Isosorbide 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). 

Nitrates have been suggested in patients who do not achieve therapeutic goals (heart rate reduction) with P-blocker therapy alone. Trials to evaluate the effects of nitrates (e.g., isosorbide mononitrate) on portal pressure, both alone and in combination with P-blockers, show enhanced reduction of portal pressure however, there is an increase in mortality when nitrates are used alone. Adverse effects are significantly higher in patients treated with the combination of non-selective P-blockers and nitrates as opposed to P-blocker monotherapy.42,43 Unfortunately,... 

Variceal bleeding is a frequent and serious event in cirrhosis, and carries an increased risk of death (SEDA-22, 218). Therapy to prevent bleeding is therefore essential in these patients. Propranolol alone has been compared with propranolol plus isosorbide-5-mononitrate in a randomized, double-blind study in 95 patients (21). The combined treatment reduced the incidence of variceal bleeding compared with propranolol alone, but without any improvement in survival Isosorbide-5-mononitrate added to propranolol appeared to be less well tolerated than propranolol alone, since seven patients had to be withdrawn from treatment because of adverse effects (four with feehngs of faintness, two with headache, one with angina-like chest pain), compared with one with atrioventricular block taking propranolol alone. 

Isosorbide-5-mononitrate has been tested with and without propranolol in a placebo-controlled study in 30 patients with liver cirrhosis and esophageal varices (22). The aim of the study was to assess the severity of previously reported adverse effects (that is renal dysfunction and hepatic encephalopathy) when vasoactive drugs are used to prevent variceal bleeding. Neither isosorbide-5-mononitrate nor propranolol alone or together had any adverse effect on subclinical hepatic encephalopathy or renal function in patients with well-compensated cirrhosis. Severe headache in those taking isosorbide caused three patients to withdraw. 

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. ... 

Orthostatic hypotension occurred when levosimendan was given with isosorbide mononitrate. The haemodynamic effects of levosimendan were not significantly altered by captopiil, carvedilol or other unnamed beta blockers, or felodipine. Levosimendan does not alter the effects of warfarin. Itraconazole does not alter the pharmacokinetics of levosimendan. Levosimendan appears not to interact adversely with alcohoL... 

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