Usage
- Losartan is prescribed for the treatment of:
- Hypertension (high blood pressure) in adults and children over 6 years of age.
- Diabetic nephropathy (kidney disease) in patients with type 2 diabetes and a history of hypertension.
- Reducing the risk of stroke in patients with hypertension and left ventricular hypertrophy (enlarged heart).
- Pharmacological Classification: Angiotensin II Receptor Blocker (ARB), also known as an Angiotensin Receptor Antagonist.
- Mechanism of Action: Losartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict (narrow). By blocking angiotensin II, losartan helps relax and widen blood vessels, which lowers blood pressure.
Alternate Names
- International Nonproprietary Name (INN): Losartan
- Brand Names: Cozaar is a common brand name for Losartan. Numerous other brand names exist internationally.
How It Works
- Pharmacodynamics: Losartan primarily works by selectively blocking the angiotensin II type 1 (AT1) receptor, preventing angiotensin II from binding and exerting its vasoconstricting effects. This vasodilation leads to a decrease in peripheral resistance and, consequently, lower blood pressure. Losartan also reduces aldosterone secretion, leading to decreased sodium and water retention. The active metabolite of losartan is even more potent than losartan itself in blocking the AT1 receptor.
- Pharmacokinetics:
- Absorption: Losartan is well-absorbed orally, but undergoes significant first-pass metabolism in the liver. Food can slow the rate but does not significantly affect the extent of losartan absorption.
- Metabolism: Losartan is extensively metabolized by cytochrome P450 enzymes, primarily CYP2C9 and 3A4, to an active carboxylic acid metabolite. This metabolite contributes significantly to the drug’s antihypertensive effect.
- Elimination: Losartan and its metabolites are eliminated primarily through biliary (fecal) and renal (urine) excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 50 mg once daily. The dose may be increased to 100 mg once daily if needed. Some patients, especially those on diuretic therapy or with intravascular volume depletion, may start with 25 mg once daily.
Children (6-16 years):
- Hypertension: Initial dose is 0.7 mg/kg (up to 50 mg total) once daily. The dose can be adjusted up to 1.4 mg/kg (maximum 100 mg) once daily based on blood pressure response.
Special Cases:
- Elderly Patients: Similar dosing to adults, but start with lower doses and titrate cautiously as elderly patients may be more sensitive to the drug’s effects. Closely monitor renal function and potassium levels.
- Patients with Renal Impairment: No dosage adjustment is usually needed for mild to moderate renal impairment. For severe renal impairment or patients on dialysis, lower starting doses are recommended.
- Patients with Hepatic Dysfunction: Initial dose of 25 mg once daily for mild to moderate impairment. Losartan is not recommended for severe hepatic impairment.
- Patients with Comorbid Conditions: For patients with diabetes and nephropathy, the initial dose is 50 mg once daily, which may be increased to 100 mg. For patients with heart failure, the initial dose is typically 12.5 mg once daily, which can be slowly titrated upwards depending on tolerability and clinical response up to a maximum of 150mg per day.
Clinical Use Cases Losartan is not typically indicated for acute settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like cardiac arrest. Its primary use is for chronic management of hypertension, diabetic nephropathy, and reducing stroke risk in specific populations.
Dosage Adjustments
- Dose adjustments may be necessary based on blood pressure response, renal function, hepatic function, and concomitant medications. Close monitoring of potassium levels is particularly important for patients with renal impairment. Genetic polymorphisms affecting drug metabolism, particularly CYP2C9, may influence response to losartan, but routine genetic testing is not currently recommended.
Side Effects
Common Side Effects:
- Dizziness, lightheadedness, fatigue
- Upper respiratory tract infections (e.g., common cold)
- Back pain, muscle cramps
- Diarrhea, indigestion
- Nasal congestion
Rare but Serious Side Effects:
- Angioedema (swelling of the face, lips, tongue, or throat)
- Hypotension (low blood pressure)
- Hyperkalemia (high potassium levels)
- Renal impairment
- Liver dysfunction
- Anemia
- Rhabdomyolysis (muscle breakdown)
Long-Term Effects:
- Chronic kidney disease may worsen in susceptible patients.
- Electrolyte imbalances, such as hyperkalemia, may occur with prolonged use.
Adverse Drug Reactions (ADR):
- Angioedema requires immediate medical attention.
- Symptomatic hypotension needs urgent management.
- Any signs of liver injury, such as jaundice or right upper quadrant pain, necessitate evaluation.
- Severe hyperkalemia warrants prompt intervention to prevent cardiac complications.
Contraindications
- Hypersensitivity to losartan or any component of the formulation.
- Pregnancy, especially the second and third trimesters.
- Coadministration with aliskiren in patients with diabetes.
- Severe hepatic impairment.
Drug Interactions
- Other Antihypertensives: Additive hypotensive effects may occur with concurrent use of other blood pressure-lowering medications (e.g., ACE inhibitors, beta-blockers, diuretics).
- Potassium-Sparing Diuretics and Potassium Supplements: Increase the risk of hyperkalemia.
- NSAIDs (Nonsteroidal Anti-inflammatory Drugs): May reduce the antihypertensive effect of losartan and increase the risk of renal impairment.
- Lithium: Losartan can increase lithium levels, increasing the risk of lithium toxicity.
- CYP2C9 Inhibitors (e.g., fluconazole): May increase losartan concentrations.
- CYP3A4 Inhibitors (e.g., ketoconazole): May also increase losartan concentrations, although to a lesser extent than CYP2C9 inhibitors.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated)
- Losartan is contraindicated during pregnancy, particularly in the second and third trimesters, due to the risk of fetal toxicity, including renal failure, oligohydramnios (low amniotic fluid), and neonatal death. If pregnancy occurs during treatment, losartan should be discontinued immediately.
- Breastfeeding: It is unknown if losartan is excreted in breast milk. Due to the potential for adverse effects on the nursing infant, use during breastfeeding is not recommended. Alternative antihypertensives should be considered.
Drug Profile Summary
- Mechanism of Action: Angiotensin II receptor blocker (ARB).
- Side Effects: Dizziness, fatigue, hypotension, hyperkalemia, renal impairment.
- Contraindications: Pregnancy, hypersensitivity, coadministration with aliskiren in diabetic patients.
- Drug Interactions: Other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended during breastfeeding.
- Dosage: 50 mg once daily initially, adjustable up to 100 mg; special cases and pediatric dosing may vary.
- Monitoring Parameters: Blood pressure, renal function, potassium levels.
Popular Combinations
- Losartan is often combined with hydrochlorothiazide (a diuretic) for enhanced blood pressure control.
Precautions
- General Precautions: Monitor renal function and electrolyte levels, particularly potassium. Assess for signs of hypotension, especially in volume-depleted patients. Evaluate for hepatic dysfunction.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: Dose adjustments may be necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Losartan?
A: For adults with hypertension, the usual starting dose is 50 mg once daily, which can be increased to 100 mg if needed. Pediatric, elderly, and patients with hepatic or renal impairment may require different dosing regimens.
Q2: What are the common side effects of Losartan?
A: Common side effects include dizziness, fatigue, upper respiratory infections, back pain, and diarrhea.
Q3: Is Losartan safe to take during pregnancy?
A: No, Losartan is contraindicated during pregnancy, especially the second and third trimesters, due to the risk of fetal harm.
Q4: Can Losartan be taken with other blood pressure medications?
A: Yes, Losartan can be taken with other antihypertensives, but careful monitoring for additive hypotensive effects is necessary.
Q5: What should I do if I miss a dose of Losartan?
A: Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not double the dose to catch up.
Q6: How does Losartan affect potassium levels?
A: Losartan can cause hyperkalemia (high potassium levels), especially in patients with renal impairment or those taking potassium-sparing diuretics. Regular monitoring of potassium levels is important.
Q7: What are the signs of an allergic reaction to Losartan?
A: Allergic reactions can manifest as swelling of the face, lips, tongue, or throat (angioedema); difficulty breathing; hives; or skin rash. Seek immediate medical attention if these occur.
Q8: Can Losartan be used to treat heart failure?
A: Yes, Losartan can be used in patients with heart failure, particularly those who are intolerant to ACE inhibitors. The initial dose is usually lower than for hypertension and titrated gradually based on clinical response and tolerability.
Q9: How long does it take for Losartan to start working?
A: The maximum blood pressure-lowering effect of losartan may take several weeks to achieve.
Q10: Does Losartan interact with grapefruit juice?
A: While grapefruit juice is known to interact with some medications, it is not considered a clinically significant interaction with losartan.
