Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3997
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Ismo (Tablet, Film Coated)
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| dailymed-instance:clinicalP... |
Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate (ISDN), and most of the clinical activity of the dinitrate is attributable to the mononitrate. The principal pharmacological action of isosorbide mononitrate, due to its nitric oxide metabolite, is direct relaxation of
vascular smooth muscle. The result is dilatation of peripheral arteries and veins, especially the latter. 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). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction,
afterload reduction, and coronary dilatation remains undefined.<br/>Pharmacodynamics: Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are
continu-ously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates.
Several well-controlled clinical trials have used exercise testing to assess the antianginal efficacy of continuously
delivered nitrates. In the large majority of these trials, active agents were indistinguishable from placebo after 24
hours (or less) of continuous therapy. Attempts to overcome tolerance by dose escalation, even to doses far in
excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several
hours has their antianginal efficacy been restored. The drug-free interval sufficient to avoid tolerance to isosorbide
mononitrate has not been completely defined. In the only regimen of twice-daily isosorbide mononitrate that has
been shown to avoid development of tolerance, the two doses of Ismo tablets are given 7 hours apart, so there is a
gap of 17 hours between the second dose of each day and the first dose of the next day. Taking account of the relatively
long half-life of isosorbide mononitrate this result is consistent with those obtained for other organic nitrates. The same
twice-daily regimen of Ismo tablets successfully avoided significant rebound/withdrawal effects. Theincidence and
magnitude of such phenomena have appeared, in studies of other nitrates, to be highly dependent upon the schedule
of nitrate administration.<br/>Pharmacokinetics: In humans, isosorbide mononitrate is not subject to first pass metabolism in the liver. The absolute bioavailability
of isosorbide mononitrate from Ismo tablets is nearly 100%. Maximum serum concentrations of isosorbide mononitrate
are achieved 30 to 60 minutes after ingestion of Ismo. The volume of distribution of isosorbide mononitrate is
approximately 0.6 L/kg, and less than 4% is bound to plasma proteins. It is cleared from the serum by denitration to
isosorbide; glucuronidation to the mononitrate glucuronide; and denitration/hydration to sorbitol. None of these
metabolites is vasoactive. Less than 1% of administered isosorbide mononitrate is eliminated in the urine. The overall
elimination half-life of isosorbide mononitrate is about 5 hours; the rate of clearance is the same in healthy young adults
, in patients with various degrees of renal, hepatic, or cardiac dysfunction, and in the elderly. In a single-dose study, the
pharmacokinetics of isosorbide mononitrate were dose-proportional up to at least 60 mg.<br/>Clinical Trials: Controlled trials of single doses of Ismo tablets have demonstrated that antianginal activity is present about 1 hour
after dosing, with peak effect seen from 1 to 4 hours after dosing. In placebo-controlled trials lasting 2 to 3 weeks,
Ismo tablets were administered twice daily, in asymmetric regimens (with interdosing intervals of 7 and 17 hours)
designed to avoid tolerance. One trial testeddoses of 10 mg and 20 mg; one trial tested doses of 20 mg, 40 mg, and
60 mg; and three trials tested only doses of 20 mg. In each trial, the subjects were persons with known chronic stable
angina, and the primary measure of efficacy was exercise tolerance on a standardized treadmill test. After initial dosing
and for at least 3 weeks, exercise tolerance in patients treated with Ismo 20 mg tablets was significantly greater than
that seen in patients treated with placebo, although there was some attenuation of effect with time. Treatment with Ismo
tablets was superior to placebo for at least 12 hours after the first dose (i.e., 5 hours after the second dose) of each day.
Significant tolerance and rebound phenomena were not observed. The 10-mg dose was not unequivocally superior to
placebo, while the effect of the 40-mg dose was similar to that of the 20-mg dose. The 60-mg dose appeared to be less
effective, and it was associated with a rebound phenomenon (early-morning worsening).
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| dailymed-instance:supply |
Ismo (isosorbide mononitrate) tablets, 20 mg, are available in bottles of 100 (NDC 67857-702-01). Each
orange, round, film-coated tablet is engraved���ISMO 20���on one side and scored on the reverse side. Store at 20 - 25��C (68 -77��F) [See USP Controlled Room Temperature]. Dispense in tight container.
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| dailymed-instance:genericDr... | |
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... |
dailymed-ingredient:D&C_Yellow_10_Aluminum_Lake,
dailymed-ingredient:FD&C_Yellow_6_Aluminum_Lake,
dailymed-ingredient:colloidal_silicon_dioxide,
dailymed-ingredient:hydroxypropyl_cellulose,
dailymed-ingredient:hydroxypropyl_methylcellulose,
dailymed-ingredient:lactose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:polysorbate_20,
dailymed-ingredient:povidone,
dailymed-ingredient:sodium_starch_glycolate,
dailymed-ingredient:titanium_dioxide
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| dailymed-instance:genericMe... |
isosorbide mononitrate
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| dailymed-instance:fullName |
Ismo (Tablet, Film Coated)
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| dailymed-instance:adverseRe... |
The table below shows the frequencies of the adverse reactions observed in more than 1% of the subjects (a) in 6
placebo-controlled domestic studies in which patients in the active-treatment arm received 20 mg of isosorbide mononitrate twice
daily, and (b) in all studies in which patients received isosorbide mononitrate in a variety of regimens. In parentheses, the same
table shows the frequencies with which these adverse reactions led to discontinuation of treatment. Overall, 11% of the patients
who received isosorbide mononitrate in the six controlled U.S. studies discontinued treatment because of adverse reactions. Most
of these discontinued because of headache.���Dizziness���and nausea were also frequently associated with withdrawal from these
studies. Other adverse reactions, each reported by fewer than 1% of exposed patients, and in many cases of uncertain relation to
drug treatment, were:: Cardiovascular: angina pectoris, arrhythmias, atrial fibrillation, hypotension, palpitations, postural hypotension, premature
ventricular contractions, supraventricular tachycardia, syncope. Dermatologic: pruritus, rash. Gastrointestinal: abdominal pain, diarrhea, dyspepsia, tenesmus, tooth disorder, vomiting. Genitourinary: dysuria, impotence, urinary frequency. Miscellaneous: asthenia, blurred vision, cold sweat, diplopia, edema, malaise, neck stiffness, rigors. Musculoskeletal: arthralgia. Neurological: agitation, anxiey, confusion, dyscoordination, hypoesthesia, hypokinesia, increased appetite, insomnia,
nervousness, nightmares. Respiratory: bronchitis, pneumonia, upper-respiratory tract infection. Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients; for futher
discussion of its diagnosis and treatment see under OVERDOSAGE.
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| dailymed-instance:indicatio... |
Ismo 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.
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| dailymed-instance:name |
Ismo
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