NitroglycerinInjection, USP

Rx Only

INDICATIONS AND USAGE
Nitroglycerin Injection is indicated for treatment of peri-operative hypertension; for control of congestive heart failure in the setting of acute myocardial infarction; for treatment of angina pectoris in patients who have not responded to sublingual nitroglycerin and β-blockers; and for induction of intraoperative hypotension.

FOR INTRAVENOUS USE ONLY. NOT FOR DIRECT INTRAVENOUS INJECTION. NITROGLYCERIN INJECTION MUST BE DILUTED IN DEXTROSE (5%) INJECTION OR SODIUM CHLORIDE (0.9%) INJECTION PRIOR TO ITS INFUSION. THE ADMINISTRATION SET USED FOR INFUSION WILL AFFECT THE AMOUNT OF NITROGLYCERIN INJECTION DELIVERED TO THE PATIENT.

CAUTION
SEVERAL PREPARATIONS OF NITROGLYCERIN FOR INJECTION ARE AVAILABLE. THEY DIFFER IN CONCENTRATION AND/OR VOLUME PER VIAL. WHEN SWITCHING FROM ONE PRODUCT TO ANOTHER, ATTENTION MUST BE PAID TO THE DILUTION AND DOSAGE AND ADMINISTRATION INSTRUCTIONS.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Allergic reactions to organic nitrates are extremely rare, but they do occur. Nitroglycerin Injection is contraindicated in patients who are allergic to it. In patients with pericardial tamponade, restrictive cardiomyopathy, or constrictive pericarditis, cardiac output is dependent upon venous return. Intravenous nitroglycerin is contraindicated in patients with these conditions.

WARNINGS
Amplification of the vasodilatory effects of nitroglycerin by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with volume expansion.
Nitroglycerin readily migrates into many plastics, including the polyvinyl chloride (PVC) 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 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 tubing; the fraction varies with time during a single infusion, and no simple correction 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 rate of the solution by the solution’s original concentration of nitroglycerin. The actual doses delivered have been less, sometimes much less, than those reported.

Some in-line intravenous filters also absorb nitroglycerin; these filters should be avoided.

Because of the problem of nitroglycerin absorption by polyvinyl chloride (PVC) tubing, Nitroglycerin Injection should be used with the least absorptive infusion tubing (i.e., non-PVC tubing) available.

DOSING INSTRUCTIONS MUST BE FOLLOWED WITH CARE. WHEN THE APPROPRIATE INFUSION SETS ARE USED, THE CALCULATED DOSE WILL BE DELIVERED TO THE PATIENT, BECAUSE THE LOSS OF NITROGLYCERIN INJECTION SEEN WITH STANDARD PVC TUBING WILL BE AVOIDED. THE DOSAGES REPORTED IN PUBLISHED STUDIES UTILIZED GENERAL-USE PVC ADMINISTRATION SETS, AND RECOMMENDED DOSES BASED ON THIS EXPERIENCE WILL BE TOO HIGH WHEN THE LOW-ABSORBING INFUSION SETS ARE USED.

PRECAUTIONS
General
Severe hypotension and shock may occur with even small doses of nitroglycerin. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy. As tolerance to other forms of nitroglycerin develops, the effect of sublingual nitroglycerin on exercise tolerance, although still observable, is somewhat blunted.

In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence.

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 trials, angina attacks have been more easily provoked than before treatment, and patients have demonstrated hemodynamic rebound and decreased exercise tolerance. The importance of these observations to routine, clinical use of intravenous nitroglycerin is not known. Lower concentrations of nitroglycerin 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.

Nitroglycerin infusions should be administered only via a pump that can maintain a constant infusion rate.

Intracoronary injection of nitroglycerin infusions has not been studied.

Drug Interactions
The vasodilating effects of nitroglycerin may be additive with those of other vasodilators. Administration of nitroglycerin infusions through the same infusion set as blood can result in pseudoagglutination and hemolysis. More generally, nitroglycerin in 5% dextrose or sodium chloride 0.9% should not be mixed with any other medication of any kind. Intravenous nitroglycerin interferes, at least in some patients, with the anticoagulant effect of heparin. In patients receiving intravenous nitroglycerin, concomitant heparin therapy should be guided by frequent measurement of the activated partial thromboplastin time.

Pregnancy: Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Nitroglycerin should be given to a pregnant woman only if clearly needed.

Nursing Mothers
It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitroglycerin is administered to a nursing woman.

Pediatric Use
Safety and effectiveness in children have not been established.

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 be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotension occurs 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 are uncommon. Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred.

OVERDOSAGE
Hemodynamic Effects
The ill effects of nitroglycerin overdose are generally the results of nitroglycerin’s capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitation; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilator effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death. In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

For additional safety information, please see Full Prescribing Information.

You are encouraged to report Adverse Drug Events to American Regent Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

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