Nitroglycerin Lingual

Nitroglycerin Lingual Spray is indicated for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.

Lingual spray, 400 mcg per spray available in either 60 or 200 metered sprays per container.

4.1 PDE-5-Inhibitors and sGC-Stimulators Do not use Nitroglycerin Lingual Spray 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 [see Drug Interactions (7.1)]. Do not use Nitroglycerin Lingual Spray in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension.

4.2 Severe Anemia Nitroglycerin Lingual Spray is contraindicated in patients with severe anemia (large doses of nitroglycerin may cause oxidation of hemoglobin to methemoglobin and could exacerbate anemia).

4.3 Increased Intracranial Pressure Nitroglycerin Lingual Spray 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).

4.4 Hypersensitivity Nitroglycerin Lingual Spray is contraindicated in patients who are allergic to nitroglycerin, other nitrates or nitrites or any excipient.

4.5 Circulatory Failure and Shock Nitroglycerin Lingual Spray is contraindicated in patients with acute circulatory failure or shock.

5.1 Tolerance 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 (2.1)].

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.

5.3 Hypertrophic Obstructive Cardiomyopathy Nitrate therapy may aggravate the angina caused by hypertrophic obstructive cardiomyopathy.

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

6.1 Clinical 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.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of nitroglycerin lingual spray 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 dermatitis Gastrointestinal: nausea, vomiting Respiratory: transient hypoxemia Cardiovascular: tachycardia

7.1 PDE-5-inhibitors and sGC-Stimulators Nitroglycerin Lingual Spray is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). PDE5 inhibitors such as avanafil, sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates. Do not use Nitroglycerin Lingual Spray in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. 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 cannot be 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 Antihypertensives Patients receiving antihypertensive drugs, beta-adrenergic blockers, and nitrates should be observed for possible additive hypotensive effects. Marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly. Beta-adrenergic blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. If beta-blockers are used with nitroglycerin in patients with angina pectoris, additional hypotensive effects may occur.

7.3 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.

8.1 Pregnancy Pregnancy Category C – Animal teratology studies have not been conducted with nitroglycerin lingual spray. Teratology studies in rats and rabbits, however, were conducted with topically applied nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day, respectively. No toxic effects on dams or fetuses were seen at any dose tested. A teratogenicity study was conducted in the third mating of F0 generation female rats administered dietary nitroglycerin for gestation day 6 to day 15 at dose levels used in the 3-generation reproduction study. In offspring of the high-dose nitroglycerin group, increased incidence of diaphragmatic hernias and decreased hyoid bone ossification were seen. The latter finding probably reflects delayed development rather than a potential teratogenic effect, thus indicating no clear evidence of teratogenicity of nitroglycerin. There are no adequate and well-controlled studies in pregnant women. Nitroglycerin should be given to pregnant women only if clearly needed.

8.3 Nursing Mothers It is not known whether nitroglycerin is excreted in human milk.

8.4 Pediatric Use Safety and effectiveness of nitroglycerin in pediatric patients have not been established.

8.5 Geriatric Use 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.