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Nitroglycerin Injection (Nitroglycerin Injection) - Warnings and Precautions

 
 



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 central 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.

Relatively nonabsorptive intravenous administration sets are available. If intravenous nitroglycerin is administered through nonabsorptive tubing, doses based upon published reports will generally be too high.

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

Solutions containing dextrose without electrolytes should not be administered through the same administration set as blood, as this may result in pseudoagglutination or hemolysis.

The intravenous administration of solutions may cause fluid overloading resulting in dilution of serum electrolyte concentrations, overhydration and congested states of pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of the injections. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentration of the injections.

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 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, anginal 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 the routine, clinical use of intravenous nitroglycerin is not known.

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.

Nitroglycerin in 5% Dextrose Injection should be administered only via an infusion pump that can maintain a constant infusion rate.

Intracoronary injection of Nitroglycerin in 5% Dextrose Injection has not been studied.

Solutions containing dextrose should be used with caution in patients with known subclinical or overt diabetes mellitus.

Laboratory Tests: Because of the propylene glycol content of intravenous nitroglycerin, serum triglyceride assays that rely on glycerol oxidase may give falsely elevated results in patients receiving this medication.

Drug Interactions: The vasodilating effects of nitroglycerin may be additive with those of other vasodilators.

Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination.

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.

Administration of Nitroglycerin in 5% Dextrose Injection through the same infusion set as blood can result in pseudoagglutination and hemolysis. More generally, Nitroglycerin in 5% Dextrose Injection should not be mixed with any other medication of any kind.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Animal carcinogenesis studies with injectable nitroglycerin have not been performed.

Rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes. At high dose, the incidences of hepatocellular carcinomas in both sexes were 52% vs. 0% in controls, and incidences of testicular tumors were 52% vs. 8% in controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice.

Nitroglycerin was weakly mutagenic in Ames tests performed in two different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, p.o., or in in vitro cytogenetic tests in rat and dog tissues.

In a three-generation 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.

Pregnancy: Pregnancy Category C: Animal teratology studies have not been conducted with nitroglycerin injection. Teratology studies in rats and rabbits were conducted with topically applied nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day, 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 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 pediatric patients have not been established.

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 greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Page last updated: 2012-07-10

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