When should sorbitrate (isosorbide dinitrate) be administered for angina symptoms?

When to Administer Isosorbide Dinitrate (Sorbitrate) for Angina

Isosorbide dinitrate should be administered for acute angina symptoms that are unrelieved after 3 doses of sublingual nitroglycerin taken 5 minutes apart, for prophylaxis before activities known to trigger angina, and as maintenance therapy for chronic stable angina using a non-tolerance producing regimen (twice daily with a nitrate-free interval). 1, 2

Acute Angina Management

• For patients experiencing acute angina symptoms, sublingual isosorbide dinitrate (5-10 mg) can be administered if symptoms persist after taking sublingual nitroglycerin 3
• If a patient has previously been prescribed nitroglycerin, they should first take 1 nitroglycerin dose sublingually for chest discomfort/pain 1
• If symptoms are unimproved or worsening 5 minutes after the first nitroglycerin dose, the patient should call emergency services (9-1-1) 1
• While awaiting emergency services, patients may take additional nitroglycerin every 5 minutes for a maximum of 3 doses if they tolerate it well 1
• For patients with chronic stable angina who experience significant improvement after one nitroglycerin dose, it is appropriate to repeat nitroglycerin every 5 minutes for a maximum of 3 doses and call emergency services if symptoms have not completely resolved 1

Intravenous Administration

• For patients with refractory or severe unstable angina in hospital settings, intravenous isosorbide dinitrate may be initiated at 10 mcg/min and increased by 10 mcg/min every 3-5 minutes until symptom relief or blood pressure response 1, 4
• If no response is seen at 20 mcg/min, increments of 10 and later 20 mcg/min can be used 1
• A ceiling dose of 200 mcg/min is commonly used, though higher doses have been safely administered 4
• Systolic blood pressure should not be titrated below 110 mmHg in previously normotensive patients or more than 25% below baseline in hypertensive patients 1
• Intravenous nitrates should be avoided in patients with initial systolic blood pressure less than 90 mmHg, or 30 mmHg below baseline, or with marked bradycardia or tachycardia 1

Maintenance Therapy for Chronic Angina

• For chronic stable angina, oral isosorbide dinitrate can be administered at 5-80 mg, 2-3 times daily, with effects lasting up to 8 hours 1
• Anti-anginal activity begins approximately 1 hour after oral dosing 2
• To avoid nitrate tolerance, use a regimen with one daily dose-free interval of at least 14 hours (e.g., dosing at 8 AM and 2 PM) 2, 5
• The maximal achievable daily duration of anti-anginal effect from isosorbide dinitrate is about 12 hours 2
• During sustained therapy, partial tolerance develops rapidly, with antianginal effects lasting only about 2 hours compared to 8 hours during acute therapy 6

Dosing Considerations

• For oral therapy, starting doses of 5-10 mg are typically effective, with hemodynamic effects usually apparent at 15 minutes, peaking between 30-120 minutes, and lasting up to 4 hours 7
• For most patients, near maximal improvement in exercise tolerance occurs with doses of 15-30 mg four times daily 6
• Higher doses (60-120 mg) do not necessarily provide additional benefit during sustained therapy 6
• Slow-release formulations can be administered at 40 mg once or twice daily with effects lasting up to 8 hours 1

Contraindications and Precautions

• Isosorbide dinitrate is contraindicated within 24 hours of sildenafil use or 48 hours of tadalafil use due to risk of profound hypotension, MI, and even death 1, 4
• Avoid in patients with severe hypotension (systolic BP <90 mmHg) 1
• Common side effects include headache and hypotension 1
• Tolerance to hemodynamic effects typically develops after 24 hours of continuous therapy 1

Special Considerations

• For vasospastic (variant) angina, calcium channel blockers together with nitrates are the mainstay of treatment 3
• When switching from intravenous to oral/topical nitrates, use a non-tolerance producing regimen (lower doses and intermittent dosing) 1
• For patients requiring nitrate therapy beyond 24 hours, periodic increases in dosage may be needed to maintain efficacy 4