Zostat Plus Tab 100/25 mg 10’s:

Potential Overview:

• Drug Name: Zostat  Plus
• Generic Name: Losartan Potassium / Hydrochlorothiazide
• Pack Size: 10 tablets
• Strength: 100 mg Losartan / 25 mg Hydrochlorothiazide

Mechanism of Action (MOA):

• Losartan (100 mg) is an angiotensin II receptor blocker (ARB). It works by blocking the effects of angiotensin II, a hormone that causes blood vessels to constrict, thereby reducing blood pressure and improving blood flow.
• Hydrochlorothiazide (25 mg) is a thiazide diuretic. It works by increasing urine output and reducing sodium reabsorption in the kidneys, which helps lower blood pressure by reducing fluid retention and decreasing vascular resistance.

The combination of both helps to manage hypertension and reduces the risk of stroke and other cardiovascular issues.

Indications:

• Hypertension (High Blood Pressure):
  Zostat Plus is used for the treatment of hypertension (high blood pressure) in patients who require more than one medication for effective blood pressure control.
• Chronic Heart Failure (in some cases):
  It may also be used to manage chronic heart failure in patients where other treatments (like ACE inhibitors) are not appropriate or well-tolerated.

Dosage:

• Initial Dose:
  • The typical starting dose for hypertension is 50 mg of Losartan + 12.5 mg of Hydrochlorothiazide once daily.
• Maintenance Dose:
  • The usual maintenance dose is 100 mg of Losartan + 25 mg of Hydrochlorothiazide once daily, though the dose may be adjusted based on patient response and tolerance.
• Note:
  • For patients with renal impairment or elderly patients, dosage adjustments may be required.
  • Should be taken once daily, with or without food.

Side Effects:

Common side effects:

• Dizziness or light-headedness, especially when standing up quickly.
• Low blood pressure (hypotension).
• Electrolyte imbalances such as low potassium or sodium levels.
• Fatigue.
• Headache.
• Cough (though less frequent than with ACE inhibitors).

Serious side effects (less common but serious):

• Angioedema (swelling of the face, lips, tongue, or throat).
• Kidney problems (e.g., kidney failure or elevated serum creatinine).
• Severe allergic reactions.
• Elevated blood sugar levels (hyperglycemia).
• Dehydration or low blood sodium (hyponatremia).
• Rash.

Precautions:

1. Kidney Function:
   • Losartan + Hydrochlorothiazide should be used cautiously in patients with renal impairment (kidney problems), as both components can affect kidney function.
2. Electrolyte Imbalance:
   • Hydrochlorothiazide may cause low levels of potassium, sodium, or magnesium, so regular monitoring of electrolytes is important.
3. Dehydration or Low Blood Pressure:
   • Ensure adequate hydration, especially during the first few doses, as both medications can cause a significant drop in blood pressure.
4. Liver Function:
   • Caution should be used in patients with liver disease, as Losartan and Hydrochlorothiazide may have altered metabolism or excretion in liver dysfunction.
5. Pregnancy and Breastfeeding:
   • Pregnancy: Zostat Plus is contraindicated during pregnancy, especially in the second and third trimesters, as it may harm the fetus.
   • Breastfeeding: Zostat Plus should be avoided during breastfeeding due to potential risks to the baby.
6. Diabetic Patients:
   • Monitoring of blood sugar is important as Hydrochlorothiazide may increase glucose levels in some patients with diabetes.

Contraindications (CI):

1. Hypersensitivity to Losartan, Hydrochlorothiazide, or Sulfonamide-derived drugs.
2. Severe Renal Impairment:
   • Contraindicated in patients with severe kidney disease (creatinine clearance <30 mL/min).
3. Severe Hepatic Impairment:
   • Contraindicated in patients with severe liver disease.
4. Pregnancy:
   • Zostat Plus is contraindicated during pregnancy, particularly in the second and third trimesters, due to risks of birth defects and fetal harm.
5. Anuria:
   • Contraindicated in patients with anuria (inability to produce urine).

Pharmacist Related Data

Chemical Formula:

1. Losartan Potassium:
   • Chemical Formula: C22H23ClN6O
2. Hydrochlorothiazide:
   • Chemical Formula: C7H8ClN3O4S2

Half-life:

1. Losartan:
   • Half-life of Losartan: Approximately 2 hours for the parent drug.
   • Half-life of active metabolite (E-3174): Approximately 6-9 hours.
2. Hydrochlorothiazide:
   • Half-life: Approximately 6-15 hours (depending on renal function).

Metabolism:

1. Losartan:
   • Metabolism:
     • Losartan is metabolized in the liver via the CYP2C9 and CYP3A4 enzymes to its active metabolite E-3174, which has a higher potency for angiotensin II receptor binding and action.
     • A small portion of Losartan is further metabolized into other metabolites, which are generally inactive.
   • Excretion:
     • About 35% of Losartan and its metabolites are excreted in the urine, and around 60% is excreted in feces.
2. Hydrochlorothiazide:
   • Metabolism:
     • Hydrochlorothiazide is minimally metabolized in the liver (less than 5%). It is mainly excreted unchanged in the urine.
   • Excretion:
     • Approximately 60-70% of Hydrochlorothiazide is excreted unchanged in the urine.

Drug Interactions:

1. With Food:
   • Losartan: Food does not significantly affect the absorption of Losartan, though it is generally recommended to take the medication at the same time each day for consistency.
   • Hydrochlorothiazide: Food does not significantly affect its absorption either, but taking it with food may reduce gastrointestinal side effects (e.g., nausea).
2. With Medicines:
   • Angiotensin-Converting Enzyme (ACE) Inhibitors and ARBs:
     • Combining with other ACE inhibitors, ARBs, or renin inhibitors may increase the risk of hypotension, hyperkalemia, and renal dysfunction.
   • Diuretics (other than Hydrochlorothiazide):
     • Combining with other diuretics can lead to excessive fluid loss, dehydration, and electrolyte imbalances (particularly low potassium levels).
   • Lithium:
     • Hydrochlorothiazide may increase lithium levels and increase the risk of lithium toxicity.
   • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):
     • NSAIDs can reduce the effectiveness of Zostat Plus by interfering with kidney function, leading to elevated blood pressure and decreased diuretic effects.
   • Potassium-Sparing Diuretics or Potassium Supplements:
     • Combining with potassium-sparing diuretics or potassium supplements may cause hyperkalemia (elevated potassium levels).
   • Digoxin:
     • Co-administration with digoxin (a heart medication) can increase the risk of digoxin toxicity.

Pharmacodynamics:

• Losartan:
  • Losartan is an angiotensin II receptor antagonist (ARB). It selectively blocks the binding of angiotensin II to its receptor (AT1), leading to vasodilation, reduced aldosterone secretion, and decreased blood pressure.
  • It helps prevent vasoconstriction, salt and water retention, and adrenergic activation associated with hypertension.
• Hydrochlorothiazide:
  • Hydrochlorothiazide is a thiazide diuretic. It works by inhibiting the reabsorption of sodium and chloride in the distal convoluted tubules of the kidneys, leading to increased urine output and a reduction in fluid retention, which helps to lower blood pressure.
• Combined Effects:
  • The combination of Losartan and Hydrochlorothiazide provides a synergistic effect: Losartan lowers blood pressure by blocking angiotensin II effects, while Hydrochlorothiazide reduces blood volume and decreases blood pressure through diuresis.

Pharmacokinetics (Absorption, Distribution, Metabolism, Excretion):

1. Absorption:
   • Losartan:
     • Rapidly absorbed after oral administration, with a bioavailability of about 33%. Peak plasma concentrations occur within 1-2 hours.
   • Hydrochlorothiazide:
     • Rapidly absorbed from the gastrointestinal tract with bioavailability of approximately 60-80%. Peak plasma concentrations occur within 1-5 hours.
2. Distribution:
   • Losartan:
     • Distributed widely in the body with a volume of distribution (Vd) of 34 L for Losartan and 500 L for its active metabolite.
     • Losartan is 95% protein-bound in the plasma, primarily to albumin.
   • Hydrochlorothiazide:
     • Volume of distribution is about 0.83 L/kg, and it is 40-70% protein-bound.
3. Metabolism:
   • Losartan:
     • Losartan is metabolized mainly in the liver via CYP2C9 and CYP3A4, producing an active metabolite (E-3174), which is more potent than Losartan itself.
   • Hydrochlorothiazide:
     • Hydrochlorothiazide undergoes minimal metabolism (less than 5%).
4. Excretion:
   • Losartan:
     • Excreted in the urine (about 35%) and in the feces (about 60%).
   • Hydrochlorothiazide:
     • Excreted primarily unchanged in the urine (60-70%).