hould be observed for possible additive hypotensive effects. marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly. beta-adrenergic blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. if beta-blockers are used with nitroglycerin in patients with angina pectoris, additional hypotensive effects may occur. 7.3 ergotamine oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. ergotamine is known to precipitate angina pectoris. therefore, patients receiving sublingual nitroglycerin should avoid ergotamine and related drugs or be monitored for symptoms of ergotism if this is not possible.

lycerin therapy, which may be severe and persistent but usually subside with continued use.

ed with up to five sprays. there are 60 or 200 metered sprays per bottle. the total number of available doses is dependent, however, on the number of sprays per use (1 or 2 sprays), and the frequency of priming. 2.3 administration instruct patients that during administration, the patient should rest, ideally in the sitting position. hold the container vertically with the valve head uppermost and the spray orifice as close to the mouth as possible. spray the dose preferably onto or under the tongue by pressing the grooved-button firmly and the mouth closed immediately after each dose. the spray should not be inhaled. the medication should not be expectorated or the mouth rinsed for 5 to 10 minutes following administration. instruct patients to familiarize themselves with the position of the spray orifice, which can be identified by the finger rest on top of the valve, in order to facilitate orientation for administration at night [see patient information ( 17 ]. the amount of liquid remaining in the container should be checked periodically. the transparent container can be used for continuous monitoring of the consumption. with the container upright and level, check to be sure the end of the center tube extends below the level of the liquid. once fluid falls below the level of the center tube, remaining sprays will not deliver intended dose.

t hypoxemia cardiovascular: tachycardia

hould be observed for possible additive hypotensive effects. marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly. beta-adrenergic blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. if beta-blockers are used with nitroglycerin in patients with angina pectoris, additional hypotensive effects may occur. 7.3 ergotamine oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. ergotamine is known to precipitate angina pectoris. therefore, patients receiving sublingual nitroglycerin should avoid ergotamine and related drugs or be monitored for symptoms of ergotism if this is not possible.

intravenous doses in pregnant rabbits up to 4 mg/kg/day for 13 days. 8.2 lactation risk summary sublingual nitroglycerin has not been studied in lactating women. it is not known if nitroglycerin is present in human milk or if nitroglycerin has effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for nitroglycerin and any potential adverse effects on the breastfed child from nitroglycerin or from the underlying maternal condition. 8.4 pediatric use safety and effectiveness of nitroglycerin in pediatric patients have not been established. 8.5 geriatric use clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between elderly (greater than or equal to 65 years) and younger (less than 65 years) patients. in general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

icardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear. therapeutic doses of nitroglycerin may reduce systolic, diastolic and mean arterial blood pressure. effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively or increased heart rate decreases diastolic filling time. elevated central venous and pulmonary capillary wedge pressures, and pulmonary and systemic vascular resistance are also reduced by nitroglycerin therapy. heart rate is usually slightly increased, presumably a reflex response to the fall in blood pressure. cardiac index may be increased, decreased, or unchanged. myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased and a more favorable supply-demand ratio can be achieved. patients with elevated left ventricular filling pressure and increased systemic vascular resistance in association with a depressed cardiac index are likely to experience an improvement in cardiac index. in contrast, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced following nitroglycerin administration. 12.3 pharmacokinetics a liver reductase enzyme is of primary importance in the metabolism of nitroglycerin to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. known sites of extrahepatic metabolism include red blood cells and vascular walls. in addition to nitroglycerin, 2 major metabolites, 1,2- and 1,3-dinitroglycerin are found in plasma. the mean elimination half-life of both 1,2- and 1,3-dinitroglycerin is about 40 minutes. the 1,2- and 1,3-dinitroglycerin metabolites have been reported to possess some pharmacological activity, whereas the glycerol mononitrate metabolites of nitroglycerin are essentially inactive. higher plasma concentrations of the dinitro metabolites, with their nearly 8-fold longer elimination half-lives, may contribute significantly to the duration of pharmacologic effect. in a pharmacokinetic study when a single 0.8 mg dose of nitroglycerin lingual spray was administered to healthy volunteers (n = 24), the mean cmax and tmax were 1,041 pg/ml and 7.5 minutes, respectively. additionally, in these subjects the mean area under the curve (auc) was 12,769 pg/ml * min. the volume of distribution of nitroglycerin following intravenous administration is 3.3 l/kg. drug interactions aspirin: coadministration of nitroglycerin with high dose aspirin (1000 mg) results in increased exposure to nitroglycerin. the vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant administration of nitroglycerin with high dose aspirin. tissue-type plasminogen activator (t-pa): concomitant administration of t-pa and intravenous nitroglycerin has been shown to reduce plasma levels of t-pa and its thrombolytic effect.

eneration reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for six months prior to mating of the f0 generation with treatment continuing through successive f1 and f2 generations. the high dose was associated with decreased feed intake and body weight gain in both sexes at all matings. no specific effect on the fertility of the f0 generation was seen. infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high- dose males. in this three-generation study there was no clear evidence of teratogenicity.

nitroglycerin lingual spray contains 20 % alcohol. do not forcefully open or burn container after use. do not spray toward flames. rx only.