Isosorbide mononitrate 30% immediate-release 70% sustained-release formulation: A review

Since the first publication of isosorbide mononitrate 30% immediate-release 70% sustained-release (IR-SR) formulation in 1985, a considerable body of literature concerning its clinical efficacy and safety has become available . Theoretically, the formulation has the advantage over conventional isosor bide mononitrate pr dinitrate (ISMN/ISDN) that it has a simpler and more pr edictable pharmacokinetic profile. The objectives of this paper are to revi ew published data so far and to see whether the theoretical advantages tran slate into better clinical effectiveness. 1. After oral administration, isosorbide mononitrate IR-SR has a rapid onse t of action (30 minutes), and effects are evident for up to 17 hours. 2. The antianginal effects of once-daily isosorbide mononitrate IR-SR incre ased with increasing dosages, were generally larger than those of either pl acebo or equipotent doses of conventional ISMN/ISDN, and were somewhat larg er than those of the beta blocker bupranolol. The effects were generally si milar to those of sustained release nifedipine. 3. Patients showed significantly greater improvement in some quality-of-lif e indices with once-daily isosorbide mononitrate IR-SR than with twice or t hree times daily regimens of conventional ISMN/ISDN. This was particularly so with mobility, psychological distress, and life satisfaction indices. 4. Tolerance did not develop after 13 months of once daily isosorbide dinit rate IR-SR. No rebound increase in incidence of ischemic episodes was obser ved after discontinuation of treatment. 5. Long-term efficacy data both of isosorbide mononitrate IR-SR and of conv entional ISMN/ISDN are limited so far. Large studies in patients with angin a pectoris and patients with heart failure addressing long-term effects are ongoing, and some of the data will be completed within the next months. Isosorbide mononitrate IR-SR has a rapid onset of action and has been shown to be clinically efficient and, in addition, to be more so than convention al ISMN / ISDN. Nitrate tolerance with continued use of the formulation has not yet been reported. Long-term effects on morbidity and mortality are cu rrently being assessed.