Country: Canada
Language: English
Source: Health Canada
ISOSORBIDE-5-MONONITRATE
DOMINION PHARMACAL
C01DA14
ISOSORBIDE MONONITRATE
60MG
TABLET (EXTENDED-RELEASE)
ISOSORBIDE-5-MONONITRATE 60MG
ORAL
100
Ethical
NITRATES AND NITRITES
Active ingredient group (AIG) number: 0120456002; AHFS:
APPROVED
2008-04-23
PRODUCT MONOGRAPH Pr DOM-ISMN (isosorbide-5-mononitrate) 60 mg extended release tablets Antianginal Agent DOMINION PHARMACAL . 6111 Royalmount Ave., Suite 100 Montreal, Quebec H4P 2T4 Date of Revision: April 12, 2011 Submission Control No.: 145482 _ _ _Page 2 of 24 _ PRODUCT MONOGRAPH NAME OF DRUG Dom-ISMN (isosorbide-5-mononitrate) 60 mg extended release tablets THERAPEUTIC CLASSIFICATION Antianginal agent ACTIONS AND CLINICAL PHARMACOLOGY As with other organic nitrates, the principal pharmacological action of isosorbide-5-mononitrate, the major active metabolite of isosorbide dinitrate (ISDN), is relaxation of vascular smooth muscle and consequent dilation 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 (pre- load). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (after-load). Dilation of the coronary arteries also occurs. The hemodynamic responses to isosorbide-5-mononitrate are similar to those produced by other nitrates. PHARMACODYNAMICS Dosage 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. Prolonged administration of nitrate drugs according to traditionally recommended dosage regimens has been shown to produce tolerance. Tolerance results in a loss of efficacy. 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, nitrate effectiveness was 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 nit Read the complete document