DESCRIPTION
id: 27d0ffe6-16ef-4c91-9122-46bcf5a4875c
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Isosorbide mononitrate (ISMN), an organic nitrate and the major biologically active metabolite of isosorbide dinitrate (ISDN), is a vasodilator with effects on both arteries and veins.
Each tablet, for oral administration, contains either 30 mg, 60 mg or 120 mg of isosorbide mononitrate in an extended-release formulation. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydrogenated castor oil, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose and talc.
The molecular formula of ISMN is C6H9NO6 and the molecular weight is 191.14. The chemical name for ISMN is 1,4:3,6-dianhydro-,D-glucitol 5-nitrate; the compound has the following structural formula:
ISMN is a white, crystalline, odorless compound which is stable in air and in solution, has a melting point of about 90°C, and an optical rotation of +144° (2% in water, 20°C).
Isosorbide mononitrate is freely soluble in water, ethanol, methanol, chloroform, ethyl acetate, and dichloromethane.
INDICATIONS AND USAGE
id: e7df3c8f-2374-4e50-88d1-149ee275d448
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Isosorbide Mononitrate Extended-Release Tablets are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.
CONTRAINDICATIONS
id: a0af5750-752b-49c4-9934-5785f0b81d75
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Isosorbide Mononitrate Extended-Release Tablets are contraindicated in patients who have shown hypersensitivity or idiosyncratic reactions to other nitrates or nitrites.
WARNINGS
id: 8cf8062a-0499-4e0c-a98c-1bf5e76b706f
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
Amplification of the vasodilatory effects of isosorbide mononitrate by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion.
The benefits of ISMN in patients with acute myocardial infarction or congestive heart failure have not been established; because the effects of isosorbide mononitrate are difficult to terminate rapidly, this drug is not recommended in these settings.
If isosorbide mononitrate is used in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.
ADVERSE REACTIONS
id: 4b2452da-1c39-4106-bd36-53527dc5c4ee
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
The table below shows the frequencies of the adverse events that occurred in >5% of the subjects in three placebo-controlled North American studies, in which patients in the active treatment arm received 30 mg, 60 mg, 120 mg, or 240 mg of Isosorbide Mononitrate Extended-Release Tablets once daily. In parentheses, the same table shows the frequencies with which these adverse events were associated with the discontinuation of treatment. Overall, 8% of the patients who received 30 mg, 60 mg, 120 mg, or 240 mg of isosorbide mononitrate in the three placebo-controlled North American studies discontinued treatment because of adverse events. Most of these discontinued because of headache. Dizziness was rarely associated with withdrawal from these studies. Since headache appears to be a dose-related adverse effect and tends to disappear with continued treatment, it is recommended that ISMN treatment be initiated at low doses for several days before being increased to desired levels.
FREQUENCY AND ADVERSE EVENTS (DISCONTINUED)a
| Three Controlled North American Studies |
| Dose |
Placebo |
30 mg |
60 mg |
120 mgPatients were started on 60 mg and titrated to their final dose.
|
240 mg
|
| Patients |
96 |
60 |
102 |
65 |
65 |
| Headache |
15% (0%) |
38% (5%) |
51% (8%) |
42% (5%) |
57% (8%) |
| Dizziness |
4% (0%) |
8% (0%) |
11% (1%) |
9% (2%) |
9% (2%) |
In addition, the three North American trials were pooled with 11 controlled trials conducted in Europe. Among the 14 controlled trials, a total of 711 patients were randomized to Isosorbide Mononitrate Extended-Release Tablets. When the pooled data were reviewed, headache and dizziness were the only adverse events that were reported by >5% of patients. Other adverse events, each reported by ≤5% of exposed patients, and in many cases of uncertain relation to drug treatment, were:
Autonomic Nervous System Disorders: Dry mouth, hot flushes.
Body as a Whole: Asthenia, back pain, chest pain, edema, fatigue, fever, flu-like symptoms, malaise, rigors.
Cardiovascular Disorders, General: Cardiac failure, hypertension, hypotension.
Central and Peripheral Nervous System Disorders: Dizziness, headache, hypoesthesia, migraine, neuritis, paresis, paresthesia, ptosis, tremor, vertigo.
Gastrointestinal System Disorders: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gastric ulcer, gastritis, glossitis, hemorrhagic gastric ulcer, hemorrhoids, loose stools, melena, nausea, vomiting.
Hearing and Vestibular Disorders: Earache, tinnitus, tympanic membrane perforation.
Heart Rate and Rhythm Disorders: Arrhythmia, arrhythmia atrial, atrial fibrillation, bradycardia, bundle branch block, extrasystole, palpitation, tachycardia, ventricular tachycardia.
Liver and Biliary System Disorders: SGOT increase, SGPT increase.
Metabolic and Nutritional Disorders: Hyperuricemia, hypokalemia.
Musculoskeletal System Disorders: Arthralgia, frozen shoulder, muscle weakness, musculoskeletal pain, myalgia, myositis, tendon disorder, torticollis.
Myo-, Endo-, Pericardial and Valve Disorders: Angina pectoris aggravated, heart murmur, heart sound abnormal, myocardial infarction, Q wave abnormality.
Platelet, Bleeding and Clotting Disorders: Purpura, thrombocytopenia.
Psychiatric Disorders: Anxiety, concentration impaired, confusion, decreased libido, depression, impotence, insomnia, nervousness, paroniria, somnolence.
Red Blood Cell Disorder: Hypochromic anemia.
Reproductive Disorders, Female: Atrophic vaginitis, breast pain.
Resistance Mechanism Disorders: Bacterial infection, moniliasis, viral infection.
Respiratory System Disorders: Bronchitis, bronchospasm, coughing, dyspnea, increased sputum, nasal congestion, pharyngitis, pneumonia, pulmonary infiltration, rales, rhinitis, sinusitis.
Skin and Appendages Disorders: Acne, hair texture abnormal, increased sweating, pruritus, rash, skin nodule.
Urinary System Disorders: Polyuria, renal calculus, urinary tract infection.
Vascular (Extracardiac) Disorders: Flushing, intermittent claudication, leg ulcer, varicose vein.
Vision Disorders: Conjunctivitis, photophobia, vision abnormal.
In addition, the following spontaneous adverse event has been reported during the marketing of isosorbide mononitrate: syncope.
DOSAGE AND ADMINISTRATION
id: df2adf8e-8570-4404-a356-9f048348ed14
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
The recommended starting dose of Isosorbide Mononitrate Extended-Release Tablets is 30 mg (given as a single 30 mg tablet or as 1/2 of a 60 mg tablet) or 60 mg (given as a single tablet) once daily. After several days, the dosage may be increased to 120 mg (given as a single 120 mg tablet or as two 60 mg tablets) once daily. Rarely, 240 mg may be required. The daily dose of Isosorbide Mononitrate Extended-Release Tablets should be taken in the morning on arising. Isosorbide Mononitrate Extended-Release Tablets should not be chewed or crushed and should be swallowed together with a half-glassful of fluid. Do not break the 30 mg tablet.
HOW SUPPLIED
id: 44095215-5c4a-4329-bc37-8eb13ce9fcd7
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Repackaged by Aphena Pharma Solutions – TN.
See
Repackaging Information
for available configurations.
|
|
|
Isosorbide Mononitrate Extended-Release Tablets, USP 30 mg are white, capsule-shaped tablets scored on one side and engraved “KU 128” on the unscored side. They are supplied as follows:
Bottles of 90 NDC 62175-128-46
Bottles of 100 NDC 62175-128-37
Bottles of 500 NDC 62175-128-41
Bottles of 1000 NDC 62175-128-43
Isosorbide Mononitrate Extended-Release Tablets, USP 60 mg are white, capsule-shaped tablets scored on one side and engraved “KU 119” on the unscored side. They are supplied as follows:
Bottles of 90 NDC 62175-119-46
Bottles of 100 NDC 62175-119-37
Bottles of 500 NDC 62175-128-41
Bottles of 1000 NDC 62175-119-43
Isosorbide Mononitrate Extended-Release Tablets, USP 120 mg are white, capsule-shaped tablets engraved “KU 129” on one side. They are supplied as follows:
Bottles of 100 NDC 62175-129-37
Bottles of 1000 NDC 62175-129-43
Store at 20°-30°C (68°-86°F) [See USP].
Distributed by:
Kremers Urban Pharmaceuticals Inc.
Princeton, NJ 08540, USA
L3958L
Rev. 4E 01/2011
Repackaging Information
id: 613d7dc1-e366-4891-b81c-333e90dc38b0
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5
Please reference the
How Supplied
section listed above for a description of individual tablets or capsules. This drug product has been received by Aphena Pharma – TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:
| Count |
120mg
|
| 4200 |
43353-917-05 |
| Count |
30mg
|
| 30 |
67544-236-30 |
| 90 |
67544-236-60 |
| 600 |
67544-236-99 |
| 3000 |
67544-236-56 |
| 9000 |
67544-236-09 |
Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children.
Repackaged by:
Cookeville, TN 38506
20140707SC
PRINCIPAL DISPLAY PANEL – 120mg
id: c2982b91-776e-4d9c-b5f3-90d8220cf57a
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
NDC 43353-917 – Isosorbide Mononitrate ER 120mg – Rx Only
