Nitroglycerin Patch Removal for Tendinopathy
Yes, you must remove the nitroglycerin patch every 12 hours (providing a 12-hour nitrate-free interval) when treating tendinopathy to prevent tolerance development and maintain therapeutic efficacy.
Rationale for the 12-Hour On/12-Hour Off Schedule
The nitrate-free interval is essential because tolerance to nitrates is dose and duration dependent, typically becoming clinically important after 24 hours of continuous therapy. 1, 2 This applies to all nitrate formulations, including transdermal patches used for tendinopathy treatment.
Evidence-Based Dosing Schedule
Apply transdermal nitroglycerin patches for only 12-14 hours daily, then remove for 10-12 hours overnight to prevent tolerance and allow recovery of the metabolic mechanisms responsible for nitrate efficacy. 3, 2
The American College of Cardiology/American Heart Association guidelines specifically recommend transdermal NTG at 0.2-0.8 mg/hour for 8-12 hours during intermittent therapy. 1, 2
A 10-12 hour daily nitrate-free interval prevents tolerance while maintaining clinical effectiveness. 3, 2
Application to Tendinopathy Treatment
Effective Dosing Protocols
For lateral epicondylitis (tennis elbow), studies used effective NTG doses of 1.25-1.44 mg/24h with continuous application schedules. 4 However, this must be interpreted in the context of tolerance prevention principles.
For Achilles tendinopathy, topical glyceryl trinitrate at 1.25 mg per 24 hours showed reduced pain with activity at 12 weeks (p=0.02) and 24 weeks (p=0.03), with 78% of tendons asymptomatic at 6 months compared to 49% in placebo group (p=0.001). 5
Meta-analysis demonstrates strong evidence (Level 1) that NTG is effective in chronic tendinopathies for pain reduction during activities of daily living (odds ratio 4.44,95% CI 2.34-8.40) and enhancing tendon strength. 6
Clinical Outcomes with Intermittent Dosing
In a study comparing continuous versus intermittent (12-hour nitrate-free interval) NTG patch application, intermittent administration significantly increased ischemic threshold and total work time at both 4th and 12th hours compared to continuous treatment. 7 This demonstrates that the nitrate-free interval maintains efficacy rather than diminishing it.
Shoulder pain from supraspinatus tendinitis treated with 5-mg NTG patches showed significant pain reduction at 24 hours (7.05±0.4 to 4.5±0.5) and 48 hours (2±0.3) with patients remaining symptom-free at 15-day follow-up. 8
Managing the Nitrate-Free Interval
Practical Implementation
Apply the patch in the morning and remove it 12 hours later (typically before bedtime) to create a consistent overnight nitrate-free period. 3, 2
The overnight removal period is strategically chosen because most tendinopathy patients experience less activity-related pain during sleep.
Addressing Breakthrough Symptoms
If patients experience breakthrough pain during the nitrate-free interval, they should continue with their prescribed rehabilitation program and standard analgesics rather than extending patch wear time, as this would promote tolerance. 2
The nitrate-free interval is reversible and allows restoration of vascular responsiveness, maintaining long-term treatment effectiveness. 2
Common Pitfalls to Avoid
Tolerance Development
Do not allow patients to wear patches continuously for 24 hours, as this will lead to loss of antianginal and therapeutic efficacy within 24 hours. 1, 2
The primary clinical sign of tolerance is loss of therapeutic efficacy—decreased symptom relief despite continued therapy at previously effective doses. 2
If tolerance develops, responsiveness can often be restored by ensuring proper nitrate-free intervals. 1, 2
Side Effects
The most commonly reported side effects are headaches and contact dermatitis. 4 Meta-analysis shows significant between-group difference in headache incidence (odds ratio 1.73,95% CI 1.01-2.97) but no significant difference in contact dermatitis (odds ratio 2.12,95% CI 0.89-5.02). 6
Two patients in one study experienced headache 24 hours after treatment initiation. 8
Combination with Rehabilitation
Topical NTG is more effective when combined with a tendon rehabilitation program rather than used as monotherapy. 4 The nitrate therapy enhances collagen synthesis in fibroblasts while the rehabilitation program addresses biomechanical factors, creating synergistic benefit.