Nitroglycerin in 5% Dextrose Injection
` For intravenous use only
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`Description
`
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`Nitroglycerin is 1,2,3-propanetriol trinitrate, an organic nitrate whose structural formula
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`is
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`whose empiric formula is C3H5N3O9, and whose molecular weight is 227.09. The
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`organic nitrates are vasodilators, active on both arteries and veins.
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`Dextrose (Dextrose Hydrous, USP) is D-glucose monohydrate, a hexose sugar whose
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`structural formula is
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`whose empiric formula is C6H12O6 • H2O, and whose molecular weight is 198.17.
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`Nitroglycerin in 5% Dextrose Injection is a sterile, nonpyrogenic solution of nitroglycerin
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`and dextrose in water for injection. The solution is clear and practically colorless. Each
`100 mL contains 10 mg, 20 mg, or 40 mg nitroglycerin (added as Diluted Nitroglycerin,
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`USP with propylene glycol); 5 g Dextrose Hydrous, USP; 0.84 mL Alcohol, USP (added
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`as a dissolution aid); and 105 mg Citric Acid Hydrous, USP (added as a buffer). The pH
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`of the solution is adjusted with sodium hydroxide and, if necessary, hydrochloric acid.
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`Although dry nitroglycerin is explosive, nitroglycerin in 5% dextrose is not.
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`Composition, osmolarity and pH are given in Table 1.
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`Reference ID: 3638427
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`Ex. 2035-0001
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`

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` Table 1
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` Composition
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`Nitroglycerin
`
`(mcg/mL)
`
`
`Dextrose
`
`
` Hydrous, USP
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` (g/L)
`
`
`
`
`100
`
`
`200
`
`
`400
`
`
`50
`
`
`50
`
`
`50
`
`
`
`
` *Osmolarity
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` (mOsmol/L)
`
` (calc)
`
`
`
` pH
`
`428
`
`
`440
`
`
`465
`
`
`
`4.0
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`(3.0 to 5.0)
`
`
`
`4.0
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`(3.0 to 5.0)
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`
`
`4.0
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`(3.0 to 5.0)
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` 25 mg Nitroglycerin
` in 5% Dextrose Injection
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`
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`50 mg Nitroglycerin
`
`in 5% Dextrose Injection
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`100 mg Nitroglycerin
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`in 5% Dextrose Injection
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`
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`* Normal physiologic osmolarity range is approximately 280 to 310 mOsmol/L.
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`Administration of substantially hypertonic solutions (≥600 mOsmol/L) may cause
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`
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`vein damage.
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`Clinical Pharmacology
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`The principal pharmacological action of nitroglycerin is relaxation of vascular smooth
`muscle and consequent dilatation of peripheral arteries and veins, especially the latter.
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`Dilatation of the veins promotes peripheral pooling of blood and decreases venous return
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`to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary
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`capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular
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`resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilatation of
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`
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`the coronary arteries also occurs. The relative importance of preload reduction, afterload
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`
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`reduction, and coronary dilatation remains undefined.
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`Dosing regimens for most chronically used drugs are designed to provide plasma
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`concentrations that are continuously greater than a minimally effective concentration.
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`This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials
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`have used exercise testing to assess the anti-anginal efficacy of continuously-delivered
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`nitrates. In the large majority of these trials, active agents were indistinguishable from
`
`placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate
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`tolerance by dose escalation, even to doses far in excess of those used acutely, have
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`consistently failed. Only after nitrates have been absent from the body for several hours
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`has their anti-anginal efficacy been restored.
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`Reference ID: 3638427
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`Ex. 2035-0002
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`

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`Pharmacokinetics: The volume of distribution of nitroglycerin is about 3 L/kg, and
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`nitroglycerin is cleared from this volume at extremely rapid rates, with a resulting serum
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`half-life of about 3 minutes. The observed clearance rates (close to 1 L/kg/min) greatly
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`
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`exceed hepatic blood flow; known sites of extrahepatic metabolism include red blood
`cells and vascular walls.
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`The first products in the metabolism of nitroglycerin are inorganic nitrate and the 1,2-and
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`1,3- dinitroglycerols. The dinitrates are less effective vasodilators than nitroglycerin, but
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`they are longer-lived in the serum, and their net contribution to the overall effect of
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`chronic nitroglycerin regimens is not known. The dinitrates are further metabolized to
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`(non-vasoactive) mononitrates and, ultimately, to glycerol and carbon dioxide.
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` To avoid development of tolerance to nitroglycerin, drug-free intervals of 10-12 hours are
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`known to be sufficient; shorter intervals have not been well studied. In one well-
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`controlled clinical trial, subjects receiving nitroglycerin appeared to exhibit a rebound or
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`withdrawal effect, so that their exercise tolerance at the end of the daily drug-free interval
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`was less than that exhibited by the parallel group receiving placebo.
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`Clinical Trials: Blinded, placebo-controlled trials of intravenous nitroglycerin have not
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`been reported, but multiple investigators have reported open-label studies, and there are
`scattered reports of studies in which intravenous nitroglycerin was tested in blinded
`fashion against sodium nitroprusside.
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`In each of these studies, therapeutic doses of intravenous nitroglycerin were found to
`reduce systolic and diastolic arterial blood pressure. The heart rate was usually
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`increased, presumably as a reflexive response to the fall in blood pressure. Coronary
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`perfusion pressure was usually, but not always, maintained.
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`Intravenous nitroglycerin reduced central venous pressure (CVP), right atrial pressure
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`(RAP), pulmonary arterial pressure (PAP), pulmonary-capillary wedge pressure (PCWP),
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`pulmonary vascular resistance (PVR), and systemic vascular resistance (SVR). When
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`these parameters were elevated, reducing them toward normal usually caused a rise in
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`cardiac output. Conversely, intravenous nitroglycerin usually reduced cardiac output
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`when it was given to patients whose CVP, RAP, PAP, PCWP, PVR, and SVR were all
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`normal.
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`Most clinical trials of intravenous nitroglycerin have been brief; they have typically
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`followed hemodynamic parameters during a single surgical procedure. In one careful
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`study, one of the few that lasted more than a few hours, continuous intravenous
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`nitroglycerin had lost almost all of its hemodynamic effect after 48 hours. In the same
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`study, patients who received nitroglycerin infusions for only 12 hours out of each 24
`demonstrated no similar attenuation of effect. These results are consistent with those
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`seen in multiple large, double-blind, placebo-controlled trials of other formulations of
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`nitroglycerin and other nitrates.
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`Reference ID: 3638427
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`Ex. 2035-0003
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`

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`Indications and Usage
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`Nitroglycerin in 5% Dextrose Injection is indicated for treatment of peri-operative
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`hypertension; for control of congestive heart failure in the setting of acute myocardial
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`infarction; for treatment of angina pectoris in patients who have not responded to
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`sublingual nitroglycerin and ß-blockers; and for induction of intraoperative hypotension.
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` Contraindications
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` Nitroglycerin in 5% Dextrose Injection is contraindicated in patients who are allergic to
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` it.
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` In patients with pericardial tamponade, restrictive cardiomyopathy, or constrictive
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` pericarditis, cardiac output is dependent upon venous return. Intravenous nitroglycerin is
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` contraindicated in patients with these conditions.
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` Solutions containing dextrose may be contraindicated in patients with known allergy to
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` corn or corn products.
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` Do not use Nitroglycerin in 5% Dextrose Injection in patients who are taking certain
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`
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` drugs for erectile dysfunction (phosphodiesterase inhibitors) such as sildenafil, tadalafil,
` or vardenafil. Concomitant use can cause severe hypotension, syncope, or myocardial
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`
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` ischemia.
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` Do not use nitroglycerin in 5% dextrose in patients who are taking the soluble guanylate
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` cyclase stimulator riociguat. Concomitant use can cause hypotension.
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` Warnings
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` Nitroglycerin readily migrates into many plastics, including the polyvinyl chloride (PVC)
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` plastics commonly used for intravenous administration sets. Nitroglycerin absorption by
` PVC tubing is increased when the tubing is long, the flow rates are low, and the
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`
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` nitroglycerin concentration of the solution is high. The delivered fraction of the
` solution's original nitroglycerin content has been 20-60% in published studies using PVC
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`tubing; the fraction varies with time during a single infusion, and no simple correction
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`
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`factor can be used. PVC tubing has been used in most published studies of intravenous
`nitroglycerin, but the reported doses have been calculated by simply multiplying the flow
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`rate of the solution by the solution's original concentration of nitroglycerin. The actual
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`doses delivered have been less, sometimes much less, than those reported.
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`Reference ID: 3638427
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`Ex. 2035-0004
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`

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`Relatively non-absorptive intravenous administration sets are available. If intravenous
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`nitroglycerin is administered through non-absorptive tubing, doses based upon
`published reports will generally be too high.
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`Some in-line intravenous filters also absorb nitroglycerin; these filters should be avoided.
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`Solutions containing dextrose without electrolytes should not be administered through the
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`same administration set as blood, as this may result in pseudoagglutination or hemolysis.
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` The intravenous administration of solutions may cause fluid overloading resulting in
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` dilution of serum electrolyte concentrations, overhydration and congested states of
` pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte
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` concentrations of the injections. The risk of solute overload causing congested states
` with peripheral and pulmonary edema is directly proportional to the electrolyte
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` concentration of the injections.
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`Precautions
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`General: Severe hypotension and shock may occur with even small doses of
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`nitroglycerin. This drug should therefore be used with caution in patients who may be
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`volume depleted or who, for whatever reason, are already hypotensive. Hypotension
`induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased
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`angina pectoris.
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`Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.
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`As tolerance to other forms of nitroglycerin develops, the effect of sublingual
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`nitroglycerin on exercise tolerance, although still observable, is somewhat blunted.
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`In industrial workers who have long-term exposure to unknown (presumably high) doses
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`
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`of organic nitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and
`even sudden death have occurred during temporary withdrawal of nitrates from these
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`workers, demonstrating the existence of true physical dependence.
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`Some clinical trials in angina patients have provided nitroglycerin for about 12
`continuous hours of every 24-hour day. During the nitrate-free intervals in some of these
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`trials, anginal attacks have been more easily provoked than before treatment, and patients
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`have demonstrated hemodynamic rebound and decreased exercise tolerance. The
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`importance of these observations to the routine, clinical use of intravenous nitroglycerin
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`is not known.
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`Lower concentrations of Nitroglycerin in 5% Dextrose Injection increase the potential
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`precision of dosing, but these concentrations increase the total fluid volume that must be
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`Reference ID: 3638427
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`Ex. 2035-0005
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`

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`delivered to the patient. Total fluid load may be a dominant consideration in patients
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`with compromised function of the heart, liver, and/or kidneys.
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`Nitroglycerin in 5% Dextrose Injection should be administered only via an infusion pump
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`that can maintain a constant infusion rate.
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` Intracoronary injection of Nitroglycerin in 5% Dextrose Injection has not been studied.
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`Solutions containing dextrose should be used with caution in patients with known sub­
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` clinical or overt diabetes mellitus.
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`Laboratory Tests: Because of the propylene glycol content of intravenous
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`nitroglycerin, serum triglyceride assays that rely on glycerol oxidase may give falsely
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`elevated results in patients receiving this medication.
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`Drug Interactions: The vasodilating effects of nitroglycerin may be additive with
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`those of other vasodilators.
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`Concomitant use of Nitroglycerin in 5% Dextrose Injection with phosphodiesterase
`inhibitors in any form is contraindicated (see Contraindications).
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`Concomitant use of nitroglycerin in 5% dextrose with riociguat, a soluble guanylate
`cyclase stimulator, is contraindicated (see Contraindications).
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`Marked symptomatic orthostatic hypotension has been reported when calcium channel
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`blockers and organic nitrates were used in combination.
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`Intravenous nitroglycerin interferes, at least in some patients, with the anticoagulant
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`effect of heparin. In patients receiving intravenous nitroglycerin, concomitant heparin
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`therapy should be guided by frequent measurement of the activated partial
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`thromboplastin time.
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`Administration of Nitroglycerin in 5% Dextrose Injection through the same infusion set
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`as blood can result in pseudoagglutination and hemolysis. More generally, Nitroglycerin
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`in 5% Dextrose Injection should not be mixed with any other medication of any kind.
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`Carcinogenesis, Mutagenesis, and Impairment of Fertility: Animal
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`carcinogenesis studies with injectable nitroglycerin have not been performed.
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`Rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years developed dose-
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`related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell
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`tumors in testes. At high dose, the incidences of hepatocellular carcinomas in both sexes
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`were 52% vs. 0% in controls and incidences of testicular tumors were 52% vs. 8% in
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`controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was
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`not tumorigenic in mice.
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`Reference ID: 3638427
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`Ex. 2035-0006
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`

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`Nitroglycerin was weakly mutagenic in Ames tests performed in two different
`laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant
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`lethal assay with male rats treated with doses up to about 363 mg/kg/day, p.o., or in in
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` vitro cytogenetic tests in rat and dog tissues.
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`In a three-generation reproduction study, rats received dietary nitroglycerin at doses up to
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` about 434 mg/kg/day for six months prior to mating of the F0 generation with treatment
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`continuing through successive F1 and F2 generations. The high-dose was associated with
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`decreased feed intake and body weight gain in both sexes at all matings. No specific
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`effect on the fertility of the F0 generation was seen. Infertility noted in subsequent
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`generations, however, was attributed to increased interstitial cell tissue and
`aspermatogenesis in the high-dose males. In this three-generation study there was no
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` clear evidence of teratogenicity.
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` Pregnancy Category C: Animal teratology studies have not been conducted with
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` nitroglycerin injection. Teratology studies in rats and rabbits were conducted with
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`topically applied nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day,
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`
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` respectively, and no toxic effects on dams or fetuses were seen. There are no adequate
` and well-controlled studies in pregnant women. Nitroglycerin should be given to a
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` pregnant woman only if clearly needed.
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`Nursing Mothers: It is not known whether nitroglycerin is excreted in human milk.
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`Because many drugs are excreted in human milk, caution should be exercised when
`nitroglycerin is administered to a nursing woman.
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`Pediatric Use: Safety and effectiveness in the pediatric population have not been
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`
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`established. However, the relationship between hemodynamic effects of nitroglycerin
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`and dose in the pediatric population have been documented in the literature.
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` Table 2
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` Studies in the literature used doses of nitroglycerin injection in pediatric patients ranging
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`
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` from 0.5 to 5 mcg/kg/min. The following chart can be used to calculate the flow rate in
` mL/hour of nitroglycerin using the 100 mcg/mL (25 mg/250 mL) concentration of
`
`
` nitroglycerin.
`
`Note: Very low infusion rates may require that a more dilute concentration of
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`nitroglycerin infusion solution be prepared.
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`Flow Rate (mL/hour)
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` Using the 100 mcg/mL (25mg/250 mL) Concentration
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`Reference ID: 3638427
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`
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`Ex. 2035-0007
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`

`
`
` Patient Weight in kg
`
`
`
`
`
`
` 10
`
`
`
` 12
`
`
`
` 14
`
`
`
` 16
`
`
`
` 18
`
`
`
` 20
`
`
`
` 2
`
`
`
` 4
`
`
`
` 6
`
`
`
` 8
`
`
`Dose
`(mcg/
`
` kg/
`
`min)
`
`
`
`
`
`
` 0.48
`
` 2.4
`
` 4.8
`
` 9.6
`
` 14.4
`
` 19.2
`
` 24
`
` 48
`
`
` 0.6
`
` 3
`
` 6
`
` 12
`
` 18
`
` 24
`
` 30
`
` 60
`
` 0.72
`
`
` 3.6
`
` 7.2
`
` 14.4
`
` 21.6
`
` 28.8
`
` 36
`
` 72
`
`
` 0.84
`
` 4.2
`
` 8.4
`
` 16.8
`
` 25.2
`
` 33.2
`
` 42
`
` 84
`
`
` 0.96
`
` 4.8
`
` 9.6
`
` 19.2
`
` 28.8
`
` 38.4
`
` 48
`
` 96
`
`
` 1.08
`
` 5.4
`
` 10.8
`
` 21.6
`
` 32.4
`
` 43.2
`
` 54
` 108
`
`
`
` 1.2
`
` 6
`
` 12
`
` 24
`
` 36
`
` 48
`
` 60
` 120
`
`
`
`
`
`
`
` 0.12
`
` 0.1*
`
` 0.36
` 0.24
`
` 0.6
`
` 0.5
`
` 1.8
`
` 1.2
`
` 1.2
`
` 1
`
` 3.6
`
` 2.4
`
` 2.4
`
` 2
`
` 7.2
`
` 4.8
`
` 3.6
`
` 3
`
` 10.8
`
` 7.2
`
` 4.8
`
` 4
`
` 14.4
`
` 9.6
`
` 6
`
` 5
`
` 18
`
` 12
` 12
` 10*
`
` 36
`
` 24
`
`
`
` *Dose not studied in pediatric trials
`
`
`Geriatric Use: Clinical studies of Nitroglycerin 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 the elderly and younger patients. In general, dose selection for an elderly patient
`
`
`
`
` should be cautious, usually starting at the low end of the dosing range reflecting the
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`
`
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` greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant
`
`
`
`disease or other drug therapy.
`
` Do not use unless vacuum is present and solution is clear.
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`Adverse Reactions
`
`
`Adverse reactions to nitroglycerin are generally dose-related and almost all of these
`reactions are the result of nitroglycerin's activity as a vasodilator. Headache, which may
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`
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`be severe, is the most commonly reported side effect. Headache may be recurrent with
`
`
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`each daily dose, especially at higher doses. Transient episodes of lightheadedness,
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`
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`occasionally related to blood pressure changes, may also occur. Hypotension occurs
`
`
`
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`infrequently, but in some patients it may be severe enough to warrant discontinuation of
`
`therapy. Syncope, crescendo angina, and rebound hypertension have been reported but
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`are uncommon.
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`Allergic reactions to nitroglycerin are also uncommon, and the great majority of those
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`reported have been cases of contact dermatitis or fixed drug eruptions in patients
`
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`receiving nitroglycerin in ointments or patches. There have been a few reports of
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`genuine anaphylactoid reactions, and these reactions can probably occur in patients
`
`receiving nitroglycerin by any route.
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`
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`Reference ID: 3638427
`
`
`
`Ex. 2035-0008
`
`

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`Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in
`
`normal-seeming patients. Methemoglobinemia is so infrequent at these doses that further
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`
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`discussion of its diagnosis and treatment is deferred (see Overdosage).
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`
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`Data are not available to allow estimation of the frequency of adverse reactions during
`
`
`treatment with Nitroglycerin in 5% Dextrose Injection.
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` Overdosage
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`Hemodynamic Effects: The ill effects of nitroglycerin overdose are generally the
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`
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`results of nitroglycerin's capacity to induce vasodilation, venous pooling, reduced cardiac
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`
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`output, and hypotension. These hemodynamic changes may have protean manifestations,
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`
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`including increased intracranial pressure, with any or all of persistent throbbing
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`headache, confusion, and moderate fever; vertigo; palpitations; visual disturbances;
`
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`nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially
`
`
`in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory
`effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and
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`bradycardia; paralysis; coma; seizures; and death.
`
`Laboratory determinations of serum levels of nitroglycerin and its metabolites are not
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`
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`widely available, and such determinations have, in any event, no established role in the
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`management of nitroglycerin overdose.
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`No data are available to suggest physiological maneuvers (e.g., maneuvers to change the
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`
`pH of the urine) that might accelerate elimination of nitroglycerin and its active
`
`
`metabolites. Similarly, it is not known which -if any- of these substances can usefully be
`
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`removed from the body by hemodialysis.
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`No specific antagonist to the vasodilator effects of nitroglycerin is known, and no
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`intervention has been subject to controlled study as a therapy of nitroglycerin overdose.
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`Because the hypotension associated with nitroglycerin overdose is the result of
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`venodilatation and arterial hypovolemia, prudent therapy in this situation should be
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`
`
`directed toward increase in central fluid volume. Passive elevation of the patient's legs
`
`may be sufficient, but intravenous infusion of normal saline or similar fluid may also be
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`necessary.
`
`The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do
`
`more harm than good.
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`
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`In patients with renal disease or congestive heart failure, therapy resulting in central
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`
`
`volume expansion is not without hazard. Treatment of nitroglycerin overdose in these
`
`
`patients may be subtle and difficult, and invasive monitoring may be required.
`
`
`
`
`
`Reference ID: 3638427
`
`
`
`Ex. 2035-0009
`
`

`
`
`Methemoglobinemia: Nitrate ions liberated during metabolism of nitroglycerin can
`
`
`oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5
`
`
`
`
`reductase activity, however, and even assuming that the nitrate moieties of nitroglycerin
`are quantitatively applied to oxidation of hemoglobin, about 1 mg/kg of nitroglycerin
`
`should be required before any of these patients manifests clinically significant (≥ 10%)
`
`methemoglobinemia. In patients with normal reductase function, significant production
`
`
`of methemoglobin should require even larger doses of nitroglycerin. In one study in
`
`
`which 36 patients received 2-4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4
`
`mg/hr, the average methemoglobin level measured was 0.2%; this was comparable to that
`
`observed in parallel patients who received placebo.
`
`
`
`Notwithstanding these observations, there are case reports of significant
`
`
`methemoglobinemia in association with moderate overdoses of organic nitrates. None of
`
`the affected patients had been thought to be unusually susceptible.
`
`
`
`
`Methemoglobin levels are available from most clinical laboratories. The diagnosis
`
`should be suspected in patients who exhibit signs of impaired oxygen delivery despite
`
`
`adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic
`
`blood is described as chocolate brown, without color change on exposure to air.
`
`When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1-2
`
`mg/kg intravenously.
`
`
`Dosage and Administration
`
`
`
`
`Nitroglycerin in 5% Dextrose Injection is intended for intravenous administration using
`
`
`sterile equipment. It should be administered only via an infusion pump that can maintain
`
`a constant infusion rate. A container which has lost its vacuum, or one in which
`
`particulate matter is visible, should not be used.
`
`Dosage is affected by the type of infusion set used (see Warnings). Although the usual
`
`
`adult starting dose in published studies has been 25 mcg/min or more, these studies used
`
`PVC tubing, so the delivered doses were less than those reported. When nonabsorptive
`
`
`
`tubing is used, doses must be reduced.
`
`
`
`
`Even using nonabsorptive tubing, the dose necessary to achieve a given response will
`
`
`
`
`vary greatly from patient to patient. Patients with normal or low left-ventricular filling
`pressure (e.g., patients with uncomplicated angina pectoris) may respond fully to as little
`
`
`
`as 5 mcg/min, while other patients may require a dose that is one or even two orders of
`
`
`
`
`magnitude higher. Continuous monitoring of blood pressure and heart rate is necessary
`
`
`in all patients receiving this medication; in many cases, invasive monitoring of
`
`
`pulmonary capillary wedge pressure will also be indicated.
`
`
`
`
`Reference ID: 3638427
`
`
`
`Ex. 2035-0010
`
`

`
`
`
` Lower concentrations of Nitroglycerin in 5% Dextrose Injection increase the potential
`
`
` precision of dosing, but these concentrations increase the total fluid volume that must be
`
`
`
` delivered to the patient. Total fluid load may be a dominant consideration in patients
` with compromised function of the heart, liver, and/or kidneys. The necessary flow rates
`
`
`
`
` to achieve various dose rates with the available concentrations are shown in the following
`
` table.
`
`
`
`Using nonabsorptive tubing, the initial adult dosage of Nitroglycerin in 5% Dextrose
`
`
`Injection should be 5 mcg/min. Subsequent titration must be guided by the clinical
`
`results, with dose increments becoming more cautious as partial response is seen. Initial
`
`
`titration should be in 5 mcg/min increments at intervals of 3 to 5 minutes. If no response
`
`is seen at 20 mcg/min, increments of 10 and even 20 mcg/min can be used. Once some
`
`hemodynamic response is observed, dosage increments should be smaller and less
`
`frequent.
`
`When the concentration is changed, the tubing must be disconnected from the patient and
`
`flushed with the new solution before therapy is continued. If this precaution is not taken,
`
`
`then depending upon the tubing, pump, and flow rate used, it might be several hours
`
`before nitroglycerin is delivered at the desired rate.
`
`
`Parenteral drug products should be inspected visually for particulate matter and
`
`discoloration prior to administration, whenever solution and container permit.
`
`
`
`
`Do not add supplementary medication to Nitroglycerin in 5% Dextrose Injection.
`
`
`
` Table 3
`
` Necessary Flow Rates (mL/hr*)
`
`
`
`
`
`
`
` 400
`
`
` 0.8
`
` 1.5
`
` 2.3
`
` 3
` 4.5
`
`
` 6
`
` 7.5
`
` 9
`
` 12
`
` 15
`
` 18
`
` 21
`
` 24
`
` 27
`
` 30
`
` 36
`
`
`
` Solution Concentration (mcg/mL)
`
` 200
`
`
`
`1.5
`
` 3.0
`
` 4.5
`
` 6
`
` 9
`
` 12
`
` 15
`
` 18
`
` 24
`
` 30
`
` 36
`
` 42
`
` 48
`
` 54
`
` 60
`
` 72
`
`
`
` 100
`
`3
`
` 6
`
` 9
`
` 12
`
` 18
`
` 24
`
` 30
`
` 36
`
` 48
`
` 60
`
` 72
`
` 84
`
` 96
`
` 108
`
` 120
`
` 144
`
`
`
`
`
`Desired
` Dose (mcg/min)
`
`
`
`
`
`5
`
` 10
`
` 15
`
` 20
`
` 30
`
` 40
`
` 50
`
` 60
`
` 80
`
` 100
`
` 120
`
` 140
`
` 160
`
` 180
`
` 200
`
` 240
`
`Reference ID: 3638427
`
`
`
`Ex. 2035-0011
`
`

`
`
` 84
`
` 168
`
` 280
`
` 96
`
` 192
`
` 320
`
` 150
`
` 300
`
` 500
` *With a set that produces 60 drops/mL, 1mL/hr = 1 drop/min.
`
`
`
` 42
`
` 48
`
` 75
`
`
`
`
`
`
`
` Size (mL)
`
`250
`
` NDC
`
` 0338-1047-02
`
`
`
` How Supplied
`
`
`
`Nitroglycerin in 5% Dextrose Injection is supplied in glass container as follows:
`
`Code
`
`1A0692
`
`Product Name
`
`
` 25 mg Nitroglycerin in
`
` 5% Dextrose Injection
`
` 50 mg Nitroglycerin in
`
` 5% Dextrose Injection
`
`100 mg Nitroglycerin in
`
` 5% Dextrose Injection
` Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat.
`
`
`
`
` Protect from freezing. It is recommended the product be stored at room temperature
` (25°C). Brief exposure up to 40°C does not adversely affect the product. Protect from
`
`
`
`
`light until time of use.
`
`
`
`
`
`
`
`
`
`
` 1A0694
`
`1A0696
`
`
`
`
`
` 250
`
`
`
` 250
`
`
`
` 0338-1049-02
`
`
`
` 0338-1051-02
`
`
`
`Baxter Healthcare Corporation
`
`Deerfield, IL 60015
`
`
`Printed in USA
`
`
`Baxter is a registered trademark of Baxter International Inc.
`
`
`
`07-19-73-514
`
`Rev. October 2014
`
`
`
`
`Reference ID: 3638427
`
`
`
`Ex. 2035-0012