DESCRIPTION
id: 65935a15-a008-1941-e053-2991aa0a5eb4
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 Isosorbide mononitrate extended-release tablet, USP, for oral administration contains either 30 mg or 60 mg of ISMN.
ISMN 30 mg tablets, USP containes the following inactive ingredients: colloidal silicon dioxide, compressible sugar, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate.
ISMN 60 mg tablets, USP contains the following inactive ingredients: colloidal silicon dioxide, compressible sugar, hydroxypropyl methylcellulose, yellow iron oxide, lactose monohydrate, magnesium stearate.
The molecular formula of ISMN is C
6H
9NO
6 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). ISMN is freely soluble in water, ethanol, methanol, chloroform, ethyl acetate and dichloromethane.
INDICATIONS AND USAGE
id: 65935a15-a00d-1941-e053-2991aa0a5eb4
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Isosorbide mononitrate extended-release tablets, USP are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of oral ISMN is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.
CONTRAINDICATIONS
id: 65935a15-a00e-1941-e053-2991aa0a5eb4
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: 65935a15-a00f-1941-e053-2991aa0a5eb4
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
Amplification of the vasodilatory effects of Isosorbide mononitrate extended-release tablets 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 ISMN are difficult to terminate rapidly, this drug is not recommended in these settings. If ISMN is used in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.
ADVERSE REACTIONS
id: 65935a15-a01c-1941-e053-2991aa0a5eb4
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 ISMN as 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 ISMN 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 Isosorbide mononitrate extended-release tablets treatment be initiated at low doses for several days before being increased to desired levels.
FREQUENCY AND ADVERSE EVENTS (DISCONTINUED)*
|
Three controlled North America Studies
|
|
Dose
|
Placebo
|
30 mg
|
60 mg
|
120 mg**
|
240 mg**
|
| *Some individuals discontinued for multiple reasons |
| ** Patients were started on 60 mg and titrated to their final dose |
| 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, somnolenc
Red Blood Cell Disorder: Hypochromic anemiae.
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 (ISMN): syncope.
DOSAGE AND ADMINISTRATION
id: 65935a15-a020-1941-e053-2991aa0a5eb4
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
The recommended starting dose of Isosorbide mononitrate extended-release tablets is 30 mg (given 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 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 30 mg tablet.
HOW SUPPLIED
id: 65935a15-a021-1941-e053-2991aa0a5eb4
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Isosorbide mononitrate extended-release tablets, USP (30 mg): White, biconvex oval shaped tablets, scored and embossed “30” on one side.
Bottle of 30 NDC 23155-519-03
Bottle of 100 NDC 23155-519-01
Bottle of 500 NDC 23155-519-05
Isosorbide mononitrate extended-release tablets, USP (60 mg): Light yellow, biconvex oval shaped tablets, scored on both sides and embossed ‘DX 31’ on one side.
Bottle of 90 NDC 23155-178-09
Bottle of 100 NDC 23155-178-01
Bottle of 500 NDC 23155-178-05
STORAGE
Store at 20° to 25°C (68° to 77°F) (see USP Controlled Room Temperature). Protect from excessive moisture.
Manufactured for:
Heritage Pharmaceuticals Inc.
Eatontown, NJ 07724 1.866.901. DRUG (3784)
Manufactured by: Dexcel Ltd.
1 Dexcel St. Or-Akiva 3060000, Israel
Issued: 11/16
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
id: 65935a15-a026-1941-e053-2991aa0a5eb4
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
