Zostat 50Mg Tab 20 s

Potential Overview:

• Drug Name: Zostat
• Generic Name: Losartan Potassium
• Pack Size: 20 tablets
• Strength: 50 mg per tablet

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Mechanism of Action (MOA):

• Losartan is an angiotensin II receptor antagonist (ARB). It works by selectively blocking the binding of angiotensin II (a potent vasoconstrictor) to its receptor type 1 (AT1) in blood vessels, the heart, kidneys, and other tissues. This leads to vasodilation (relaxation of blood vessels), reduced secretion of aldosterone, lower blood pressure, and reduced workload on the heart.
• Losartan also helps reduce salt and water retention, which further contributes to lowering blood pressure and reducing the strain on the cardiovascular system.

Indications:

1. Hypertension (High Blood Pressure):
   • Zostat is primarily used for the treatment of hypertension to help lower blood pressure and reduce the risk of cardiovascular events like stroke, heart attack, and kidney problems.
2. Chronic Heart Failure:
   • Zostat may be used in patients with chronic heart failure, particularly those who have an intolerance to ACE inhibitors, to help reduce the risk of hospitalization and death.
3. Chronic Kidney Disease (in patients with diabetes):
   • It can be used to protect the kidneys from damage due to diabetic nephropathy (diabetes-related kidney damage) in type 2 diabetic patients.

Dosage:

• Adults:
  • Initial Dose: The typical starting dose for hypertension is 50 mg once daily.
  • Maintenance Dose: The usual maintenance dose is 50 mg to 100 mg once daily, depending on the patient’s response.
• For Heart Failure:
  • Initial Dose: Start with 12.5 mg once daily, gradually increasing to 50 mg once daily, as tolerated.
• For Diabetic Nephropathy:
  • Typically, 50 mg once daily is used, and the dose may be adjusted.
• Elderly or Hepatic Impairment:
  • A lower starting dose (e.g., 25 mg daily) may be recommended for elderly patients or those with liver issues.

Side Effects:

Common side effects:

• Dizziness or light-headedness (especially when standing up quickly)
• Fatigue
• Headache
• Cough (though less frequent than ACE inhibitors)
• Nausea
• Back pain
• Diarrhea

Serious side effects (less common but serious):

• Angioedema (swelling of the face, lips, tongue, or throat)
• Kidney problems (e.g., kidney failure, elevated serum creatinine levels)
• Low blood pressure (hypotension)
• Elevated potassium levels (hyperkalemia)
• Rash or other allergic reactions

Precautions:

1. Kidney Function:
   • Losartan should be used with caution in patients with renal (kidney) impairment, as it may affect kidney function and lead to elevated creatinine or potassium levels. Regular kidney function tests are advised.
2. Electrolyte Imbalance:
   • Losartan can cause hyperkalemia (elevated potassium levels) and hyponatremia (low sodium levels). Monitoring of electrolytes is important.
3. Liver Function:
   • Liver impairment: Losartan is metabolized in the liver, and doses may need to be adjusted for patients with liver problems.
4. Pregnancy and Breastfeeding:
   • Pregnancy: Losartan should be avoided during pregnancy, particularly in the second and third trimesters, as it may cause harm to the fetus.
   • Breastfeeding: Losartan should be avoided during breastfeeding as it is not known whether the drug is excreted in breast milk.
5. Hypotension (Low Blood Pressure):
   • Losartan may cause a sudden drop in blood pressure, especially after the first dose. Caution is recommended for patients who are volume-depleted (e.g., those on diuretics) or have salt depletion.

Contraindications (CI):

1. Hypersensitivity to Losartan or any of its ingredients.
2. Pregnancy:
   • Losartan is contraindicated during pregnancy, particularly in the second and third trimesters due to potential harm to the fetus (e.g., kidney problems, low amniotic fluid, and fetal death).
3. Severe Renal Impairment:
   • Contraindicated in patients with severe kidney disease or those who are anuric (lack of urine production).
4. Biliary Obstruction:
   • Not recommended for patients with severe liver problems or biliary obstruction.
5. Angioedema History:
   • Contraindicated in patients with a history of angioedema (swelling of the deeper layers of skin), especially related to ACE inhibitors or other ARBs.

Pharmacist Related Data

Chemical Formula:

• Losartan Potassium
  • Chemical Formula: C22H23ClN6O

Half-life:

1. Losartan (Parent Drug):
   • Half-life: Approximately 2 hours.
2. E-3174 (Active Metabolite):
   • Half-life: Approximately 6-9 hours.

Metabolism:

• Losartan is extensively metabolized in the liver primarily by CYP2C9 and CYP3A4 enzymes to its active metabolite, E-3174, which has a greater potency than the parent drug in blocking the angiotensin II receptor.
• A small portion of Losartan is further metabolized into other metabolites, which are mostly inactive.
• Hydrolysis of Losartan also occurs in the liver before the formation of the active metabolite.

Drug Interactions:

1. With Food:
   • Losartan has a low impact on its absorption when taken with or without food, though consistency in timing (e.g., with or without meals) can help reduce variability in absorption.
2. With Medications:
   • ACE Inhibitors / ARBs:
     • Combining Losartan with other angiotensin-converting enzyme (ACE) inhibitors or ARBs increases the risk of hypotension, hyperkalemia, and kidney dysfunction.
   • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):
     • NSAIDs can reduce the effectiveness of Losartan by affecting kidney function, leading to elevated blood pressure and decreased renal blood flow.
   • Lithium:
     • Hydrochlorothiazide (when combined with Losartan in some formulations) can increase lithium levels, raising the risk of lithium toxicity.
   • Diuretics (other than Hydrochlorothiazide):
     • Combining Losartan with other diuretics can increase the risk of hypotension and electrolyte imbalance (e.g., low potassium levels).
   • Potassium Supplements or Potassium-Sparing Diuretics:
     • Concomitant use may result in hyperkalemia, especially in patients with renal impairment.
   • CYP2C9 and CYP3A4 Inhibitors:
     • Drugs that inhibit CYP2C9 and CYP3A4 (e.g., fluconazole) can increase the plasma levels of Losartan and its metabolite.

Pharmacodynamics:

1. Losartan is an angiotensin II receptor antagonist (ARB). It works by selectively blocking the AT1 receptors that Angiotensin II binds to.
   • Angiotensin II is a hormone that causes vasoconstriction, increased aldosterone secretion, and increased blood pressure.
   • By blocking AT1 receptors, Losartan induces vasodilation and reduces the effects of angiotensin II, leading to lowered blood pressure and decreased cardiac workload.
   • Losartan also reduces aldosterone secretion, leading to decreased sodium retention and reduced fluid volume.
2. Active Metabolite (E-3174):
   • The active metabolite of Losartan, E-3174, binds to the AT1 receptor more strongly and has a prolonged effect compared to the parent compound, contributing to the sustained blood pressure-lowering effects.

Pharmacokinetics (Absorption, Distribution, Metabolism, Excretion):

1. Absorption:
   • Losartan is well absorbed after oral administration, with a bioavailability of about 33%.
   • Peak plasma concentration is typically reached within 1-2 hours of oral administration.
2. Distribution:
   • Losartan is widely distributed throughout the body with a volume of distribution (Vd) of 34 L.
   • It is highly protein-bound in plasma (approximately 99%), primarily bound to albumin.
3. Metabolism:
   • Losartan is primarily metabolized by the CYP2C9 enzyme in the liver to form the active metabolite E-3174.
   • The active metabolite has a half-life of 6-9 hours and is about 10-40 times more potent in blocking the AT1 receptor compared to Losartan.
   • A small portion of Losartan undergoes further metabolism to produce inactive metabolites.
4. Excretion:
   • Losartan and its metabolites are mainly excreted through the feces (approximately 60%) and a smaller portion in the urine (approximately 35%).
   • Only about 4% of the administered dose is excreted unchanged in the urine.