Cardinor Plus

Approved Indications:

• Essential Hypertension: Indicated for the management of high blood pressure, especially in patients not adequately controlled on monotherapy.
• Hypertension with Fluid Retention: Particularly effective in patients with concurrent mild fluid overload.
• Hypertension in Patients with Left Ventricular Hypertrophy: Helps reduce the risk of cardiovascular events.
• Stable Hypertensive Patients Requiring Combination Therapy: For patients stabilized on individual components at the same dose.

Off-label/Clinically Accepted Uses:

• Post-myocardial infarction (with hypertension): Beta-blocker component aids in secondary prevention of cardiac events.
• Hypertensive heart failure (mild fluid overload): When thiazide diuretic use is justified in mild volume excess.

Adults:

• Initial Dose: One tablet daily (e.g., Bisoprolol Fumarate 2.5 mg + Hydrochlorothiazide 6.25 mg).
• Titration: Dose may be adjusted based on clinical response, typically up to:
• 5 mg/6.25 mg once daily
• 10 mg/6.25 mg once daily
• Max Dose: 10 mg Bisoprolol + 6.25 mg Hydrochlorothiazide per day.

Elderly:

• Start at the lowest dose; monitor renal function and blood pressure closely.

Renal Impairment:

• Avoid in severe renal impairment (CrCl <30 mL/min). Use with caution in moderate impairment.

Hepatic Impairment:

• Caution advised. Start at the lowest dose and monitor liver function.

Pediatric Use:

• Not recommended due to lack of safety and efficacy data.

Administration Route:

• Oral; once daily in the morning, with or without food.

Bisoprolol Fumarate is a cardioselective beta-1 adrenergic receptor blocker. It reduces heart rate, cardiac output, and suppresses renin activity by blocking beta-1 receptors in the heart and kidney, leading to decreased blood pressure.
Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubules of the nephron. This leads to increased excretion of sodium and water, reducing plasma volume and peripheral vascular resistance. The combination results in complementary antihypertensive effects via different mechanisms.

Bisoprolol:

• Absorption: ~90% bioavailability; unaffected by food.
• Distribution: Low plasma protein binding (~30%).
• Metabolism: Partially hepatic (CYP3A4), with ~50% excreted unchanged.
• Half-life: ~10–12 hours.
• Elimination: Renal (~50% unchanged), fecal (~15%).

Hydrochlorothiazide:

• Absorption: ~60–80% oral bioavailability.
• Distribution: ~40–68% plasma protein bound.
• Metabolism: Not significantly metabolized.
• Half-life: ~6–15 hours.
• Elimination: Renal, primarily unchanged.

• Pregnancy: Avoid use, especially in the 2nd and 3rd trimesters. Thiazides may cause fetal electrolyte imbalances or fetal growth restriction.
• Lactation: Both drugs are excreted in breast milk. Use is not recommended during breastfeeding due to potential effects on infant cardiovascular or renal function.

• Primary Class: Antihypertensive Combination
• Subclasses:
• Beta-blocker: Bisoprolol (Selective β1 blocker)
• Thiazide Diuretic: Hydrochlorothiazide

• Known hypersensitivity to Bisoprolol, Hydrochlorothiazide, or sulfonamide-derived drugs.
• Severe bradycardia, AV block (2nd or 3rd degree), cardiogenic shock, or overt heart failure.
• Anuria or severe renal dysfunction.
• Hepatic coma or pre-coma.
• Symptomatic hypotension.

• Cardiac Monitoring: Use cautiously in patients with conduction abnormalities, ischemic heart disease, or heart failure.
• Electrolyte Imbalance: Monitor potassium, sodium, and magnesium levels due to HCTZ-induced diuresis.
• Renal Function: Risk of acute kidney injury, particularly with volume depletion.
• Gout: May precipitate or worsen hyperuricemia.
• Diabetes: May mask hypoglycemia symptoms and affect glucose control.
• Photosensitivity: Use sun protection with long-term thiazide use.

Common:

• Cardiovascular: Bradycardia, hypotension
• Metabolic: Hyperuricemia, hypokalemia
• Gastrointestinal: Nausea, abdominal pain
• Neurologic: Fatigue, dizziness, headache

Serious/Rare:

• Arrhythmias, AV block
• Stevens-Johnson Syndrome (HCTZ-related)
• Pancreatitis
• Hepatic dysfunction
• Electrolyte imbalance (hyponatremia, hypochloremia)

Onset & Severity:

• Most common effects occur within 1–2 weeks of initiation; dose-related and often reversible.

• With NSAIDs: May blunt antihypertensive effect and increase renal risk.
• With Other Antihypertensives: Additive hypotensive effect.
• With Digitalis Glycosides: Increased risk of bradycardia and AV block.
• With Lithium: Increased serum lithium levels and toxicity (HCTZ-related).
• With Insulin/Oral Antidiabetics: May mask hypoglycemia (bisoprolol).
• CYP3A4 Interactions: Moderate inhibition/induction may affect bisoprolol metabolism.

• Latest Hypertension Guidelines (AHA/ESC): Combination therapy now recommended for Stage 2 hypertension or high-risk Stage 1 patients.
• Guideline Preference: Fixed-dose combinations preferred for better adherence.
• Safety Updates: Emphasis on renal function and electrolyte monitoring with thiazide combinations.

• Temperature: Store below 30°C (room temperature).
• Humidity: Protect from excessive moisture.
• Light: Store in original packaging to protect from light.
• Handling: No special reconstitution needed. Do not freeze.