Brand names: Nitro-Bid, Nitro-Dur, NitroMist, Nitrostat
Drug class: Nitrates and Nitrites

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Nitroglycerin, an organic nitrate, is a vasodilating agent.

Uses for Nitroglycerin

Angina

Management of angina pectoris secondary to CAD.

Short-acting preparations (e.g., sublingual tablets, lingual aerosol or spray) are used for acute relief of angina; also may be used for acute prophylactic management in situations likely to provoke angina attacks.

The ointment and transdermal preparations are indicated for prevention of angina due to coronary artery disease; the onset of action of these dosage forms is not sufficiently rapid enough to abort an acute anginal episode.

Expert guidelines recommend antianginal therapy with either a β-blocker, calcium channel blocker, or long-acting nitrate for relief of angina in patients with chronic coronary disease. Sublingual nitroglycerin or nitroglycerin spray is recommended for immediate short-term relief of angina.

Nitroglycerin also is used for relief of angina in patients with non-ST-segment-elevation MI (NSTEMI) or ST-segment-elevation MI (STEMI).

Expert guidelines recommend sublingual nitroglycerin (0.3–0.4 mg every 5 minutes for up to 3 doses) for relief of ongoing ischemic pain in patients with NSTEMI; IV nitroglycerin may be used in patients with heart failure, hypertension, or persistent ischemia not relieved with sublingual nitroglycerin and administration of a β-blocker. Topical nitrates may be an acceptable alternative to IV therapy in patients who do not have refractory or recurrent ischemia.

Guidelines also state that IV nitroglycerin may be beneficial in patients with ST-segment-elevation MI (STEMI) and heart failure or hypertension.

Hypertension

IV nitroglycerin is used for treatment of perioperative hypertension and for induction of intraoperative hypotension.

IV nitroglycerin also has been used to control BP in perioperative hypertension, especially hypertension associated with cardiovascular procedures; to control BP in patients with severe hypertension^{† [off-label]} or in hypertensive crises^{† [off-label]} for the immediate reduction of BP in patients in whom such reduction is considered an emergency (hypertensive emergencies), especially those associated with coronary complications (e.g., coronary ischemia, acute coronary insufficiency, acute left ventricular failure, postoperative hypertension [especially following coronary bypass surgery]) and/or acute pulmonary edema; and to produce controlled hypotension during surgical procedures.

Heart Failure and Low-output Syndromes

IV nitroglycerin has been used in the management of acutely decompensated (e.g., congestive) heart failure and other low cardiac-output states^{† [off-label]}.

Current guidelines recommend a combination of drug therapies (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-blockers, aldosterone receptor antagonists) in adults with heart failure to reduce morbidity and mortality.

IV vasodilators not shown to improve outcomes in patients hospitalized for heart failure; however, IV nitroglycerin may be considered as adjunct to diuretic therapy for relief of dyspnea in patients hospitalized for acutely decompensated heart failure who do not have symptomatic hypotension.

Particularly useful in patients with heart failure and hypertension, coronary ischemia, or substantial mitral regurgitation.

Tachyphylaxis may develop within 24 hours; some patients may develop resistance to even high doses.

Nitroglycerin Dosage and Administration

Administration

Administer lingually, sublingually, topically, or by IV infusion.

Lingual Administration

Administer nitroglycerin lingual preparations (aerosol or solution) using a metered-dose spray pump.

Spray lingual aerosol or solution onto or under tongue and immediately close mouth; do not inhale spray.

Do not expectorate the drug or rinse the mouth for 5–10 minutes following administration.

Lingual nitroglycerin may be inadequately absorbed, with resultant decreased efficacy, in patients with dry oral mucous membranes (e.g., xerostomia).

Sublingual Administration

Sublingual tablets are dissolved under the tongue. Do not swallow.

Sublingual nitroglycerin may be inadequately absorbed, with resultant decreased efficacy, in patients with dry oral mucous membranes (e.g., xerostomia).

Transdermal Administration (Transdermal System)

Apply nitroglycerin transdermal system topically to the skin as directed by manufacturer.

Preferably apply at same time each day to areas of clean, dry, hairless skin of the upper arm or body; do not apply to extremities below knee or elbow.

Avoid skin areas with irritation, extensive scarring, or calluses; rotate application sites to avoid skin irritation.

Remove transdermal systems from site(s) of application prior to defibrillation or cardioversion since altered electrical conductivity and enhanced potential for electrical arcing may occur.

Topical Administration (Ointment)

Apply topically using manufacturer-supplied applicator.

Spread on any non-hairy skin area (usually the chest or back) in a thin, uniform layer without massaging or rubbing. Tape applicator into place on skin.

Application of the ointment over the chest may provide additional psychological effect.

Avoid placement of ointment on areas of chest where defibrillation paddles typically are placed due to potential for altered electrical conductivity.

IV Administration

Because nitroglycerin readily migrates into many plastics, the manufacturers’ specific instructions for dilution, dosage, and administration must be carefully followed.

Do not admix with other drugs.

Dilution

Must dilute commercially available injection concentrate in 5% dextrose or 0.9% sodium chloride injection before administration.

Dilute and store only in glass bottles; avoid using filters since some filters absorb nitroglycerin.

Standardize 4 Safety

Standardized concentrations for nitroglycerin have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].

Dosage

Carefully adjust dose according to the patient’s requirements and response; use smallest effective dosage.

For IV administration, must consider the type of IV administration set used (PVC or non-PVC) in dosage estimations. IV dosages commonly used in early published studies were based on the use of PVC administration sets and are too high when non-PVC administration sets are used.

Continuously monitor BP, heart rate, and other appropriate parameters (e.g., pulmonary capillary wedge pressure). Must maintain adequate systemic BP and coronary perfusion pressure.

Some patients with normal or low left ventricular filling pressures or pulmonary capillary wedge pressure may be extremely sensitive to the effects of IV nitroglycerin and may respond fully to dosages as low as 5 mcg/minute; these patients require particularly careful monitoring and dosage titration.

Adults

Angina

Acute Symptomatic Relief and Acute Prophylactic Management

Lingual

1 or 2 sprays (0.4 or 0.8 mg, respectively) as a lingual solution or aerosol at the onset of an attack.

May give additional single sprays at intervals of approximately every 5 minutes as necessary if relief is not attained after initial spray(s); do not exceed 3 sprays in a 15-minute period.

If pain persists after a total of 3 doses within a 15-minute period, seek prompt medical attention.

If used prophylactically, may administer 5–10 minutes before situations likely to provoke angina attacks.

Sublingual

Sublingual tablets: 0.3–0.6 mg at the first sign of an acute anginal attack. If relief not attained after a single dose, may give additional doses at 5-minute intervals. If pain persists after a total of 3 doses within a 15-minute period, or if the pain is different from that typically experienced, seek prompt medical attention.

If used prophylactically, may administer a dose of nitroglycerin (as sublingual tablets) 5–10 minutes before engaging in activities likely to provoke angina attacks.

Long-term Prophylactic Management of Angina

Topical (Transdermal System)

Initially, one transdermal dosage system applied every 24 hours, using system delivering the smallest available dose of nitroglycerin in its dosage series.

Nitrate-free interval of 10–14 hours recommended to minimize occurrence of tolerance; however, the minimum nitrate-free interval necessary for restoration of full first-dose effects not determined.

May adjust dosage by changing to the next larger dosage system in the series or using a combination of dosage systems in the series.

Do not use transdermal systems to treat acute attacks of angina.

Topical (Ointment)

2% Ointment: Initially, 0.5 inch (approximately 7.5 mg), as squeezed from the tube, twice daily (once in the morning and repeat in 6 hours), suggested. When dose to be applied is in multiples of whole inches, may use unit-dose preparations that provide the equivalent of 1 inch of the 2% ointment.

May double dose to 1 inch (approximately 15 mg) and subsequently double again to 2 inches (approximately 30 mg) if tolerated to achieve adequate response.

Titrate dosage upward until angina is effectively controlled or adverse effects preclude further increases.

Amount of nitroglycerin reaching the circulation varies directly with the size of application area and amount of ointment applied. Generally, spread over an area approximately the size of the applicator (3.5 by 2.25 inches); however, may use a larger area (e.g., 6 by 6-inch area).

To minimize the occurrence of tolerance to the effects of nitroglycerin, a nitrate-free interval of 10–14 hours has been recommended; however, the minimum nitrate-free interval necessary has not been determined.

Do not use ointment to treat acute attacks of angina.

IV

Manufacturer states usual initial dosage is 5 mcg/minute when using a nonadsorptive (e.g., non-PVC) administration set; increase by 5 mcg/minute every 3–5 minutes until BP response is obtained or infusion rate is 20 mcg/minute. If no effect is obtained with 20 mcg/minute, may increase dosage by increments of 10 mcg/minute or, if necessary, by 20 mcg/minute. Higher dosages generally required when a PVC administration set is used; manufacturer states usual initial dosage is 25 mcg/minute with such administration sets. Titrate dosage according to patient's response.

NSTE ACS

Sublingual, then IV (if necessary)

0.3–0.4 mg every 5 minutes for up to 3 doses as a sublingual preparation in patients with continuing ischemic pain. Assess need for IV nitroglycerin, if not contraindicated.

IV

IV nitroglycerin may be useful in patients with heart failure, hypertension, or persistent ischemia not relieved with sublingual nitroglycerin and administration of a β-blocker.

Manufacturer states usual initial dosage is 5 mcg/minute when using a nonadsorptive (e.g., non-PVC) administration set; increase by 5 mcg/minute every 3–5 minutes until BP response is obtained or infusion rate is 20 mcg/minute. If no effect is obtained with 20 mcg/minute, may increase dosage by increments of 10 mcg/minute or, if necessary, by 20 mcg/minute. Higher dosages generally required when a PVC administration set is used; manufacturer states usual initial dosage is 25 mcg/minute with such administration sets. Titrate dosage according to patient's response.

Continuously monitor BP and heart rate during administration.

STEMI

IV

Some experts recommend continuous IV infusion at an initial rate of 10 mcg/minute, increasing the dosage as necessary based on hemodynamic and clinical response. Dosage will vary considerably among patients; adjust based on individual requirements, BP response, and adverse effects.

Manufacturer states the recommended initial dosage is 5 mcg/minute when using a nonadsorptive (e.g., non-PVC) administration set; increase by 5 mcg/minute every 3–5 minutes until BP response is obtained or infusion rate is 20 mcg/minute. If no effect is obtained with 20 mcg/minute, may increase dosage by increments of 10 mcg/minute or, if necessary, by 20 mcg/minute. Higher dosages generally required when a PVC administration set is used; manufacturer states usual initial dosage is 25 mcg/minute with such administration sets. Titrate dosage according to patient's response.

Continuously monitor BP and heart rate during administration.

Hypertension

Perioperative Hypertension or Induction of Intraoperative Hypotension

IV

Initially, 5 mcg/minute (per manufacturer) when using a nonadsorptive (e.g., non-PVC) administration set; increase by 5 mcg/minute every 3–5 minutes until BP response is obtained or infusion rate reaches 20 mcg/minute. If no effect is obtained with 20 mcg/minute, may increase dosage by increments of 10 mcg/minute or, if necessary, by 20 mcg/minute. Higher dosages generally required when a PVC administration set is used; manufacturer states initial dosage of 25 mcg/minute or greater has been used in studies with such administration sets. Titrate dosage according to patient's response and possible adverse effects.

Hypertensive Emergency† [off-label]

IV

Initially, 5 mcg/minute according to some experts; increase by 5 mcg/minute every 3–5 minutes until BP response is obtained or infusion rate reaches 20 mcg/minute.

Always consider the risks of overly aggressive therapy in any hypertensive crisis.

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment.

Renal Impairment

No dosage adjustments necessary for renal impairment.

Geriatric Patients

Cautious dosage selection, usually starting at the low end of the dosing range, because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Nitroglycerin

Contraindications

• Known hypersensitivity to nitroglycerin, other nitrates or nitrites, or any ingredient in the formulation.

• Use of topical nitroglycerin (transdermal system) in those allergic to adhesives used in the system.

• Use of sublingual nitroglycerin tablets in patients with early MI, severe anemia, or increased intracranial pressure.

• Concomitant use of selective phosphodiesterase (PDE) inhibitors (e.g., sildenafil, tadalafil, vardenafil).

• Concomitant use of soluble guanylate cyclase (sGC) stimulators (e.g., riociguat).

Warnings/Precautions

Warnings

Concomitant Use with Selective Phosphodiesterase (PDE) Inhibitors

Selective PDE type 5 inhibitors can potentiate the hypotensive effects of organic nitrates and nitrites, possibly resulting in potentially life-threatening hypotension and/or hemodynamic compromise.

PDE type 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) are contraindicated in patients receiving organic nitrates or nitrites in any form (e.g., orally, sublingually, transmucosally, parenterally), given regularly or intermittently, or nitric oxide donors since severe, potentially fatal hypotensive episodes can occur.

Clinicians unfamiliar with their patients’ drug history, especially those involved in emergency care (e.g., for presumed MI or ischemia), should take a careful history so that concomitant use of organic nitrates or nitrites with selective PDE inhibitors can be avoided.

Warn all patients receiving organic nitrates or nitrites about the potential interaction between the drugs and selective PDE inhibitors, even if they currently are not receiving the drugs, since there is substantial potential for patients to receive the drugs from another clinician, from a friend, with little or no clinical intervention (e.g., via the Internet), or illicitly.

Warn all patients taking either selective PDE inhibitors or organic nitrates or nitrites of the potential consequences of taking the drugs within close proximity (e.g., within 24 hours of sildenafil; possibly more prolonged periods of risk with longer-acting PDE inhibitors) of taking a nitrate- or nitrite-containing preparation.

Concomitant Use with sGC Stimulators

Concomitant use of nitrates (e.g., nitroglycerin) or nitrites (e.g., amyl nitrite) with a sGC stimulator (e.g., riociguat) can cause additive hypotensive effects. Such concomitant use is contraindicated.

Cardiovascular Effects

Severe hypotension, particularly in upright position, can occur even with low nitroglycerin doses, particularly in the elderly.

Use with caution in patients who are volume depleted or have preexisting hypotension.

Paradoxical bradycardia and angina exacerbation may accompany hypotension.

Benefits in acute MI and CHF not established. If used in these conditions, careful clinical or hemodynamic monitoring for possible hypotension or tachycardia is recommended.

Avoid long-acting dosage forms in the early management of acute MI or CHF since the effects are difficult to terminate rapidly should excessive hypotension or tachycardia occur.

Sensitivity Reactions

Contact dermatitis or fixed drug eruptions reported in patients receiving nitroglycerin ointment or transdermal system. Anaphylactoid reaction reported; possibly may occur with any route.

General Precautions

Tolerance and Dependence

Tolerance to the vascular and antianginal effects of individual nitrates and cross-tolerance among the drugs may occur with repeated, prolonged use or excessive doses.

Intermittent dosing of nitrates (e.g., use of a nitrate-free interval of 10–14 hours daily) has been used in an attempt to minimize or prevent the development of tolerance to the hemodynamic and antianginal effects of the drugs.

Nitrate dependence is possible; withdrawal manifestations (e.g., ischemic symptoms, MI, sudden death) can occur. During the nitrate-free intervals in some trials, anginal attacks have been more easily provoked than before treatment, and patients have demonstrated hemodynamic rebound and decreased exercise tolerance.

Specific Populations

Pregnancy

Sublingual tablets: Category B. Sublingual nitroglycerin has been used for the treatment of angina during pregnancy without fetal harm.

Lingual aerosol, lingual solution, ointment, transdermal system: Category C.

Injection: Data regarding pregnancy lacking.

Some experts state that use of nitroglycerin during pregnancy does not appear to present a risk to the fetus; however, experience with the drug in pregnant women is limited. Use during pregnancy only if clearly needed.

Lactation

Not known whether nitroglycerin is distributed into milk. The low molecular weight of nitroglycerin suggests that some distribution into milk may occur. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether they respond different than younger adults.

May aggravate angina caused by hypertrophic cardiomyopathy, particularly in the elderly.

Cautious dosage selection, usually starting at the low end of the dosing range, because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Common Adverse Effects

Headache (pulsating or throbbing sensation, potentially severe); hypotension (may cause dizziness, weakness, other signs of cerebral ischemia); cutaneous vasodilation with transient flushing.

Drug Interactions

Specific Drugs or Laboratory Tests

Nitroglycerin Pharmacokinetics

Absorption

Bioavailability

Absorbed percutaneously through skin and oral mucosa.

Topical (transdermal system) provides continuous, controlled release of nitroglycerin to the skin where the drug undergoes percutaneous absorption.

Rates of delivery and absorption of nitroglycerin from transdermal systems vary depending on the specific preparation; consult the individual manufacturers’ information.

Onset and Duration

The approximate onset and duration of action of various dosage forms of nitroglycerin are as follows:

Plasma Concentrations

Following topical application of transdermal system, steady-state plasma concentrations attained by about 2 hours; prolonged onset compared with other currently available dosage forms.

Distribution

Extent

Unknown if nitroglycerin is distributed into milk.

Plasma Protein Binding

Nitroglycerin: about 60% bound.

Elimination

Metabolism

Metabolized to 1,3-glyceryl dinitrate, 1,2-glyceryl dinitrate, and glyceryl mononitrate.

Glyceryl mononitrate, which is inactive, is the principal metabolite.

Dinitrate metabolites are metabolized further to inactive mononitrates and are metabolized ultimately to glycerol and carbon dioxide.

Extrahepatic sites of metabolism include red blood cells and vascular walls.

Half-life

Nitroglycerin: 1–4 minutes.

Stability

Handle undiluted nitroglycerin cautiously since it is a powerful explosive that can be exploded by percussion or excessive heat.

Storage

Oral

Sublingual Tablets

Store in original glass container at 20–25°C.

Advise patients to keep sublingual tablets in the original container and to close it tightly immediately after each use in order to prevent loss of potency.

Lingual Aerosol

Store at 25°C (may be exposed to 15–30°C).

Contains a highly flammable propellant (butane); do not forcefully open container, spray toward a flame, or place into a fire for disposal.

Lingual Solution in Spray Pump

Store at 25°C (may be exposed to 15–30°C).

Contains 20% alcohol; do not forcefully open container, spray toward a flame, or place into a fire or incinerator for disposal.

Topical

Ointment

Tight containers at 20–25°C.

Advise patients to tightly close multiple-dose containers of nitroglycerin ointment immediately after each use.

Transdermal System

Sealed, single-dose containers at 15–30°C; avoid temperature extremes and/or humidity.

Parenteral

IV Solutions

Concentrate for injection: store at 15–30°C; avoid freezing.

Premixed solution in 5% dextrose injection: 25°C; avoid freezing and excessive heat.

Actions

• Principal pharmacologic property is relaxation of vascular smooth muscle, resulting in generalized vasodilation.

• Peripheral venous resistance is decreased via a selective action on venous capacitance vessels and results in venous pooling of blood and decreased venous return to the heart.

• Vasodilatory effect on arteriolar resistance is not as great as the action on the venous side; as a result of this combined action, both venous filling pressure (preload) and, to a lesser extent, arterial impedance (afterload) are reduced.

• By decreasing myocardial oxygen consumption, nitrates and nitrites alter the imbalance of myocardial oxygen supply and consumption which is thought to cause angina pectoris.

• Because of hemodynamic profile, nitrates and nitrites are particularly beneficial in patients with left ventricular systolic dysfunction or CHF.

• Both direct vasodilatory effects on the coronary bed and drug-induced prevention of episodic coronary artery vasoconstriction increase total coronary blood flow.

• After therapeutic doses, cardiac output may increase transiently and then decrease.

• In addition to vascular smooth muscle, nitrates and nitrites relax bronchial, biliary (including the gallbladder, biliary ducts, and sphincter of Oddi), GI (including the esophagus), ureteral, and uterine smooth muscle; also relax all smooth muscle irrespective of autonomic innervation and are functional antagonists of norepinephrine, acetylcholine, and histamine occurs.

Advice to Patients

• Advise patients of the likelihood of headache, particularly with initial nitrate therapy.

• Advise patients to take nitrates as directed, particularly since tolerance can occur.

• Advise patients to tightly close multiple-dose containers of nitroglycerin ointment immediately after each use.

• Instruct patients to discard cotton from tablet bottle once the original container is opened.

• Instruct patients to keep the sublingual tablets in the original container or in a supplemental container specifically labeled as being suitable for nitroglycerin tablets, and to close it tightly immediately after each use in order to prevent loss of potency.

• Instruct patients receiving nitroglycerin for relief of acute attacks of angina pectoris to consult a clinician or go to a hospital emergency room immediately if chest pain is not relieved after 3 doses approximately every 5 minutes, because inability to relieve chest pain may indicate acute MI.

• Importance of clinicians unfamiliar with their patients’ drug history, especially those involved in emergency care (e.g., for presumed MI or ischemia), to take a careful history so that concomitant use with selective PDE inhibitors can be avoided.

• Warn all patients receiving organic nitrates or nitrites about the potential interaction between the drugs and selective PDE inhibitors, even if they currently are not receiving the drugs, since there is substantial potential for patients to receive the drugs from another clinician, from a friend, with little or no clinical intervention (e.g., via the Internet), or illicitly.

• Warn all patients taking either selective PDE inhibitors or organic nitrates or nitrites of the potentially severe and life-threatening hemodynamic consequences of taking the drugs within close proximity (e.g., within 24 hours of sildenafil; possibly more prolonged periods of risk with longer-acting PDE inhibitors) of taking a nitrate- or nitrite-containing preparation.

• Inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• How do you take GoNitro to treat an angina attack (chest pain)?
• What is the shelf life of nitroglycerin tablets?

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