water. Do not crush or chew. Dose is not influenced by food.
The combination exerts a multi-pronged attack on hypertension. Losartan selectively and competitively antagonizes the AT1 receptor, blocking the vasoconstrictor and aldosterone-secreting effects of angiotensin II. Amlodipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle, causing peripheral arterial vasodilation and reduced peripheral vascular resistance. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule of the nephron, increasing excretion of sodium, chloride, and water, thereby reducing plasma volume.
Pregnancy: CONTRANDICATED in second and third trimesters (Pregnancy Category D). Drugs that act directly on the RAAS can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected. First trimester use should be avoided unless no alternative exists.
Driving: Dizziness, lightheadedness, or syncope may occur, especially during initiation or dose escalation. Patients should be cautioned about operating machinery or driving until their response is known.
| Other Antihypertensives (Diuretics, Beta-blockers, ACEi) | Additive hypotensive effect. Risk of severe hypotension. | Major |
| NSAIDs (e.g., Ibuprofen, Diclofenac) | May reduce antihypertensive effect of losartan/HCTZ. Increase risk of renal impairment, especially in volume-depleted patients. | Major |
| Lithium | HCTZ reduces renal clearance of lithium, increasing risk of lithium toxicity. | Major |
| Potassium supplements / Potassium-sparing diuretics (Spironolactone, Amiloride) | Increased risk of hyperkalemia due to losartan. | Major |
| Digoxin | HCTZ-induced hypokalemia/hypomagnesemia may increase risk of digoxin toxicity. | Moderate |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | May increase amlodipine levels, increasing risk of hypotension and edema. | Moderate |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin) | May decrease amlodipine levels, reducing efficacy. | Moderate |
| Allopurinol | Increased risk of hypersensitivity reactions when combined with HCTZ. | Moderate |
| Antidiabetic drugs (Insulin, Sulfonylureas) | HCTZ may decrease glucose tolerance, requiring dose adjustment. | Moderate |
| Cholestyramine, Colestipol | May reduce absorption of HCTZ. Administer HCTZ at least 4 hours before these resins. | Moderate |
| Alcohol, Barbiturates, Narcotics | Potentiation of orthostatic hypotension. | Moderate |
Same composition (Losartan (50mg) + Amlodipine (5mg) + Hydrochlorothiazide (12.5mg)), different brands: