Nitrolingual

Nitrolingual Pumpspray is indicated for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease. Nitrolingual Pumpspray is a nitrate vasodilator indicated for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.

At the onset of an attack, administer onto or under the tongue. Repeat every 5 minutes as needed. Do up to three metered sprays within a 15-minute period. If chest pain persists, advise prompt medical attention. May be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.

2.1Recommended Dosage Instruct the

patient to administer one or two metered sprays (400 mcg of nitroglycerin per spray) at the onset of an attack onto or under the tongue. A spray may be repeated approximately every five minutes as needed. No more than three metered sprays are recommended within a 15-minute period.

If the chest pain persists after a total of three sprays, advise prompt medical attention. Nitrolingual Pumpspray may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.

2.2Priming The

pump must be primed prior to the first use. Each metered spray of Nitrolingual Pumpspray delivers 48 mg of solution containing 400 mcg of nitroglycerin after an initial priming of five sprays. It will remain adequately primed for 6 weeks. If the product is not used within 6 weeks it can be adequately re-primed with one spray.

If the product is not used within 3 months it can be adequately re-primed with up to five sprays. There are 60 or 200 metered sprays per bottle. The total number of available doses is dependent, however, on the number of sprays per use (1 or 2 sprays), and the frequency of priming.

2.3Administration Instruct

patients that during administration, the patient should rest, ideally in the sitting position. Hold the container vertically with the valve head uppermost and the spray orifice as close to the mouth as possible. Spray the dose preferably onto or under the tongue by pressing the grooved-button firmly and the mouth closed immediately after each dose.

THE SPRAY SHOULD NOT BE INHALED. The medication should not be expectorated or the mouth rinsed for 5 to 10 minutes following administration. Instruct patients to familiarize themselves with the position of the spray orifice, which can be identified by the finger rest on top of the valve, in order to facilitate orientation for administration at night . The amount of liquid remaining in the container should be checked periodically. The transparent container can be used for continuous monitoring of the consumption.

With the container upright and level, check to be sure the end of the center tube extends below the level of the liquid. Once fluid falls below the level of the center tube, remaining sprays will not deliver intended dose.

Tolerance: Excessive use may lead to tolerance. Hypotension: Severe hypotension may occur.

5.1Tolerance 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 . 5. 2 Hypotension 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 doses.

5.3Hypertrophic Obstructive Cardiomyopathy Nitrate

therapy may aggravate the angina caused by hypertrophic obstructive cardiomyopathy.

5.4Headache Nitroglycerin

produces dose-related headaches, especially at the start of nitroglycerin therapy, which may be severe and persistent but usually subside with continued use.

Use of phosphodiesterase type 5 (PDE-5) Inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulator (riociguat). ( 4.1 , 7.1 ) Severe anemia. Increased intracranial pressure. Hypersensitivity to Nitrolingual Pumpspray or to other nitrates or nitrites or any excipient. 4.1 P DE-5 - I nhibitors and sGC- S timulators Do not use Nitrolingual Pumpspray in patients who are taking PDE-5-Inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil. Concomitant use can cause severe hypotension, syncope, or myocardial ischemia . Do not use Nitrolingual Pumpspray in patients who are taking soluble guanylate cyclase (sGC) stimulators, such as riociguat. Concomitant use can cause hypotension.

4.2Severe Anemia Nitrolingual Pumpspray

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

4.3Increased I

ntracranial P ressure Nitrolingual Pumpspray 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 Nitrolingual Pumpspray

is contraindicated in patients who are allergic to nitroglycerin, other nitrates or nitrites or any excipient. 4. 5 Circulatory F ailure and S hock Nitrolingual Pumpspray is contraindicated in patients with acute circulatory failure or shock.

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 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.

Most common adverse reactions occurring at a frequency greater than 2 % are headache, dizzinesss and paresthesia. To report SUSPECTED ADVERSE REACTIONS, contact Independence Pharmaceuticals, LLC at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda. gov/medwatch.

6.1Clinical Trials Experience Because

clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse reactions occurring at a frequency greater than 2 % and greater than placebo included: headache, dizziness, and paresthesia.

6.2Postmarketing Experience The

following adverse reactions have been identified during post-approval use of Nitrolingual Pumpspray and other nitroglycerin drugs. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure. Neurologic: weakness, drowsiness Dermatologic: cutaneous vasodilation, flushing, drug rash, exfoliative dermatitits Gastrointestinal: nausea, vomiting Respiratory: transient hypoxemia Cardiovascular: tachycardia