Usage
- Medical Conditions: Hydrochlorothiazide + Losartan is prescribed for the treatment of hypertension (high blood pressure) in patients whose blood pressure is not adequately controlled by monotherapy. It is also used to reduce the risk of stroke in hypertensive patients with left ventricular hypertrophy.
- Pharmacological Classification: Antihypertensive; it combines a thiazide diuretic (hydrochlorothiazide) with an angiotensin II receptor blocker (ARB) (losartan).
- Mechanism of Action: This combination lowers blood pressure by two distinct mechanisms. Hydrochlorothiazide increases the excretion of sodium and water by the kidneys, reducing blood volume. Losartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict. The combination leads to a synergistic reduction in blood pressure.
Alternate Names
- No widely used alternate names for the combined formulation.
- Brand Names: Hyzaar
How It Works
- Pharmacodynamics: Hydrochlorothiazide reduces blood volume, while losartan causes vasodilation and decreases systemic vascular resistance. Their combined effect results in a significant lowering of blood pressure.
- Pharmacokinetics: Losartan is orally absorbed and extensively metabolized in the liver to its active metabolite, EXP 3174, which has a longer half-life. Hydrochlorothiazide is well absorbed orally and acts directly on the distal convoluted tubule in the kidneys.
- Mode of Action: Losartan selectively blocks the angiotensin II type 1 (AT1) receptor, inhibiting the vasoconstrictor and aldosterone-secreting effects of angiotensin II. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule, increasing sodium and water excretion.
- Elimination Pathways: Losartan and its active metabolite are excreted primarily in the bile and feces, with some renal excretion. Hydrochlorothiazide is excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- Initial dose: Losartan 50 mg/Hydrochlorothiazide 12.5 mg once daily.
- If blood pressure remains uncontrolled after 2-3 weeks, the dose may be increased to 100 mg/25 mg once daily.
- Maximum Dose: Losartan 100 mg/Hydrochlorothiazide 25 mg once daily.
Children:
- Not recommended for children under 18 years of age. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with lower doses and titrate cautiously.
- Patients with Renal Impairment: No initial dosage adjustment is generally necessary for mild to moderate impairment. Not recommended for severe renal impairment (creatinine clearance <30 mL/min). Close monitoring of potassium and creatinine levels is essential.
- Patients with Hepatic Dysfunction: Contraindicated in patients with severe hepatic impairment. Use with caution in mild to moderate impairment.
- Patients with Comorbid Conditions: Caution in patients with diabetes, heart failure, gout, and systemic lupus erythematosus.
Clinical Use Cases
- This combination is primarily indicated for chronic hypertension management and is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments:
- Dose adjustments may be necessary based on individual patient response and tolerability. Closely monitor blood pressure, electrolyte levels, and renal function.
Side Effects
Common Side Effects:
- Dizziness, lightheadedness, headache
- Hypotension
- Electrolyte imbalances (hypokalemia, hyponatremia)
Rare but Serious Side Effects:
- Angioedema
- Acute renal failure
- Liver dysfunction
Long-Term Effects:
- Potential for electrolyte imbalances with prolonged use.
Adverse Drug Reactions (ADR):
- Angioedema, anaphylaxis, severe hypotension
Contraindications
- Hypersensitivity to losartan, hydrochlorothiazide, or sulfonamides.
- Anuria
- Pregnancy (especially 2nd and 3rd trimesters)
- Concomitant use of aliskiren in patients with diabetes or renal impairment.
Drug Interactions
- Other antihypertensive medications (additive hypotensive effects)
- Potassium supplements or potassium-sparing diuretics (increased risk of hyperkalemia)
- Lithium (increased lithium levels)
- NSAIDs (reduced antihypertensive effect, increased risk of renal impairment)
- Alcohol (increased risk of hypotension)
- Grapefruit juice (may increase losartan levels)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated in the 2nd and 3rd trimesters).
- Fetal Risks: May cause fetal or neonatal injury, including hypotension, renal failure, and death.
- Breastfeeding: Not recommended; hydrochlorothiazide is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Angiotensin II receptor blocker and thiazide diuretic.
- Side Effects: Dizziness, headache, hypotension, electrolyte imbalances.
- Contraindications: Hypersensitivity, anuria, pregnancy, concomitant use of aliskiren with diabetes or renal impairment.
- Drug Interactions: Other antihypertensives, potassium supplements, lithium, NSAIDs.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended during breastfeeding.
- Dosage: 50/12.5 mg once daily, up to 100/25 mg daily.
- Monitoring Parameters: Blood pressure, electrolytes (potassium, sodium, chloride), renal function (creatinine, BUN).
Popular Combinations
- It is itself a popular combination and is not typically combined with other antihypertensives in a single pill. If needed, other antihypertensives may be added separately.
Precautions
- Monitor blood pressure and electrolyte levels.
- Correct volume depletion before starting therapy.
- Caution in patients with renal or hepatic impairment, diabetes, heart failure, and SLE.
- Avoid alcohol.
- Monitor for signs of angioedema.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydrochlorothiazide + Losartan?
A: The initial dose is Losartan 50 mg/Hydrochlorothiazide 12.5 mg once daily, which can be increased to a maximum of 100 mg/25 mg once daily if needed.
Q2: Can this combination be used in pregnant women?
A: No, it is contraindicated during the second and third trimesters of pregnancy due to potential fetal harm.
Q3: What are the common side effects?
A: Common side effects include dizziness, lightheadedness, headache, and hypotension.
Q4: Are there any significant drug interactions?
A: Yes, it interacts with other antihypertensives, potassium supplements, lithium, and NSAIDs.
Q5: What should be monitored in patients taking this medication?
A: Blood pressure, electrolyte levels (particularly potassium), and renal function should be monitored.
Q6: How does this combination work to lower blood pressure?
A: Hydrochlorothiazide reduces blood volume through diuresis, while losartan blocks angiotensin II receptors, leading to vasodilation.
Q7: Can this medication be used in patients with renal impairment?
A: Use with caution; dosage adjustments may be necessary. It is contraindicated in severe renal impairment.
Q8: What should I do if a patient experiences angioedema?
A: Discontinue the medication immediately and provide appropriate medical care. Angioedema can be a life-threatening side effect.
Q9: Are there specific dosage recommendations for elderly patients?
A: Start with a lower dose and titrate up cautiously, as elderly patients are more susceptible to side effects.
