Imdur (Isosorbide Mononitrate) Should Not Be Stopped Abruptly
Imdur should not be stopped abruptly in patients with angina and coronary artery disease due to the risk of rebound angina, acute myocardial infarction, and potentially sudden death from nitrate withdrawal. 1
Evidence of Nitrate Withdrawal Syndrome
The FDA drug label for isosorbide mononitrate explicitly warns about physical dependence and withdrawal phenomena observed in industrial workers with long-term nitrate exposure. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates, demonstrating true physical dependence. 1
While this evidence comes primarily from occupational exposure to high doses, the FDA acknowledges that the clinical significance for routine therapeutic use is not fully established. However, the catastrophic potential outcomes (MI and sudden death) mandate a cautious approach. 1
Mechanism of Withdrawal Risk
Nitrate therapy works through vasodilation and reduction of myocardial oxygen demand. Abrupt cessation can lead to:
- Rebound coronary vasoconstriction 1
- Paradoxical increase in angina pectoris 1
- Loss of antianginal protection without gradual adaptation 2
The controlled-release formulation of Imdur maintains plasma nitrate levels high enough for daytime protection while allowing nighttime levels to drop sufficiently to avoid tolerance development during once-daily dosing. 2 Abrupt discontinuation disrupts this carefully balanced pharmacokinetic profile.
Clinical Approach to Discontinuation
If Imdur must be discontinued, taper the dose gradually over several days to weeks rather than stopping abruptly. 1 While specific tapering protocols are not established in guidelines, a reasonable approach based on the pharmacology would be:
- Reduce from 60 mg once daily to 30 mg once daily for 3-7 days
- Then reduce to 30 mg every other day for 3-7 days before complete cessation
- Monitor closely for recurrent angina symptoms throughout the taper
Important Caveats
Patients must be counseled that headaches are a marker of drug activity, and they should not alter their dosing schedule to avoid headaches, as this may result in loss of antianginal efficacy. 1 This is particularly relevant because patients who self-adjust or skip doses due to headaches may inadvertently create an abrupt withdrawal scenario.
Aspirin or acetaminophen can successfully relieve nitrate-induced headaches without compromising antianginal efficacy. 1
Contraindication Context
The only scenario where immediate discontinuation might be necessary is severe hypotension, particularly with upright posture, which can occur even with small doses. 1 In such cases, the immediate hemodynamic risk may outweigh withdrawal concerns, but this requires urgent medical supervision and alternative antianginal strategies.