Nitroglycerin is a stabilized sublingual compressed nitroglycerin tablet that contains 0.3 mg, 0.4 mg, or 0.6 mg nitroglycerin USP; as well as calcium stearate powder, colloidal silicon dioxide, hydrogenated vegetable oil, lactose monohydrate, and pregelatinized starch.

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

Molecular weight: 227.09

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.

Mechanism of Action: Nitroglycerin forms free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation. 

Pharmacodynamics: 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 administration. 

Pharmacokinetics and Drug MetabolismAbsorption: 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 (C max) and area under the plasma concentration-time curves (AUC) increase dose-proportionally following 0.3 to 0.6 mg nitroglycerin. 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. 

Table 1

Distribution: The volume of distribution (V Area) 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. 

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

Nitroglycerin sublingual tablets are contraindicated in patients who are allergic to it.  

Sublingual nitroglycerin therapy is contraindicated in patients with early myocardial infarction, severe anemia, increased intracranial pressure, and those with a known hypersensitivity to nitroglycerin. 

Administration of nitroglycerin sublingual tablets are contraindicated in patients who are using a phosphodiesterase-5 (PDE-5) inhibitor (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride) since these compounds have been shown to potentiate the hypotensive effects of organic nitrates.

Do not use nitroglycerin sublingual tablets in patients who are taking the soluble guanylate cyclase stimulator riociguat. Concomitant use can cause hypotension.

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

Headache that may be severe and persistent may occur immediately after use. 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.

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. 

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 likely to do more harm than good. 

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 in association with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial PO 2. 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.

One tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack. The dose may be repeated approximately every 5 minutes until relief is obtained. 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, prompt medical attention is recommended. Nitroglycerin may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack. 

During administration the patient should rest, preferably in the sitting position. 

No dosage adjustment is required in patients with renal failure.  

Nitroglycerin sublingual tablets are supplied in 3 strengths (0.3 mg, 0.4 mg, and 0.6 mg) in bottles containing 100 tablets each, with color-coded labels, and in color-coded Patient Convenience Packages of 4 bottles of 25 tablets each. 

0.3 mg sublingual tablets are white to off-white, modified rectangle shaped tablets debossed with "CL" on one side and "3" on the other side and are supplied in bottles of 100 tablets.  

Bottle of 100 NDC 43598-435-01

0.4 mg sublingual tablets are white to off-white, modified rectangle shaped tablets debossed with "CL" on one side and "4" on the other side and are supplied in bottles of 25 and 100 tablets.  

Bottle of 100 NDC 43598-436-01

Convenience Package NDC 43598-436-11

0.6 mg sublingual tablets are white to off-white, modified rectangle shaped tablets debossed with "CL" on one side and "6" on the other side and are supplied in bottles of 100 tablets.  

Bottle of 100 NDC 43598-437-01

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

Rx only

Manufactured by:

Ingenus Pharmaceuticals NJ, LLC

Fairfield, NJ 07004, USA

Manufactured for:

Dr. Reddy’s Laboratories Inc.

Princeton, New Jersey 08540, USA

Revised: 0217

Nitroglycerin Sublingual Tablets, USP

(nahy-truh-glis-er-in)

Read this information carefully before you start nitroglycerin sublingual tabletsand 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, ask your doctor. Your doctor will know if nitroglycerin sublingual tabletis right for you. 

What is nitroglycerin?

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

What is Angina?

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 tabletscan relieve this pain. 

Who should not use nitroglycerin sublingual tablets?

Do not use nitroglycerin sublingual tabletsif you are allergic to organic nitrates (like the active ingredient in nitroglycerin sublingual tablets). 

You should not take nitroglycerin sublingual tabletsif you have the following conditions:

• very recent heart attack
• severe anemia
• increased pressure in the head 

Do not take nitroglycerin sublingual tabletswith 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. 

Do not take nitroglycerin sublingual tabletsif 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?

Before using nitroglycerin sublingual tablets, tell your doctor if:

• You are taking any medicines that are used to treat angina, heart failure, or an irregular heartbeat.
• You are taking any medicines that reduce blood pressure.
• You are taking any diuretics (water pills).
• You are taking medications to treat depression or psychiatric illness.
• You are taking ergotamine or similar drugs for migraine headaches.
• You are taking aspirin.
• You are taking the blood thinner medicine heparin.
• You are taking any medicines for erectile dysfunction.
• You are pregnant or plan to become pregnant.
• You are breastfeeding. 

How should I take nitroglycerin sublingual tablets?

• Do not chew, crush, or swallow nitroglycerinsublingual tablets.
• You should sit down when taking nitroglycerinsublingual tablets and use caution when you stand up. This eliminates the possibility of falling due to lightheadedness or dizziness.
• One tablet should be dissolved under the tongue or in the oral cavity at the first sign of chest pain.
• The dose may be repeated approximately every 5 minutes, until the chest pain is relieved.
• If the pain persists after a total of 3 tablets in a 15-minute, period, or is different than you typically experience, call your doctor or seek emergency help.
• Nitroglycerin sublingual tabletsmay be used 5 to 10 minutes prior to activities that might cause chest pain.
• You may feel a burning or tingling sensation in your mouth when you take nitroglycerin sublingual tablets.

  What should I avoid while taking nitroglycerin sublingual tablets?

• Do not breastfeed. It is not known if nitroglycerinwill pass through your milk.
• Do not consume alcohol while taking nitroglycerin sublingual tablets, as this can lower your blood pressure.
• Do not start any new prescription or non-prescription medicines or supplements, unless you check with your doctor first. 

What are the possible side effects of nitroglycerin sublingual tablets?

Nitroglycerinmay cause the following side effects:

• headache
• vertigo (a major symptom of balance disorder)
• dizziness
• weakness
• heart palpitations (unusual awareness of the heartbeat)
• low blood pressure upon rising from a seated position
• nausea and vomiting
• sweating
• paleness
• fainting
• flushing (warm or red condition of your skin)
• other skin reactions that may be severe 

Nitroglycerin sublingual tabletsmay cause a false test result of decreased serum cholesterol. 

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

How do I store nitroglycerin sublingual tablets?

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

Store nitroglycerin  sublingualtabletsat 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].  

General advice about nitroglycerin sublingual tablets

Sometimes doctors will prescribe a medicine for a condition that is not included in the patient information leaflets. Only use nitroglycerin sublingual tabletsthe way your doctor told you to. Do not give nitroglycerin sublingual tabletsto 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 call Dr. Reddy’s Medical Information Department, at 1-888-375-3784.  

To reorder additional Patient Package Inserts contact Dr. Reddy’s Customer Service at 1-866-733-3952.

Rx Only

Manufactured by:

Ingenus Pharmaceuticals NJ, LLC

Fairfield, NJ 07004, USA

Manufactured for:

Dr. Reddy’s Laboratories Inc.

Princeton, New Jersey 08540, USA

Revised: 0217

0.3 mg : Container Label: 100's

0.3 mg: Container Carton Label: 100's

0.4 mg: Container Label: 25's

0.4 mg : Container Carton Label: 4 x 25's count

0.6 mg : Container Label: 100's

0.6 mg: Container Carton Label: 100's

0.4 mg: Container Label : 100's

0.4 mg : Container Carton Label: 100's