Isosorbide mononitrate contraindications
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]
Isosorbide mononitrate extended-release tablets are contraindicated in patients who have shown hypersensitivity or idiosyncratic reactions to other nitrates or nitrites.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No evidence of carcinogenicity was observed in rats exposed to Isosorbide Mononitrate (ISMN) in their diets at doses of up to 900 mg/kg/day for the first 6 months and 500 mg/kg/day for the remaining duration of a study in which males were dosed for up to 121 weeks and females were dosed for up to 137 weeks. No evidence of carcinogenicity was observed in mice exposed to isosorbide mononitrate in their diets for up to 104 weeks at doses of up to 900 mg/kg/day.
ISMN did not produce gene mutations (Ames test, mouse lymphoma test) or chromosome aberrations (human lymphocyte and mouse micronucleus tests) at biologically relevant concentrations.
No effects on fertility were observed in a study in which male and female rats were administered doses of up to 750 mg/kg/day beginning, in males, 9 weeks prior to mating, and in females, 2 weeks prior to mating.
Pregnancy
Teratogenic Effects
Pregnancy category B. In studies designed to detect effects of ISMN on embryo-fetal development, doses of up to 240 or 248 mg/kg/day, administered to pregnant rats and rabbits, were unassociated with evidence of such effects. These animal doses are about 100 times the maximum recommended human dose (120 mg in a 50 kg woman) when comparison is based on body weight; when comparison is based on body surface area, the rat dose is about 17 times the human dose and the rabbit dose is about 38 times the human dose. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Isosorbide mononitrate extended-release tablets should be used during pregnancy only if clearly needed.
Nonteratogenic Effects
Neonatal survival and development and incidence of stillbirths were adversely affected when pregnant rats were administered oral doses of 750 (but not 300) mg ISMN/kg/day during late gestation and lactation. This dose (about 312 times the human dose when comparison is based on body weight and 54 times the human dose when comparison is based on body surface area) was associated with decreases in maternal weight gain and motor activity and evidence of impaired lactation.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ISMN is administered to a nursing mother.
Pediatric Use
The safety and effectiveness of ISMN in pediatric patients have not been established.
Geriatric Use
Clinical studies of Isosorbide Mononitrate Extended-release Tablets did not include sufficient information on patients age 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience for Isosorbide Mononitrate Extended-release tablets has not identified differences in response between elderly and younger patients. Clinical experience for organic nitrates reported in the literature identified a potential for severe hypotension and increased sensitivity to nitrates in the elderly. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the doing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of the concomitant disease or other drug therapy.
Elderly patients may have reduced baroreceptor function and may develop severe orthostatic hypotension when vasodilators are used. Isosorbide Mononitrate Extended-release Tablets should therefore be used with caution in elderly patients who may be volume depleted, on multiple medications or who, for whatever reason, are already hypotensive. Hypotension induced by isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.
Elderly patients may be more susceptible to hypotension and may be at greater risk of falling at therapeutic doses of nitroglycerin.
Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy, particularly in the elderly.[1]
References
- ↑ "ISOSORBIDE MONONITRATE TABLET [ZYDUS PHARMACEUTICALS (USA) INC.]". Retrieved 30 January 2014.