1. Clinical Overview
Isosorbide mononitrate is a long-acting organic nitrate used primarily for the prophylaxis and treatment of angina pectoris. It is a major active metabolite of isosorbide dinitrate. In the Indian context, it is a cornerstone in the management of chronic stable angina, often preferred for its predictable pharmacokinetics and reduced potential for tolerance development compared to other nitrates when dosed appropriately.
| Onset | Duration | Bioavailability |
|---|---|---|
| 30 to 60 minutes | 6 to 10 hours | Approximately 93% |
2. Mechanism of Action
Isosorbide mononitrate is a prodrug that is denitrated to release nitric oxide (NO). NO activates intracellular guanylyl cyclase, leading to increased synthesis of cyclic guanosine monophosphate (cGMP). Elevated cGMP causes dephosphorylation of myosin light chains, resulting in smooth muscle relaxation, particularly in venous capacitance vessels, arteries, and coronary vasculature.
3. Indications & Uses
- Prophylaxis of chronic stable angina pectoris (effort angina)
- Prevention of angina attacks
4. Dosage & Administration
Adult Dosage: For angina prophylaxis: Initially 20mg twice daily (with a 7-hour interval) or 30-60mg once daily as a sustained-release formulation. The standard 30mg immediate-release tablet is often given as 30mg once in the morning or 20mg twice daily (e.g., 8 AM and 3 PM) to ensure a nitrate-free interval. Dose may be titrated up to 120mg daily in divided doses based on response and tolerance.
Administration: Take tablet whole with a glass of water, with or without food. For immediate-release tablets, the twice-daily regimen should have doses spaced 7 hours apart (e.g., 8 AM and 3 PM) to provide a daily nitrate-low period. Do not crush or chew sustained-release formulations. Sit or lie down if feeling dizzy after taking the dose.
5. Side Effects
Common side effects may include:
- Headache (often dose-related and may diminish with continued use)
- Dizziness, lightheadedness
- Flushing
- Postural hypotension
- Nausea
- Weakness
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Phosphodiesterase-5 Inhibitors (Sildenafil, Tadalafil, Vardenafil) | Profound, life-threatening hypotension | Contraindicated |
| Other Vasodilators (e.g., ACE inhibitors, ARBs, Calcium channel blockers, Alpha-blockers) | Additive hypotensive effect | Major |
| Alcohol | Enhanced vasodilation and hypotension | Major |
| Heparin | Possible decreased anticoagulant effect of heparin | Moderate |
| Dihydroergotamine | May reduce the anti-anginal effect of nitrates and increase ergotamine-induced vasoconstriction | Moderate |
| Antihypertensives | Potentiated hypotension | Moderate |
| Tricyclic Antidepressants (TCAs) | Hypotensive effects may be potentiated | Moderate |
| Riociguat | Hypotensive effects may be potentiated as both increase cGMP | Major |
7. Patient Counselling
- DO take the medication exactly as prescribed, maintaining the specific timing to ensure a 'nitrate-free' period.
- DO sit or lie down at the first sign of dizziness or lightheadedness.
- DO inform all healthcare providers (including dentists) that you are on this medication.
- DO keep a diary of angina attacks to discuss with your doctor.
- DONT suddenly stop taking this medication without consulting your doctor, as it may worsen angina.
- DONT take erectile dysfunction drugs (like Viagra, Cialis) while on this medicine.
- DONT consume alcohol.
- DONT crush or chew sustained-release tablets.
8. Toxicology & Storage
Overdose: Severe hypotension with persistent throbbing headache, vertigo, palpitations, visual disturbances, flushing, sweating (followed by cold and clammy skin), nausea, vomiting, syncope, air hunger, dyspnea, bradycardia or tachycardia, heart block, methemoglobinemia (cyanosis, dyspnea, anxiety), coma, seizures, and death.
Storage: Store below 30°C, in a cool, dry place, protected from light and moisture. Keep in the original blister pack or container. Keep out of reach of children. Do not use after the expiry date printed on the pack.