Nitroglycerin, an organic nitrate, is a vasodilating agent.
Nitroglycerin is used for the acute relief of angina pectoris secondary to coronary artery disease, for prophylactic management in situations likely to provoke angina attacks, and for long-term prophylactic management of chronic stable angina.802, 806, 807, 809 The drug is commercially available in various dosage forms and preparations.802, 806, 807, 809 Short-acting preparations (e.g., sublingual tablets, lingual aerosol) are used for acute relief of angina, but also may be used for prophylactic management in situations likely to provoke an angina attack.802, 806, 807, 809 The ointment and transdermal preparations are indicated for the 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.216, 600
Guidelines for the management of patients with chronic coronary disease have been published by the American Heart Association (AHA), American College of Cardiology (ACC), and other experts.1101 The guidelines recommend antianginal therapy with either a β-blocker, a calcium channel blocker, or a long-acting nitrate for relief of angina in patients with chronic coronary disease.1101 Sublingual nitroglycerin or nitroglycerin spray is recommended for immediate short-term relief of angina.1101 Studies comparing nitroglycerin spray with the sublingual formulation have shown the spray to be more effective and efficient at relieving angina with less headache.1101
Non-ST-Segment-Elevation Acute Coronary Syndromes
Nitroglycerin is used for relief of angina in patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS).1100 Patients with NSTE ACS have either unstable angina or non-ST-segment-elevation MI (NSTEMI); because these conditions are part of a continuum of acute myocardial ischemia and have indistinguishable clinical features upon presentation, the same initial treatment strategies are recommended.805, 1100 The American Heart Association/American College of Cardiology (AHA/ACC) guideline for the management of patients with NSTE ACS recommends sublingual nitroglycerin (0.3-0.4 mg every 5 minutes for up to 3 doses) for the relief of ongoing ischemic pain in patients with NSTE ACS; IV nitroglycerin may be used in patients with persistent ischemia who do not respond to sublingual therapy and administration of a β-blocker or those with heart failure or hypertension.1100 Topical nitrates may be used as an alternative to IV nitroglycerin for patients who do not have refractory or recurrent ischemia.1100 Nitrates should not be administered to patients with hypotension or those who have received a phosphodiesterase inhibitor, and should be used with caution in patients with right ventricular infarction.1100
ST-Segment Elevation Myocardial Infarction (STEMI)
Nitroglycerin is used for the management of ongoing chest pain in patients with STEMI.217, 218, 240, 241, 242, 527 Nitroglycerin injection is specifally indicated for control of congestive heart failure (CHF) in the setting of acute MI.811, 812 The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the management of STEMI states that IV nitroglycerin may be beneficial in patients with STEMI and heart failure or hypertension.527 The manufacturer of some other formulations of nitroglycerin state that the benefits of these formulations in patients with acute MI or CHF have not been established; if the drug is used in this setting, careful hemodynamic and clinical monitoring is essential because of the possibility of hypotension and tachycardia.216, 600, 806 In addition to potentially alleviating ischemic myocardial pain, beneficial hemodynamic effects of nitroglycerin include vasodilation of the coronary arteries (especially at or near the site of recent plaque disruption), peripheral arteries, and venous capacitance vessels; however, the drug generally does not reduce myocardial injury associated with epicardial coronary artery occlusion unless there is substantial vasospasm.236, 527 Although studies conducted prior to the routine use of reperfusion therapy suggested a mortality benefit with nitrates in patients with acute MI, this benefit was not confirmed in 2 large randomized controlled studies.243, 244, 801
IV nitroglycerin is used for the treatment of perioperative hypertension and for induction of intraoperative hypotension.811, 812
IV nitroglycerin also has been used to control blood pressure in perioperative hypertension, especially hypertension associated with cardiovascular procedures; to control blood pressure in patients with severe hypertension† or in hypertensive crises† for the immediate reduction of blood pressure 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.500, 502, 812, 1200
Hypertensive emergencies are those rare situations requiring immediate blood pressure reduction, although not necessarily to normal ranges, in order to prevent or limit target organ damage.1200 Examples of such emergency situations include hypertensive encephalopathy, intracerebral hemorrhage, unstable angina pectoris, acute myocardial infarction (MI), acute left ventricular failure with pulmonary edema, dissecting aortic aneurysm, and eclampsia.1200 Elevated blood pressure alone, in the absence of symptoms or new or progressive target organ damage, rarely is a hypertensive crisis requiring emergency therapy.1200
Heart Failure and Low-output Syndromes
IV nitroglycerin has been used effectively for the treatment of acutely decompensated (e.g., congestive) heart failure† or other low cardiac output states†, including those associated with acute MI.524 (See ST-Segment Elevation Myocardial Infarction [STEMI] undr Uses.) The precipitating cause of acute heart failure decompensation should be carefully assessed to inform appropriate treatment, optimize outcomes, and prevent future acute events in patients with heart failure.524 Current guidelines for the management of heart failure in adults generally recommend inhibition of the renin-angiotensin-aldosterone system with a combination of drug therapies, including neurohormonal antagonists (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-adrenergic blocking agents [β-blockers], aldosterone receptor antagonists), to inhibit the detrimental compensatory mechanisms in heart failure and reduce morbidity and mortality.524, 701, 703, 800 IV vasodilators have not been shown to improve outcomes in patients hospitalized for heart failure; however, in the absence of symptomatic hypotension, IV nitroglycerin may be considered as an adjunct to diuretic therapy for relief of dyspnea in patients hospitalized for acutely decompensated heart failure.524 IV nitroglycerin causes venodilation, which lowers preload and may help to rapidly reduce pulmonary congestion.524 Patients with heart failure and hypertension, coronary ischemia, or substantial mitral regurgitation are often considered ideal candidates for the use of IV nitroglycerin.524 However, tachyphylaxis to nitroglycerin may develop within 24 hours, and up to 20% of those with heart failure may have inadequate response to even high doses.524
Nitroglycerin is administered lingually, sublingually, topically, or by IV infusion.216, 600, 806, 807, 809, 811, 812
Sublingual and Lingual Administration
Nitroglycerin tablets for sublingual administration are dissolved under the tongue and should not be swallowed.809
Nitroglycerin lingual preparations (aerosol or solution in a spray pump) are administered using a metered-dose spray pump; the aerosol or solution should be administered onto or under the tongue and not inhaled.806, 807 Do not expectorate the drug or rinse the mouth for 5-10 minutes following administration.806, 807 The possibility that lingual or sublingual nitroglycerin may be inadequately absorbed, with resultant decreased efficacy, in patients with dry oral mucous membranes (e.g., xerostomia) should be considered.219, 220
Transdermal Administration (Transdermal System)
Nitroglycerin transdermal system is preferably applied at the same time each day to areas of clean, dry, hairless skin of the upper arm or body; the system should not be applied to the extremities below the knee or elbow.216 Skin areas with irritation, extensive scarring, or calluses should be avoided, and application sites should be rotated to avoid causing skin irritation.216 Nitroglycerin transdermal systems should be removed from the site(s) of application prior to attempting defibrillation or cardioversion since altered electrical conductivity and enhanced potential for electrical arcing may occur.216
Topical Administration (Ointment)
When applied topically as an ointment, the appropriate amount of nitroglycerin ointment should be squeezed onto the manufacturer-supplied applicator and placed ointment side down on the desired non-hairy area of skin (usually on the chest or back).600 The ointment is then spread on the skin area in a thin, uniform layer without massaging or rubbing and using the applicator to prevent absorption of the ointment through the fingers.600 Using the size of the applicator to measure the coverage area allows the ointment to be absorbed through a smaller area of skin than that used in clinical trials; the clinical importance of this difference is not known.600 The applicator should be taped into place after application.600 To protect clothing, plastic wrap held in place by an elastic bandage, hosiery, or tape may be used to cover the ointment applicator.600 Application of the ointment over the chest may provide an additional psychological effect.600 As with transdermal nitroglycerin systems, nitroglycerin ointment has been reported to alter electrical conductivity, and some clinicians suggest that areas of the chest where defibrillation paddles typically are placed not be used for application of the ointment if possible.206
The commercially available injection concentrate must be diluted in 5% dextrose or 0.9% sodium chloride injection before administration.811 The drug should be diluted and stored only in glass bottles; avoid using filters since some filters absorb nitroglycerin.811 Nitroglycerin also is commercially available as a premixed solution in 5% dextrose injection for IV administration.812 Because nitroglycerin readily migrates into many plastics, the manufacturers' specific instructions for dilution, dosage, and administration must be carefully followed. 811, 812
Nitroglycerin injection should not be admixed with other drugs.811, 812
Standardized concentrations for IV nitroglycerin have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 49, 50Multidisciplinary expert panels were convened to determine recommended standard concentrations. 49, 50Because 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. 49, 50 For additional information on S4S (including updates that may be available), see [Web].49, 50
Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
Adults | 100 mcg/mL 200 mcg/mL 400 mcg/mL | mcg/min |
Pediatric patients (<50 kg) | 200 mcg/mL | mcg/kg/min |
400 mcg/mL |
Dosage of nitroglycerin must be carefully adjusted according to the patient's requirements and response and the smallest effective dosage should be used.811, 812 When nitroglycerin is administered IV, the type of IV administration set used, polyvinyl chloride (PVC) or non-PVC, must be considered in dosage estimations.811, 812 It should be noted that 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. 811, 812
Continuous monitoring of blood pressure and heart rate, as well as other appropriate parameters (e.g., pulmonary capillary wedge pressure), must be performed in all patients.811, 812 Adequate systemic blood pressure and coronary perfusion pressure must be maintained.811, 812 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.811, 812
For the acute relief of angina pectoris, 1 or 2 sprays (0.4 or 0.8 mg, respectively) of nitroglycerin as a lingual solution or aerosol may be administered.806, 807 If relief is not attained after the initial spray(s), additional single sprays may be given at 5-minute intervals as necessary; no more than 3 sprays should be given in a 15-minute period.806, 807 If pain persists after a total of 3 doses within a 15-minute period, prompt medical attention is recommended.806, 807 Nitroglycerin lingual solution or aerosol also may be used prophylactically 5-10 minutes before situations likely to provoke angina attacks.806, 807
For the acute relief of angina pectoris, the manufacturer recommends 0.3-0.6 mg of nitroglycerin as sublingual tablets, placed under the tongue and allowed to dissolve at the first sign of an acute attack.809 Most patients respond within 5 minutes of taking 1 or 2 doses. If relief is not attained after a single dose during an acute attack, additional doses may be given at 5-minute intervals.809 If chest pain persists after a total of 3 doses within a 15-minute period, or if the pain is different from the pain that is typically experienced, patients should be advised to seek prompt medical attention.809 For prophylactic management in situations likely to provoke angina attacks, nitroglycerin sublingual tablets may be administered 5-10 minutes prior to engaging in such activities.809
Transdermal and Topical Dosage
When a nitroglycerin transdermal system is used for the long-term prophylactic management of angina pectoris, the usual initial adult dosage is one transdermal dosage system, delivering the smallest available dose of nitroglycerin in its dosage series, applied every 24 hours.216 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 for restoration of full first-dose effects of nitrate therapy has not been determined.601 Dosage may be adjusted by changing to the next larger dosage system in the series or by a combination of dosage systems in the series.216 The transdermal systems should not be used to treat acute attacks of angina.216
When nitroglycerin is applied topically as an ointment, a suggested initial dosage is 0.5 inch (as squeezed from the tube) of the 2% ointment (i.e., approximately 7.5 mg) applied twice daily (once upon arising in the morning and repeated 6 hours later).600, 601 When the dose to be applied is in multiples of whole inches, unit-dose preparations that provide the equivalent of 1 inch of the 2% ointment also may be used.600 The initial dose may be doubled (i.e., increased to 1 inch or approximately 15 mg) and subsequently doubled again (i.e., increased to 2 inches or approximately 30 mg) if tolerated in patients failing to respond adequately.600 Doses used in clinical trials have ranged from 0.5-2 inches (approximately 7.5-30 mg).600 Dosage should be titrated upward until angina is effectively controlled or adverse effects preclude further dosage increases.600
The amount of nitroglycerin reaching the circulation varies directly with the size of the area of application and the amount of ointment applied.600 Coverage of an area approximately the size of the applicator (3.5 by 2.25 inches) should be sufficient to obtain the desired clinical effects, however, a larger area may be used.600 In clinical trials, the ointment generally has been spread over an area of 6 by 6 inches.600, 601, 602
As with other nitroglycerin formulations, all regimens of nitroglycerin ointment should include a daily nitrate-free interval to avoid development of tolerance.600, 601, 602 It is not known whether nitroglycerin ointment is effective in preventing exertional angina for longer than 7 hours after application of a dose.600
The onset of action of topical nitroglycerin ointment is not sufficiently rapid to treat acute attacks of angina; therefore, the ointment should not be used for this purpose.600
The recommended initial adult IV dosage when non-PVC administration sets are used is 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or until the infusion rate is 20 mcg/minute.812 If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and if later necessary, by increments of 20 mcg/minute.812 When PVC administration sets are used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute.812 Dosage is then titrated according to the response and tolerance of the patient.812
Non-ST-Segment-Elevation Acute Coronary Syndromes
For the treatment of continuing ischemic pain in patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS), sublingual nitroglycerin 0.3-0.4 mg every 5 minutes for up to 3 doses is recommended.1100
Following use of sublingual nitroglycerin, the need for IV nitroglycerin should be assessed, if not contraindicated; experts state that 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.1100
The recommended initial adult IV dosage of nitroglycerin when a nonadsorptive (e.g., non-PVC) administration set is used is 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or until the infusion rate is 20 mcg/minute.812 If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute.812 When a PVC administration set is used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute.812 Dosage should be titrated according to the patient's response.812 Blood pressure and heart rate should be continuously monitored during IV administration.812
ST-Segment Elevation Myocardial Infarction (STEMI)
When IV nitroglycerin is used after acute MI, some experts recommend an initial continuous IV infusion rate of 10 mcg/minute, increasing the dosage as necessary according to hemodynamic and clinical response.527 Dosage will vary considerably among patients and should be adjusted based on individual requirements, blood pressure response, and adverse effects.527, 812 The manufacturer states that the usual initial adult dosage of nitroglycerin when a nonadsorptive (e.g., non-PVC) administration set is used is 5 mcg/minute; the rate may be increased by 5 mcg/minute every 3-5 minutes until blood pressure response is obtained or the infusion rate is 20 mcg/minute.812 If no effect is obtained with 20 mcg/minute, dosage may be further increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute.812 When a PVC administration set is used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute.812 Dosage should then be titrated according to the patient's response.812 Blood pressure and heart rate should be continuously monitored during IV administration.812
Continuous IV infusions of nitroglycerin have been given for 12 hours with no attenuation of effect.812
When nitroglycerin is used to control perioperative hypertension or for the induction of intraoperative hypotension, the manufacturer recommends an initial adult IV dosage (using a nonadsorptive [e.g., non-PVC] administration set) of 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or an infusion rate of 20 mcg/minute is reached.812 If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute.812 When a PVC administration set is used, higher dosages generally are required; an initial infusion rate of 25 mcg/minute or greater has been used in studies employing PVC tubing.812 Dosage should be titrated according to the patient's response and possible adverse effects.812 Blood pressure and heart rate should be continuously monitored during IV administration; in many cases, invasive monitoring of pulmonary capillary wedge pressure is indicated.812
When nitroglycerin is used IV in hypertensive emergencies†, some experts recommend an initial adult dosage of 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes up to a maximum of 20 mcg/minute.1200 Adults with a hypertensive emergency with a compelling indication (e.g., eclampsia or severe preeclampsia or pheochromocytoma crisis) should have their systolic blood pressure reduced to less than 140 mm Hg during the first hour and, in patients with acute aortic dissection, to less than 120 mm Hg within the first 20 minutes.1200
The risks of overly aggressive therapy in any hypertensive crisis must always be considered.542, 1200 The initial goal of IV nitroglycerin therapy for a hypertensive emergency in adults without a compelling indication is to reduce systolic blood pressure by no more than 25% within the first hour, followed by further blood pressure reduction if stable to 160/110 or 160/100 mm Hg within the next 2-6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.1200
The approximate onset and duration of action of various dosage forms of nitroglycerin are as follows:
Dosage Form | Onset | Duration |
|---|---|---|
sublingual | within 2 min | up to 30 min |
ointment | 30 min | 3 h |
oral extended-release | 1 h | up to 12 h |
Dosage Form | Onset | Duration |
|---|---|---|
sublingual | 2 min | up to 30 min |
ointment | within 1 h | 3-6 h |
The onset of action of transdermal systems of nitroglycerin is delayed and the duration prolonged compared with other currently available dosage forms of the drug. Transdermal systems of the drug are designed to provide continuous, controlled release of nitroglycerin to the skin from which the drug undergoes percutaneous absorption. The rates of delivery and absorption of the drug vary depending on the specific preparation, and the individual manufacturers' information should be consulted for specific descriptions of these rates and other characteristics of the preparation. The rate of delivery is linearly dependent on the active surface area of the applied system. In general, each transdermal system contains a reservoir of excess nitroglycerin, which establishes a concentration gradient to promote delivery of the drug out of the system and into the skin, and not all of the drug is delivered from the system during normal use. The preparations currently are labeled in terms of the approximate rate of drug delivery per hour; previously, they were labeled in terms of the approximate rate of drug delivery per 24 hours.
Several studies suggest that percutaneous absorption of nitroglycerin ointment varies with the site of application, with application to the chest resulting in higher blood concentrations of the drug and greater hemodynamic effects than application to the extremities; however, there are conflicting data, and further studies are needed to more fully evaluate the effect of the application site on absorption and hemodynamic effects.
Nitroglycerin is widely distributed in the body. It is not known if nitroglycerin is distributed into milk.
At plasma concentrations of 50-500 ng/mL, nitroglycerin is about 60% bound to plasma proteins while its metabolites, 1,3-glyceryl dinitrate and 1,2-glyceryl dinitrate, are approximately 60 and 30% bound, respectively.
The plasma half-life of nitroglycerin is about 1-4 minutes. Clearance of nitroglycerin occurs at a rate of about 1 L/kg per minute.
Nitroglycerin is metabolized to 1,3-glyceryl dinitrate, 1,2-glyceryl dinitrate, and glyceryl mononitrate. In animals, the vasodilator effects of nitroglycerin are 10-14 times greater than those of the dinitrate metabolites. Glyceryl mononitrate, which is inactive, is the principal metabolite. The dinitrate metabolites are metabolized further to inactive mononitrates and are metabolized ultimately to glycerol and carbon dioxide. Clearance of nitroglycerin exceeds hepatic blood flow. Extrahepatic sites of metabolism include red blood cells and vascular walls.
Nitroglycerin an organic nitrate, is a vasodilator with peripheral and coronary vascular effects.1100
Nitroglycerin sublingual tablets should be stored in the original glass container at 20-25°C and tightly capped after each use to prevent loss of tablet potency.809
Nitroglycerin lingual spray pump and lingual aerosol should be stored at 25°C but may be exposed to temperatures ranging from 15-30°C.806, 807 Because the contents of nitroglycerin lingual spray or lingual aerosol contain 20% alcohol or a highly flammable propellant (butane), respectively, the containers should not be forcefully opened, sprayed toward a flame, or placed into a fire or incinerator for disposal.806, 807 Nitroglycerin ointment should be stored in tight containers at 20-25°C.600 Nitroglycerin transdermal systems should be stored at 15-30°C; do not store in the refrigerator.216
Since nitroglycerin readily migrates into many plastics, nitroglycerin IV solutions should be diluted and stored only in glass bottles; since some filters also absorb nitroglycerin, use of filters with IV solutions should be avoided.811, 812 Nitroglycerin IV solutions should not be admixed with other drugs.811, 812 Specialized references and the manufacturers' labeling should be consulted for specific stability and compatibility 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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Lingual | Aerosol | 0.4 mg/spray* | Nitroglycerin Lingual Spray | |
NitroMist® | Evus | |||
Solution | 0.4 mg/spray* | Nitroglycerin Lingual Spray | ||
Parenteral | For injection concentrate, for IV infusion | 5 mg/mL (50 mg) | Nitroglycerin Injection | |
Sublingual | Tablets | 0.3 mg* | Nitroglycerin Sublingual Tablets | |
Nitrostat® | Pfizer | |||
0.4 mg* | Nitroglycerin Sublingual Tablets | |||
Nitrostat® | Pfizer | |||
0.6 mg* | Nitroglycerin Sublingual Tablets | |||
Nitrostat® | Pfizer | |||
Topical | Ointment | 2% | Nitro-Bid® | Fougera |
Transdermal System | 0.1 mg/hour (total nitroglycerin content and transdermal system size may vary by manufacturer)* | Nitro-Dur® | Merck | |
Nitroglycerin Transdermal System | ||||
0.2 mg/hour (total nitroglycerin content and transdermal system size may vary by manufacturer)* | Nitro-Dur® | Ingenus | ||
Nitroglycerin Transdermal System | ||||
0.3 mg/hour (60 mg/15 cm2) | Nitro-Dur® | Ingenus | ||
0.4 mg/hour (total nitroglycerin content and transdermal system size may vary by manufacturer)* | Nitro-Dur® | Ingenus | ||
Nitroglycerin Transdermal System | ||||
0.6 mg/hour (total nitroglycerin content and transdermal system size may vary by manufacturer)* | Nitro-Dur® | Ingenus | ||
Nitroglycerin Transdermal System | ||||
0.8 mg/hour (160 mg/40 cm2) | Nitro-Dur® | Ingenus |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV use only | 100 mcg/mL (25 or 50 mg) Nitroglycerin in 5% Dextrose* | Nitroglycerin in 5% Dextrose Injection | |
200 mcg/mL (50 mg) Nitroglycerin in 5% Dextrose* | Nitroglycerin in 5% Dextrose Injection | |||
400 mcg/mL (100 or 200 mg) Nitroglycerin in 5% Dextrose* | Nitroglycerin in 5% Dextrose Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
20. Assinder DF, Chasseaud LF, Taylor T. Plasma isosorbide dinitrate concentrations in human subjects after administration of standardizing and sustained-release formulations. J Pharm Sci . 1977; 66:775-8. [PubMed 577507]
49. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]
50. ASHP. Standardize 4 Safety: adult continuous infusion standard. Updated 2025 June. From ASHP website. Updates may be available at ASHP website. [Web]
201. Parker JO, Farrell B, Lahey KA et al. Effects of intervals between doses on the development of tolerance to isosorbide dinitrate. N Engl J Med . 1987; 316:1440-4. [PubMed 3574424]
202. Silber S, Krause KH, Theisen K. Nitrate-tolerance: dependence on dosage intervals? Circulation . 1984; 70(Suppl 2):II-289. Abstract No. 753.
203. Col J, Col-Debeys C, Lavenne-Pardonge E et al. Propylene glycol-induced heparin resistance during nitroglycerin infusion. Am Heart J . 1985; 110(1 Part 1):171-3. [PubMed 3925740]
204. Habbab MA, Haft JI. Heparin resistance induced by intravenous nitroglycerin: a word of caution when both drugs are used concomitantly. Arch Intern Med . 1987; 147:857-60. [PubMed 3107486]
205. Babka JC. Does nitroglycerin explode? N Engl J Med . 1983; 309:379. Letter.
206. Parke JD, Higgins SE. Hazards associated with chest application of nitroglycerin ointments. JAMA . 1982; 248:427. [PubMed 6806492]
207. Kuhnen R, Nitsch J, Lüderitz B. Explosion von Nitropflastern bei Defibrillation. Dtsch Med Wochenschr . 1985; 110:37.
212. Robertson D, Stevens RM. Nitrates and glaucoma. JAMA . 1977; 237:117. [PubMed 576138]
213. Wizemann AJS, Wizemann V. Organic nitrate therapy in glaucoma. Am J Ophthalmol . 1980; 90:106-9. [PubMed 6772033]
214. Sveska KJ. Nitrates may not be contraindicated in patients with glaucoma. Drug Intell Clin Pharm . 1985; 19:361.
215. Wisznia KI, Lazar M, Leopold IH. Oral isosorbide and intraocular pressure. Am J Ophthalmol . 1970; 70:630-4. [PubMed 4248312]
216. Ingenus Pharmaceuticals. Nitro-Dur (nitroglycerin) patch prescribing information. Orlando, FL; 2017 Sep.
217. Jugdutt BI, Warnica JW. Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications: effect of timing, dosage, and infarct location. Circulation . 1988; 78:906-19. [PubMed 3139326]
218. Yusuf S, Collins R, McMahon S et al. Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of randomized trials. Lancet . 1988; 1:1088-92. [PubMed 2896919]
219. Sreebny LM, Valdini A. Xerostomia: a neglected symptom. Arch Intern Med . 1987; 147:1333-7. [PubMed 3300589]
220. Rasler FE. Ineffectiveness of sublingual nitroglycerin in patients with dry mucous membranes. N Engl J Med . 1986; 314:181. [PubMed 3079881]
221. Straehl P, Galeazzi RL. Isosorbide dinitrate bioavailability, kinetics, and metabolism. Clin Pharmacol Ther . 1985; 38:140-9. [PubMed 4017416]
222. Thadani U, Whitsett T. Relationship of pharmacokinetic and pharmacodynamic properties of organic nitrates. Clin Pharmacokinet . 1988; 15:32-43. [PubMed 3135973]
223. Bogaert MG. Clinical pharmacokinetics of organic nitrates. Clin Pharmacokinet . 1983; 8:410-21. [PubMed 6414751]
224. Schwarz. Dilitrate®-SR (isosorbide dinitrate) sustained release capsules prescribing information. Milwaukee, WI; 1998 Sep.
225. Sorbitrate® (isosorbide dinitrate) prescribing information. In: Physicians' desk reference. 54th ed. Montvale NJ: Medical Economics Company Inc; 2000:566-8.
226. Chasseaud LF, Darragh A, Doyle E et al. Isosorbide dinitrate plasma concentrations and bioavailability in human subjects after administration of standard oral and sublingual formulations. J Pharm Sci . 1984; 699-71.
227. Schaumann W. Pharmacokinetics of isosorbide dinitrate and isosorbide-5-mononitrate. Int J Clin Pharmacol Ther Toxicol . 1989; 27:445-53. [PubMed 2681004]
228. Fung HL. Pharmacokinetics and pharmacodynamics of isosorbide dinitrate. Am Heart J . 1985; 110(1 Part 2):213-6. [PubMed 4013997]
229. Taylor T, Chasseaud LF, Major RM et al. Bioequivalence of a sustained-release isosorbide dinitrate formulation at steady-state. Biopharm Drug Dispos . 1985; 6:119-29. [PubMed 4005392]
230. Chasseaud LF, Doyle E, Taylor T et al. Bioavailability of isosorbide dinitrate and its two mononitrate metabolites from sustained-release formulations. Int J Clin Pharmacol Ther Toxicol . 1983; 21:514-8. [PubMed 6642789]
231. Morrison RA, Wiegland UW, Jahnchen E et al. Isosorbide dinitrate kinetics and dynamics after intravenous, sublingual, and percutaneous dosing in angina. Clin Pharmacol Ther . 1983; 33:747-56. [PubMed 6851405]
232. Smith D, Aldrich W, Dey M et al. A pharmacokinetic model for issorbidedinitrate, isosorbide-2-mononitrate, and isosorbide-5-mononitrate. Drug Metab Dispos . 1990; 18:429-34. [PubMed 1976063]
233. Abshagen U, Betzien G, Endele R et al. Pharmacokinetics and metabolism of isosorbide-dinitrate after intravenous and oral administration. Eur J Clin Pharmacol . 1985; 27:637-44. [PubMed 3987768]
234. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med . 1993; 153:154-83. [PubMed 8422206]
236. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardiac infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardiac Infarction). From website. 1996; 28:1328-428. [Web]
240. Come PC, Pitt B. Nitroglycerin-induced severe hypotension and bradycardia in patients with acute myocardial infarction. Circulation . 1976; 54:624-8. [PubMed 822962]
241. Kinch JW, Ryan TJ. Right ventricular infarction. N Engl J Med . 1994; 330:1211-7. [PubMed 8139631]
242. Bussmann WD, Passek D, Seidel W et al. Reduction of CK and CK-MB indexes of infarct size by intravenous nitroglycerin. Circulation . 1981; 63:615-22. [PubMed 6780232]
243. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet . 1994; 343:1115-22. [PubMed 7910229]
244. ISIS-4: a randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet . 1995; 345:669-85.
245. Becker RC, Corroa JM, Bovill EG et al. Intravenous nitroglycerin-induced heparin resistance: a qualitative antithrombin II abnormality. Am Heart J . 1990; 119:1254-61. [PubMed 2112878]
246. Bode V, Welzel D, Franz G et al. Absence of drug interaction between heparin and nitroglycerin: randomized placebo-controlled cross-over study. Arch Intern Med . 1990; 150:2117-9. [PubMed 2121114]
247. Gonzalez ER, Jones HD, Graham S et al. Assessment of the drug interaction between intravenous nitroglycerin and heparin. Ann Pharmacother . 1992; 26:1512-4. [PubMed 1482804]
248. Fung HL, Chung SJ, Bauer JA et al. Biochemical mechanism of organic nitrtae action. Am J Cardiol . 1992; 70(Supp 5):4-10B.
249. Luscher TF. Endothelium-derived nitric oxide: the endogenous nitrovasodilator in th ehuman cardiovascular system. Eur Heart Journal . 1991; 12(Supp E):2-11.
250. Abrams J. Hemodynamic effects of nitroglycerin and long-acting nitrates. Am Heart J . 1985; 110:216-24. [PubMed 3925741]
251. Winbury MM. Redistribution of left ventricular blood flow produced by nitroglycerin: an example of integration of the macro- and microcirculation. Circ Res . 1971; 28(Supp I):140-7.
252. Gorman MW, Sparks HV Jr. Nitroglycerin causes vasodilation within ischaemic myocardium. Cardiovasc Res . 1980; 14:515-21. [PubMed 6783307]
253. Brown BG, Bolson E, Peterson RB et al. The mechanisms of nitroglycerin action: stenosis vasodilation as a major component of drug response. Circulation . 1981; 64:1089-97. [PubMed 6794931]
254. Needleman P, Jakschik B, Johnson EM Jr. Sulfhydryl requirement for relaxation of vascular smooth muscle. J Pharmacol Exp Ther . 1973; 187:324-31. [PubMed 4201275]
255. Cohn JN, Archibald DG, Ziesches S et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study. N Engl J Med . 1986; 314:1547-52. [PubMed 3520315]
256. Cohn JN, Johnson G, Ziesche et al. A comparison of enalapril with hydralazine—isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med . 1991; 325:303-10. [PubMed 2057035]
257. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol . 1999; 83:9A-38A.
259. Webb DJ, Freestone S, Allen MJ et al. Sildenafil citrate and blood-pressure-lowering drugs: Results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol . 1999; 83:21-8c. [PubMed 10073779]
260. Cheitkin MD, Hutter AM, Brindis RG for the American College or Cardiology and American Heart Association. Technology and Practice Executive Committee [duplicate publication of Cheitkin MD, Hutter AM, Brindis RG for the American College or Cardiology and American Heart Association. ACC/AHA expert consensus document: use of sildenafil (viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol . 1999; 33:273-82.
261. Wallis RM, Corbin JD, Francis SH et al. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol . 1999; 83:3-12c.
262. Pfizer. Viagra® (sildenafil citrate) prescribing information. New York, NY; 1999 June.
263. Zusman RM, Morales A, Glasser DB et al. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol . 1999; 83:35-44c.
264. Goldenberg MM. Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction. Clin Ther . 1998; 20:1033-48. [PubMed 9916601]
265. Nandwani R, Goutlay Y. Possible interaction between sildenafil and HIV combination therapy. Lancet . 1999; 353:840.
266. Anon. Summary of reports of death in Viagra users received from marketing (late March) through mid-November 1998. From FDA web site [no longer available online]. [Web]
267. Aldridge J, Measham F. Sildenafil (Viagra) is used as a recreational drug in England. BMJ . 1999; 318:669. [PubMed 10066221]
268. Anon. How to buy almost any drug without a prescription: 1000 Mexican pharmacy contacts - 450 Caribbean pharmacies. From the Drugquest Web Site (http:/www.drugquest.com/doorway.htm) [no longer available online].
269. Anon. Prescription free pharmaceuticals by e-mail at incredibly low prices. From the Vitality Health Products Web Site [no longer available online]. [Web]
270. Anon. Viagra. From the 4nRx Web Site. [Web]
271. Pfizer. Dear doctor letter to emergency physicians regarding Viagra contraindication: concomitant administration of an organic nitrate. From FDA web site [no longer available online]. 1998 May 22. [Web]
272. Kloner RA. Erectile dysfunction and sildenafil citrate and cardiologists. Am J Cardiol . 1999; 83:576-82. [PubMed 10073864]
273. Pfizer, New York, NY. Personal communication on sildenafil.
274. Steers WD. Viagra-after one year. Urology . 1999; 54:12-7. [PubMed 10414719]
275. Langtry HD, Markham A. Sildenafil: a review of its use in erectile dysfunction. Drugs . 1999; 57:967-89. [PubMed 10400408]
276. Agency for Health Care Policy and Research. Diagnosing and managing unstable angina. 1994. (AHCPR publication no. 94-0603)
277. Théroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation . 1997; 97:1195-206.
278. Tonkin AM, Aroney CN. Guidelines for managing patients with unstable angina: rating the evidence and rationale for treatment. Med J Aust . 1997; 16:644-7.
279. Zaacks SM, Liebson PR, Calvin JE et al. Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J Am Coll Cardiol . 1999; 33:107-18.
280. Cairns J, Théroux P, Armstrong P et al. Unstable angina—Report from a Canadian expert round table. Can J Cardiol . 1996; 12:1279-92. [PubMed 8987969]
281. Armstrong K, Schwartz JS, Asch DA. Direct sale of sildenafil (Viagra) to consumers over the Internet. N Engl J Med . 1999; 341:1389-92. [PubMed 10536133]
282. Arora RR, Meilli L. Acute myocardial infarction after the use of sildenafil. N Engl J Med . 1999; 341:700.
283. Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology . 1999; 91:307-10. [PubMed 10422958]
284. Goldstein I, Lue TF, Padma-Nathan H et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med . 1998; 338:1397-404. [PubMed 9580646]
285. Anon. Sildenafil: an oral drug for impotence. Med Lett Drugs Ther . 1998; 40:51-52. [PubMed 9599594]
286. Reviewers' comments (personal observations) on sildenafil.
287. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol . 1999; 84:11-7N.
288. Padma-Nathan H. A new era in the treatment of erectile dysfunction. Am J Cardiol . 1999; 84:18-23N. [PubMed 10404845]
289. Heart and Stroke Foundation of Canada and Canadian Cardiovascular Society. A statement on the use of sildenafil in the management of sexual dysfunction in patients with cardiovascular disease. Can J Cardiol . 1999; 15:396-9. [PubMed 10348610]
295. Nyberg G, Blychert LO, Jonsson UE. Pharmacokinetics of isosorbide-5-mononitrate in a controlled-release (Durules) formulation. Br J Clinical Pharmacol . 1985; 20:541P.
296. Kampmann JP. Pharmacokinetics of various preparations of organic nitrates. Drugs . 1987; 33(Suppl 4):5-8. [PubMed 3113910]
297. Jonsson UE. Various administration forms of nitrates and their possibilities. Drugs . 1987; 33(Suppl 4):23-31. [PubMed 3304960]
298. Gunasekara NS, Noble S. Isosorbide 5-mononitrate: a review of a sustained-release formulation (Imdur®) in stable angina pectoris. Drugs . 1999; 57:261-77. [PubMed 10188765]
299. Laufen H, Leitold M. The effect of food on the oral absorption of isosorbide-5-mononitrate. Br J Clin Pharmacol . 1984; 18:967-8. [PubMed 6529537]
300. Kosoglou T, Kazierad DJ, Schentag JJ et al. Effect of food on the oral bioavailability of isosorbide-5-mononitrate administered as an extended-release tablet. J Clin Pharmacol . 1995; 35:151-8. [PubMed 7751425]
301. Thomson AH, Miller SHK, Green ST et al. The effect of food on the absorption of slow-release isosorbide-5-mononitrate tablets. Eur J Clin Pharmacol . 1988; 34:47-50. [PubMed 3360048]
303. Kirsten R, Nelson K, Kirsten D et al. Clinical pharmacokinetics of vasodilators: part II. Clin Pharmacokinet . 1998; 35:9-36. [PubMed 9673832]
304. Wagner F, Siefert F, Trenk D et al. Relationship between pharmacokinetics and hemodynamic tolerance to isosorbide-5-mononitrate. Eur J Clin Pharmacol . 1990; 38(Suppl 1):S53-9. [PubMed 2354713]
305. Waller DG. Optimal nitrate therapy with a once-daily sustained-release formulation of isosorbide mononitrate. J Cardiovasc Pharmacol . 1999; 34(Suppl 2):S21-7. [PubMed 10499557]
306. Kinlay S, Wall RC, Page JH et al. Effect of wetting the mouth on aortic blood pressure just before taking sublingual nitrates. Am J Cardiol . 1996; 78:555-8. [PubMed 8806342]
307. Jonsson UE. Development of long-acting nitrate delivery systems. Eur J Clin Pharmacol . 1990; 38(Suppl 1):S15-9. [PubMed 2113000]
309. Prakash A, Markham A. Long-acting isosorbide mononitrate. Drugs . 1999; 57:93-9. [PubMed 9951954]
310. Vogt D, Trenk D, Bonn R et al. Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration. Eur J Clin Pharmacol . 1994; 46:319-24. [PubMed 7957516]
311. Taylor T, Chasseaud LF, Doyle E et al. Isosorbide dinitrate pharmacokinetics. Arzneim Forsch . 1982; 32:1329-33.
312. Taylor IW, Major RM, Chasseaud LF et al. Saliva concentrations of isosorbide dinitrate, isosorbide-2-mononitrate and isosorbide-5-mononitrate. Br J Clin Pharmacol . 1984; 17:585-7. [PubMed 6733004]
313. Udhoji VN, Heng MK. Hemodynamic effects of high-dose sustained-action oral isosorbide dinitrate in stable angina. Am J Med . 1984; 76:234-40. [PubMed 6364805]
314. Trenk D, Hinder M, Stengele E et al. Comparison of the initial hemodynamic effects of immediate-release versus sustained-release isosorbide-5-mononitrate following single oral doses. J Clin Pharmacol . 2000; 40:168-76. [PubMed 10664923]
315. Evers J, Bonn R, Boertz A et al. Pharmacokinetics of isosorbide-5-nitrate during hemodialysis and peritoneal dialysis. Eur J Clin Pharmacol . 1987; 32:503-5. [PubMed 3622599]
316. Ergotamine (Ergostat) interactions: Nitroglycerin. In: Hansten PD, Horn JR. Drug interactions & updates. Vancouver, WA: Applied Therapeutics; 1997:263.
317. Rutherford JD. Nitrate tolerance in angina therapy: how to avoid it. Drugs . 1995; 49:196-9. [PubMed 7729327]
318. Abrams J, Elkayam U, Thadani U et al. Tolerance: an historical overview. Am J Cardiol . 1998; 81(Suppl 1A):3-14A.
319. Glasser SP. Clinical mechanisms of nitrate action. Am J Cardiol . 1998; 81(1A):49-53A.
320. Loscalzo J. Antiplatelet and antithrombotic effects of organic nitrates. Am J Cardiol . 1992; 70:18-22B.
321. Parke-Davis. Nitrostat (nitroglycerin) tablets prescribing information. In: Physicians' desk reference. 54th ed. Montvale, NJ: Medical Economics Company Inc; 2000:2271-2.
322. Raehl CL, Nolan PE. Ischemic heart disease: anginal syndromes. In: Young LY, Koda-Kimble MA, eds. Applied therapeutics: the clinical use of drugs. 6th ed. Vancouver, WA: Applied Therapeutics, Inc; 1995:13-6-13-11.
323. Flaherty JT. Nitrate tolerance: a review of the evidence. Drugs . 1989; 37:523-50. [PubMed 2661197]
324. Raehl CL, Nolan PE. Ischemic heart disease: anginal syndromes. In: Koda-Kimble MA, Young LY, eds. Applied therapeutics: the clinical use of drugs. 6th ed. Vancouver, WA: Applied Therapeutics, Inc; 1995:13-1-25.
325. ISMO (isosorbide mononitrate) tablets. In: MedWatch: summary of safety-related drug labeling changes approved by FDA. Rockville, MD: US Food and Drug Administration; 1999 Jun.
329. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med . 1993; 153:154-83. [PubMed 8422206]
331. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)
332. Bayer Health Care. Levitra® (vardenafil hydrochloride) tablets prescribing information. West Haven, CT; 2003 Aug.
333. Lilly ICOS LLC. Cialis® (tadalafil) tablets prescribing information. Indianapolis, IN; 2003 Nov.
334. Kloner RA, Hutter AM, Emmick JT et al. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol . 2003: 42:1855-60.
335. Coleman CI, Carabino JM, Vergara CM et al. Vardenafil: an oral selective phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction. Formulary . 2003; 38:131-48.
336. NitroMed, Inc. BiDil (isosorbide dinitrate and hydralazine hydrochloride) tablets prescribing information. Lexington, MA; 2005 Jun 23.
337. Taylor AL, Ziesche S, Yancy C et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med . 2004; 351:2049-57. [PubMed 15533851]
338. Anon. BiDil for heart failure. Med Lett Drugs Ther . 2005; 47:77-8. [PubMed 16186789]
500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)
502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens . 2013; 31:1281-357. [PubMed 23817082]
524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation . 2013; 128:e240-327.
527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation . 2013; 127:e362-425.
542. Marik PE, Varon J. Hypertensive crises: challenges and management. Chest . 2007; 131:1949-62. [PubMed 17565029]
600. Fougera. Nitro-Bid® (nitroglycerin 2%) ointment prescribing information. Melville, NY; 2021 Aug
601. Thadani U. Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance. Am J Cardiovasc Drugs . 2014; 14:287-301. [PubMed 24664980]
602. Boden WE, Finn AV, Patel D et al. Nitrates as an integral part of optimal medical therapy and cardiac rehabilitation for stable angina: review of current concepts and therapeutics. Clin Cardiol . 2012; 35:263-71. [PubMed 22528319]
701. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J . 2016; :.
703. Ansara AJ, Kolanczyk DM, Koehler JM. Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck. J Clin Pharm Ther . 2016; 41:119-27. [PubMed 26992459]
800. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation . 2016; :.
801. Soukoulis V, Boden WE, Smith SC et al. Nonantithrombotic medical options in acute coronary syndromes: old agents and new lines on the horizon. Circ Res . 2014; 114:1944-58. [PubMed 24902977]
802. Boden WE, Padala SK, Cabral KP et al. Role of short-acting nitroglycerin in the management of ischemic heart disease. Drug Des Devel Ther . 2015; 9:4793-805. [PubMed 26316714]
803. Lamas GA, Escolar E, Faxon DP. Examining treatment of ST-elevation myocardial infarction: the importance of early intervention. J Cardiovasc Pharmacol Ther . 2010; 15:6-16. [PubMed 20061507]
804. Bayer. Adempas® (riociguat) tablets prescribing information. Whippany, NJ; 2017 Feb.
805. Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet . 2017; 389:197-210. [PubMed 27502078]
806. Evus. NitroMist® (nitroglycerin) lingual aerosol prescribing information. Scotsdale, AZ; 2019 Sep.
807. Padagis. Nitroglycerin lingual spray prescribing information. Allegan, MI; 2022 Sept.
808. Anderson JL, Morrow DA. Acute Myocardial Infarction. N Engl J Med . 2017; 376:2053-2064. [PubMed 28538121]
809. Viatris Specialty. NitroStat® (nitroglycerin) sublingual tablet prescribing information. Morgantown, WV; 2023 Feb.
811. American Regent. Nitroglycerin injection prescribing information. Shirley, NY; 2021 Jul.
812. Baxter. Nitroglycerin in 5% dextrose injection prescribing information. Deerfield, IL; 2016 Aug.
825. Nitroglycerin. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:1036-8.
1100. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation . 2014; 130:e344-426.
1101. Virani SS, Newby LK, Arnold SV et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023 Aug 29;148(9):e9-e119. doi: 10.1161/CIR.0000000000001168. Epub 2023 Jul 20. Erratum in: Circulation. 2023 Sep 26;148(13):e148. doi: 10.1161/CIR.0000000000001183. Erratum in: Circulation. 2023 Dec 5;148(23):e186. doi: 10.1161/CIR.0000000000001195. PMID: 37471501.
1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension . 2018; 71:el13-e115. [PubMed 29133356]