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Angina pectoris: Treatment (immediate-release only) and prevention of angina pectoris caused by coronary artery disease. Note: The onset of action of oral isosorbide mononitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.
Hypersensitivity to isosorbide mononitrate, other nitrates or nitrites, or any component of the formulation; concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, or vardenafil) or riociguat.
Canadian labeling: Additional contraindications (not in US labeling): Acute circulatory failure associated with marked hypotension (shock and states of collapse); postural hypotension; myocardial insufficiency due to obstruction (eg, in the presence of aortic or mitral stenosis or of constrictive pericarditis); increased intracranial pressure; severe anemia.
Angina pectoris: Oral: Note: Tolerance to nitrate effects develops with chronic exposure. Dose escalation does not overcome this effect. Tolerance can only be overcome by short periods of nitrate absence from the body. Recommended twice daily dosage regimens incorporate this interval. Short periods of nitrate withdrawal may help minimize tolerance.
Immediate release: 20 mg twice daily with the 2 doses given 7 hours apart (eg, 8 AM and 3 PM) to decrease tolerance development; patients with small stature may initiate therapy with 5 mg twice daily and titrate to at least 10 mg twice daily in first 2 to 3 days of therapy.
Extended release: Initial: 30 to 60 mg once daily in the morning; may titrate after several days to 120 mg once daily; rarely, 240 mg once daily may be required
Refer to adult dosing; initiate with lowest recommended dose.
No dosage adjustment necessary.
Hemodialysis: Supplemental dose is not necessary. Dose after dialysis (Aronoff 2007)
Continuous ambulatory peritoneal dialysis: Supplemental dose is not necessary.
No dosage adjustment necessary.
Do not administer around-the-clock. Immediate release tablet should be scheduled twice daily with doses 7 hours apart (8 AM and 3 PM); administer extended release tablet once daily in the morning upon rising with a half-glassful of fluid. Do not chew or crush extended release tablets; may be divided in half. Due to insoluble matrix embedding, extended release tablets that are scored may be split (Gunasekara 1999).
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Generic: 10 mg, 20 mg
Tablet Extended Release 24 Hour, Oral:
Imdur: 30 mg [DSC], 60 mg [DSC] [scored]
Imdur: 120 mg [DSC]
Generic: 30 mg, 60 mg, 120 mg
Alcohol (Ethyl): May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dapoxetine: May enhance the orthostatic hypotensive effect of Vasodilators (Organic Nitrates). Monitor therapy
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Vasodilators (Organic Nitrates). Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Avoid combination
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy
Riociguat: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Riociguat. Avoid combination
Rosiglitazone: Vasodilators (Organic Nitrates) may enhance the adverse/toxic effect of Rosiglitazone. Specifically, a greater risk of ischemia and other adverse effects has been associated with this combination in some pooled analyses. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tetracaine (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Blood pressure, heart rate
>10%: Central nervous system: Headache (13% to 35%)
1% to 10%:
Cardiovascular: Angina pectoris ( ≤2%), flushing ( ≤2%)
Central nervous system: Dizziness ( ≤4%), fatigue ( ≤4%), pain ( ≤4%), emotional lability ( ≤2%)
Dermatologic: Pruritus ( ≤2%), skin rash ( ≤2%)
Gastrointestinal: Nausea ( ≤3%), abdominal pain ( ≤2%), diarrhea ( ≤2%)
Hypersensitivity: Hypersensitivity reaction ( ≤2%)
Respiratory: Upper respiratory infection ( ≤4%), increased cough ( ≤2%)
<1% (Limited to important or life-threatening): Bradycardia, cardiac arrhythmia, cerebrovascular accident, dyspnea, edema, hypertension, hypotension, methemoglobinemia (rare; overdose), myocardial infarction, orthostatic hypotension, pallor, palpitations, paresthesia, tachycardia
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 (eg, operating machinery or driving).
- 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 (eg, intracranial hemorrhage, traumatic brain injury). The Canadian labeling contraindicates use in patients with increased intracranial pressure.
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. The Canadian labeling contraindicates use in acute circulatory failure associated with marked hypotension, postural hypotension, and myocardial insufficiency due to obstruction (eg, in the presence of aortic or mitral stenosis or of constrictive pericarditis).
- Hypertrophic cardiomyopathy (HCM): Avoid use in patients with HCM with outflow tract obstruction; nitrates may reduce preload, exacerbating obstruction and cause hypotension or syncope and/or worsening of heart failure (Gersh 2011).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- PDE-5 inhibitors: Avoid concurrent use with PDE-5 inhibitors (eg, sildenafil, tadalafil, vardenafil). When nitrate administration becomes medically necessary, may administer nitrates only if 24 hours have elapsed after use of sildenafil or vardenafil (48 hours after tadalafil use) (O 'Connor 2010).
Dosage forms related issues:
- Extended-release tablets: Empty matrix ghosts" (tablets) may pass in patients via colostomy or in the stool; this is of no concern.
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. Dose escalation does not overcome this effect.
B
Adverse events have been observed in some animal reproduction studies. Nitric oxide donors, such as isosorbide, have been evaluated for pre-eclampsia and cervical ripening; isosorbide mononitrate use in these conditions is not currently recommended (Kalidindi 2012; Ramirez 2011).
Nitroglycerin and other nitrates form free radical nitric oxide. In smooth muscle, nitric oxide activates guanylate cyclase which increases guanosine 3 '5 ' monophosphate (cGMP) leading to dephosphorylation of myosin light chains and smooth muscle relaxation. Produces a vasodilator effect on the peripheral veins and arteries with more prominent effects on the veins. Primarily reduces cardiac oxygen demand by decreasing preload (left ventricular end-diastolic pressure); may modestly reduce afterload; dilates coronary arteries and improves collateral flow to ischemic regions.
Rapid and complete
Vd: ~0.6 L/kg
Hepatic
Predominantly urine (2% as unchanged drug); feces (1%)
30 to 45 minutes (Thadani 1987)
Plasma: 30 to 60 minutes
Immediate release: ≥6 hours (Thadani1987); Extended release: ≥12 to 24 hours (Anderson 2007)
~5 to 6 hours (Thadani 1987)
<5%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache. Have patient report immediately to prescriber angina, severe dizziness, passing out, bradycardia, or tachycardia (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.