Angina pectoris, prevention:
Note: For prevention of recurrent angina, may use in combination with other anti-anginal therapy (eg, beta-blocker) (Ref).
Immediate release: Oral: 20 mg twice daily; administer second dose at least 7 hours after the first dose (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: Oral: 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Moderately dialyzable (AUC0-8 decreased 30% with a 4-hour dialysis session (Ref)): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Not significantly dialyzed (Ref): No dosage adjustment necessary (Ref).
No dosage adjustment necessary.
Refer to adult dosing; initiate with lowest recommended dose.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 10 mg, 20 mg
Tablet Extended Release 24 Hour, Oral:
Generic: 30 mg, 60 mg, 120 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Imdur: 60 mg
Generic: 60 mg
Do not administer around-the-clock. IR tablet should be scheduled twice daily with doses 7 hours apart (8 AM and 3 PM); administer ER tablet once daily in the morning upon rising with a half-glassful of fluid. Do not chew or crush ER tablets; may be divided in half. Due to insoluble matrix embedding, ER tablets that are scored may be split (Ref).
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Scored tablets may be cut in half. Alternatively, may switch to IR formulation.
Angina pectoris, prevention: 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.
Imdur may be confused with Imuran, Inderal LA, K-Dur
Monoket may be confused with Monopril
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Central nervous system: Headache (≤57%), dizziness (≤11%)
1% to 10%:
Cardiovascular: Abnormal heart sounds (≤5%), atrial arrhythmia (≤5%), atrial fibrillation (≤5%), bradycardia (≤5%), bundle branch block (≤5%), cardiac arrhythmia (≤5%), cardiac failure (≤5%), chest pain (≤5%), ECG abnormality (Q wave: ≤5%), edema (≤5%), exacerbation of angina pectoris (≤5%), extrasystoles (≤5%), flushing (≤5%), heart murmur (≤5%), hypertension (≤5%), hypotension (≤5%), intermittent claudication (≤5%), myocardial infarction (≤5%), palpitations (≤5%), tachycardia (≤5%), varicose veins (≤5%), ventricular tachycardia (≤5%), cardiovascular toxicity (2%)
Central nervous system: Anxiety (≤5%), confusion (≤5%), depression (≤5%), drowsiness (≤5%), fatigue (≤5%), hypoesthesia (≤5%), insomnia (≤5%), lack of concentration (≤5%), malaise (≤5%), migraine (≤5%), myasthenia (≤5%), nervousness (≤5%), neuritis (≤5%), nightmares (≤5%), paresis (≤5%), paresthesia (≤5%), rigors (≤5%), vertigo (≤5%), pain (4%), emotional lability (2%)
Dermatologic: Abnormal hair texture (≤5%), acne vulgaris (≤5%), diaphoresis (≤5%), leg ulcer (≤5%), pruritus (≤5%), skin rash (≤5%)
Endocrine & metabolic: Decreased libido (≤5%), hot flash (≤5%), hyperuricemia (≤5%), hypokalemia (≤5%)
Gastrointestinal: Abdominal pain (≤5%), constipation (≤5%), diarrhea (≤5%), dyspepsia (≤5%), flatulence (≤5%), gastric ulcer (≤5%), gastric ulcer with hemorrhage (≤5%), gastritis (≤5%), glossitis (≤5%), hemorrhoids (≤5%), loose stools (≤5%), melena (≤5%), nausea (≤5%), vomiting (≤5%), xerostomia (≤5%)
Genitourinary: Atrophic vaginitis (≤5%), impotence (≤5%), mastalgia (≤5%), urinary tract infection (≤5%)
Hematologic & oncologic: Hypochromic anemia (≤5%), nonthrombocytopenic purpura (≤5%), thrombocytopenia (≤5%)
Hepatic: Increased serum alanine aminotransferase (≤5%), increased serum aspartate aminotransferase (≤5%)
Hypersensitivity: Hypersensitivity reaction (2%)
Infection: Bacterial infection (≤5%), candidiasis (≤5%), viral infection (≤5%)
Neuromuscular & skeletal: Arthralgia (≤5%), asthenia (≤5%), back pain (≤5%), musculoskeletal pain (≤5%), myalgia (≤5%), myositis (≤5%), shoulder stiffness (frozen shoulder: ≤5%), tendinopathy (≤5%), torticollis (≤5%), tremor (≤5%)
Ophthalmic: Blepharoptosis (≤5%), conjunctivitis (≤5%), photophobia (≤5%), visual disturbance (≤5%)
Otic: Otalgia (≤5%), perforated tympanic membrane (≤5%), tinnitus (≤5%)
Renal: Nephrolithiasis (≤5%), polyuria (≤5%)
Respiratory: Bronchitis (≤5%), bronchospasm (≤5%), cough (≤5%), dyspnea (≤5%), flu-like symptoms (≤5%), increased bronchial secretions (≤5%), nasal congestion (≤5%), pharyngitis (≤5%), pneumonia (≤5%), pulmonary infiltrates (≤5%), rales (≤5%), rhinitis (≤5%), sinusitis (≤5%), upper respiratory infection (1% to 4%), increased cough (2%)
Miscellaneous: Fever (≤5%), nodule (≤5%)
<1%, postmarketing, and/or case reports: Acute myocardial infarction, amblyopia, anorexia, asthma, bitter taste, cerebrovascular accident, increased thirst, muscle cramps, neck pain, pallor, prostatic disease, restlessness, syncope, weight loss
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.
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) (Rangel-Castilla 2008).
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 with left ventricular outflow tract obstruction: Avoid use in patients with hypertrophic cardiomyopathy with left ventricular outflow tract obstruction; nitrates may reduce preload, exacerbating obstruction and cause hypotension or syncope and/or worsening of heart failure (AHA/ACC [Ommen 2021]).
Concurrent drug therapy issues:
• 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.
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy
Dapoxetine: May enhance the orthostatic hypotensive effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Vasodilators (Organic Nitrates). Risk C: 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. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: 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. Risk C: Monitor therapy
Rilmenidine: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Rilmenidine. Risk C: Monitor therapy
Riociguat: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Riociguat. Risk X: 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. Risk C: 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. Risk C: Monitor therapy
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).
It is not known if isosorbide mononitrate is excreted in breast milk. The manufacturer recommends that caution be exercised when administering isosorbide mononitrate to nursing women.
Blood pressure, heart rate
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.
Onset of action: 30 to 45 minutes (Thadani 1987)
Duration: Immediate release: ≥6 hours (Thadani 1987); Extended release: ≥12 to 24 hours (Anderson 2007)
Absorption: Rapid and complete
Distribution: Vd: ~0.6 L/kg
Protein binding: <5%
Metabolism: Hepatic
Bioavailability: ~100%
Half-life elimination: 5 to 6 hours (Thadani 1987)
Time to peak, plasma: 30 to 60 minutes
Excretion: Predominantly urine (2% as unchanged drug); feces (1%)
Tablet, 24-hour (Isosorbide Mononitrate ER Oral)
30 mg (per each): $0.52 - $3.35
60 mg (per each): $0.54 - $4.28
120 mg (per each): $0.76 - $8.80
Tablets (Isosorbide Mononitrate Oral)
10 mg (per each): $0.85
20 mg (per each): $0.89
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