Zosartan-K Tab 50 Mg 20’s

Mechanism of Action (MOA):

• Losartan is an angiotensin II receptor antagonist (ARB). It selectively blocks the action of angiotensin II by binding to and inhibiting the angiotensin II type 1 (AT1) receptors in various tissues. Angiotensin II is a potent vasoconstrictor and plays a central role in regulating blood pressure and fluid balance.
• By blocking angiotensin II, losartan:
  • Lowers blood pressure (by vasodilation).
  • Reduces aldosterone secretion, which leads to decreased sodium and water retention.
  • Helps in the relaxation of blood vessels, thus lowering systemic vascular resistance and improving cardiac output.

This makes it an effective treatment for hypertension and provides renal protection in patients with conditions like diabetic nephropathy.

Indications:

1. Hypertension (High Blood Pressure):
   • Losartan is used to treat essential hypertension (high blood pressure) either alone or in combination with other antihypertensive agents.
2. Chronic Kidney Disease (Diabetic Nephropathy):
   • In patients with type 2 diabetes, losartan can help slow the progression of kidney disease in those with proteinuria (excessive protein in urine).
3. Heart Failure (in combination with other medications):
   • Can be used in the management of heart failure in patients with left ventricular dysfunction.
4. Post-Myocardial Infarction (Post-heart attack):
   • Used to reduce the risk of cardiovascular complications following a heart attack, particularly to prevent remodeling of the heart’s tissue.

Dosage:

1. Hypertension:
   • Initial Dose: 50 mg once daily.
   • Maintenance Dose: Typically 50-100 mg/day in one or two divided doses, depending on the patient’s blood pressure response.
2. Chronic Kidney Disease (Diabetic Nephropathy):
   • Initial Dose: 50 mg once daily.
   • Maintenance Dose: Can be increased to 100 mg/day, depending on response and tolerability.
3. Heart Failure (In combination therapy):
   • Starting Dose: Usually 12.5 mg to 25 mg once daily, which may be gradually increased based on tolerance.
4. Post-Myocardial Infarction:
   • Starting Dose: 12.5 mg once daily, and increase to 50 mg/day based on tolerance.

Renal Impairment:

• Adjust the dose in patients with renal impairment (creatinine clearance <30 mL/min), usually starting at a lower dose and monitoring carefully.

Side Effects:

• Common Side Effects:
  • Dizziness or lightheadedness (especially when standing up quickly).
  • Fatigue.
  • Elevated potassium levels (hyperkalemia).
  • Nausea.
• Serious Side Effects:
  • Angioedema (swelling of the deeper layers of the skin, particularly around the face and throat).
  • Hypotension (low blood pressure), especially after the first dose.
  • Kidney dysfunction (acute kidney injury or worsening renal function).
  • Elevated blood potassium levels (hyperkalemia), which can be dangerous.
  • Hepatotoxicity (liver damage, although rare).

Precautions:

• Renal Impairment: Monitor kidney function regularly, especially in those with pre-existing kidney disease.
• Electrolyte Imbalances: Monitor potassium levels, as hyperkalemia may occur. Hypotension can also occur, especially in those with volume depletion.
• Pregnancy: Contraindicated in pregnancy, particularly during the second and third trimesters, due to potential teratogenic effects (harm to the fetus).
• Liver Disease: Use with caution in patients with liver dysfunction. Adjustments may be needed.
• Angioedema: If symptoms of angioedema occur (e.g., swelling of the lips, face, or throat), discontinue use immediately and seek emergency medical help.
• Aortic Stenosis or Severe Heart Disease: Monitor closely in patients with certain cardiovascular conditions.

Contraindications (CI):

1. Hypersensitivity: Contraindicated in patients with known allergy to Losartan or other ARBs.
2. Pregnancy: Losartan should be avoided during pregnancy, especially during the second and third trimesters, due to the risk of fetal harm, including kidney failure, skull hypoplasia, and other abnormalities.
3. Severe Renal Impairment: Contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min) unless prescribed with caution.
4. Bilateral Renal Artery Stenosis: Contraindicated in patients with bilateral renal artery stenosis or stenosis of the solitary kidney, as it may worsen renal function.

Pharmacist Related Data

Chemical Formula:

• C22H23ClN6O (Losartan potassium)

Half-life:

• The half-life of Losartan is approximately 2 hours for the parent drug. However, its active metabolite (E-3174) has a longer half-life of about 6 to 9 hours.

Metabolism:

• Losartan is extensively metabolized in the liver primarily by the cytochrome P450 enzyme CYP2C9 to its active metabolite E-3174.
• The active metabolite is responsible for most of the pharmacological effects.
• A small portion of losartan is also metabolized to inactive metabolites.
• Losartan does not significantly affect the metabolism of other drugs metabolized by CYP450 enzymes, which makes it relatively free from drug-drug interactions.

Drug Interactions:

1. With Food:
   • Food does not significantly affect the absorption of losartan. It can be taken with or without food.
2. With Medications:
   • Potassium-Sparing Diuretics (e.g., spironolactone): Increased risk of hyperkalemia (high potassium levels) when combined with losartan.
   • ACE Inhibitors: The combination of ARBs like losartan with ACE inhibitors (e.g., enalapril, lisinopril) increases the risk of renal dysfunction, hyperkalemia, and hypotension.
   • Lithium: Losartan may increase lithium levels and the risk of lithium toxicity.
   • NSAIDs (e.g., ibuprofen, naproxen): Concurrent use with NSAIDs may reduce the antihypertensive effect of losartan and increase the risk of kidney damage.
   • Diuretics: When combined with diuretics, losartan can increase the risk of hypotension (low blood pressure) and renal dysfunction.
   • Rifampin: Rifampin may reduce the plasma concentration of losartan, diminishing its effectiveness.

Pharmacodynamics:

• Losartan is an angiotensin II receptor blocker (ARB). It works by selectively inhibiting the binding of angiotensin II (a potent vasoconstrictor) to its receptor, AT1, found in vascular smooth muscle and other tissues.
• Blocking angiotensin II results in:
  1. Vasodilation (widening of blood vessels), leading to reduced blood pressure.
  2. Reduced aldosterone secretion, resulting in decreased sodium and water retention by the kidneys.
  3. Improved renal function in patients with diabetic nephropathy by lowering intra-glomerular pressure.
  4. Reduced cardiac remodeling after a heart attack, decreasing the workload on the heart and improving outcomes in heart failure patients.

Pharmacokinetics:

1. Absorption:
   • Losartan is well absorbed after oral administration, with about 33% bioavailability.
   • The Cmax (peak plasma concentration) occurs within 1-2 hours after oral dosing.
2. Distribution:
   • Losartan is widely distributed throughout the body and is highly bound to plasma proteins (approximately 99%).
   • It is not significantly distributed to the brain and has a low volume of distribution (Vd of approximately 34 L).
3. Metabolism:
   • Losartan is primarily metabolized in the liver by CYP2C9 to the active metabolite E-3174, which has a much higher potency than losartan itself in blocking the angiotensin II receptor.
   • Losartan also undergoes minimal CYP3A4 metabolism.
4. Excretion:
   • Losartan and its metabolites are primarily excreted in the urine, with a small fraction excreted in feces.
   • The half-life of the active metabolite (E-3174) is approximately 6 to 9 hours, giving it a prolonged effect.
   • Renal excretion accounts for about 35% of the drug dose, and excretion via feces is around 60%.