ities and with central volume expansion. 7. 2 antihypertensives patients receiving antihypertensive drugs, beta-adrenergic blockers, and nitrates should 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.

iomyopathy. 5.4 headache nitroglycerin produces dose-related headaches, especially at the start of nitroglycerin therapy, which may be severe and persistent but usually subside with continued use.

ed spray of nitrolingual pumpspray delivers 48 mg of solution containing 400 mcg of nitroglycerin after an initial priming of five sprays. it will remain adequately primed for 6 weeks. if the product is not used within 6 weeks it can be adequately re-primed with one spray. if the product is not used within 3 months it can be adequately re-primed 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.

estimate their frequency reliably or establish a causal relationship to drug exposure. neurologic: weakness, drowsiness dermatologi c: cutaneous vasodilation, flushing, drug rash, exfoliative dermatitits gastrointestinal: nausea, vomiting respiratory: transient hypoxemia cardiovascular: tachycardia

ities and with central volume expansion. 7. 2 antihypertensives patients receiving antihypertensive drugs, beta-adrenergic blockers, and nitrates should 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 u se 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.

rabbits up to 4 mg/kg/day for 13 days.

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 nitrolingual pumpspray was administered to healthy volunteers (n = 24), the mean c max and t max 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.

x 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 f 0 generation with treatment continuing through successive f 1 and f 2 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 f 0 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.

dy, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for six months prior to mating of the f 0 generation with treatment continuing through successive f 1 and f 2 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 f 0 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.

nitrolingual pumpspray ? it is best to use nitrolingual pumpspray while you are resting and in a sitting position. do not shake the nitrolingual pumpspray container. priming nitrolingual pumpspray : before you use nitrolingual pumpspray for the first time, you must prime it. to prime your nitrolingual pumpspray, follow the steps below: step 1. remove the plastic cap from the container. (see figure b) figure b step 2. hold the container upright and facing away from yourself and others. press down on the top of the grooved button 5 times. (see figure c) figure c your nitrolingual pumpspray is now primed. you are ready to give your first dose. if you do not use your nitrolingual pumpspray within 6 weeks, you will need to prime it again by pressing down on the top of the grooved button 1 time. if you do not use your nitrolingual pumpspray within 3 months, you will need to re-prime it by pressing down on the top of the grooved button up to 5 times. giving a dose of nitrol i ngual pumpspray : step 3. hold your nitrolingual pumpspray container upright with your index finger on top of the grooved button. step 4. open your mouth and bring the nitrolingual pumpspray container as close to your mouth as possible. step 5. press down on the top of the grooved button firmly with your index finger to release the spray onto or under your tongue. (see figure d). the grooved button can help you make sure the canister is turned to the correct position if you are administering the spray in the dark. figure d step 6. release the grooved button and close your mouth right away. avoid swallowing right after using nitrolingual pumpspray. do not spit out nitrolingual pumpspray or rinse your mouth for 5 to 10 minutes after using nitrolingual pumpspray. step 7. if a second dose of nitrolingual pumpspray is needed, repeat steps 3 through 6 above. step 8. replace the plastic cap. check the level of the fluid in your nitrolingual pumpspray container regularly. check the container in an upright position. the end of the center tube should be covered by the fluid in the nitrolingual pumpspray container. if the level of the fluid falls below the end of the center tube, sprays will not provide enough nitrolingual pumpspray. replace your nitrolingual pumpspray container before the fluid level falls below the end of the center tube. how should i store nitrolingual pumpspray? store nitrolingual pumpspray at room temperature between 68°f - 77°f (20°c - 25°c). do not forcefully open or burn the nitrolingual pumpspray container after use. do not spray nitrolingual pumpspray toward flames. keep nitrolingual pumpspray and all medicines out of the reach of children . this instructions for use has been approved by the u.s. food and drug administration. manufactured for allegis pharmaceuticals, llc canton, ms 39046 by g. pohl-boskamp gmbh & co. kg, 25551 hohenlockstedt, germany. revised: 07/2019 the following trademarks are either registered trademarks or trademarks of pohl-boskamp in the united states and / or other countries: pohl-boskamp word mark; pohl-boskamp logo; nitrolingual word mark; nitrolingual pumpspray shapes, nitrolingual pumpspray colors. nitrolingual pumpspray parts:figure a remove the plastic cap from the container. (see figure b) hold the container upright and facing away from yourself and others. press down on the top of the grooved button 5 times. (see figure c) press down on the top of the grooved button firmly with your index finger to release the spray onto or under your tongue. (see figure d). the grooved button can help you make sure the canister is turned to the correct position if you are administering the spray in the dark.