isosorbide mononitrate
Imdur, ISMO, Isotrate ER, Monoket

Available forms
Available by prescription only
Tablets: 10 mg, 20 mg
Tablets (extended-release): 30 mg, 60 mg, 120 mg

Indications and dosages
 Prevention of angina pectoris caused by coronary artery disease (but not to abort acute anginal attacks). Adults: 20 mg P.O. b.i.d., with doses 7 hours apart and first dose on awakening. For extended-release tablets, 30 to 60 mg P.O. once daily, on arising. After several days, dosage may be increased to 120 mg once daily; rarely, 240 mg may be needed.

Pharmacodynamics
Antianginal action: Drug is the major active metabolite of isosorbide dinitrate. It relaxes vascular smooth muscle and consequently dilates peripheral arteries and veins. Dilation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilation of the coronary arteries also occurs.

Pharmacokinetics
Absorption: Absolute bioavailability is almost 100%.
Distribution: Volume of distribution is about 0.6 L/kg. Less than 4% is bound to plasma proteins.
Metabolism: Drug isn’t subject to first-pass metabolism in the liver.
Excretion: Less than 1% of isosorbide mononitrate is eliminated in urine. Overall elimination half-life of drug is about 5 hours.

Contraindications and precautions
Contraindicated in patients with hypersensitivity or idiosyncrasy to nitrates, severe hypotension, shock, or acute MI with low left ventricular filling pressure. Use cautiously in patients with hypotension or blood volume depletion (such as from diuretic therapy).

Interactions
Drug-drug. Calcium channel blockers, organic nitrates: Causes marked symptomatic orthostatic hypotension. Dosage adjustments of either class of agents may be needed.
Drug-lifestyle. Alcohol use: Increases vasodilation. Discourage alcohol use.

Adverse reactions
CNS: headache (sometimes with throbbing), dizziness, weakness, fainting.
CV: flushing, orthostatic hypotension, tachycardia, palpitations, ankle edema,
GI: nausea, vomiting.
Musculoskeletal: arthralgia.
Respiratory: bronchitis, pneumonia, upper respiratory tract infection.
Skin: cutaneous vasodilation, rash.
Other: hypersensitivity reactions, sublingual burning.

Effects on lab test results
None reported.

Overdose and treatment
Signs and symptoms of overdose may include increased intracranial pressure; persistent, throbbing headache; confusion; moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially with upright position); air hunger; dyspnea, later followed by reduced ventilatory effort; diaphoresis, with skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.
 No specific antagonist to vasodilator effects of drug is known. However, drug is significantly removed from the blood during hemodialysis.
 If drug is ingested, induce emesis or perform gastric lavage followed by activated charcoal administration. Because drug is rapidly and completely absorbed, however, gastric lavage may be effective only with recent ingestion. Treat severe hypotension and reflex tachycardia by elevating legs and administering I.V. fluids. Epinephrine is ineffective in reversing severe hypotension caused by overdose, and epinephrine and related compounds are contraindicated. Administer oxygen and artificial ventilation if needed. Monitor methemoglobin levels as indicated.

Special considerations
• Drug-free interval sufficient to avoid tolerance to drug isn’t completely defined. The recommended regimen involves two daily doses given 7 hours apart, with a gap of 17 hours between the second dose of 1 day and the first dose of the next day. Considering the relatively long half-life of drug, this result is consistent with those obtained for other organic nitrates.
• The asymmetric twice-daily regimen successfully avoids significant rebound or withdrawal effects. In studies of other nitrates, the occurrence and magnitude of such phenomena appear to be highly dependent on the schedule of nitrate administration.
 ALERT Onset of action of oral drug isn’t sufficiently rapid to be useful in aborting an acute anginal episode.
• Benefits of drug in patients with acute MI or heart failure haven’t been established. Because effects of drug are difficult to terminate rapidly, its use isn’t recommended in such patients. If it’s used, however, careful clinical or hemodynamic monitoring must be performed to avoid the hazards of hypotension and tachycardia.
• Monitor blood pressure, especially in those susceptible to hypotension.
• Methemoglobinemia has occurred in patients receiving other organic nitrates and probably could occur as an adverse reaction. Significant methemoglobinemia has occurred with moderate overdoses of organic nitrates. Suspect methemoglobinemia in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate PaO₂. Classically, methemoglobinemic blood is chocolate brown, without color change on exposure to air. Treatment of choice for methemoglobinemia is methylene blue, 1 to 2 mg/kg I.V.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.

Patient education
• Tell patient to follow prescribed dosing schedule carefully (two doses taken 7 hours apart) to maintain antianginal effect and to prevent tolerance.
• Caution patient that extended-release tablets shouldn’t be crushed or chewed.
• Warn patient that daily headaches sometimes accompany treatment with nitrates, including isosorbide mononitrate, and are a marker of drug activity. Patient shouldn’t alter treatment schedule, because attempts to reduce headaches also will reduce antianginal efficacy. Tell patient to treat headaches with aspirin or acetaminophen.
• Warn patient to avoid alcohol while taking drug because of increased risk of light-headedness.
• Tell patient to rise slowly from recumbent or seated position to avoid light-headedness caused by sudden decrease in blood pressure.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use