Losartan Potassium + Hydrochlorothiazide

Approved Indications:

• Essential Hypertension:
  Indicated for the treatment of hypertension in patients not adequately controlled with monotherapy of either losartan or hydrochlorothiazide.
• Hypertension with Left Ventricular Hypertrophy (LVH):
  Reduces the risk of stroke in hypertensive patients with LVH.

Clinically Accepted Off-Label Uses:

• Hypertension with Fluid Retention or Edema:
  Useful in hypertensive patients who require both blood pressure control and mild diuresis.
• Chronic Kidney Disease (CKD) without Diabetes:
  May be used to slow progression of CKD in hypertensive patients with proteinuria, where monotherapy is insufficient.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Adults:

Hypertension (High Blood Pressure):

• Initial dose: Losartan 50 mg + Hydrochlorothiazide 12.5 mg once daily.
• If blood pressure is not adequately controlled after 3–6 weeks, the dose may be increased to Losartan 100 mg + Hydrochlorothiazide 12.5 mg once daily.
• If further control is required, the maximum recommended dose is Losartan 100 mg + Hydrochlorothiazide 25 mg once daily.
• This combination is typically prescribed for patients whose blood pressure is not sufficiently controlled with either Losartan or Hydrochlorothiazide alone.

Pediatric Use:

• Combination therapy is generally not recommended in children; monotherapy with Losartan is preferred for patients aged ≥6 years.

Elderly:

• No initial dose adjustment required. Monitor renal function and volume status.

Renal Impairment:

• Mild to moderate (CrCl >30 mL/min): Use with caution
• Severe impairment or anuria: Contraindicated

Hepatic Impairment:

• Mild to moderate: Use lower starting dose (e.g., losartan 25 mg) with caution
• Severe hepatic impairment: Use not recommended

Maximum Recommended Dose

• Adults: Losartan 100 mg + Hydrochlorothiazide 25 mg once daily.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Losartan Potassium is an angiotensin II receptor blocker (ARB) that selectively blocks the binding of angiotensin II to the AT1 receptor, preventing vasoconstriction and aldosterone-mediated fluid retention. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, resulting in increased excretion of sodium, water, and potassium. The combination of these agents provides a synergistic antihypertensive effect, with losartan counteracting diuretic-induced hypokalemia and hydrochlorothiazide enhancing blood pressure reduction through natriuresis and volume depletion.

Losartan:

• Absorption: Rapid; peak concentration in ~1 hour
• Bioavailability: ~33%
• Active metabolite: EXP3174
• Protein binding: ~99%
• Metabolism: Hepatic (CYP2C9 and CYP3A4)
• Half-life: 2 hours (losartan), 6–9 hours (metabolite)
• Excretion: 35% in urine, 60% in feces

Hydrochlorothiazide:

• Absorption: Rapid oral absorption
• Bioavailability: ~60–80%
• Peak plasma time: 1–2.5 hours
• Protein binding: ~60%
• Metabolism: Not metabolized
• Half-life: 6–15 hours
• Excretion: Primarily excreted unchanged in urine

Pregnancy:

• Category D (second and third trimesters):
  Can cause fetal injury and death. Contraindicated in pregnancy. Discontinue immediately if pregnancy is detected.

Lactation:

• Losartan: Unknown if excreted in human milk; avoid if possible
• Hydrochlorothiazide: Detected in breast milk; may reduce milk production and cause electrolyte imbalance in the infant
• Recommendation: Not advised during breastfeeding

• Primary Class: Antihypertensive agent
• Subclasses:
• Losartan: Angiotensin II Receptor Blocker (ARB)
• Hydrochlorothiazide: Thiazide Diuretic
• Combination Class: ARB + Thiazide Diuretic (Fixed-dose combination)

• Hypersensitivity to losartan, hydrochlorothiazide, or any component of the formulation
• Pregnancy
• Anuria or severe renal impairment (CrCl <30 mL/min)
• Severe hepatic impairment
• Refractory electrolyte disturbances (e.g., hypokalemia, hyponatremia)
• Concomitant use with aliskiren in patients with diabetes
• History of sulfonamide allergy (due to HCTZ component)

• Fetal Toxicity: Discontinue immediately if pregnancy is confirmed
• Electrolyte Imbalance: Monitor for hypokalemia, hyponatremia, and hypomagnesemia
• Volume Depletion: May cause symptomatic hypotension
• Renal Impairment: Risk of renal function deterioration; monitor serum creatinine and eGFR
• Photosensitivity: Hydrochlorothiazide may increase sensitivity to sunlight
• Hyperuricemia: May increase uric acid levels and trigger gout
• Hyperglycemia: May affect glycemic control in diabetic patients
• Hepatic Dysfunction: Use with caution in mild-to-moderate hepatic impairment

Common Side Effects:

• Cardiovascular: Dizziness, orthostatic hypotension
• Renal/Metabolic: Elevated creatinine, hypokalemia, hyperuricemia
• Gastrointestinal: Nausea, abdominal discomfort
• Neurological: Headache, fatigue
• Musculoskeletal: Muscle cramps
• Dermatologic: Photosensitivity, rash

Serious or Rare Side Effects:

• Angioedema (rare with losartan)
• Severe hypotension
• Acute renal failure
• Pancreatitis
• Hepatic dysfunction
• Stevens-Johnson syndrome (rare)

Timing and Severity:

• Diuretic-related side effects may occur early
• Electrolyte imbalances and renal dysfunction may occur later with chronic use

• Potassium supplements/potassium-sparing diuretics: Risk of hyperkalemia
• NSAIDs: May reduce antihypertensive effect and worsen renal function
• Lithium: Risk of lithium toxicity
• Alcohol or sedatives: Additive hypotensive effects
• Diabetic medications: Hydrochlorothiazide may reduce insulin or hypoglycemic agent efficacy
• Digitalis glycosides: Increased risk of arrhythmias with hypokalemia
• Bile acid sequestrants (e.g., cholestyramine): May reduce HCTZ absorption
• CYP2C9 inhibitors: May affect losartan metabolism

• 2023 ACC/AHA and ESC Hypertension Guidelines:
  Reaffirm fixed-dose ARB + thiazide as a preferred second-line combination in patients not achieving target BP with monotherapy.
• KDIGO CKD Guidelines:
  Supports use in patients with proteinuria and hypertension, if tolerated, though monotherapy with ARBs is generally preferred in CKD.
• FDA Warnings:
  Reinforced black box warning on use during pregnancy due to fetal toxicity.

• Temperature: Store below 30°C (86°F)
• Humidity: Protect from excessive moisture
• Light: Keep in original packaging to protect from light
• Handling Instructions:
• Do not remove from blister until time of use
• Do not use beyond expiration date
• No refrigeration or reconstitution needed