What is the recommended treatment and dosage for angina pectoris using Isosorbide monohydrate?

Isosorbide Mononitrate for Angina Pectoris Treatment

For angina pectoris, isosorbide mononitrate should be started at 20 mg twice daily (conventional formulation) or 30-60 mg once daily (extended-release formulation), with the extended-release formulation taken in the morning to provide coverage throughout the day. 1

Dosage Forms and Administration

Conventional (Immediate-Release) Formulation

• Starting dose: 20 mg twice daily
• Dosing schedule: Morning and mid-day (to avoid nitrate-free interval at night)
• Maximum dose: 20 mg three times daily

Extended-Release Formulation

• Starting dose: 30-60 mg once daily
• Timing: Take in the morning upon arising
• Titration: May increase to 120 mg once daily after several days if needed
• Maximum dose: 240 mg once daily (rarely required)
• Administration: Swallow whole with fluid; do not crush or chew

Mechanism of Action

Isosorbide mononitrate works through several mechanisms:

1. Venous dilation: Promotes peripheral pooling of blood, decreasing venous return to the heart
2. Preload reduction: Reduces left ventricular end-diastolic pressure
3. Afterload reduction: Arteriolar relaxation reduces systemic vascular resistance
4. Coronary dilation: Improves blood flow to the myocardium

Clinical Evidence and Efficacy

Isosorbide mononitrate has demonstrated significant anti-anginal and anti-ischemic effects:

• Conventional formulation at 20 mg 2-3 times daily has shown persistent anti-anginal effects 2
• Extended-release formulation (60 mg once daily) provides effective prophylaxis for up to 12 hours 3
• Long-term studies show sustained efficacy with significant reduction in angina frequency and nitroglycerin consumption 4

A 3-year study showed that patients treated with isosorbide mononitrate 20 mg 2-3 times daily experienced:

• 78% reduction in ST-segment depression
• 98% reduction in nitroglycerin consumption
• 57% of patients became completely symptom-free 4

Important Considerations

Nitrate Tolerance

• Prevention strategy: Maintain a daily nitrate-free interval of 10-12 hours 5
• Caution: Tolerance develops rapidly with continuous high-dose therapy (50 mg three times daily) 2
• Optimal regimen: For conventional formulation, use 20 mg twice daily rather than higher doses three times daily 2

Contraindications

• Avoid concomitant use with phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) due to risk of profound hypotension 5
• Avoid in patients with severe hypotension (systolic BP <90 mmHg) 6
• Use with caution in patients with aortic stenosis due to risk of marked hypotension 6

Side Effects

• Common: Headache (usually mild to moderate and improves with continued therapy)
• Others: Hypotension, flushing, dizziness
• Management: Headache typically diminishes over time and rarely leads to treatment discontinuation 3

Treatment Algorithm

1. Initial therapy:

   • For most patients: Start with extended-release formulation 30-60 mg once daily in the morning
   • For elderly or hypotension-prone patients: Start with 20 mg immediate-release twice daily

2. Dose titration:

   • If using extended-release: After several days, may increase to 120 mg once daily if needed
   • If using immediate-release: May increase to 20 mg three times daily if needed

3. Monitoring:

   • Assess symptom relief and exercise tolerance
   • Monitor for hypotension, especially when initiating therapy or increasing doses
   • Evaluate for headache, which typically diminishes over time

4. Long-term management:

   • Continue effective dose
   • For extended-release formulation: Maintain once-daily morning dosing
   • For immediate-release formulation: Maintain twice-daily dosing with at least 7 hours between doses

Special Populations

• Elderly patients: No significant dose adjustment needed based on age alone, though starting at lower doses may be prudent 1
• Renal impairment: No dose adjustment required as elimination half-life is not prolonged in chronic renal failure 1
• Hepatic impairment: No specific dose adjustment recommendations, but use caution

By following this treatment approach, isosorbide mononitrate can effectively reduce angina frequency, decrease nitroglycerin consumption, and improve quality of life in patients with angina pectoris.