Isosorbide dinitrate adverse effects

Isosorbide is rapidly absorbed and undergoes rapid first-pass metaboHsm by the Hver. The bioavaUabUity of the subHngual and chewable tablets is 59% and 22%, respectively, for the regular tablet. Isosorbide is metabolized to isosorbide-2-mononitrate and isosorbide-5-mononitrate, both of which have pharmacologic activity. The elimination half-Hves of subHngual and po isosorbide dinitrate ate 1 and 4 h, respectively. Those of the 2- and 5-mononitrate metaboHtes are 1.5—3.1 h and 4—5.6 h, respectively. The two metaboHtes prolong the elimination half-life of the dinitrate. Adverse effects with isosorbide are similar to those described for nitroglycerin (99). 

The adverse effects of the nitrates are unaffected by the chemical form or by the route of administration. The spectrum and frequency of adverse effects for the individual drugs, such as glyceryl trinitrate, isosorbide dinitrate, and isosorbide-5-mononitrate, appear to be similar. 

Compared with placebo, the combination of hydralazine and isosorbide dinitrate (ISDN) reduced mortality in patients receiving diuretics and digoxin (but not ACE inhibitors or /3-blockers). However, another trial comparing the combination with an ACE inhibitor found that mortality was lower in the ACE inhibitor group. Adverse effects (primarily headache and gastrointestinal complaints) with combined hydralazine-ISDN were common, limiting their use in many patients. Patient compliance also was an important issue because hydralazine-ISDN therapy was given four times daily in these trials. Whether less frequent administration provides equivalent benefit is unknown. 

Comparative studies In a randomized blinded comparison of botulinum toxin with isosorbide dinitrate in the treatment of chronic anal fissure, adverse effects were similar in the two groups [51. ... 

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