Included as part of the PRECAUTIONS section.
Excessive use may lead to the development of tolerance.
Only the smallest number of doses required for effective relief of the acute
angina attack should be used [see DOSAGE AND ADMINISTRATION].
Severe hypotension, particularly with upright posture,
may occur even with small doses of nitroglycerin particularly in patients with
constrictive pericarditis, aortic or mitral stenosis, patients who may be
volume-depleted, or are already hypotensive. Hypotension induced by
nitroglycerin may be accompanied by paradoxical bradycardia and increased
angina pectoris. Symptoms of severe hypotension (nausea, vomiting, weakness,
pallor, perspiration and collapse/syncope) may occur even with therapeutic
Hypertrophic Obstructive Cardiomyopathy
Nitrate therapy may aggravate the angina caused by
hypertrophic obstructive cardiomyopathy.
Nitroglycerin produces dose-related headaches, especially
at the start of nitroglycerin therapy, which may be severe and persistent but
usually subside with continued use.
Patient Counseling Information
Advise the patient to read the
FDA-approved Instructions for Use.
Impairment Of Fertility
Animal carcinogenesis studies
with sublingual 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. 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 cytogenic
tests in rat and dog tissues and for chromosomal aberration in Chinese hamster
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.
Use In Specific Populations
Limited published data on the use of
nitroglycerin are insufficient to determine a drug associated risk of major
birth defects or miscarriage. In animal reproduction studies, there were no
adverse developmental effects when nitroglycerin was administered intravenously
to rabbits or intraperitoneally to rats during organogenesis at doses greater
than 64-times the human dose [see Data].
The estimated background risk of major birth defects and
miscarriage for the indicated population is unknown. In the U.S. general
population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
No embryotoxic or postnatal development effects were
observed with transdermal application in pregnant rabbits and rats at doses up
to 240 mg/kg/day for 13 days, at intraperitoneal doses in pregnant rats up to
20 mg/kg/day for 11 days, and at intravenous doses in pregnant rabbits up to 4
mg/kg/day for 13 days.
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.
Safety and effectiveness of nitroglycerin in pediatric
patients have not been established.
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.