nitroglycerin 400 MCG Sublingual Tablet
Generic Name: NITROGLYCERIN
Brand Name: NITROGLYCERIN
- Substance Name(s):
- NITROGLYCERIN
DRUG INTERACTIONS
7 Ergotamine: Increased bioavailability of ergotamine.
Avoid concomitant use.
( 7.2 ) 7.1 PDE-5-Inhibitors and sGC-Stimulators Nitroglycerin is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE-5).
PDE-5-Inhibitors such as avanafil, sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates.
Nitroglycerin is contraindicated in patients who are taking soluble guanylate cyclase (sGC) stimulators.
Concomitant use can cause hypotension.
The time course and dose dependence of these interactions have not been studied, and use within a few days of one another is not recommended.
Appropriate supportive care for the severe hypotension 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.
7.2 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.
OVERDOSAGE
10 10.1 Signs and Symptoms, Methemoglobinemia Nitrate overdosage may result in: severe hypotension, persistent throbbing headache, vertigo, palpitation, visual disturbance, flushing and perspiring skin (later becoming cold and cyanotic), nausea and vomiting (possibly with colic and even bloody diarrhea), syncope (especially in the upright posture), methemoglobinemia with cyanosis and anorexia, initial hyperpnea, dyspnea and slow breathing, slow pulse (dicrotic and intermittent), heart block, increased intracranial pressure with cerebral symptoms of confusion and moderate fever, paralysis and coma followed by clonic convulsions, and possibly death due to circulatory collapse.
Case reports of clinically significant methemoglobinemia are rare at conventional doses of organic nitrates.
The formation of methemoglobin is dose-related and in the case of genetic abnormalities of hemoglobin that favor methemoglobin formation, even conventional doses of organic nitrates could produce harmful concentrations of methemoglobin.
10.2 Treatment of Overdosage As hypotension associated with nitroglycerin overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume.
No specific antagonist to the vasodilator effects of nitroglycerin is known.
Keep the patient recumbent in a shock position and comfortably warm.
Passive movement of the extremities may aid venous return.
Intravenous infusion of normal saline or similar fluid may also be necessary.
Administer oxygen and artificial ventilation, if necessary.
If methemoglobinemia is present, administration of methylene blue (1% solution), 1–2 mg per kilogram of body weight intravenously, may be required unless the patient is known to have G-6-PD deficiency.
If an excessive quantity of nitroglycerin has been recently swallowed gastric lavage may be of use.
As epinephrine is ineffective in reversing the severe hypotensive events associated with overdosage, it is not recommended for resuscitation.
DESCRIPTION
11 Nitroglycerin tablets are stabilized sublingual compressed tablets that contains 0.3 mg, 0.4 mg, or 0.6 mg nitroglycerin; as well as lactose monohydrate, NF; glyceryl monostearate, NF; pregelatinized starch, NF; calcium stearate, NF powder; and silicon dioxide, colloidal, NF.
Nitroglycerin, an organic nitrate, is a vasodilating agent.
The chemical name for nitroglycerin is 1, 2, 3 propanetriol trinitrate and the chemical structure is: C 3 H 5 N 3 0 9 Molecular weight: 227.09 Chemical Structure
HOW SUPPLIED
16 /STORAGE AND HANDLING Nitroglycerin tablets are supplied as white, round, flat-faced tablets in 3 strengths (0.3 mg, 0.4 mg, and 0.6 mg) in bottles containing 100 tablets each, with color-coded labels, and in color-coded Patient Convenience Packages of 4 bottles of 25 tablets each.
0.3 mg: Coded “N” on one side and “3” on the other.
NDC 59762-4921-1—Bottle of 100 tablets 0.4 mg: Coded “N” on one side and “4” on the other.
NDC 59762-3304-3—Convenience Package NDC 59762-3304-1—Bottle of 100 tablets 0.6 mg: Coded “N” on one side and “6” on the other.
NDC 59762-0489-1—Bottle of 100 tablets Store at Controlled Room Temperature 20°–25°C (68°–77°F) [see USP].
Nitroglycerin should be kept in the original glass container and must be tightly capped after each use to prevent loss of tablet potency.
GERIATRIC USE
8.5 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.
DOSAGE FORMS AND STRENGTHS
3 Nitroglycerin is supplied as white, round, flat-faced tablets in three strengths: 0.3 mg (Coded with “N” on one side and “3” on the other) 0.4 mg (Coded with “N” on one side and “4” on the other) 0.6 mg (Coded with “N” on one side and “6” on the other) Sublingual tablets, 0.3 mg; 0.4 mg; 0.6 mg.
( 3 )
MECHANISM OF ACTION
12.1 Mechanism of Action Nitroglycerin forms free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3’5′ monophosphate (cyclic GMP) in smooth muscle and other tissues.
These events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation.
INDICATIONS AND USAGE
1 Nitroglycerin is indicated for the acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease.
Nitroglycerin is a nitrate vasodilator indicated for relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.
( 1 )
PEDIATRIC USE
8.4 Pediatric Use The safety and effectiveness of nitroglycerin in pediatric patients have not been established.
PREGNANCY
8.1 Pregnancy Risk Summary 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%, respectively.
Data Animal Data No embryotoxic or postnatal development effects were observed with transdermal application in pregnant rabbits and rats at doses up to 80 and 240 mg/kg/day, respectively, at intraperitoneal doses in pregnant rats up to 20 mg/kg/day from gestation day 7–17, and at intravenous doses in pregnant rabbits up to 4 mg/kg/day from gestation day 6–18.
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Tolerance: Excessive use may lead to tolerance.
( 5.1 ) Hypotension: Severe hypotension may occur.
( 5.2 ) 5.1 Tolerance Excessive use may lead to the development of tolerance.
Only the smallest dose required for effective relief of the acute angina attack should be used.
A decrease in therapeutic effect of sublingual nitroglycerin may result from use of long-acting nitrates.
5.2 Hypotension Severe hypotension, particularly with upright posture, may occur 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 doses.
5.3 Hypertrophic Obstructive Cardiomyopathy Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.
5.4 Headache Nitroglycerin produces dose-related headaches, especially at the start of nitroglycerin therapy, which may be severe and persist but usually subside with continued use.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).
DOSAGE AND ADMINISTRATION
2 Administer one tablet under the tongue or in the buccal pouch at the first sign of an acute anginal attack.
Allow tablet to dissolve without swallowing.
One additional tablet may be administered every 5 minutes until relief is obtained.
No more than three tablets are recommended within a 15-minute period.
If the pain persists after a total of 3 tablets in a 15-minute period, or if the pain is different than is typically experienced, seek prompt medical attention.
Nitroglycerin may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.
For patients with xerostomia, a small sip of water prior to placing the tablet under the tongue may help maintain mucosal hydration and aid dissolution of the tablet.
Administer nitroglycerin at rest, preferably in the sitting position.
At the onset of an attack, administer one tablet under the tongue or buccal pouch.
One additional tablet may be administered every 5 minutes as needed.
No more than 3 total tablets are recommended within a 15 minute period.
( 2 ) If chest pain persists after three tablets, seek prompt medical attention.
( 2 ) May be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.
( 2 )