Drug information of isosorbide mononitrate

Mechanism of effect

Organic nitrate that causes systemic venodilation, decreasing preload; enters vascular smooth muscle and is converted to nitric oxide, leading to activation of cyclic guanosine monophosphate and vasodilation.

Relaxes smooth muscle via dose-dependent dilation of arterial and venous beds to reduce both preload and afterload, as well as myocardial oxygen demand; also improves coronary collateral circulation, lowering blood pressure, increasing heart rate, and causing occasional paradoxical bradycardia.

Pharmacodynamic

Isosorbide mononitrate , the long-acting metabolite of isosorbide dinitrate, is used as a vasodilatory agent in the management of angina pectoris. By dilating the vessels, it lowers the blood pressure and reduces the left ventricular preload and afterload, therefore, leads to a reduction of myocardial oxygen requirement.

Pharmacokinetics

Absorption

• Bioavailability: Immediate release, 93-100%; extended release, 77-80%
• Onset (antianginal effects): Immediate release, 60 min; extended release, 60 min
• Onset (hemodynamic effects): Immediate release, 10-30 min; extended release, ≥6 hr
• Duration (antianginal effects): Immediate release, 5-7 hr; extended release, 8 hr
• Duration (hemodynamic effects): Immediate release, 10-30 min; extended release, ≥6 hr
• Peak plasma time: Immediate release, 30-60 min; extended release, 3-4.5 hr

Distribution

Protein bound: <5%

Vd: 0.6 L/kg

Metabolism

Metabolized in liver via conjugation

Metabolites: Isosorbide, 5-isosorbide mononitrate glucuronide, sorbitol (inactive)

Elimination

Half-life: Parent drug, 6.2-6.6 hr; glucuronide metabolite, 6 hr; sorbitol metabolite, 9 hr

Excretion: Urine (2%); feces (1%)

Drug indications

Dosage

Angina Pectoris

Prevention of angina pectoris caused by coronary artery disease

Immediate release: 5-10 mg PO twice daily initially (5 mg in small patients) given each dose 7 hr apart; increased to 10 mg PO q12hr by day 2 or 3; maintenance: 20 mg PO q12hr

Extended release: 30-60 mg PO once daily in the morning initially; may be increased to 120 mg PO once daily; wait at least 3 days between increases.

Dosing considerations

Take on empty stomach, 30 minutes before meals or 1 hour after meal

Extended-release tablet should be swallowed whole; must not be chewed, crushed, or split

Side effects

Interactions

Alerts

• Concerns related to adverse effects:

CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness.

Hypotension/bradycardia: Severe hypotension can occur; paradoxical bradycardia and increased angina pectoris can accompany hypotension. Orthostatic hypotension can also occur; ethanol can accentuate this. Severe hypotension, particularly with upright posture, may occur with even small doses.

Intracranial pressure increased: Nitrates may precipitate or aggravate increased intracranial pressure and subsequently may worsen clinical outcomes in patients with neurologic injury.

• Disease-related concerns:

Cardiovascular disease: Not recommended for use in patients with acute myocardial infarction (MI) or heart failure (has not been studied). Use with caution in volume depletion and moderate hypotension, and with extreme caution with inferior wall MI and suspected right ventricular infarctions.

• Other warnings/precautions:

Appropriate use: Extended-release: Not intended for the immediate relief of acute attacks of angina pectoris.

Tolerance: Appropriate dosing intervals are needed to minimize tolerance development. Tolerance can only be overcome by short periods of nitrate absence from the body.

Points of recommendation

Patient should not take erectile dysfunction medicine (Viagra, Cialis, Levitra, Stendra, Staxyn, sildenafil, avanafil, tadalafil, vardenafil) while taking isosorbide mononitrate. Taking these medicine together can cause a sudden and serious decrease in blood pressure.

Patient should seek emergency medical attention if he/she have early symptoms of a heart attack (chest pain or pressure, pain spreading to your jaw or shoulder, sweating, general ill feeling).

Patient should not stop taking this medicine suddenly. Stopping suddenly could cause a severe angina attack.

Isosorbide mononitrate can cause severe headaches, especially when patient first start using it. These headaches may gradually become less severe as he/she continue to use the medication. Patient should not stop taking isosorbide mononitrate.

Patient should use this medicine regularly to prevent an angina attack. He/she must get prescription refilled before runing out of medicine completely.

Pregnancy level

Breast feeding warning

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