What is the recommended dosage and treatment plan for Isosorbide (isosorbide dinitrate or isosorbide mononitrate) for patients with angina pectoris?

From the Guidelines

Isosorbide dinitrate and isosorbide mononitrate are recommended for angina pectoris, with a typical starting dose of 5-20 mg taken orally 2-3 times daily for isosorbide dinitrate and 20 mg twice daily for isosorbide mononitrate, as evidenced by the 2013 ACCF/AHA guidelines 1. The dosing regimens for each formulation are as follows:

• Isosorbide dinitrate: 5-80 mg, 2 or 3 times daily, with extended-release formulations usually dosed at 40-80 mg once or twice daily 1.
• Isosorbide mononitrate: 20 mg twice daily, with extended-release versions beginning at 60-240 mg once daily 1. These medications work by dilating blood vessels, reducing the heart's workload and oxygen demand. To prevent nitrate tolerance, a daily nitrate-free interval of 10-14 hours is recommended, typically overnight 1. Common side effects include headache, dizziness, and hypotension. Patients should take the medication with water, avoid alcohol which can worsen hypotension, and rise slowly from sitting or lying positions to prevent dizziness. These medications should not be taken with phosphodiesterase-5 inhibitors like sildenafil as this combination can cause dangerous drops in blood pressure. Key considerations for treatment include:
• Monitoring for signs of nitrate tolerance and adjusting the dosing regimen as needed 1.
• Educating patients on the importance of adhering to the prescribed dosing regimen and potential side effects 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION As noted under " CLINICAL PHARMACOLOGY," multiple-dose studies with isosorbide dinitrate and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for isosorbide dinitrate tablets must provide a daily dose-free interval to minimize the development of this tolerance With immediate-release isosorbide dinitrate, it appears that one daily dose-free interval must be at least 14 hours long. As also noted under " CLINICAL PHARMACOLOGY," the effects of the second and later doses have been smaller and shorter-lasting than the effects of the first Large controlled studies with other nitrates suggest that no dosing regimen with isosorbide dinitrate tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day. As with all titratable drugs, it is important to administer the minimum dose which produces the desired clinical effect The usual starting dose of isosorbide dinitrate is 5 mg to 20 mg, two or three times daily. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. Some patients may require higher doses. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen. The recommended starting dose of isosorbide mononitrate extended-release tablets, USP is 30 mg (given as a single 30 mg tablet or as 1/2 of a 60 mg tablet) or 60 mg (given as a single tablet) once daily. After several days, the dosage may be increased to 120 mg (given as a single 120 mg tablet or as two 60 mg tablets) once daily. Rarely, 240 mg may be required. The daily dose of isosorbide mononitrate extended-release tablets, USP should be taken in the morning on arising. Isosorbide mononitrate extended-release tablets, USP should not be chewed or crushed and should be swallowed together with a half-glassful of fluid.

The recommended dosage for isosorbide dinitrate is 5 mg to 20 mg, two or three times daily, with a daily dose-free interval of at least 14 hours to minimize tolerance. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended 2. For isosorbide mononitrate, the recommended starting dose is 30 mg or 60 mg once daily, with possible increases to 120 mg once daily after several days 3. Key points to consider in the treatment plan for patients with angina pectoris include:

• Administering the minimum dose that produces the desired clinical effect
• Providing a daily dose-free interval to minimize tolerance
• Taking the daily dose of isosorbide mononitrate in the morning on arising
• Swallowing isosorbide mononitrate tablets whole, without chewing or crushing, with a half-glassful of fluid.

From the Research

Recommended Dosage and Treatment Plan for Isosorbide

The recommended dosage and treatment plan for isosorbide (isosorbide dinitrate or isosorbide mononitrate) for patients with angina pectoris vary depending on the specific formulation and patient response.

• Isosorbide dinitrate can be administered sublingually, orally, or intravenously, with typical dosages ranging from 5-30 mg for sublingual administration and 10-60 mg for oral administration 4, 5, 6.
• Isosorbide mononitrate can be administered orally or intravenously, with typical dosages ranging from 20-60 mg for oral administration and 20 mg for intravenous administration 7, 8.
• The treatment plan for isosorbide typically involves intermittent therapy with once-daily ingestion of high-dose sustained-release formulations to prevent tolerance development 4.
• A daily low-nitrate interval is required to prevent tolerance development, with a 12-h patch-free interval recommended to prevent tolerance in most patients 4.

Administration Routes and Formulations

Different administration routes and formulations of isosorbide are available, including:

• Sublingual isosorbide dinitrate, which can provide rapid relief from angina pectoris symptoms 5.
• Oral isosorbide dinitrate and isosorbide mononitrate, which can provide sustained-release formulations for once-daily administration 4, 7.
• Intravenous isosorbide dinitrate and isosorbide mononitrate, which can be used for severe unstable angina pectoris or in patients who are refractory to conventional medical therapy 6, 8.

Efficacy and Safety

The efficacy and safety of isosorbide for angina pectoris have been demonstrated in various studies:

• Isosorbide has been shown to be effective in terminating acute attacks of angina pectoris and in the prophylaxis of symptomatic and asymptomatic myocardial ischemia 4.
• Isosorbide mononitrate has been shown to be effective in reducing angina pectoris symptoms and improving electrocardiogram examination results in patients with coronary heart disease 8.
• The most frequently reported adverse event with isosorbide is headache, which is usually mild to moderate and improves with long-term therapy 7.