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

{ "type": "p", "children": [], "text": "GONITRO is indicated for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease." }

Administer one or two packets (400 mcg of nitroglycerin per packet) at the onset of an attack under the tongue. One additional packet may be administered every five minutes as needed. No more than three packets are recommended within a 15-minute period. If the chest pain persists after a total of threepackets, seek prompt medical attention. GONITRO may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack. 

Administer GONITRO at rest, ideally in the sitting position. To administer, empty the contents of a packet under the tongue, close mouth and breath normally. Allow powder to dissolve without swallowing. Do not rinse or spit for 5 minutes after dosing.

GONITRO (nitroglycerin) sublingual powder, in packets containing 400 mcg of nitroglycerin.

Do not use GONITRO 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 GONITRO in patients who are taking soluble guanylate cyclase (sGC) stimulators, such as riociguat. Concomitant use can cause hypotension.

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

GONITRO 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).

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

GONITRO is contraindicated in patients with acute circulatory failure or shock.

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)].

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.

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.

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.

The following adverse reactions have been identified during post-approval use of GONITRO 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

GONITRO 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.

GONITRO 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.

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.

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.

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 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. 

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. 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.

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.

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 GONITRO 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.

Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for nitroglycerin is 1,2,3-propanetriol trinitrate (C3H5N3O9). The compound has a molecular weight of 227.09. The chemical structure is:

{ "type": "p", "children": [], "text": "Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for nitroglycerin is 1,2,3-propanetriol trinitrate (C3H5N3O9). The compound has a molecular weight of 227.09. The chemical structure is:" }

GONITRO is a powder containing nitroglycerin. Each packet of GONITRO delivers 400 mcg of nitroglycerin when administered under the tongue. The sublingual powder is formulated with the following inactive ingredients: anhydrous dibasic calcium phosphate, isomalt, medium-chain triglycerides, peppermint oil, and oleoyl polyoxylglycerides.

{ "type": "p", "children": [], "text": "GONITRO is a powder containing nitroglycerin. Each packet of GONITRO delivers 400 mcg of nitroglycerin when administered under the tongue. The sublingual powder is formulated with the following inactive ingredients: anhydrous dibasic calcium phosphate, isomalt, medium-chain triglycerides, peppermint oil, and oleoyl polyoxylglycerides." }

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. This eventually leads to dephosphorylation of myosin light chains, which regulates the contractile state in smooth muscle and results in vasodilatation.

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload). Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (after load), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.

Therapeutic doses of nitroglycerin may reduce systolic, diastolic and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively or increased heart rate decreases diastolic filling time.

Elevated central venous and pulmonary capillary wedge pressures, and pulmonary and systemic vascular resistance are also reduced by nitroglycerin therapy. Heart rate is usually slightly increased, presumably a reflex response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged. Myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased and a more favorable supply-demand ratio can be achieved. Patients with elevated left ventricular filling pressure and increased systemic vascular resistance in association with a depressed cardiac index are likely to experience an improvement in cardiac index. In contrast, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced following nitroglycerin administration.

In a pharmacokinetic study a single 800 mcg dose of GONITRO was administered sublingually to healthy volunteers (n = 32), the mean Cmax and tmax for GTN were 1,700 pg/mL and 7 minutes, respectively. Additionally, in these subjects the mean area under the curve (AUC) for GTN was 12,300 pg/mL . min.

The results of the study indicate that the sublingual absorption of GTN is higher following the administration of GONITRO compared to Nitrolingual® Pumpspray.

A liver reductase enzyme is of primary importance in the metabolism of nitroglycerin to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. Known sites of extrahepatic metabolism include red blood cells and vascular walls. In addition to nitroglycerin, 2 major metabolites, 1,2- and 1,3-dinitroglycerin are found in plasma. The mean elimination half-life of both 1,2- and 1,3-dinitroglycerin is about 40 minutes. The 1,2- and 1,3-dinitroglycerin metabolites have been reported to possess some pharmacological activity, whereas the glycerol mononitrate metabolites of nitroglycerin are essentially inactive. Higher plasma concentrations of the dinitro metabolites, with their nearly 8-fold longer elimination half-lives, may contribute significantly to the duration of pharmacologic effect.

The volume of distribution of nitroglycerin following intravenous administration is 3.3 L/kg.

Drug interactions

Aspirin: Coadministration of nitroglycerin with high dose aspirin (1000 mg) results in increased exposure to nitroglycerin. The vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant administration of nitroglycerin with high dose aspirin.

Tissue-type plasminogen activator (t-PA): Concomitant administration of t-PA and intravenous nitroglycerin has been shown to reduce plasma levels of t-PA and its thrombolytic effect.

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 ovary cells.

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.

In a randomized, double-blind single-dose, 5-period cross-over study in 51 patients with exertional angina pectoris significant dose-related increases in exercise tolerance, time to onset of angina and ST-segment depression were seen following doses of 200-1600 mcg of sublingual nitroglycerin as compared to placebo.

{ "type": "p", "children": [], "text": "In a randomized, double-blind single-dose, 5-period cross-over study in 51 patients with exertional angina pectoris significant dose-related increases in exercise tolerance, time to onset of angina and ST-segment depression were seen following doses of 200-1600 mcg of sublingual nitroglycerin as compared to placebo." }

The drug showed a profile of mild to moderate adverse events.

{ "type": "p", "children": [], "text": "The drug showed a profile of mild to moderate adverse events." }

Each box of GONITRO (nitroglycerin) sublingual powder, contains 12, 36 or 96 packets.

{ "type": "p", "children": [], "text": "Each box of GONITRO (nitroglycerin) sublingual powder, contains 12, 36 or 96 packets." }

Each packet contains 400 mcg of nitroglycerin.

{ "type": "p", "children": [], "text": "Each packet contains 400 mcg of nitroglycerin." }

GONITRO is available as:• Box of 12 packets NDC 70007-400-12• Box of 36 packets NDC 70007-400-36• Box of 96 packets NDC 70007-400-96

{ "type": "p", "children": [], "text": "GONITRO is available as:• Box of 12 packets NDC 70007-400-12• Box of 36 packets NDC 70007-400-36• Box of 96 packets NDC 70007-400-96" }

Store at 20°C - 25°C (68°F - 77°F); excursions permitted between 5°C – 40°C (41°F – 104°F).

{ "type": "p", "children": [], "text": "Store at 20°C - 25°C (68°F - 77°F); excursions permitted between 5°C – 40°C (41°F – 104°F). " }

Rx Only.

{ "type": "p", "children": [], "text": "Rx Only." }

Advise the patient to read the FDA-approved Instructions for Use.

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved Instructions for Use." }

Manufactured forEspero Pharmaceuticals, Inc.Jacksonville, FL 32250(800) 235-6520by G. Pohl-Boskamp GmbH & Co. KG25551 Hohenlockstedt, Germany.

{ "type": "p", "children": [], "text": "Manufactured forEspero Pharmaceuticals, Inc.Jacksonville, FL 32250(800) 235-6520by G. Pohl-Boskamp GmbH & Co. KG25551 Hohenlockstedt, Germany." }

U.S. Patent No. 9,101,592

{ "type": "p", "children": [], "text": "U.S. Patent No. 9,101,592" }

Instructions for Use GONITRO (GO-NYE-troh) (nitroglycerin) sublingual powder

{ "type": "p", "children": [], "text": "\nInstructions for Use\n\nGONITRO (GO-NYE-troh)\n\n(nitroglycerin) \n\nsublingual powder\n" }

Read these Instructions for Use before you start taking GONITRO and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

{ "type": "p", "children": [], "text": "Read these Instructions for Use before you start taking GONITRO and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment." }

Important information:

{ "type": "p", "children": [], "text": "\nImportant information:\n" }

{ "type": "ul", "children": [ "\nGONITROis for use under the tongue.\n\n", "A dose of GONITROmay be either 1 or 2 packets. Follow your healthcare provider’s instructions about how many packets you should take for each dose. After you take your first dose of GONITRO, you may take 1 additional packet of GONITROevery 5 minutes, if needed.\n", "\nYou should not take more than 3 packets of GONITRO within 15 minutes.\n\n", "\nGet emergency medical help right away if you still have chest pain after taking a total of 3 packets of GONITRO.\n\n", "It is best to take GONITROwhile you are resting and in a sitting position. " ], "text": "" }

Taking a dose of GONITRO Step 1.  Hold the packet of GONITROupright with the notch and red arrow line at the top of the packet. Step 2.  Tap the bottom of the GONITRO packet so that the powder settles at the bottom of the packet. Step 3.Hold the GONITROpacket at the notch. Hold the packet as close to your mouth as possibleand tear along   the red arrow line. Step 4. Lift up your tongue. Step 5.  Pour all of the powder in the GONITRO packet under your tongue. Step 6. Close your mouth right away and breathe normally through your nose. Allow all of the powder to dissolve before you swallow. Do not rinse your mouth or spit for 5 minutes after taking GONITRO. Step 7. If another dose of GONITROis needed, repeat Steps 1 through 6.

{ "type": "p", "children": [], "text": "\nTaking a dose of GONITRO\n\nStep 1.  Hold the packet of GONITROupright with the notch and red arrow line at the top of the packet. \nStep 2.  Tap the bottom of the GONITRO packet so that the powder settles at the bottom of the packet. \nStep 3.Hold the GONITROpacket at the notch. Hold the packet as close to your mouth as possibleand tear along   the red arrow line. \nStep 4. Lift up your tongue.\nStep 5.  Pour all of the powder in the GONITRO packet under your tongue.\nStep 6. Close your mouth right away and breathe normally through your nose. Allow all of the powder to dissolve before you swallow. Do not rinse your mouth or spit for 5 minutes after taking GONITRO.\nStep 7. If another dose of GONITROis needed, repeat Steps 1 through 6." }

{ "type": "ul", "children": [ "Regularly check the number of packets remaining in your GONITRO box and refill your prescription when there are three packets remaining. " ], "text": "" }

How should I store GONITRO

{ "type": "p", "children": [], "text": "\nHow should I store GONITRO\n" }

Store GONITROat room temperature between 68°F to 77°F (20°C to 25°C). 

{ "type": "p", "children": [], "text": "Store GONITROat room temperature between 68°F to 77°F (20°C to 25°C). " }

Keep GONITROand all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep GONITROand all medicines out of the reach of children." }

These Instructions for Use have been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "These Instructions for Use have been approved by the U.S. Food and Drug Administration." }

Manufactured forEspero Pharmaceuticals, Inc.Jacksonville, FL 32250(800) 235-6520by G. Pohl-Boskamp GmbH & Co. KG25551 Hohenlockstedt, Germany.

{ "type": "p", "children": [], "text": "Manufactured forEspero Pharmaceuticals, Inc.Jacksonville, FL 32250(800) 235-6520by G. Pohl-Boskamp GmbH & Co. KG25551 Hohenlockstedt, Germany." }

Issued: 06/2016

{ "type": "p", "children": [], "text": "Issued: 06/2016" }

Prinicpal Display Panel NDC 70007-400-36GONITRO™(nitroglycerin)sublingual powder400 mcg per packet36 single dose packets

Prinicpal Display Panel NDC 70007-400-96GONITRO™(nitroglycerin)sublingual powder400 mcg per packet96 single dose packets

Nitroglycerin Sublingual Tablets are indicated for the acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease.

{ "type": "p", "children": [], "text": "Nitroglycerin Sublingual Tablets are indicated for the acute relief of an attack or acute 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.

{ "type": "p", "children": [], "text": "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 Sublingual Tablets may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.

{ "type": "p", "children": [], "text": "Nitroglycerin Sublingual Tablets 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.

{ "type": "p", "children": [], "text": "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 Sublingual Tablets at rest, preferably in the sitting position.

{ "type": "p", "children": [], "text": "Administer Nitroglycerin Sublingual Tablets at rest, preferably in the sitting position." }

Nitroglycerin Sublingual Tablets are supplied as white or off-white, round tablets in three strengths:

{ "type": "p", "children": [], "text": "Nitroglycerin Sublingual Tablets are supplied as white or off-white, round tablets in three strengths:" }

0.3 mg (Engraved with “V” on one side and “3” on the other)0.4 mg (Engraved with “V” on one side and “4” on the other)0.6 mg (Engraved with “V” on one side and “6” on the other)

{ "type": "p", "children": [], "text": "0.3 mg (Engraved with “V” on one side and “3” on the other)0.4 mg (Engraved with “V” on one side and “4” on the other)0.6 mg (Engraved with “V” on one side and “6” on the other)" }

Do not use Nitroglycerin Sublingual Tablets 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 [see Drug Interactions (7.1)].

Do not use Nitroglycerin Sublingual Tablets in patients who are taking the soluble guanylate cyclase stimulators, such as riociguat. Concomitant use can cause hypotension.

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

Nitroglycerin Sublingual Tablets 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).

Nitroglycerin Sublingual Tablets are contraindicated in patients who are allergic to nitroglycerin, other nitrates or nitrites or any excipient.

Nitroglycerin Sublingual Tablets are contraindicated in patients with acute circulatory failure or shock.

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.

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.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

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

The following adverse reactions are discussed in more detail elsewhere in the label:

{ "type": "p", "children": [], "text": "The following adverse reactions are discussed in more detail elsewhere in the label:" }

{ "type": "", "children": [], "text": "" }

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.

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "Flushing, drug rash, and exfoliative dermatitis have been reported in patients receiving nitrate therapy." }

Nitroglycerin Sublingual Tablets are 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 Sublingual Tablets are 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.

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.

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.

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.

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

Clinical studies of Nitroglycerin Sublingual Tablets 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.

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.

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.

Nitroglycerin Sublingual Tablets are stabilized sublingual compressed nitroglycerin tablets that contain 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 colloidal silicon dioxide, NF.

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Nitroglycerin, an organic nitrate, is a vasodilating agent. The chemical name for nitroglycerin is 1, 2, 3 propanetriol trinitrate and the chemical structure is:

{ "type": "p", "children": [], "text": "Nitroglycerin, an organic nitrate, is a vasodilating agent. The chemical name for nitroglycerin is 1, 2, 3 propanetriol trinitrate and the chemical structure is:" }

C3H5N3O9

{ "type": "p", "children": [], "text": "C3H5N3O9\n" }

Molecular weight: 227.09

{ "type": "p", "children": [], "text": "Molecular weight: 227.09" }

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.

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload).

Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.

Therapeutic doses of nitroglycerin may reduce systolic, diastolic, and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively, or increased heart rate decreases diastolic filling time.

Elevated central venous and pulmonary capillary wedge pressures, and pulmonary and systemic vascular resistance are also reduced by nitroglycerin therapy. Heart rate is usually slightly increased, presumably due to a compensatory response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged. Myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased and a more favorable supply-demand ratio can be achieved. Patients with elevated left ventricular filling pressures and increased systemic vascular resistance in association with a depressed cardiac index are likely to experience an improvement in cardiac index. In contrast, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced following nitroglycerin administration.

Consistent with the symptomatic relief of angina, digital plethysmography indicates that onset of the vasodilatory effect occurs approximately 1 to 3 minutes after sublingual nitroglycerin administration and reaches a maximum by 5 minutes postdose. Effects persist for at least 25 minutes following Nitroglycerin Sublingual Tablets administration.

Absorption

Nitroglycerin is rapidly absorbed following sublingual administration of Nitroglycerin Sublingual Tablets. Mean peak nitroglycerin plasma concentrations occur at a mean time of approximately 6 to 7 minutes postdose (Table 1). Maximum plasma nitroglycerin concentrations (Cmax) and area under the plasma concentration-time curves (AUC) increase dose-proportionally following 0.3 to 0.6 mg Nitroglycerin Sublingual Tablets. The absolute bioavailability of nitroglycerin from Nitroglycerin Sublingual Tablets is approximately 40% but tends to be variable due to factors influencing drug absorption, such as sublingual hydration and mucosal metabolism.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 1</span> </caption> <col width="33%"/> <col width="34%"/> <col width="33%"/> <thead> <tr class="First"> <th align="left" class="Lrule Toprule" valign="top"></th><th align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Mean Nitroglycerin (SD) Values</span></th> </tr> <tr> <th align="left" class="Lrule" valign="top"></th><th align="center" class="Lrule" valign="top"><span class="Bold">2 × 0.3 mg</span></th><th align="center" class="Lrule Rrule" valign="top"><span class="Bold">1 × 0.6 mg</span></th> </tr> <tr class="Last"> <th align="left" class="Botrule Lrule" valign="middle"><span class="Bold">Parameter</span></th><th align="center" class="Botrule Lrule" valign="middle"><span class="Bold">Nitroglycerin Sublingual Tablets</span></th><th align="center" class="Botrule Lrule Rrule" valign="middle"><span class="Bold">Nitroglycerin Sublingual Tablets</span></th> </tr> </thead> <tbody> <tr class="First"> <td class="Botrule Lrule Toprule" valign="top"> <p class="First">C<span class="Sub">max</span>, ng/mL</p> </td><td align="center" class="Botrule Lrule Toprule" valign="top"> <p class="First">2.3 (1.7)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.1 (1.5)</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First">T<span class="Sub">max</span>, min</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">6.4 (2.5)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7.2 (3.2)</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First">AUC(0–∞), min</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">14.9 (8.2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14.9 (11.4)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule" valign="top"> <p class="First">t<span class="Sub">½</span>, min</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">2.8 (1.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.6 (0.6)</p> </td> </tr> </tbody> </table></div>

Distribution

The volume of distribution (VArea) of nitroglycerin following intravenous administration is 3.3 L/kg. At plasma concentrations between 50 and 500 ng/mL, the binding of nitroglycerin to plasma proteins is approximately 60%, while that of 1,2- and 1,3-dinitroglycerin is 60% and 30%, respectively.

Metabolism

A liver reductase enzyme is of primary importance in the metabolism of nitroglycerin to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. Known sites of extrahepatic metabolism include red blood cells and vascular walls. In addition to nitroglycerin, 2 major metabolites 1,2- and 1,3-dinitroglycerin, are found in plasma. Mean peak 1,2- and 1,3-dinitroglycerin plasma concentrations occur at approximately 15 minutes postdose. The elimination half-life of 1,2- and 1,3-dinitroglycerin is 36 and 32 minutes, respectively. The 1,2- and 1,3-dinitroglycerin metabolites have been reported to possess approximately 2% and 10%, respectively, of the pharmacological activity of nitroglycerin. Higher plasma concentrations of the dinitro metabolites, along with their nearly 10-fold longer elimination half-lives, may contribute significantly to the duration of pharmacologic effect. Glycerol mononitrate metabolites of nitroglycerin are biologically inactive.

Elimination

Nitroglycerin plasma concentrations decrease rapidly, with a mean elimination half-life of 2 to 3 minutes. Half-life values range from 1.5 to 7.5 minutes. Clearance (13.6 L/min) greatly exceeds hepatic blood flow. Metabolism is the primary route of drug elimination.

Drug interactions

Aspirin: Coadministration of nitroglycerin with high dose aspirin (1000 mg) results in increased exposure to nitroglycerin. The vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant administration of nitroglycerin with high dose aspirin.

Tissue-type plasminogen activator (t-PA): Concomitant administration of t-PA and intravenous nitroglycerin has been shown to reduce plasma levels of t-PA and its thrombolytic effect.

Animal carcinogenesis studies with sublingually administered nitroglycerin have not been performed.

Carcinogenicity potential of nitroglycerin was evaluated in rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years. Rats 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 males was 48% and in females was 33%, compared to 0% in untreated controls. 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 mutagenic in Ames tests performed in 2 different laboratories. Nevertheless, 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, PO, or in ex vivo cytogenetic tests in rat and dog cells.

In a 3-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for 6 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 3-generation study, there was no clear evidence of teratogenicity.

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.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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This product's label may have been updated. For full prescribing information, please visit www.solcohealthcare.com.

{ "type": "p", "children": [], "text": "This product's label may have been updated. For full prescribing information, please visit www.solcohealthcare.com." }

Manufactured by:Viwit Pharmaceutical Co., Ltd. 389 West Shannan Road, Tengzhou Industrial Park, Shandong, China.

{ "type": "p", "children": [], "text": "\nManufactured by:Viwit Pharmaceutical Co., Ltd.\n389 West Shannan Road, Tengzhou Industrial Park, Shandong, China." }

Distributed by:Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "\nDistributed by:Solco Healthcare US, LLC\n" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

Read this information carefully before you start Nitroglycerin (nītrō-glisĕr-in) Sublingual Tablets and each time you refill your prescription. There may be new information. This information does not replace talking with your doctor. If you have any questions about Nitroglycerin Sublingual Tablets, ask your doctor. Your doctor will know if Nitroglycerin Sublingual Tablets are right for you.

{ "type": "p", "children": [], "text": "Read this information carefully before you start Nitroglycerin (nītrō-glisĕr-in) Sublingual Tablets and each time you refill your prescription. There may be new information. This information does not replace talking with your doctor. If you have any questions about Nitroglycerin Sublingual Tablets, ask your doctor. Your doctor will know if Nitroglycerin Sublingual Tablets are right for you." }

What are Nitroglycerin Sublingual Tablets?

{ "type": "p", "children": [], "text": "\nWhat are Nitroglycerin Sublingual Tablets? \n" }

Nitroglycerin Sublingual Tablets are a type of medicine known as an organic nitrate and are vasodilating agent. It is used to treat a type of chest pain called angina.

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets are a type of medicine known as an organic nitrate and are vasodilating agent. It is used to treat a type of chest pain called angina." }

What is Angina?

{ "type": "p", "children": [], "text": "\nWhat is Angina? \n" }

Angina is a pain or discomfort that keeps coming back when part of your heart does not get enough blood. Angina feels like a pressing or squeezing pain, usually in your chest under the breastbone. Sometimes you can feel it in your shoulders, arms, neck, jaws, or back. Nitroglycerin Sublingual Tablets can relieve this pain.

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Who should not use Nitroglycerin Sublingual Tablets?

{ "type": "p", "children": [], "text": "\nWho should not use Nitroglycerin Sublingual Tablets?\n" }

Do not use Nitroglycerin Sublingual Tablets if you are allergic to organic nitrates (like the active ingredient in Nitroglycerin Sublingual Tablets).

{ "type": "p", "children": [], "text": "Do not use Nitroglycerin Sublingual Tablets if you are allergic to organic nitrates (like the active ingredient in Nitroglycerin Sublingual Tablets)." }

You should not take Nitroglycerin Sublingual Tablets if you have the following conditions:

{ "type": "p", "children": [], "text": "You should not take Nitroglycerin Sublingual Tablets if you have the following conditions:" }

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Do not take Nitroglycerin Sublingual Tablets with drugs for erectile dysfunction, like VIAGRA® (sildenafil citrate), CIALIS® (tadalafil), or LEVITRA® (vardenafil hydrochloride), as this may lead to extreme lowering of your blood pressure.

{ "type": "p", "children": [], "text": "Do not take Nitroglycerin Sublingual Tablets with drugs for erectile dysfunction, like VIAGRA® (sildenafil citrate), CIALIS® (tadalafil), or LEVITRA® (vardenafil hydrochloride), as this may lead to extreme lowering of your blood pressure.\n" }

Do not take Nitroglycerin Sublingual Tablets if you take medicines called guanylate cyclase stimulators which include riociguat, a medicine that treats pulmonary arterial hypertension and chronic-thromboembolic pulmonary hypertension.

{ "type": "p", "children": [], "text": "Do not take Nitroglycerin Sublingual Tablets if you take medicines called guanylate cyclase stimulators which include riociguat, a medicine that treats pulmonary arterial hypertension and chronic-thromboembolic pulmonary hypertension." }

What should I tell my doctor before taking Nitroglycerin Sublingual Tablets?

{ "type": "p", "children": [], "text": "\nWhat should I tell my doctor before taking Nitroglycerin Sublingual Tablets?\n" }

Before using Nitroglycerin Sublingual Tablets, tell your doctor if:

{ "type": "p", "children": [], "text": "Before using Nitroglycerin Sublingual Tablets, tell your doctor if:" }

{ "type": "", "children": [], "text": "" }

How should I take Nitroglycerin Sublingual Tablets?

{ "type": "p", "children": [], "text": "\nHow should I take Nitroglycerin Sublingual Tablets?\n" }

{ "type": "", "children": [], "text": "" }

What should I avoid while taking Nitroglycerin Sublingual Tablets?

{ "type": "p", "children": [], "text": "\nWhat should I avoid while taking Nitroglycerin Sublingual Tablets?\n" }

{ "type": "", "children": [], "text": "" }

What are the possible side effects of Nitroglycerin Sublingual Tablets?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of Nitroglycerin Sublingual Tablets?\n" }

Nitroglycerin Sublingual Tablets may cause the following side effects:

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets may cause the following side effects:" }

{ "type": "", "children": [], "text": "" }

Tell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of Nitroglycerin Sublingual Tablets. For a complete list, ask your doctor or pharmacist.

{ "type": "p", "children": [], "text": "Tell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of Nitroglycerin Sublingual Tablets. For a complete list, ask your doctor or pharmacist." }

How do I store Nitroglycerin Sublingual Tablets?

{ "type": "p", "children": [], "text": "\nHow do I store Nitroglycerin Sublingual Tablets?\n" }

Nitroglycerin Sublingual Tablets should be kept in the original glass container and tightly capped after each use to prevent loss of tablet potency.

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets should be kept in the original glass container and tightly capped after each use to prevent loss of tablet potency." }

Store Nitroglycerin Sublingual Tablets at room temperature (between 68° and 77°F).

{ "type": "p", "children": [], "text": "Store Nitroglycerin Sublingual Tablets at room temperature (between 68° and 77°F)." }

General advice about Nitroglycerin Sublingual Tablets

{ "type": "p", "children": [], "text": "\nGeneral advice about Nitroglycerin Sublingual Tablets\n" }

Sometimes doctors will prescribe a medicine for a condition that is not included in the patient information leaflets. Only use Nitroglycerin Sublingual Tablets the way your doctor told you to. Do not give Nitroglycerin Sublingual Tablets to other people, even if they have the same symptoms you have. It may harm them.

{ "type": "p", "children": [], "text": "Sometimes doctors will prescribe a medicine for a condition that is not included in the patient information leaflets. Only use Nitroglycerin Sublingual Tablets the way your doctor told you to. Do not give Nitroglycerin Sublingual Tablets to other people, even if they have the same symptoms you have. It may harm them." }

You can ask your pharmacist or doctor for information about Nitroglycerin Sublingual Tablets, or you can contact Solco Healthcare US, LLC at 1-866-257-2597.

{ "type": "p", "children": [], "text": "You can ask your pharmacist or doctor for information about Nitroglycerin Sublingual Tablets, or you can contact Solco Healthcare US, LLC at 1-866-257-2597." }

Manufactured by:Viwit Pharmaceutical Co., Ltd. 389 West Shannan Road, Tengzhou Industrial Park, Shandong, China.

{ "type": "p", "children": [], "text": "\nManufactured by:Viwit Pharmaceutical Co., Ltd.\n389 West Shannan Road, Tengzhou Industrial Park, Shandong, China." }

Distributed by:Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "\nDistributed by:Solco Healthcare US, LLC\n" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

Revised April 2025

{ "type": "p", "children": [], "text": "\n\nRevised April 2025\n" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 43547-985-10

{ "type": "p", "children": [], "text": "NDC 43547-985-10" }

Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets, USP\n" }

0.3 mg/tablet

{ "type": "p", "children": [], "text": "\n0.3 mg/tablet\n" }

100 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "100 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

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See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.3 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.3 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Waring- Close tightly immediately after each use to prevent loss of potency.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency." }

Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 43547-985-10 Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "NDC 43547-985-10\nNitroglycerin Sublingual Tablets, USP\n" }

0.3 mg/tablet

{ "type": "p", "children": [], "text": "\n0.3 mg/tablet\n" }

100 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "100 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\n" }

See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.3 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.3 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Please note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release.

{ "type": "p", "children": [], "text": "\nPlease note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release." }

If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended.

{ "type": "p", "children": [], "text": "If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended." }

Waring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf

{ "type": "p", "children": [], "text": "Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 433547-986-10

{ "type": "p", "children": [], "text": "NDC 433547-986-10" }

Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets, USP\n" }

0.4 mg / tablet

{ "type": "p", "children": [], "text": "\n0.4 mg / tablet\n" }

100 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "100 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\n" }

See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.4 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.4 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Waring- Close tightly immediately after each use to prevent loss of potency.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency." }

Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 43547-986-04

{ "type": "p", "children": [], "text": " NDC 43547-986-04" }

Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets, USP\n" }

0.4 mg / tablet

{ "type": "p", "children": [], "text": "\n0.4 mg / tablet\n" }

4 Bottles × 25 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "4 Bottles × 25 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\n" }

See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.4 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.4 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Please note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release.

{ "type": "p", "children": [], "text": "\nPlease note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release." }

If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended.

{ "type": "p", "children": [], "text": "If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended." }

Waring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf

{ "type": "p", "children": [], "text": "Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 433547-986-10

{ "type": "p", "children": [], "text": "NDC 433547-986-10" }

Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets, USP\n" }

0.4 mg / tablet

{ "type": "p", "children": [], "text": "\n0.4 mg / tablet\n" }

100 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "100 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\n" }

See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.4 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.4 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Waring- Close tightly immediately after each use to prevent loss of potency.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency." }

Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 43547-086-10

{ "type": "p", "children": [], "text": "NDC 43547-086-10" }

Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets, USP\n" }

0.4 mg / tablet

{ "type": "p", "children": [], "text": "\n0.4 mg / tablet\n" }

100 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "100 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\n" }

See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.4 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.4 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Please note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release.

{ "type": "p", "children": [], "text": "\nPlease note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release." }

If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended.

{ "type": "p", "children": [], "text": "If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended." }

Waring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf

{ "type": "p", "children": [], "text": "Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 43547-987-10 Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "NDC 43547-987-10\nNitroglycerin Sublingual Tablets, USP\n" }

0.6 mg/tablet

{ "type": "p", "children": [], "text": "\n0.6 mg/tablet\n" }

100 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "100 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\n" }

See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.6 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.6 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Waring- Close tightly immediately after each use to prevent loss of potency.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency." }

Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

ALWAYS DISPENSE WITH PATIENT PACKAGE INSERT

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\nPATIENT PACKAGE INSERT\n" }

NDC 43547-987-10

{ "type": "p", "children": [], "text": "NDC 43547-987-10" }

Nitroglycerin Sublingual Tablets, USP

{ "type": "p", "children": [], "text": "\nNitroglycerin Sublingual Tablets, USP\n" }

0.6 mg/tablet

{ "type": "p", "children": [], "text": "\n0.6 mg/tablet\n" }

100 Sublingual Tablets Rx only

{ "type": "p", "children": [], "text": "100 Sublingual Tablets\nRx only\n" }

Store at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].

{ "type": "p", "children": [], "text": "\nStore at Controlled Room Temperature 20°-25℃ (68°-77℉) [see USP].\n" }

DOSAGE AND USE

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\n" }

See accompanying prescribing information.

{ "type": "p", "children": [], "text": "See accompanying prescribing information." }

Each tablet contains 0.6 mg nitroglycerin.

{ "type": "p", "children": [], "text": "Each tablet contains 0.6 mg nitroglycerin." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all drugs out of the reach of children.\n" }

Please note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release.

{ "type": "p", "children": [], "text": "\nPlease note- You may feel a “burning or tingling” sensation at the site of tablet placement. Lack of “burning or tingling” in your mouth does not indicate failure of Nitroglycerin release." }

If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended.

{ "type": "p", "children": [], "text": "If the pain persists after a total of 3 tablets in a 15-minute period, or is different than you typically experience, prompt medical attention is recommended." }

Waring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container.

{ "type": "p", "children": [], "text": "\nWaring- Close tightly immediately after each use to prevent loss of potency. Keep these tablets in the original container." }

Do not crush, chew, or swallow Nitroglycerin Tablets.

{ "type": "p", "children": [], "text": "\nDo not crush, chew, or swallow Nitroglycerin Tablets.\n" }

Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf

{ "type": "p", "children": [], "text": "Print Patient Information at: www.solcohealhecare.com/druglabeling/nitroglycerin-sublingual-tablets.pdf" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Solco Healthcare US, LLC

{ "type": "p", "children": [], "text": "Solco Healthcare US, LLC" }

Somerset, NJ 08873, USA

{ "type": "p", "children": [], "text": "Somerset, NJ 08873, USA" }

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

{ "type": "p", "children": [], "text": "NitroMist is indicated for acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease." }

At the onset of an attack, one metered spray or two metered sprays should be administered on or under the tongue. A spray may be repeated approximately every 5 minutes as needed. If two sprays are used initially, the patient may only administer one more spray after waiting 5 minutes. No more than 3 metered sprays are recommended within a 15-minute period. If chest pain persists after a total of 3 sprays, prompt medical attention is recommended. NitroMist may be used prophylactically 5 minutes to 10 minutes before engaging in activities that might precipitate an acute attack.

After an initial priming of 10 sprays, each metered spray of NitroMist delivers 33 mg of solution containing 400 mcg of nitroglycerin. It will remain adequately primed for 6 weeks. If the product is not used within 6 weeks, it can be adequately re-primed with 2 sprays. NitroMist is available in either 230 metered sprays or 90 metered sprays per container, but the total number of available doses depends on the number of sprays per use (1 spray or 2 sprays), and the frequency of priming.

During use the patient should rest, ideally in the sitting position. The container should be held vertically with the valve head uppermost and the spray orifice as close to the mouth as possible. The dose should preferably be sprayed into the mouth on or under the tongue by pressing the button firmly and the mouth should be closed immediately after each dose. THE SPRAY SHOULD NOT BE INHALED. Patients should be instructed 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 level of the liquid in the container should be periodically checked. While the container is in the upright position, if the liquid reaches the top or middle of the hole on the side of the container, one should order more. When the liquid reaches the bottom of the hole, the remaining doses will have less than label content.

Lingual aerosol, 400 mcg per spray, is available in either 230 metered sprays or 90 metered sprays per container.

{ "type": "p", "children": [], "text": "Lingual aerosol, 400 mcg per spray, is available in either 230 metered sprays or 90 metered sprays per container. " }

Administration of NitroMist is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), as PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates. Do not use NitroMist in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension. [see DRUG INTERACTIONS (7.1)].

NitroMist is contraindicated in patients with severe anemia.

NitroMist is contraindicated in patients with increased intracranial pressure.

NitroMist is contraindicated in patients who have shown hypersensitivity to it or to other nitrates or nitrites. Skin reactions consistent with hypersensitivity have been observed with organic nitrates.

Excessive use may lead to the development of tolerance. Only the smallest number of doses required for effective relief of the acute anginal attack should be used [see DOSAGE AND ADMINISTRATION (2)].

As tolerance to other forms of nitroglycerin develops, the effect of sublingual nitroglycerin on exercise tolerance, although still observable, is reduced.

Severe hypotension, particularly with upright posture, may occur even with small doses of nitroglycerin. The drug should therefore be used with caution in patients who may be volume-depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris.

The benefits of NitroMist in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use NitroMist in these conditions, careful clinical or hemodynamic monitoring must be used because of the possibility of hypotension and tachycardia.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

Nitroglycerin produces dose-related headaches, which may be severe. Tolerance to headaches occurs.

Headache, which may be severe and persistent, may occur immediately after nitroglycerin use.

Flushing, drug rash and exfoliative dermatitis have been reported in patients receiving nitrate therapy.

Postural hypotension, as manifest by vertigo, weakness, palpitation, and other symptoms, 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.

Administration of NitroMist is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates. Do not use NitroMist in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use may result in severe hypotension, syncope, or myocardial ischemia.

The time course and dose dependence of this interaction 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. The use of any form of nitroglycerin during the early days of acute myocardial infarction requires particular attention to hemodynamic monitoring and clinical status.

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.

Labetolol blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. If labetolol is used with nitroglycerin in patients with angina pectoris, additional hypotensive effects may occur.

Coadministration of aspirin and nitroglycerin has been reported to result in increased nitroglycerin maximum concentrations by as much as 67% and AUC by 73% when administered as a single dose. The vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

Intravenous administration of nitroglycerin decreases the thrombolytic effect of tissue-type plasminogen activator (t-PA). Plasma levels of t-PA are reduced when coadministered with nitroglycerin. Therefore, caution should be observed in patients receiving nitroglycerin during t-PA therapy.

Intravenous nitroglycerin reduces the anticoagulant effect of heparin. Activated partial thromboplastin times (APTT) should be monitored in patients receiving heparin and intravenous nitroglycerin. It is not known if this effect occurs following single nitroglycerin doses.

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.

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 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.

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 or the breastfed child. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s need for nitroglycerin and any potential adverse effects on the breastfed child from nitroglycerin or from the underlying maternal condition.

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

Clinical studies of NitroMist 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 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.

Signs and symptoms of hemodynamic effects: The effects of nitroglycerin overdose are generally the results of nitroglycerin’s capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; tachycardia; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); dyspnea, later followed by reduced ventilatory effort, diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.

{ "type": "p", "children": [], "text": "\nSigns and symptoms of hemodynamic effects: The effects of nitroglycerin overdose are generally the results of nitroglycerin’s capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; tachycardia; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); dyspnea, later followed by reduced ventilatory effort, diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.\n \n\n " }

No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the 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. Passive elevation of the patient’s legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

{ "type": "p", "children": [], "text": "No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the 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. Passive elevation of the patient’s legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary." }

The use of epinephrine or other arterial vasoconstrictors in this setting is not recommended.

{ "type": "p", "children": [], "text": "The use of epinephrine or other arterial vasoconstrictors in this setting is not recommended." }

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

{ "type": "p", "children": [], "text": "In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin overdose in these patients may be subtle and difficult, and invasive monitoring may be required." }

Methemoglobinemia: Methemoglobinemia has been rarely reported with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate arterial PO 2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

{ "type": "p", "children": [], "text": "\nMethemoglobinemia: Methemoglobinemia has been rarely reported with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate arterial PO\n \n \n 2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.\n \n\n " }

If methemoglobinemia is present, intravenous administration of methylene blue, 1 mg/kg to 2 mg/kg of body weight, may be required.

{ "type": "p", "children": [], "text": "If methemoglobinemia is present, intravenous administration of methylene blue, 1 mg/kg to 2 mg/kg of body weight, may be required." }

Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for nitroglycerin is 1,2,3-propanetriol trinitrate (C 3H 5N 3O 9). The compound has a molecular weight of 227.09. The chemical structure is:

{ "type": "p", "children": [], "text": "Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for nitroglycerin is 1,2,3-propanetriol trinitrate (C\n \n \n 3H\n \n \n 5N\n \n \n 3O\n \n \n 9). The compound has a molecular weight of 227.09. The chemical structure is:\n \n\n " }

      CH 2 – ONO 2      

{ "type": "p", "children": [], "text": "\n\t\t     \n\tCH\n \n \n 2 – ONO\n \n \n 2\n\t\t     \n\t\n \n\n " }

      CH – ONO 2      

{ "type": "p", "children": [], "text": "\n\t\t     \n\tCH – ONO\n \n \n 2\n\t\t     \n\t\n \n\n " }

      CH 2 – ONO 2

{ "type": "p", "children": [], "text": "\n\t\t     \n\tCH\n \n \n 2 – ONO\n \n \n 2\n" }

NitroMist (nitroglycerin) lingual aerosol is a metered-dose spray containing 230 metered sprays or 90 metered sprays of nitroglycerin per container. This product delivers 400 mcg of nitroglycerin per actuation in the form of spray droplets on or under the tongue. Inactive ingredients: caprylic/capric diglycerol succinate, peppermint oil, L(-)-menthol, n-butane.

{ "type": "p", "children": [], "text": "NitroMist (nitroglycerin) lingual aerosol is a metered-dose spray containing 230 metered sprays or 90 metered sprays of nitroglycerin per container. This product delivers 400 mcg of nitroglycerin per actuation in the form of spray droplets on or under the tongue. Inactive ingredients: caprylic/capric diglycerol succinate, peppermint oil, L(-)-menthol, n-butane." }

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. This eventually leads to dephosphorylation of myosin light chains, which regulates the contractile state in smooth muscle and results in vasodilatation.

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload). Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (after load), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.

Therapeutic doses of nitroglycerin may reduce systolic, diastolic and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively or increased heart rate decreases diastolic filling time.

Elevated central venous and pulmonary capillary wedge pressures, and pulmonary and systemic vascular resistance are also reduced by nitroglycerin therapy. Heart rate is usually slightly increased, presumably a reflex response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged. Myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased and a more favorable supply-demand ratio can be achieved. Patients with elevated left ventricular filling pressure and increased systemic vascular resistance in association with a depressed cardiac index are likely to experience an improvement in cardiac index. In contrast, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced following nitroglycerin administration.

Nitroglycerin is rapidly absorbed following lingual spray administration. In a pharmacokinetic study when a single 1200 mcg dose (three activations of a 400 mcg dose) of NitroMist was administered to healthy volunteers (n=12), all subjects had detectable trinitroglycerin plasma levels (mean C max 0.8 ng/mL ± 0.7 ng/mL and t max of 8 minutes, range 4 minutes to 15 minutes) beginning at 2 minutes post-dose and higher levels of the 1,2- (mean C max 3.7 ng/mL ± 1 ng/mL and t max 34 minutes ± 21 minutes, range 15 minutes to 90 minutes) and 1,3-dinitroglycerin metabolites (mean C max 1 ng/mL ± 0.3 ng/mL and mean t max 41 minutes ± 20 minutes, range 20 minutes to 90 minutes).

The volume of distribution of nitroglycerin following intravenous administration is 3.3 L/kg.

A liver reductase enzyme is of primary importance in the metabolism of nitroglycerin to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. Known sites of extrahepatic metabolism include red blood cells and vascular walls. In addition to nitroglycerin, 2 major metabolites, 1,2- and 1,3-dinitroglycerin are found in plasma. The mean elimination half-life of both 1,2- and 1,3-dinitroglycerin is about 40 minutes. The 1,2- and 1,3-dinitroglycerin metabolites have been reported to possess some pharmacological activity, whereas the glycerol mononitrate metabolites of nitroglycerin are essentially inactive. Higher plasma concentrations of the dinitro metabolites, with their nearly 8-fold longer elimination half-lives, may contribute significantly to the duration of pharmacologic effect.

In the above referenced pharmacokinetic study the average initial half-lives (T ½α) of nitroglycerin, and its 1,2- and 1,3-dinitroglycerin metabolites were estimated to be 3 minutes, 10 minutes, and 11 minutes, respectively. The half-life of disappearance of the nitroglycerin (T ½β) (5 minutes) was significantly less than the half-life of appearance (T ½α) of the 1,2- and 1,3-dinitroglycerin metabolites suggesting the possibility of an additional compartment into which the nitroglycerin disappears from plasma prior to being metabolized into the dinitroglycerin metabolites. A second indication of this other compartment is that the appearance of nitroglycerin metabolites in plasma was delayed in some subjects, with zero plasma levels seen for 4 minutes to 6 minutes after dosing. In some subjects, nitroglycerin metabolites appeared only after nitroglycerin C max had been observed.

Animal carcinogenicity studies with sublingually administered or lingual spray 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 the highest dose, the incidences of hepatocellular carcinomas was 52% compared to 0% in untreated controls. 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 found to have reverse mutation activity in the Salmonella typhimurium strain TA1535 (Ames assay). A similar mutation in S. typhimurium strain was also reported for other NO donors. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with oral doses of up to about 363 mg/kg/day or in ex vitro  cytogenic tests in rat and dog tissues. In vitro cytogenetic assay using Chinese hamster ovary cells showed no chromosomal aberrations.

In a 3-generation reproduction study, rats received dietary nitroglycerin at doses up to about 408 mg/kg/day (males) to 452 mg/kg/day (females) for 5 months (females) or 6 months (males) prior to mating of the F 0 generation with treatment continuing through successive F 1 and F 2 generations. The highest 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 F 0 generation was seen. Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high-dose males.

In a randomized, double-blind, single-center, single-administration, placebo-controlled, 4-period cross-over study in 30 subjects with stable angina pectoris, statistically significant dose-related increases in exercise tolerance were seen following doses of 200 mcg, 400 mcg, and 800 mcg of nitroglycerin delivered by NitroMist compared to placebo.

{ "type": "p", "children": [], "text": "In a randomized, double-blind, single-center, single-administration, placebo-controlled, 4-period cross-over study in 30 subjects with stable angina pectoris, statistically significant dose-related increases in exercise tolerance were seen following doses of 200 mcg, 400 mcg, and 800 mcg of nitroglycerin delivered by NitroMist compared to placebo." }

Each box of NitroMist contains one glass bottle coated with red/orange transparent plastic which assists in containing the glass and medication should the bottle be shattered. NitroMist is available as an 8.5 g (Net Content) of nitroglycerin lingual aerosol that will deliver 230 metered sprays containing 400 mcg of nitroglycerin per actuation or as a 4.1 g (Net Content) of nitroglycerin lingual aerosol that will deliver 90 metered sprays containing 400 mcg of nitroglycerin per actuation.

{ "type": "p", "children": [], "text": "Each box of NitroMist contains one glass bottle coated with red/orange transparent plastic which assists in containing the glass and medication should the bottle be shattered. NitroMist is available as an 8.5 g (Net Content) of nitroglycerin lingual aerosol that will deliver 230 metered sprays containing 400 mcg of nitroglycerin per actuation or as a 4.1 g (Net Content) of nitroglycerin lingual aerosol that will deliver 90 metered sprays containing 400 mcg of nitroglycerin per actuation." }

230 metered sprays: NDC 73262-430-08 90 metered sprays: NDC 73262-430-04

{ "type": "p", "children": [], "text": "230 metered sprays: NDC 73262-430-08 \n \n \n 90 metered sprays: NDC 73262-430-04\n \n\n " }

{ "type": "ul", "children": [ "Storage\n \n \n Store at room temperature (25\n \n \n °C, 77\n \n \n °F); excursions permitted to 15\n \n \n ° to 30\n \n \n °C (59\n \n \n ° to 85\n \n \n °F) \n \n \n \n", "Handling\n \n \n NitroMist contains a highly flammable propellant (butane). Do not forcefully open a NitroMist bottle, do not have the container burned after use, and do not spray directly toward flames.\n \n \n " ], "text": "" }

NitroMist should not be used in patients who are using medications for erectile dysfunction such as sildenafil, vardenafil, and tadalafil. These products have been shown to increase the hypotensive effects of nitrate drugs such as NitroMist.

Patients should be instructed that prior to initial use of NitroMist Lingual aerosol, the pump must be primed by pressing the actuator button 10 times to ensure proper dose priming. If the product is not used for more than 6 weeks, the bottle can be adequately re-primed with 2 sprays.

NitroMist is meant to be sprayed on or under the tongue at the beginning of angina or to prevent an angina attack. Treatment with nitroglycerin products such as NitroMist may be associated with lightheadedness on standing, especially just after rising from a laying or seated position. This effect may be more frequent in patients who have consumed alcohol, since alcohol use contributes to hypotension. If possible, patients should be seated when taking NitroMist. This reduces the likelihood of falling due to lightheadedness or dizziness [ see DOSAGE AND ADMINISTRATION (2.3)].

Headaches can sometimes accompany treatment with nitroglycerin. In patients who get these headaches, the headaches may indicate activity of the drug. Tolerance to headaches develops.

Flushing, drug rash and exfoliative dermatitis have been reported in patients receiving nitrate therapy.

The NitroMist bottle should not be forcefully opened. Because NitroMist contains a highly flammable propellant (butane), do not have the container burned after use and do not spray directly towards flames.

While the container is in the upright position, if the liquid reaches the top to middle of the hole on the side of the container, a new supply should be obtained. When the liquid reaches the bottom of the hole, the remaining doses will have less than label content .

Manufactured for Evus Pharmaceuticals, LLC Scottsdale, AZ 85258 USA by Dynamit Nobel GmbH, Leverkusen, Germany

Marketed and Distributed by: Evus Pharmaceuticals, LLC Scottsdale, AZ 85258 USA

NitroMist is a registered trademark of Evus Pharmaceuticals

141110

143F003 Revised 09/2019

NDC 73262-430-08 NITROMIST (Nitroglycerin) Lingual Aerosol 400 mcg/spray contains approximately 230 sprays for use on or under the tongue

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NDC 73262-430-08

{ "type": "p", "children": [], "text": "NDC 73262-430-08" }

NITROMIST (Nitroglycerin) Lingual Aerosol 400 mcg/spray contains approximately 230 sprays for use on or under the tongue

{ "type": "p", "children": [], "text": "NITROMIST\n \n\n(Nitroglycerin) Lingual Aerosol\n \n\n400 mcg/spray\n \n\ncontains approximately\n \n\n230 sprays for use on or\n \n\nunder the tongue\n " }

NDC 73262-430-04

{ "type": "p", "children": [], "text": "NDC 73262-430-04" }

NITROMIST (Nitroglycerin) Lingual Aerosol 400 mcg/spray contains approximately 90 sprays for use on or under the tongue

{ "type": "p", "children": [], "text": "NITROMIST\n \n\n(Nitroglycerin) Lingual Aerosol\n \n\n400 mcg/spray\n \n\ncontains approximately\n \n\n90 sprays for use on or\n \n\nunder the tongue\n " }

NDC 73262-430-04

{ "type": "p", "children": [], "text": "NDC 73262-430-04" }

NITROMIST (Nitroglycerin) Lingual Aerosol 400 mcg/spray contains approximately 90 sprays for use on or under the tongue

{ "type": "p", "children": [], "text": "NITROMIST\n \n\n(Nitroglycerin) Lingual Aerosol\n \n\n400 mcg/spray\n \n\ncontains approximately\n \n\n90 sprays for use on or\n \n\nunder the tongue\n " }

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

{ "type": "p", "children": [], "text": "Nitrolingual Pumpspray is indicated for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease." }

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. 

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.

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  [see Patient Information (17)].

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.

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

{ "type": "p", "children": [], "text": "Lingual spray, 400 mcg per spray available in either 60 or 200 metered sprays per container." }

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 [see Drug Interactions (7.1)].

Do not use Nitrolingual Pumpspray in patients who are taking soluble guanylate cyclase (sGC) stimulators, such as riociguat. Concomitant use can cause hypotension.

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

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).

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

Nitrolingual Pumpspray is contraindicated in patients with acute circulatory failure or shock.

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)].

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.

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.

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.

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 

Nitrolingual Pumpspray 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.

Nitrolingual Pumpspray 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.

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.

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.

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 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.

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. 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.

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. 

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 Nitrolingual Pumpspray 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.

Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for nitroglycerin is 1,2,3-propanetriol trinitrate (C3H5N3O9). The compound has a molecular weight of 227.09.

{ "type": "p", "children": [], "text": "Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for nitroglycerin is 1,2,3-propanetriol trinitrate (C3H5N3O9). The compound has a molecular weight of 227.09. " }

The chemical structure is:

{ "type": "p", "children": [], "text": "The chemical structure is:\n" }

CH 2–ONO 2 | CH–ONO 2 | CH 2–ONO 2

{ "type": "p", "children": [], "text": "CH\n2–ONO\n2\n\n|\nCH–ONO\n2\n\n|\nCH\n2–ONO\n2\n" }

Nitrolingual Pumpspray (nitroglycerin lingual spray 400 mcg) is a metered dose spray containing nitroglycerin. This product delivers nitroglycerin (400 mcg per spray, 60 or 200 metered sprays) in the form of spray droplets onto or under the tongue.

{ "type": "p", "children": [], "text": "Nitrolingual Pumpspray (nitroglycerin lingual spray 400 mcg) is a metered dose spray containing nitroglycerin. This product delivers nitroglycerin (400 mcg per spray, 60 or 200 metered sprays) in the form of spray droplets onto or under the tongue. " }

Inactive ingredients: medium-chain triglycerides, dehydrated alcohol, medium-chain partial glycerides, peppermint oil, sodium lactate, lactic acid.

{ "type": "p", "children": [], "text": "Inactive ingredients: medium-chain triglycerides, dehydrated alcohol, medium-chain partial glycerides, peppermint oil, sodium lactate, lactic acid." }

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. This eventually leads to dephosphorylation of myosin light chains, which regulates the contractile state in smooth muscle and results in vasodilatation.

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload). Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (after load), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.

Therapeutic doses of nitroglycerin may reduce systolic, diastolic and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively or increased heart rate decreases diastolic filling time.

Elevated central venous and pulmonary capillary wedge pressures, and pulmonary and systemic vascular resistance are also reduced by nitroglycerin therapy. Heart rate is usually slightly increased, presumably a reflex response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged. Myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased and a more favorable supply-demand ratio can be achieved. Patients with elevated left ventricular filling pressure and increased systemic vascular resistance in association with a depressed cardiac index are likely to experience an improvement in cardiac index. In contrast, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced following nitroglycerin administration.

A liver reductase enzyme is of primary importance in the metabolism of nitroglycerin to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. Known sites of extrahepatic metabolism include red blood cells and vascular walls. In addition to nitroglycerin, 2 major metabolites, 1,2- and 1,3-dinitroglycerin are found in plasma. The mean elimination half-life of both 1,2- and 1,3-dinitroglycerin is about 40 minutes. The 1,2- and 1,3-dinitroglycerin metabolites have been reported to possess some pharmacological activity, whereas the glycerol mononitrate metabolites of nitroglycerin are essentially inactive. Higher plasma concentrations of the dinitro metabolites, with their nearly 8-fold longer elimination half-lives, may contribute significantly to the duration of pharmacologic effect.

In a pharmacokinetic study when a single 0.8 mg dose of Nitrolingual Pumpspray was administered to healthy volunteers (n = 24), the mean C max and t max were 1,041 pg/ml and 7.5 minutes, respectively. Additionally, in these subjects the mean area under the curve (AUC) was 12,769 pg/ml * min.

The volume of distribution of nitroglycerin following intravenous administration is 3.3 L/kg.

Drug interactions

Aspirin: Coadministration of nitroglycerin with high dose aspirin (1000 mg) results in increased exposure to nitroglycerin. The vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant administration of nitroglycerin with high dose aspirin.

Tissue-type plasminogen activator (t-PA): Concomitant administration of t-PA and intravenous nitroglycerin has been shown to reduce plasma levels of t-PA and its thrombolytic effect.

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 ovary cells.

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 F 0generation 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.

In a randomized, double-blind single-dose, 5-period cross-over study in 51 patients with exertional angina pectoris significant dose-related increases in exercise tolerance, time to onset of angina and ST-segment depression were seen following doses of 0.2, 0.4, 0.8 and 1.6 mg of nitroglycerin delivered by metered pumpspray as compared to placebo.

{ "type": "p", "children": [], "text": "In a randomized, double-blind single-dose, 5-period cross-over study in 51 patients with exertional angina pectoris significant dose-related increases in exercise tolerance, time to onset of angina and ST-segment depression were seen following doses of 0.2, 0.4, 0.8 and 1.6 mg of nitroglycerin delivered by metered pumpspray as compared to placebo." }

The drug showed a profile of mild to moderate adverse events.

{ "type": "p", "children": [], "text": "The drug showed a profile of mild to moderate adverse events." }

Each box of Nitrolingual Pumpspray contains one glass bottle coated with red transparent plastic which assists in containing the glass and medication should the bottle be shattered. Each bottle contains 4.9 g or 14.1 g (Net Contents) of nitroglycerin lingual spray which will deliver 60 or 200 metered sprays containing 400 mcg of nitroglycerin per spray after priming.

{ "type": "p", "children": [], "text": "Each box of Nitrolingual Pumpspray contains one glass bottle coated with red transparent plastic which assists in containing the glass and medication should the bottle be shattered. Each bottle contains 4.9 g or 14.1 g (Net Contents) of nitroglycerin lingual spray which will deliver 60 or 200 metered sprays containing 400 mcg of nitroglycerin per spray after priming." }

Nitrolingual Pumpspray is available as:

{ "type": "p", "children": [], "text": "Nitrolingual Pumpspray is available as:" }

{ "type": "ul", "children": [ "60-dose (4.9 g) single bottle NDC 21724-100-50", "200-dose (14.1 g) single bottle NDC 21724-100-41" ], "text": "" }

Store at 20°C - 25°C (68°F - 77°F); excursions permitted to 15°C - 30°C (59°F - 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20°C - 25°C (68°F - 77°F); excursions permitted to 15°C - 30°C (59°F - 86°F) [see USP Controlled Room Temperature]." }

Note: Nitrolingual Pumpspray contains 20 % alcohol. Do not forcefully open or burn container after use. Do not spray toward flames.

{ "type": "p", "children": [], "text": "Note: Nitrolingual Pumpspray contains 20 % alcohol. Do not forcefully open or burn container after use. Do not spray toward flames." }

Rx Only.

{ "type": "p", "children": [], "text": "Rx Only." }

Advise the patient to read the FDA-approved patient labeling (Instructions for Use)

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Instructions for Use)" }

The following trademarks are either registered trademarks or trademarks of Pohl-Boskamp in the United States and/or other countries: Pohl-Boskamp word mark; Pohl-Boskamp logo; Nitrolingual® word mark; Nitrolingual® Pumpspray shapes, Nitrolingual® Pumpspray colors.

{ "type": "p", "children": [], "text": "The following trademarks are either registered trademarks or trademarks of Pohl-Boskamp in the United States and/or other countries: Pohl-Boskamp word mark; Pohl-Boskamp logo; Nitrolingual® word mark; Nitrolingual® Pumpspray shapes, Nitrolingual® Pumpspray colors.\n" }

U.S. Patent No. 7,872,049

{ "type": "p", "children": [], "text": "U.S. Patent No. 7,872,049" }

Manufactured for: Independence Pharmaceuticals, LLC Mason, OH 45040 USA by G. Pohl-Boskamp GmbH & Co. KG, 25551 Hohenlockstedt, Germany.

{ "type": "p", "children": [], "text": "Manufactured for:\nIndependence Pharmaceuticals, LLC\nMason, OH 45040 USA\nby G. Pohl-Boskamp GmbH & Co. KG,\n25551 Hohenlockstedt, Germany.\n" }

Nitrolingual® Pumpspray (nī-trō-ling´gwal) (nitroglycerin) lingual spray

{ "type": "p", "children": [], "text": "\nNitrolingual® Pumpspray (nī-trō-ling´gwal)\n\n(nitroglycerin)\n\nlingual spray\n" }

Read this Instructions for Use before you start using Nitrolingual Pumpspray and each time you get your prescription refilled. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you start using Nitrolingual Pumpspray and each time you get your prescription refilled. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment." }

Important information:

{ "type": "p", "children": [], "text": "\nImportant information:\n" }

{ "type": "ul", "children": [ "\nNitrolingual Pumpspray is for use on to or under the tongue. Do not inhale Nitrolingual Pumpspray.\n ", "A dose of Nitrolingual Pumpspray may be either 1 or 2 sprays. Follow your healthcare provider’s instructions about how many sprays you should use for each dose. Doses should be separated by approximately 5 minutes.", "\nYou should not use more than 3 sprays of Nitrolingual Pumpspray within 15 minutes.\n", "\nGet emergency medical help right away if you still have chest pain after using a total of 3 sprays of Nitrolingual Pumpspray.\n " ], "text": "" }

Nitrolingual Pumpspray parts:

{ "type": "p", "children": [], "text": "\nNitrolingual Pumpspray parts:\n" }

Figure A

{ "type": "p", "children": [], "text": "\nFigure A\n" }

How should I use Nitrolingual Pumpspray?

{ "type": "p", "children": [], "text": "\nHow should I use Nitrolingual Pumpspray?\n" }

{ "type": "ul", "children": [ "It is best to use Nitrolingual Pumpspray while you are resting and in a sitting position.", "\nDo not shake the Nitrolingual Pumpspray container.\n " ], "text": "" }

Priming Nitrolingual Pumpspray:

{ "type": "p", "children": [], "text": "\nPriming Nitrolingual Pumpspray:\n" }

Before you use Nitrolingual Pumpspray for the first time, you must prime it. To prime your Nitrolingual Pumpspray, follow the steps below:

{ "type": "p", "children": [], "text": "Before you use Nitrolingual Pumpspray for the first time, you must prime it. To prime your Nitrolingual Pumpspray, follow the steps below:" }

Step 1. Remove the plastic cap from the container. (See Figure B)

{ "type": "p", "children": [], "text": "\nStep 1. Remove the plastic cap from the container. (See Figure B)\n" }

Figure B

{ "type": "p", "children": [], "text": "Figure B" }

Step 2. Hold the container upright and facing away from yourself and others. Press down on the top of the grooved button 5 times. (See Figure C)

{ "type": "p", "children": [], "text": "\nStep 2. Hold the container upright and facing away from yourself and others. Press down on the top of the grooved button 5 times. (See Figure C)\n" }

Figure C

{ "type": "p", "children": [], "text": "Figure C" }

{ "type": "ul", "children": [ "Your Nitrolingual Pumpspray is now primed. You are ready to give your first dose.", "If you do not use your Nitrolingual Pumpspray within 6 weeks, you will need to prime it again by pressing down on the top of the grooved button 1 time.", "If you do not use your Nitrolingual Pumpspray within 3 months, you will need to re-prime it by pressing down on the top of the grooved button up to 5 times. " ], "text": "" }

Giving a dose of Nitrolingual Pumpspray:

{ "type": "p", "children": [], "text": "\nGiving a dose of Nitrolingual Pumpspray:\n" }

Step 3. Hold your Nitrolingual Pumpspray container upright with your index finger on top of the grooved button.

{ "type": "p", "children": [], "text": "\nStep 3. Hold your Nitrolingual Pumpspray container upright with your index finger on top of the grooved button.\n" }

Step 4. Open your mouth and bring the Nitrolingual Pumpspray container as close to your mouth as possible.

{ "type": "p", "children": [], "text": "\nStep 4. Open your mouth and bring the Nitrolingual Pumpspray container as close to your mouth as possible.\n" }

Step 5. Press down on the top of the grooved button firmly with your index finger to release the spray onto or under your tongue. (See Figure D). The grooved button can help you make sure the canister is turned to the correct position if you are administering the spray in the dark.

{ "type": "p", "children": [], "text": "\nStep 5. Press down on the top of the grooved button firmly with your index finger to release the spray onto or under your tongue. (See Figure D). The grooved button can help you make sure the canister is turned to the correct position if you are administering the spray in the dark.\n" }

Figure D

{ "type": "p", "children": [], "text": "Figure D" }

Step 6. Release the grooved button and close your mouth right away. Avoid swallowing right after using Nitrolingual Pumpspray. Do not spit out Nitrolingual Pumpspray or rinse your mouth for 5 to 10 minutes after using Nitrolingual Pumpspray.

{ "type": "p", "children": [], "text": "\nStep 6. Release the grooved button and close your mouth right away. Avoid swallowing right after using Nitrolingual Pumpspray. Do not spit out Nitrolingual Pumpspray or rinse your mouth for 5 to 10 minutes after using Nitrolingual Pumpspray.\n" }

Step 7. If a second dose of Nitrolingual Pumpspray is needed, repeat Steps 3 through 6 above.  

{ "type": "p", "children": [], "text": "\nStep 7. If a second dose of Nitrolingual Pumpspray is needed, repeat Steps 3 through 6 above.  \n" }

Step 8. Replace the plastic cap.

{ "type": "p", "children": [], "text": "\nStep 8. Replace the plastic cap.\n" }

Check the level of the fluid in your Nitrolingual Pumpspray container regularly.

{ "type": "p", "children": [], "text": "Check the level of the fluid in your Nitrolingual Pumpspray container regularly." }

{ "type": "ul", "children": [ "Check the container in an upright position.", "The end of the center tube should be covered by the fluid in the Nitrolingual Pumpspray container. If the level of the fluid falls below the end of the center tube, sprays will not provide enough Nitrolingual Pumpspray.", "Replace your Nitrolingual Pumpspray container before the fluid level falls below the end of the center tube." ], "text": "" }

How should I store Nitrolingual Pumpspray?

{ "type": "p", "children": [], "text": "\nHow should I store Nitrolingual Pumpspray?\n" }

{ "type": "ul", "children": [ "Store Nitrolingual Pumpspray at room temperature between 68°F - 77°F (20°C - 25°C).", "Do not forcefully open or burn the Nitrolingual Pumpspray container after use.", "Do not spray Nitrolingual Pumpspray toward flames." ], "text": "" }

Keep Nitrolingual Pumpspray and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep Nitrolingual Pumpspray and all medicines out of the reach of children.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.  

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration.  " }

Manufactured for: Independence Pharmaceuticals, LLC Mason, OH 45040 USA by G. Pohl-Boskamp GmbH & Co. KG, 25551 Hohenlockstedt, Germany.

{ "type": "p", "children": [], "text": "Manufactured for:\nIndependence Pharmaceuticals, LLC\nMason, OH 45040 USA\nby G. Pohl-Boskamp GmbH & Co. KG,\n25551 Hohenlockstedt, Germany." }

Revised: 05/2024

{ "type": "p", "children": [], "text": "Revised: 05/2024" }

The following trademarks are either registered trademarks or trademarks of Pohl-Boskamp in the United States and / or other countries: Pohl-Boskamp word mark; Pohl-Boskamp logo; Nitrolingual® word mark; Nitrolingual® Pumpspray shapes, Nitrolingual® Pumpspray colors.

{ "type": "p", "children": [], "text": "The following trademarks are either registered trademarks or trademarks of Pohl-Boskamp in the United States and / or other countries:\nPohl-Boskamp word mark; Pohl-Boskamp logo; Nitrolingual® word mark; Nitrolingual® Pumpspray shapes, Nitrolingual® Pumpspray colors." }

NDC 21724-100-50

{ "type": "p", "children": [], "text": "NDC 21724-100-50" }

Nitrolingual® Pumpspray (nitroglycerin lingual spray) 400 mcg per spray. 60 Metered Sprays 4.9 g Net Contents   Rx Only   Pat. #7,872,049 Store at 20ºC−25ºC (68ºF−77ºF); excursions permitted to 15ºC−30ºC (59ºF−86ºF)[See USP Controlled Room Temperature]. Keep out of the reach of children.

{ "type": "p", "children": [], "text": "\nNitrolingual® Pumpspray\n(nitroglycerin lingual spray)\n400 mcg per spray. 60 Metered Sprays\n4.9 g Net Contents   Rx Only   Pat. #7,872,049\nStore at 20ºC−25ºC (68ºF−77ºF);\nexcursions permitted to 15ºC−30ºC \n(59ºF−86ºF)[See USP Controlled Room \nTemperature].\nKeep out of the reach of children.\n" }

10281/2

{ "type": "p", "children": [], "text": "10281/2" }

NDC 21724-100-50 Rx Only 

{ "type": "p", "children": [], "text": "\nNDC 21724-100-50\nRx Only \n" }

Nitrolingual® Pumpspray (nitroglycerin lingual spray)

{ "type": "p", "children": [], "text": "\nNitrolingual® Pumpspray\n(nitroglycerin lingual spray)" }

400 mcg per spray 60 Metered Sprays

{ "type": "p", "children": [], "text": "\n400 mcg per spray\n60 Metered Sprays\n" }

DO NOT SHAKE HOLD CONTAINER UPRIGHT PRIME BEOFRE USE

{ "type": "p", "children": [], "text": "\nDO NOT SHAKE HOLD CONTAINER UPRIGHT PRIME BEOFRE USE\n" }

4.9 g Net Contents    

{ "type": "p", "children": [], "text": "\n\n\n4.9 g Net Contents    \n" }

12078/2

{ "type": "p", "children": [], "text": "12078/2" }

NDC 21724-100-41 Nitrolingual® Pumpspray (nitroglycerin lingual spray) 400 mcg per Spray Delivers 200 Metered Sprays (12 g) 14.1 g Net Contents   Rx Only   Pat. #7,872,049

{ "type": "p", "children": [], "text": "NDC 21724-100-41\nNitrolingual® Pumpspray\n(nitroglycerin lingual spray)\n400 mcg per Spray\nDelivers 200 Metered Sprays (12 g)\n14.1 g Net Contents   Rx Only   Pat. #7,872,049\n" }

Store at 20ºC−25ºC (68ºF−77ºF); excursions permitted to 15ºC−30ºC (59ºF−86ºF)

{ "type": "p", "children": [], "text": "Store at 20ºC−25ºC (68ºF−77ºF);\nexcursions permitted to\n15ºC−30ºC (59ºF−86ºF)\n\n\n" }

[See USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "\n[See USP Controlled Room Temperature]." }

10507/2

{ "type": "p", "children": [], "text": "10507/2" }

NDC 21724-100-41 Rx Only 

{ "type": "p", "children": [], "text": "\nNDC 21724-100-41\nRx Only \n" }

Nitrolingual® Pumpspray (nitroglycerin lingual spray)

{ "type": "p", "children": [], "text": "\nNitrolingual® Pumpspray\n(nitroglycerin lingual spray)" }

400 mcg per spray 200 Metered Sprays

{ "type": "p", "children": [], "text": "\n400 mcg per spray\n200 Metered Sprays\n" }

DO NOT SHAKE HOLD CONTAINER UPRIGHT PRIME BEOFRE USE

{ "type": "p", "children": [], "text": "\nDO NOT SHAKE HOLD CONTAINER UPRIGHT PRIME BEOFRE USE\n" }

14.1 g Net Contents    

{ "type": "p", "children": [], "text": "\n14.1 g Net Contents    \n" }

10028/2

{ "type": "p", "children": [], "text": "10028/2" }

Nitroglycerin ointment 0.4% is indicated for the treatment of moderate to severe pain associated with chronic anal fissure.

{ "type": "p", "children": [], "text": "Nitroglycerin ointment 0.4% is indicated for the treatment of moderate to severe pain associated with chronic anal fissure." }

Apply 1 inch of ointment (375 mg of ointment equivalent to 1.5 mg of nitroglycerin) intra-anally every 12 hours for up to 3 weeks. A finger covering, such as plastic-wrap, disposable surgical glove or a finger cot, should be placed on the finger to apply the ointment. To obtain a 1.5 mg dose of nitroglycerin, the covered finger is laid alongside the 1 inch dosing line on the carton.

{ "type": "p", "children": [], "text": "Apply 1 inch of ointment (375 mg of ointment equivalent to 1.5 mg of nitroglycerin) intra-anally every 12 hours for up to 3 weeks. A finger covering, such as plastic-wrap, disposable surgical glove or a finger cot, should be placed on the finger to apply the ointment. To obtain a 1.5 mg dose of nitroglycerin, the covered finger is laid alongside the 1 inch dosing line on the carton." }

Refer to carton for accurate dosage guide. The tube is gently squeezed until a line of ointment the length of the measuring line is expressed onto the covered finger. The ointment is gently inserted into the anal canal using the covered finger no further than to the first finger joint and the ointment is applied around the side of the anal canal. If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus. Treatment may be continued for up to three weeks. Nitroglycerin ointment is not for oral, ophthalmic, or intravaginal use. Hands should be washed after application of the ointment [see Patient Instruction].

{ "type": "p", "children": [], "text": "Refer to carton for accurate dosage guide. The tube is gently squeezed until a line of ointment the length of the measuring line is expressed onto the covered finger. The ointment is gently inserted into the anal canal using the covered finger no further than to the first finger joint and the ointment is applied around the side of the anal canal. If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus. Treatment may be continued for up to three weeks. Nitroglycerin ointment is not for oral, ophthalmic, or intravaginal use. Hands should be washed after application of the ointment [see Patient Instruction]." }

Ointment, 0.4% w/w (4 mg /1 g) in 30 g tubes.

{ "type": "p", "children": [], "text": "Ointment, 0.4% w/w (4 mg /1 g) in 30 g tubes." }

Administration of nitroglycerin ointment is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), such as sildenafil, vardenafil, and tadalafil, as these are shown to potentiate the hypotensive effects of organic nitrates [see DRUG INTERACTIONS (7.1)].

Nitroglycerin ointment is contraindicated in patients with severe anemia.

Nitroglycerin ointment is contraindicated in patients with increased intracranial pressure.

Nitroglycerin ointment is contraindicated in patients who have shown hypersensitivity to it or to other nitrates or nitrites. Skin reactions consistent with hypersensitivity have been observed with organic nitrates.

Venous and arterial dilatation as a consequence of nitroglycerin treatment including nitroglycerin ointment, can decrease venous blood returning to the heart and reduce arterial vascular resistance and systolic pressure. Exercise caution when treating patients with any of the following conditions: blood volume depletion, existing hypotension, cardiomyopathies, congestive heart failure, acute myocardial infarction, or poor cardiac function for other reasons. If patients with any of these conditions are treated with nitroglycerin ointment, monitor cardiovascular status and clinical condition. The adverse reactions of nitroglycerin ointment are likely to be more pronounced in the elderly.

Nitroglycerin ointment produces dose-related headaches, which may be severe. Tolerance to headaches occurs.

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 practice.

{ "type": "p", "children": [], "text": "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 practice." }

The most common adverse reaction of nitroglycerin ointment applied to the anal canal is headache.

{ "type": "p", "children": [], "text": "The most common adverse reaction of nitroglycerin ointment applied to the anal canal is headache." }

Headache may be recurrent following each dose. Headaches are typically of short duration and can be treated with an analgesic, e.g. acetaminophen, and are reversible upon discontinuation of treatment.

{ "type": "p", "children": [], "text": "Headache may be recurrent following each dose. Headaches are typically of short duration and can be treated with an analgesic, e.g. acetaminophen, and are reversible upon discontinuation of treatment." }

In Study REC-C-001, a double-blind, placebo-controlled trial in patients with a painful chronic anal fissure, the most frequent (>2%) adverse reactions reported were as follows (Table 1)

{ "type": "p", "children": [], "text": "In Study REC-C-001, a double-blind, placebo-controlled trial in patients with a painful chronic anal fissure, the most frequent (>2%) adverse reactions reported were as follows (Table 1)" }

Table 1: Incidence of Adverse Reactions (> 2%) in Study REC-C-001

{ "type": "p", "children": [], "text": "\nTable 1: Incidence of Adverse Reactions (> 2%) in Study REC-C-001\n" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="452.865"> <colgroup> <col width="37.4449339207048%"/> <col width="16.7400881057269%"/> <col width="14.5374449339207%"/> <col width="16.7400881057269%"/> <col width="14.5374449339207%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="top"></td><td align="center" class="Rrule" colspan="2" valign="top"><span class="Bold">Nitroglycerin<br/> Ointment<br/> N = 123</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="top"><span class="Bold">Placebo</span> <br/> <span class="Bold">N = 124</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"><span class="Bold">System Organ Class</span> <br/> Preferred term<br/> </td><td align="center" class="Rrule" valign="top"><span class="Bold">Patients<br/> n (%)</span> <br/> </td><td align="center" class="Rrule" valign="top"><span class="Bold">Events<br/> n</span> <br/> </td><td align="center" class="Rrule" valign="top"><span class="Bold">Patients<br/> n (%)</span> <br/> </td><td align="center" class="Rrule" valign="top"><span class="Bold">Events<br/> n</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="5" valign="top"><span class="Bold">Nervous system disorders</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Headache<br/> </td><td align="center" class="Rrule" valign="top">79 (64)<br/> </td><td align="center" class="Rrule" valign="top">938<br/> </td><td align="center" class="Rrule" valign="top">51 (41)<br/> </td><td align="center" class="Rrule" valign="top">225<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">Dizziness<br/> </td><td align="center" class="Rrule" valign="top">6 (5)<br/> </td><td align="center" class="Rrule" valign="top">26<br/> </td><td align="center" class="Rrule" valign="top">0<br/> </td><td align="center" class="Rrule" valign="top">0<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"452.865\">\n<colgroup>\n<col width=\"37.4449339207048%\"/>\n<col width=\"16.7400881057269%\"/>\n<col width=\"14.5374449339207%\"/>\n<col width=\"16.7400881057269%\"/>\n<col width=\"14.5374449339207%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td class=\"Lrule Rrule\" valign=\"top\"></td><td align=\"center\" class=\"Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">Nitroglycerin<br/> Ointment<br/> N = 123</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">Placebo</span>\n<br/>\n<span class=\"Bold\">N = 124</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">System Organ Class</span>\n<br/> Preferred term<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Patients<br/> n (%)</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Events<br/> n</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Patients<br/> n (%)</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"><span class=\"Bold\">Events<br/> n</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Nervous system disorders</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Headache<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">79 (64)<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">938<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">51 (41)<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">225<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" valign=\"top\">Dizziness<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">6 (5)<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">26<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">0<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\">0<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Hypotension

{ "type": "p", "children": [], "text": "\nHypotension\n" }

Transient episodes of light-headedness, occasionally related to blood pressure changes, also may occur. Hypotension (including orthostatic hypotension) occurs infrequently, but in some patients may be severe enough to warrant discontinuation of therapy.

{ "type": "p", "children": [], "text": "Transient episodes of light-headedness, occasionally related to blood pressure changes, also may occur. Hypotension (including orthostatic hypotension) occurs infrequently, but in some patients may be severe enough to warrant discontinuation of therapy." }

Allergic Reactions Flushing, allergic reactions, and application site reactions (including drug rash and exfoliative dermatitis) have been reported rarely.

{ "type": "p", "children": [], "text": "\nAllergic Reactions\n\nFlushing, allergic reactions, and application site reactions (including drug rash and exfoliative dermatitis) have been reported rarely." }

Methemoglobinemia

{ "type": "p", "children": [], "text": "\nMethemoglobinemia\n" }

In rare cases, therapeutic doses of organic nitrates have caused methemoglobinemia [see OVERDOSAGE (10)].

{ "type": "p", "children": [], "text": "\nIn rare cases, therapeutic doses of organic nitrates have caused methemoglobinemia [see OVERDOSAGE (10)].\n" }

Phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates.

The time course of the interaction appears to be related to the half-life of the PDE5 inhibitor, however, the dose dependence of this interaction has not been studied. Use of nitroglycerin ointment within a few days of PDE5 inhibitors is contraindicated.

Patients receiving antihypertensive drugs, beta-adrenergic blockers, and other nitrates should be observed for possible additive hypotensive effects when using nitroglycerin ointment Marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly.

Beta-blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. If beta-blockers are used with nitroglycerin ointment in patients with angina pectoris, additional hypotensive effects may occur.

Coadministration of aspirin (at doses between 500 mg and 1000 mg) and nitroglycerin has been reported to result in increased nitroglycerin maximum concentrations by as much as 67% and AUC by 73% when administered as a single dose. The pharmacological effects of nitroglycerin ointment may be enhanced by concomitant administration of aspirin.

Intravenous administration of nitroglycerin decreases the thrombolytic effect of tissue-type plasminogen activator (t-PA). Plasma levels of t-PA are reduced when coadministered with nitroglycerin. Therefore, caution should be observed in patients receiving nitroglycerin ointment during t-PA therapy.

Although an interaction has been reported between intravenous heparin and intravenous nitroglycerin (resulting in a decrease in the anticoagulant effect of heparin), the data are not consistent. If patients are to receive intravenous heparin and nitroglycerin ointment concurrently, the anticoagulation status of the patient must be checked.

Oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and consequently increases its oral bioavailability. Ergotamine is known to precipitate angina pectoris. Therefore the possibility of ergotism in patients receiving nitroglycerin ointment should be considered.

The vasodilating effects of nitroglycerin have been shown to be additive to the effects observed with alcohol.

Risk Summary There are no data on the use of nitroglycerin ointment intra-anally during pregnancy to determine a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, no malformations were observed in offspring of pregnant rats and rabbits administered nitroglycerin by topical or dietary route during the period of organogenesis ( see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data  Animal Data Animal reproduction studies in rats and rabbits 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.

An animal reproduction study was conducted in rats with nitroglycerin administered in the diet at levels up to 1% content (approximately 430 mg/kg/day) on days 6 to 15 of gestation. In offspring of the high-dose group, an increased but not statistically significant incidence of diaphragmatic hernias was noted together with decreased hyoid bone ossification. The latter finding probably reflects delayed development, thus indicating no clear evidence of a potential teratogenic effect of nitroglycerin.

Risk Summary There are no data on the presence of nitroglycerin in either human or animal milk following topical administration, or the effects of nitroglycerin on milk production. A publication describing 40 lactating patients who used nitroglycerin ointment to treat chronic anal fissures for varied durations did not report signs of adverse effects in their breastfed infants, however, the dosing regimens were not described. The developmental and health benefits of breastfeeding should be considered along with the clinical need for nitroglycerin ointment and any potential adverse effects on the breastfed infant from nitroglycerin ointment or from the underlying maternal condition.

The safety and effectiveness of nitroglycerin ointment in pediatric patients under 18 years of age have not been established.

Clinical studies of nitroglycerin ointment did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Clinical data from the published literature indicate that the elderly demonstrate increased sensitivity to nitrates, which may be therapeutic but also manifest by more frequent or severe hypotension and related dizziness or fainting. Increased sensitivity may reflect the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Nitroglycerin toxicity is generally mild. The estimated adult oral lethal dose of nitroglycerin is 200 mg to 1,200 mg. Infants may be more susceptible to toxicity from nitroglycerin. Consultation with a poison center should be considered.

{ "type": "p", "children": [], "text": "Nitroglycerin toxicity is generally mild. The estimated adult oral lethal dose of nitroglycerin is 200 mg to 1,200 mg. Infants may be more susceptible to toxicity from nitroglycerin. Consultation with a poison center should be considered." }

Laboratory determinations of serum levels of nitroglycerin and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of nitroglycerin overdose.

{ "type": "p", "children": [], "text": "Laboratory determinations of serum levels of nitroglycerin and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of nitroglycerin overdose." }

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of nitroglycerin and its active metabolites. Similarly, it is not known which, if any, of these substances can usefully be removed from the body by hemodialysis. No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the 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. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

{ "type": "p", "children": [], "text": "No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of nitroglycerin and its active metabolites. Similarly, it is not known which, if any, of these substances can usefully be removed from the body by hemodialysis. No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the 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. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary." }

The use of epinephrine or other arterial vasoconstrictors in this setting is not recommended.

{ "type": "p", "children": [], "text": "The use of epinephrine or other arterial vasoconstrictors in this setting is not recommended." }

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin ointment overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

{ "type": "p", "children": [], "text": "In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin ointment overdose in these patients may be subtle and difficult, and invasive monitoring may be required." }

Methemoglobinemia Methemoglobinemia has been rarely reported with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate arterial PO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

{ "type": "p", "children": [], "text": "\nMethemoglobinemia\n Methemoglobinemia has been rarely reported with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate arterial PO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air." }

If methemoglobinemia is present, intravenous administration of methylene blue, 1 to 2 mg/kg of body weight, may be required.

{ "type": "p", "children": [], "text": "If methemoglobinemia is present, intravenous administration of methylene blue, 1 to 2 mg/kg of body weight, may be required." }

Nitroglycerin ointment, USP 0.4% is intended for intra-anal use. Nitroglycerin is 1,2,3,-propanetriol trinitrate, an organic nitrate vasodilator whose structural formula is as follows:

{ "type": "p", "children": [], "text": "Nitroglycerin ointment, USP 0.4% is intended for intra-anal use. Nitroglycerin is 1,2,3,-propanetriol trinitrate, an organic nitrate vasodilator whose structural formula is as follows:" }

and whose molecular weight is 227.09. Nitroglycerin ointment, USP 0.4% contains 0.4% nitroglycerin w/w (4 mg nitroglycerin/1 g ointment), propylene glycol, lanolin, sorbitan sesquioleate, paraffin wax, and white petrolatum. Nitroglycerin ointment, USP 0.4% is available in tubes with a one-inch dosing line on the carton allowing the measurement of approximately 375 mg of nitroglycerin ointment, USP 0.4% (1.5 mg nitroglycerin) for application.

{ "type": "p", "children": [], "text": "and whose molecular weight is 227.09. Nitroglycerin ointment, USP 0.4% contains 0.4% nitroglycerin w/w (4 mg nitroglycerin/1 g ointment), propylene glycol, lanolin, sorbitan sesquioleate, paraffin wax, and white petrolatum. Nitroglycerin ointment, USP 0.4% is available in tubes with a one-inch dosing line on the carton allowing the measurement of approximately 375 mg of nitroglycerin ointment, USP 0.4% (1.5 mg nitroglycerin) for application." }

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. This leads to dephosphorylation of myosin light chains, which regulates the contractile state in smooth muscle and results in vasodilatation.

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Intra- anal application of nitroglycerin reduces sphincter tone and resting intra-anal pressure.

Absorption: In six healthy subjects, the average absolute bioavailability of nitroglycerin applied to the anal canal as a 0.2% w/w ointment was approximately 50% of the 0.75 mg nitroglycerin dose.

Distribution: The volume of distribution of nitroglycerin following intravenous administration is about 3 L/kg. At plasma concentrations between 50 and 500 ng/mL, the binding of nitroglycerin to plasma proteins is approximately 60%, while that of 1,2- and 1,3-dinitroglycerin is 60% and 30%, respectively.

Metabolism: Nitroglycerin is metabolized by a liver reductase enzyme to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. Known sites of extrahepatic metabolism include red blood cells and vascular walls. In addition to nitroglycerin, the two major metabolites, 1,2- and 1,3- dinitroglycerols are found in plasma. The contribution of metabolites to the relaxation of the internal anal sphincter is unknown. The dinitrates are further metabolized to nonvasoactive mononitrates and ultimately to glycerol and carbon dioxide.

Elimination: Metabolism is the primary route of drug elimination. Nitroglycerin plasma concentrations decrease rapidly with a mean elimination half-life of two to three minutes. Half-life values range from 1.5 to 7.5 minutes. Clearance (13.6 L/min) greatly exceeds hepatic blood flow.

Carcinogenesis

Animal carcinogenicity studies with topically applied 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 the highest dose, the incidence of hepatocellular carcinomas was 52% compared to 0% in untreated controls. Incidence 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.

Mutagenesis

Nitroglycerin was mutagenic in the in vitro bacterial reverse mutation (Ames) assay with Salmonella typhimurium. A similar mutation in this S. typhimurium was also reported with other NO donors.There was no evidence of clastogenic potential in multiple assays including a rodent dominant lethal assay, an in vitro Chinese Hamster Ovary assay that was conducted in the absence of metabolic activation, and several in vivo chromosomal aberration assays conducted in rats and dogs.

Impairment of Fertility

In a three-generation reproduction study, rats received dietary nitroglycerin at doses up to approximately 434 mg/kg/day for 6 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.

Nitroglycerin ointment was evaluated in a 3-week double-blind, randomized, multi-center, placebo- controlled study. Patients with a painful chronic anal fissure for at least 6 weeks and moderate or severe pain prior to treatment (≥ 50 mm on the 100mm visual analog scale, VAS) were randomized to receive 0.4% (1.5mg) nitroglycerin or placebo ointment applied to the anal canal every 12 hours. Pain as assessed by the change in VAS from baseline to Days 14-18 was lower in patients receiving 0.4% ointment compared to placebo. The mean change from baseline was 44mm for nitroglycerin ointment and 37mm for placebo. The difference in the mean change in pain between nitroglycerin ointment and placebo was -7.0mm (95% Confidence Interval: -13.6 to -0.4mm).

{ "type": "p", "children": [], "text": "Nitroglycerin ointment was evaluated in a 3-week double-blind, randomized, multi-center, placebo- controlled study. Patients with a painful chronic anal fissure for at least 6 weeks and moderate or severe pain prior to treatment (≥ 50 mm on the 100mm visual analog scale, VAS) were randomized to receive 0.4% (1.5mg) nitroglycerin or placebo ointment applied to the anal canal every 12 hours. Pain as assessed by the change in VAS from baseline to Days 14-18 was lower in patients receiving 0.4% ointment compared to placebo. The mean change from baseline was 44mm for nitroglycerin ointment and 37mm for placebo. The difference in the mean change in pain between nitroglycerin ointment and placebo was -7.0mm (95% Confidence Interval: -13.6 to -0.4mm)." }

Nitroglycerin ointment, USP 0.4% is available in 30 g (NDC 21922-048-05) aluminum tubes with polyethylene screw caps.

{ "type": "p", "children": [], "text": "Nitroglycerin ointment, USP 0.4% is available in 30 g (NDC 21922-048-05) aluminum tubes with polyethylene screw caps." }

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]." }

Keep the tube tightly closed immediately after each use. Use within 8 weeks of first opening.

{ "type": "p", "children": [], "text": "Keep the tube tightly closed immediately after each use. Use within 8 weeks of first opening." }

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)" }

Interaction with PDE5 inhibitors

{ "type": "p", "children": [], "text": "\nInteraction with PDE5 inhibitors\n" }

Advise patient not to use nitroglycerin ointment with medications for erectile dysfunction such as Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil). These products have been shown to increase the hypotensive effects of nitroglycerin ointment and other nitrate drugs [see Contraindications (4)].

{ "type": "p", "children": [], "text": "Advise patient not to use nitroglycerin ointment with medications for erectile dysfunction such as Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil). These products have been shown to increase the hypotensive effects of nitroglycerin ointment and other nitrate drugs [see Contraindications (4)]." }

Hypotension

{ "type": "p", "children": [], "text": "\nHypotension\n" }

Advise patients that treatment with nitroglycerin ointment may be associated with light-headedness on standing, especially just after rising from a lying or seated position. The effect may be more frequent in patients who have also consumed alcohol, since alcohol use contributes to hypotension. Advise patients to stand up from the supine or sitting position slowly.

{ "type": "p", "children": [], "text": "Advise patients that treatment with nitroglycerin ointment may be associated with light-headedness on standing, especially just after rising from a lying or seated position. The effect may be more frequent in patients who have also consumed alcohol, since alcohol use contributes to hypotension. Advise patients to stand up from the supine or sitting position slowly." }

Headaches

{ "type": "p", "children": [], "text": "\nHeadaches\n" }

Advise patients that headaches sometimes accompany treatment with nitroglycerin ointment. For patients who get these headaches, the headaches may indicate the activity of the drug. Tolerance to headaches develops. Advise patients that if they experience headache they should not alter the schedule of their nitroglycerin ointment treatment to avoid the occurrence of headache. An analgesic, such as acetaminophen, may be used to prevent or relieve the headaches.

{ "type": "p", "children": [], "text": "Advise patients that headaches sometimes accompany treatment with nitroglycerin ointment. For patients who get these headaches, the headaches may indicate the activity of the drug. Tolerance to headaches develops. Advise patients that if they experience headache they should not alter the schedule of their nitroglycerin ointment treatment to avoid the occurrence of headache. An analgesic, such as acetaminophen, may be used to prevent or relieve the headaches." }

Dizziness

{ "type": "p", "children": [], "text": "\nDizziness\n" }

Advise patients that dizziness has been reported as a side-effect of treatment with nitroglycerin ointment. Advise patients not to drive or operate machinery immediately after applying nitroglycerin ointment.

{ "type": "p", "children": [], "text": "Advise patients that dizziness has been reported as a side-effect of treatment with nitroglycerin ointment. Advise patients not to drive or operate machinery immediately after applying nitroglycerin ointment." }

Manufactured by: Encube Ethicals Pvt. Ltd. Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post: Mardol, Ponda,

{ "type": "p", "children": [], "text": "Manufactured by:\nEncube Ethicals Pvt. Ltd.\n Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post: Mardol, Ponda, " }

Goa - 403 404, India.

{ "type": "p", "children": [], "text": "Goa - 403 404, India." }

Distributed by: Encube Ethicals, Inc. 200 Meredith Drive, Suite 202

{ "type": "p", "children": [], "text": "Distributed by:\nEncube Ethicals, Inc.\n 200 Meredith Drive, Suite 202 " }

Durham, NC 27713 USA

{ "type": "p", "children": [], "text": "Durham, NC 27713 USA" }

Revised: 10/2024

{ "type": "p", "children": [], "text": "Revised: 10/2024" }

 Nitroglycerin (nye" troe glis' er in) Ointment 0.4%

{ "type": "p", "children": [], "text": "\n Nitroglycerin (nye\" troe glis' er in) Ointment 0.4%\n" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="First Last"> <td class="Lrule Rrule" valign="middle">IMPORTANT: For intra-anal use only </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n<tbody class=\"Headless\">\n<tr class=\"First Last\">\n<td class=\"Lrule Rrule\" valign=\"middle\">IMPORTANT: For intra-anal use only </td>\n</tr>\n</tbody>\n</table></div>" }

Read the Patient Information that comes with nitroglycerin ointment before you start using the product and each time you get a refill because there may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. If you have any questions about nitroglycerin ointment, ask your healthcare provider.

{ "type": "p", "children": [], "text": "Read the Patient Information that comes with nitroglycerin ointment before you start using the product and each time you get a refill because there may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. If you have any questions about nitroglycerin ointment, ask your healthcare provider." }

What is nitroglycerin ointment? Nitroglycerin ointment is a prescription medicine used to treat moderate to severe pain caused by chronic anal fissures. An anal fissure is a tear in the skin lining the anal canal.

{ "type": "p", "children": [], "text": "\nWhat is nitroglycerin ointment?\n Nitroglycerin ointment is a prescription medicine used to treat moderate to severe pain caused by chronic anal fissures. An anal fissure is a tear in the skin lining the anal canal." }

Nitroglycerin ointment is not suitable for children and adolescents under the age of 18 years because it has not been assessed in people in this age group.

{ "type": "p", "children": [], "text": "Nitroglycerin ointment is not suitable for children and adolescents under the age of 18 years because it has not been assessed in people in this age group." }

Who should not use nitroglycerin ointment?

{ "type": "p", "children": [], "text": "\nWho should not use nitroglycerin ointment?\n" }

Do not use nitroglycerin ointment if you:

{ "type": "p", "children": [], "text": "\nDo not use nitroglycerin ointment if you:\n" }

{ "type": "ul", "children": [ "are taking a medicine for erectile dysfunction (male impotence), for example Viagra (sildenafil), Cialis (tadalafil) or Levitra (vardenafil).", "have been told by your doctor that you have severe anemia (low numbers of red blood cells in your blood)", "have increased intracranial pressure or high pressure within your skull e.g. following head trauma or bleeding in your brain", "are allergic to any of the ingredients in nitroglycerin ointment or if you have had allergic reactions to similar medicines in the past. See the end of this leaflet for a list of ingredients in nitroglycerin ointment." ], "text": "" }

What should I tell my healthcare provider before using nitroglycerin ointment?

{ "type": "p", "children": [], "text": "\nWhat should I tell my healthcare provider before using nitroglycerin ointment?\n" }

Tell your healthcare provider about all your medical conditions, including if you:

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all your medical conditions, including if you:\n" }

{ "type": "ul", "children": [ "have low blood pressure", "have recently had a heart attack", "have heart or blood vessel disorders", "suffer from migraine or recurrent headaches", "are pregnant or plan to become pregnant. It is not known if nitroglycerin ointment will harm your unborn baby.", "are breast-feeding or plan to breast-feed. It is not known if the components of nitroglycerin ointment will harm your child if you breast-feed." ], "text": "" }

Nitroglycerin ointment may lower your blood pressure. When getting up from a lying or sitting position, you should get up slowly, otherwise you might feel faint.

{ "type": "p", "children": [], "text": "Nitroglycerin ointment may lower your blood pressure. When getting up from a lying or sitting position, you should get up slowly, otherwise you might feel faint." }

Tell your healthcare provider about all the medicines you take, including prescription and non- prescription medicines, vitamins and herbal supplements. Other medicines may affect how nitroglycerin ointment works. Nitroglycerin ointment may also affect how other medicines work.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take, including prescription and non- prescription medicines, vitamins and herbal supplements. Other medicines may affect how nitroglycerin ointment works. Nitroglycerin ointment may also affect how other medicines work." }

Specifically, tell your doctor if you are taking any of the following:

{ "type": "p", "children": [], "text": "Specifically, tell your doctor if you are taking any of the following:" }

{ "type": "ul", "children": [ "other nitroglycerin containing products", "a medicine for erectile dysfunction (male impotence), for example sildenafil, tadalafil or vardenafil (see the section above ‘Who should not use nitroglycerin ointment’)", "medicines used to treat high blood pressure", "are taking aspirin, ergotamine (used to treat migraine) or are receiving tissue-type plasminogen activator (used to help dissolve blood clots formed in blood vessels in the heart, lungs and brain)", "are to be given heparin. If so, close monitoring of your blood will be required as your dose of heparin may need to be altered. Please discuss with your doctor before stopping nitroglycerin ointment." ], "text": "" }

How should nitroglycerin ointment be used? 

{ "type": "p", "children": [], "text": "\nHow should nitroglycerin ointment be used? \n" }

 Use nitroglycerin ointment exactly as prescribed. See detailed Patient Instructions for Applying nitroglycerin ointment at the end of this Patient Information leaflet.

{ "type": "p", "children": [], "text": "\n Use nitroglycerin ointment exactly as prescribed. See detailed Patient Instructions for Applying nitroglycerin ointment at the end of this Patient Information leaflet." }

Treatment may be continued for up to 3 weeks. If your anal pain does not get better after using nitroglycerin ointment you should talk to your doctor.

{ "type": "p", "children": [], "text": "Treatment may be continued for up to 3 weeks. If your anal pain does not get better after using nitroglycerin ointment you should talk to your doctor." }

What should I avoid while using nitroglycerin ointment? Do not drive or operate machinery immediately after applying nitroglycerin ointment. If you feel dizzy or light-headed after applying the ointment do not drive or operate machinery until the dizziness has stopped.

{ "type": "p", "children": [], "text": "\nWhat should I avoid while using nitroglycerin ointment?\n Do not drive or operate machinery immediately after applying nitroglycerin ointment. If you feel dizzy or light-headed after applying the ointment do not drive or operate machinery until the dizziness has stopped." }

Avoid consuming alcohol while you are being treated with nitroglycerin ointment as your blood pressure is more likely to be affected if you consume alcoholic beverages.

{ "type": "p", "children": [], "text": "Avoid consuming alcohol while you are being treated with nitroglycerin ointment as your blood pressure is more likely to be affected if you consume alcoholic beverages." }

What are the possible side effects of nitroglycerin ointment?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of nitroglycerin ointment?\n" }

Nitroglycerin ointment can cause serious side-effects: Stop using the ointment and seek medical attention immediately if you have an allergic reaction. You may have swelling of the face, lips, tongue or throat, or difficulty breathing.

{ "type": "p", "children": [], "text": " Nitroglycerin ointment can cause serious side-effects: Stop using the ointment and seek medical attention immediately if you have an allergic reaction. You may have swelling of the face, lips, tongue or throat, or difficulty breathing." }

Common side-effects of nitroglycerin ointment are:

{ "type": "p", "children": [], "text": "Common side-effects of nitroglycerin ointment are:" }

{ "type": "ul", "children": [ "Headaches, which can be severe. You could take painkillers for this (such as acetaminophen). If the headaches are unpleasant, you may need to ask your doctor whether you should stop using nitroglycerin ointment.", "Dizziness, faintness on standing, or light-headedness" ], "text": "" }

These are not all the possible side effects of nitroglycerin ointment. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. For more information, ask your healthcare provider or pharmacist.

{ "type": "p", "children": [], "text": "These are not all the possible side effects of nitroglycerin ointment. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. For more information, ask your healthcare provider or pharmacist." }

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088.

{ "type": "p", "children": [], "text": "Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088." }

How should I store nitroglycerin ointment?

{ "type": "p", "children": [], "text": "\nHow should I store nitroglycerin ointment?\n" }

{ "type": "ul", "children": [ "Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature].", "Keep the tube tightly closed immediately after each use.", "Use within 8 weeks of first opening." ], "text": "" }

Keep nitroglycerin ointment out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep nitroglycerin ointment out of the reach of children.\n" }

Do not use nitroglycerin ointment after the expiry date which is stated on the label and carton after ‘EXP.’ The expiry date refers to the last day of that month.

{ "type": "p", "children": [], "text": "Do not use nitroglycerin ointment after the expiry date which is stated on the label and carton after ‘EXP.’ The expiry date refers to the last day of that month." }

General information about nitroglycerin ointment

{ "type": "p", "children": [], "text": "\nGeneral information about nitroglycerin ointment\n" }

Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use nitroglycerin ointment for a condition for which it is not prescribed. Do not give nitroglycerin ointment to other people, even if they have the same symptoms you have. It may harm them.

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use nitroglycerin ointment for a condition for which it is not prescribed. Do not give nitroglycerin ointment to other people, even if they have the same symptoms you have. It may harm them." }

This Patient Information leaflet summarizes the most important information about nitroglycerin ointment. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about nitroglycerin ointment that is written for health professionals.

{ "type": "p", "children": [], "text": "This Patient Information leaflet summarizes the most important information about nitroglycerin ointment. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about nitroglycerin ointment that is written for health professionals." }

For more information call 1-833-285-4151

{ "type": "p", "children": [], "text": "For more information call 1-833-285-4151" }

Patient Instructions for Use When do I apply the ointment? Apply the ointment every 12 hours exactly as your doctor has told you to.

{ "type": "p", "children": [], "text": "\nPatient Instructions for Use When do I apply the ointment?\n Apply the ointment every 12 hours exactly as your doctor has told you to." }

How do I apply the ointment?

{ "type": "p", "children": [], "text": "\nHow do I apply the ointment?\n" }

Cover your finger with plastic-wrap, a disposable surgical glove or a finger cot.

{ "type": "p", "children": [], "text": "Cover your finger with plastic-wrap, a disposable surgical glove or a finger cot." }

Lay the covered finger alongside the 1 inch dosing line marked on the side of the medicine box (see figure below) so that the tip of your finger is at one end of the dosing line. Starting at the tip of the finger, squeeze the ointment onto your finger for the same length marked on the box.

{ "type": "p", "children": [], "text": "Lay the covered finger alongside the 1 inch dosing line marked on the side of the medicine box (see figure below) so that the tip of your finger is at one end of the dosing line. Starting at the tip of the finger, squeeze the ointment onto your finger for the same length marked on the box." }

Refer to carton for accurate dosage guide.

{ "type": "p", "children": [], "text": "Refer to carton for accurate dosage guide." }

Gently insert the finger with the ointment into the anal canal, up to the first finger joint. Carefully smear the ointment around the inner sides of the anal canal. If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus.

{ "type": "p", "children": [], "text": "Gently insert the finger with the ointment into the anal canal, up to the first finger joint. Carefully smear the ointment around the inner sides of the anal canal. If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus." }

What do I do after I have applied the ointment? Throw away the finger covering in the garbage, out of the reach of children and pets. Wash your hands.

{ "type": "p", "children": [], "text": "\nWhat do I do after I have applied the ointment?\n Throw away the finger covering in the garbage, out of the reach of children and pets. Wash your hands." }

What are the ingredients in nitroglycerin ointment? Active ingredient: nitroglycerin Inactive ingredients: propylene glycol, lanolin, sorbitan sesquioleate, paraffin wax and white petrolatum.

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in nitroglycerin ointment?\n Active ingredient: nitroglycerin Inactive ingredients: propylene glycol, lanolin, sorbitan sesquioleate, paraffin wax and white petrolatum." }

Manufactured by: Encube Ethicals Pvt. Ltd. Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post: Mardol, Ponda, Goa - 403 404, India.

{ "type": "p", "children": [], "text": "Manufactured by:\nEncube Ethicals Pvt. Ltd.\n Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post: Mardol, Ponda, Goa - 403 404, India." }

Distributed by: Encube Ethicals, Inc. 200 Meredith Drive, Suite 202 Durham, NC 27713 USA

{ "type": "p", "children": [], "text": "Distributed by:\nEncube Ethicals, Inc.\n 200 Meredith Drive, Suite 202 Durham, NC 27713 USA" }

Revised: 10/2024

{ "type": "p", "children": [], "text": "Revised: 10/2024" }

NDC 21922-048-05 Nitroglycerin Ointment, USP 0.4% 30 g Rx only Carton Label

{ "type": "p", "children": [], "text": "NDC 21922-048-05\nNitroglycerin Ointment, USP 0.4%\n 30 g Rx only Carton Label" }