Molecule Info

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Description

Isosorbide Mononitrate (diluted), USP, an organic nitrate, is a vasodilator with effects on both arteries and veins. The molecular formula is C6H9NO6 and the molecular weight is 191.14. The chemical name for Isosorbide Mononitrate is 1,4:3,6-Dianhydro-D-glucitol 5-nitrate.

Isosorbide Mononitrate tablets, USP, for oral administration, contain 10 mg or 20 mg of Isosorbide Mononitrate (diluted), USP. In addition, each tablet contains the following inactive ingredients: calcium stearate, colloidal silicon dioxide, corn starch, FD&C Blue #1HT Aluminum Lake, lactose monohydrate, microcrystalline cellulose, and talc.

Indication(s) & Dosage

Isosorbide Mononitrate (ISMN) tablets are indicated for the prevention and treatment 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.

Management of angina, Heart failure
Adult: 20 mg 2-3 times daily,oral. Dose may range from 20-120 mg daily.
Elderly: Intiate at lower doses.

Administration
Should be taken with food.
Overdosage
Symptoms: Increased intracranial pressure, with or without persistent throbbing headache, confusion and moderate fever, vertigo, palpitations, visual disturbances, nausea and vomiting.
Contraindications
Severe hypotension or anaemia, hypovolaemia, heart failure due to obstruction, or raised intracranial pressure due to head trauma or cerebral haemorrhage.
Warning

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 Isosorbide Mononitrate 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.

Special Precautions
Severe renal or severe hepatic impairment, hypothyroidism, malnutrition, or hypothermia. Caution in patients who are already hypotensive. May aggravate angina caused by hypertrophic cardiomyopathy. Tolerance may develop after long-term treatment. Lactation.
Adverse Drug Reaction(s)
Hypotension, tachycardia, flushing, headache, dizziness, palpitation, syncope, confusion. Nausea, vomiting, abdominal pain. Restlessness, weakness and vertigo. Dry mouth, chest pain, back pain, oedema, fatigue, abdominal pain, constipation, diarrhoea, dyspepsia and flatulence.
Potentially Fatal: Severe hypotension and cardiac failure.
Drug Interactions
Hypotensive effects may be increased when used with alcohol or vasodilators. Concurrent use with calcium channel blockers may lead to marked orthostatic hypotension.
Potentially Fatal: Significant hypotension may occur when used with phosphodiesterase-5 inhibitors. Please consult detailed drug interactions before prescribing.
Lab Interference
False decrease in serum cholesterol.
Pregnancy Category (FDA)
Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Storage
Oral: Store at 20-25°C.
Pharmacology
Isosorbide Mononitrate - Clinical Pharmacology

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 is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation 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.

Pharmacodynamics: Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continuously 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 Isosorbide Mononitrate 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 asymmetric twice-daily regimen of Isosorbide Mononitrate tablets successfully avoided significant rebound/withdrawal effects. The incidence and magnitude of such phenomena have appeared, in studies of other nitrates, to be highly dependent upon the schedule of nitrate administration.

Pharmacokinetics: Isosorbide Mononitrate is rapidly and completely absorbed from the gastrointestinal tract. In humans, Isosorbide Mononitrate is not subject to first pass metabolism in the liver. The absolute bioavailability of Isosorbide Mononitrate tablets is nearly 100%. Peak plasma concentrations usually occur in about 30-60 minutes. Isosorbide Mononitrate exhibits dose proportionality over the recommended dose range. Food does not significantly affect the absorption or bioavailability of Isosorbide Mononitrate. Metoprolol coadministration did not change the pharmacokinetics of Isosorbide Mononitrate. The volume of distribution is approximately 0.6 L/Kg. Plasma protein binding of Isosorbide Mononitrate was found to be less than 5%.

When radiolabelled Isosorbide Mononitrate was administered to humans in order to elucidate the metabolic fate, about half of the dose was found denitrated and renally excreted as isosorbide and sorbitol. One quarter of the dose was accounted for as conjugates of the parent drug in the urine. None of these metobolites is vasoactive. Only two percent (2%) of the dose was excreted as unchanged drug.

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. When radiolabelled, Isosorbide Mononitrate was administered to humans, ninety-three percent (93%) of the dose was excreted within 48 hours into the urine. Renal excretion was virtually complete after 5 days; fecal excretion amounted to only 1% of the dose.

Isosorbide Mononitrate has no known effect on renal and hepatic function. In patients with varying degrees of renal failure, dosage adjustment does not appear necessary. In patients with liver cirrhosis, the pharmacokinetic parameters after a single dose of Isosorbide Mononitrate were similar to the values found in healthy volunteers.

Isosorbide Mononitrate is significantly removed from the blood during hemodialysis; however, an additional dose to compensate for drug lost is not necessary. In patients undergoing continuous ambulatory peritoneal dialysis, blood levels are similar to patients not on dialysis.

Clinical Trials: The acute and chronic antianginal efficacy of Isosorbide Mononitrate has been confirmed in clinical trials. The clinical efficacy of Isosorbide Mononitrate was studied in 21 stable angina pectoris patients. After single dose administration of Isosorbide Mononitrate, 20 mg, the exercise capacity was increased by 42.7% after one hour, 29.6% after 6 hours, and by 25% after eight hours when compared to placebo. Controlled trials of single doses of Isosorbide Mononitrate tablets have demonstrated that antianginal activity is present about 1 hour after dosing, with peak effect seen from 1-4 hours after dosing.

In one multicenter placebo-controlled trial, Isosorbide Mononitrate was found to be safe and effective during acute and chronic (3 weeks) treatment of angina pectoris. Two hundred fourteen (214) patients were enrolled in the trial; 54 patients were randomized to receive placebo and 106 patients were randomized to receive 10 or 20 mg of Isosorbide Mononitrate twice daily seven hours apart. The largest effect of Isosorbide Mononitrate, compared to placebo, was on day

one — dose one. Although 14 hours after the first dose of day 14, the increase in exercise tolerance due to Isosorbide Mononitrate was statistically significant, the increase was about half of that seen 2 hours after the first dose of day one. On day 21, two hours after the first dose the effect of Isosorbide Mononitrate was 60 to 70% of that seen on day one.

Isosorbide mononitrate relaxes vascular smooth muscles by stimulating cyclic-GMP and thereby tt decreases left ventricular pressure (preload) and arterial resistance (postload).
Onset: 20 min (oral as conventional tab).
Duration: 8-10 hr (oral as conventional tab).
Absorption: Readily absorbed from the GIT (oral); peak plasma concentrations after 1 hr.
Distribution: Widely distributed: Smooth muscle cells of the blood vessels.
Metabolism: Converted to inactive metabolites including isosorbide and isosorbide glucuronide.
Excretion: Via urine (2% as unchanged); 4-5 hr (elimination half-life).

ATC Classification
C01DA14 - isosorbide mononitrate; Belongs to the class of organic nitrate vasodilators. Used in the treatment of cardiac disease.

Brand/Product Info


Total Products : 13             
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
A-CARD The Acme Laboratories Ltd. Isosorbide mononitrate 20mg Tablet 100's: 142.00 MRP
Angifix 20 Incepta Pharmaceuticals Limited Diluted Isosorbide Mononitrate BP equivalent to Isosorbide-5-Mononitrate 20 Tablet 10x5's:MRP 71 Tk
ESMO Square Pharmaceuticals Ltd. Isosorbide Mononitrate 20mg Tablet 100's: 142.00 MRP
ESMO Square Pharmaceuticals Ltd. Isosorbide Mononitrate 20mg Tablet 10x10's: 143.00 MRP
ESMO LA Square Pharmaceuticals Ltd. Isosorbide Mononitrate 50mg Capsule 30's: 210.60 MRP
ISM Aristopharma Ltd. Isosorbide mononitrate 20mg Tablet 100's: 140.00 MRP
ISOCONTIN The White Horse Pharma Isosorbide mononitrate 20mg Tablet 50's: 71.00 MRP
MONATE Beximco Pharmaceuticals Ltd Isosorbide Mononitrate 20 mg Tablet 100's: 142.00 MRP
MONITEN ACI Ltd. Isosorbide mononitrate 20mg Tablet 100's: 142.00 MRP
MONOCARD Drug International Ltd Isosorbide mononitrate 20mg Tablet 100's: 150.00 MRP
MONOCARD SR Drug International Ltd Isosorbide mononitrate 50mg Capsule (sustained release) 40's: 280.00 MRP
MONOTRATE Sun Pharmaceutical (Bangladesh) Ltd. Isosorbide-5-mononitrate 20mg Tablet 50's: 71.00 MRP
MONOTRATE OD Sun Pharmaceutical (Bangladesh) Ltd. Isosorbide-5-mononitrate 50mg Tablet 30's: 123.90 MRP
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