Nitrostat

1 INDICATIONS AND USAGE NITROSTAT is indicated for the acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease. INDICATIONS AND USAGE NITROSTAT is a nitrate vasodilator indicated for relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.

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. NITROSTAT 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 NITROSTAT at rest, preferably in the sitting position. DOSAGE AND ADMINISTRATION • 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. • If chest pain persists after three tablets, seek prompt medical attention. • May be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.

5 WARNINGS AND PRECAUTIONS

5.1Tolerance 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.

5.2Hypotension 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.

5.3Hypertrophic Obstructive Cardiomyopathy Nitrate

therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

5.4Headache Nitroglycerin

produces dose-related headaches, especially at the start of nitroglycerin therapy, which may be severe and persist but usually subside with continued use. WARNINGS AND PRECAUTIONS • Tolerance: Excessive use may lead to tolerance. • Hypotension: Severe hypotension may occur.

4 CONTRAINDICATIONS

4.1PDE-5-Inhibitors and

sGC-Stimulators Do not use NITROSTAT in patients who are taking PDE-5 Inhibitors, such as avanafil, sildenafil, tadalafil, vardenafil hydrochloride. Concomitant use can cause severe hypotension, syncope, or myocardial ischemia . Do not use NITROSTAT in patients who are taking the soluble guanylate cyclase stimulators, such as riociguat. Concomitant use can cause hypotension.

4.2Severe Anemia

NITROSTAT is contraindicated in patients with severe anemia (large doses of nitroglycerin may cause oxidation of hemoglobin to methemoglobin and could exacerbate anemia).

4.3Increased Intracranial Pressure

NITROSTAT may precipitate or aggravate increased intracranial pressure and thus should not be used in patients with possible increased intracranial pressure (e.g., cerebral hemorrhage or traumatic brain injury).

4.4Hypersensitivity

NITROSTAT is contraindicated in patients who are allergic to nitroglycerin, other nitrates or nitrites or any excipient.

4.5Circulatory Failure and Shock

NITROSTAT is contraindicated in patients with acute circulatory failure or shock. CONTRAINDICATIONS • Use of phosphodiesterase type 5 (PDE-5) inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulators. (4.1, 7.1) • Severe anemia • Increased intracranial pressure • Hypersensitivity to NITROSTAT or to other nitrates or nitrites or any excipient • Circulatory failure and shock

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy 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 . 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.

8.2Lactation Risk Summary 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.

8.4Pediatric Use The

safety and effectiveness of nitroglycerin in pediatric patients have not been established.

8.5Geriatric Use Clinical

studies of NITROSTAT 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.

The following adverse reactions are discussed in more detail elsewhere in the label: • Hypotension • Headache • Hypersensitivity Vertigo, dizziness, weakness, palpitation, and other manifestations of postural hypotension may develop occasionally, particularly in erect, immobile patients. Marked sensitivity to the hypotensive effects of nitrates (manifested by nausea, vomiting, weakness, diaphoresis, pallor, and collapse) may occur at therapeutic doses. Syncope due to nitrate vasodilatation has been reported.

Flushing, drug rash, and exfoliative dermatitis have been reported in patients receiving nitrate therapy. ADVERSE REACTIONS Most common adverse reactions occurring at a frequency greater than 2% are headache, dizziness and paresthesia. To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.