Nitroglycerin Ointment Application Duration
Nitroglycerin ointment should be applied for 8-12 hours daily with a 10-14 hour nitrate-free interval to prevent tolerance development. 1, 2
Recommended Application Protocol
Duration of Application
- Apply nitroglycerin ointment for 8-12 hours during the day
- Remove the ointment after this period to create a 10-14 hour nitrate-free interval (typically overnight)
- This intermittent application prevents the development of nitrate tolerance 1, 2
Dosage Information
- Typical dosage ranges from 0.2-0.8 mg/h 1
- Clinical trials have used doses ranging from 1/2 inch (7.5 mg) to 2 inches (30 mg) of ointment 2
- The ointment is typically applied to approximately 36 square inches (232 square centimeters) of truncal skin 2
Mechanism and Rationale
Nitroglycerin ointment provides effective anti-anginal effects for up to 7 hours after a single application 3. However, continuous application beyond 24 hours leads to the development of tolerance, with complete loss of efficacy 2, 4.
The FDA drug label specifically notes that "to avoid development of tolerance to nitroglycerin, drug-free intervals of 10-12 hours are known to be sufficient" 2. This is supported by clinical evidence showing that continuous therapy with nitrates produces pharmacologic tolerance 5.
Important Considerations
Preventing Tolerance
- Tolerance develops rapidly with continuous nitrate exposure 4
- A nitrate-free interval is essential to restore nitrate sensitivity 1, 4
- The maximal achievable daily duration of anti-anginal effect from nitroglycerin ointment is approximately 12 hours 2
Application Technique
- The rate and extent of nitroglycerin absorption may vary with the site and area of skin over which the ointment is spread 2
- Apply to clean, dry skin, avoiding areas with cuts or irritation
- Spread evenly over a non-hairy area of skin (typically chest, back, abdomen, or upper arms)
Monitoring and Precautions
- Monitor for headache and hypotension, which are common side effects 6
- Nitroglycerin should be avoided in patients with:
- Systolic blood pressure <90 mmHg or ≥30 mmHg below baseline
- Concurrent use of phosphodiesterase-5 inhibitors (within 24-48 hours)
- Right ventricular infarction
- Severe aortic stenosis 1
Clinical Evidence
The recommendation for intermittent application is based on strong evidence showing that continuous nitrate therapy leads to tolerance. Studies have demonstrated that providing nitrate-free intervals effectively restores nitrate sensitivity 4. A simple method to minimize tolerance with transdermal nitroglycerin is to remove the application at bedtime and reapply in the morning, allowing a patch-free period during the night when most patients experience fewer angina attacks 7.
This approach optimizes the anti-anginal effects during daytime hours while preventing the development of tolerance that would otherwise render the medication ineffective.