ISDN

1 Dosing Considerations Dosing regimens should account for the possible development of tolerance to ISDN and cross tolerance to other nitrates and nitrites. Multiple-dose studies with isosorbide dinitrate and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance.

A daily dose-free interval is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen. See 7 WARNINGS AND PRECAUTIONS, Dependence, Tolerance and/or Abuse Liability. 2 Recommended Dose and Dosage Adjustment Sublingual Administration (tablets dissolve in 20 seconds in the mouth) 5 to 10 mg sublingually (1 to 2 sublingual 5 mg tablets), every 2 to 4 hours for the prophylaxis of acute angina; may be supplemented by a dose of 5 to 10 mg sublingually prior to stressful situations likely to provoke an attack of angina.

Oral Administration 20 to 120 mg daily in divided doses, according to therapeutic and patient response.

Pediatrics (< 18 years of age):

Health Canada has not authorized an indication for pediatric use. 4 Administration The 5mg ISDN sublingual tablet should be placed under the tongue, and will dissolve in approximately 20 seconds. The 10 mg and 30 mg ISDN oral tablets should be swallowed whole with a glass of water.

5 Missed Dose If the patient misses a dose, inform the patient to skip the missed dose and take the next dose at the regular dosing schedule.

1 Adverse Reaction Overview Adverse reactions to isosorbide dinitrate are generally dose-related, and almost all of these reactions are the result of isosorbide dinitrate's activity as a vasodilator. As with nitroglycerin and other nitrates, vascular headache occurs and it may be severe and persistent.

This adverse effect occurs most frequently at the beginning of therapy. Headache usually can be controlled by temporary dosage reduction, concomitant administration of suitable analgesics or by administering the drug during meals. These headaches usually disappear within 1 week of continuous, uninterrupted therapy.

It is usually best to advise the patient of their possible occurrence and of their importance in regard to the prevention of angina. Drug and/or exfoliative dermatitis occasionally occur. Signs of cerebral ischemia associated with postural hypotension such as weakness, transient episodes of dizziness may occasionally develop.

Cutaneous vasodilatation with flushing may occur. Rarely a marked sensitivity to the hypotensive effects of the drug and severe response (nausea, vomiting, restlessness, perspiration and collapse) can occur and alcohol may enhance this effect.

Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon. ISDN (Isosorbide Dinitrate Tablets) Page 10 of 21 Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal- seeming patients.

Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred. See 5 OVERDOSAGE.

4 Geriatrics 2025-05 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 1 INDICATIONS ..............................................................................................................

1 Pediatrics ................................................................................................................. 2 Geriatrics .................................................................................................................

4 2 CONTRAINDICATIONS ................................................................................................. 4 4 DOSAGE AND ADMINISTRATION ................................................................................. 1 Dosing Considerations.............................................................................................

2 Recommended Dose and Dosage Adjustment ....................................................... 4 Administration......................................................................................................... 5 Missed Dose ............................................................................................................

5 5 OVERDOSAGE ............................................................................................................. 5 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.................................. 7 7 WARNINGS AND PRECAUTIONS ..................................................................................

1 Special Populations ................................................................................................. 1 Pregnant Women ................................................................................................

4 Geriatrics 2025-05 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 1 INDICATIONS ..............................................................................................................

1 Pediatrics ................................................................................................................. 2 Geriatrics .................................................................................................................

4 2 CONTRAINDICATIONS ................................................................................................. 4 4 DOSAGE AND ADMINISTRATION ................................................................................. 1 Dosing Considerations.............................................................................................

2 Recommended Dose and Dosage Adjustment ....................................................... 4 Administration......................................................................................................... 5 Missed Dose ............................................................................................................

5 5 OVERDOSAGE ............................................................................................................. 5 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.................................. 7 7 WARNINGS AND PRECAUTIONS ..................................................................................

1 Special Populations ................................................................................................. 1 Pregnant Women ................................................................................................