Skip to main content

Nitroglycerin (Monograph)

Brand names: GoNitro, Minitran, Nitro-Bid, Nitro-Dur, Nitrolingual, ... show all 8 brands
Drug class: beta-Adrenergic Blocking Agents

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

Warning

A standardized concentration for this drug has been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. The drug is included in a standard concentration list which may apply to an IV or oral compounded liquid formulation. For additional information, see the ASHP website [Web].

Introduction

Nitroglycerin, an organic nitrate, is a vasodilating agent.

Uses for Nitroglycerin

Chronic Stable Angina

Management of angina pectoris secondary to CAD.600 802 806 807 809 810 811 817 823 1101

Short-acting preparations (e.g., sublingual nitroglycerin tablets, nitroglycerin spray) used for acute relief of angina; also may be usedb for acute prophylactic management in situations likely to provoke angina attacks.802 806 807 809 817 823 1101

Sublingual nitroglycerin is considered the drug of choice for acute relief of angina pectoris because it has a rapid onset of action, is inexpensive, and its efficacy is well established.b

Long-acting preparations (e.g., oral or topical nitroglycerin) used for long-term prophylactic management of chronic stable angina.600 810 811 1101

While β-blockers are recommended as the anti-ischemic drugs of choice in most patients with chronic stable angina, long-acting nitroglycerin preparations may be substituted or added in patients who do not tolerate or respond adequately to β-blockers.1101

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Acute symptomatic relief of chest pain in patients with NSTE ACS, including unstable angina and non-ST-segment-elevation MI (NSTEMI).1100

Sublingual nitroglycerin (0.3–0.4 mg every 5 minutes for up to 3 doses) is recommended in patients with NSTE ACS who have continuing ischemic pain; 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.1100 Topical or oral nitrates may be an acceptable alternative to IV therapy in patients who do not have refractory or recurrent ischemia.1100

Acute MI

Management of patients with acute MI.217 218 240 241 242 527 808 812

Expert guidelines for the management of ST-segment-elevation MI (STEMI) state that IV nitroglycerin may be beneficial in patients with STEMI and heart failure or hypertension.527

Experts state there is no role for the routine use of oral nitrates during the convalescent phase of STEMI.527

Systemic hypotension with resultant worsening of myocardial ischemia is a potential complication of nitroglycerin therapy.236 Therefore, avoid use in patients with or at risk of hypotension.527

Avoid use in patients with marked bradycardia (e.g., <50 bpm) or tachycardia (e.g., >100 bpm)240 527 and those with suspected right ventricular infarction.241 527

Hypertension

IV nitroglycerin is 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.500 502 1200 b

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].524

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.524 701 703 800

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.524

Particularly useful in patients with heart failure and hypertension, coronary ischemia, or substantial mitral regurgitation.524

Tachyphylaxis may develop within 24 hours; some patients may develop resistance to even high doses.524

Cocaine-induced Acute Coronary Syndrome

Used adjunctively in the management of cocaine overdose† [off-label] to reverse coronary vasoconstriction and/or relieve hypertension or chest discomfort.696

Nitroglycerin Dosage and Administration

General

Hypertensive Emergency

Administration

Administer lingually, sublingually, intrabuccally, orally, topically, or by IV infusion.b

Lingual, sublingual, or intrabuccal nitroglycerin may be inadequately absorbed, with resultant decreased efficacy, in patients with dry oral mucous membranes (e.g., xerostomia).219 220

Patient should be sitting immediately after lingual, sublingual, or intrabuccal administration of nitroglycerin.b

Lingual Administration

Administer nitroglycerin solution lingually using a metered-dose spray pump.807 The spray pump delivers 0.4 mg of nitroglycerin per metered spray.807 The 4.9-g lingual spray pump bottle usually delivers about 60 metered sprays; the 14.6-g bottle delivers about 200 metered sprays.807

Administer nitroglycerin aerosol lingually using a metered-dose spray container.806 The lingual aerosol container delivers 0.4 mg of nitroglycerin per metered spray.806 The 4.1-g aerosol container usually delivers about 90 metered sprays; the 8.5-g container delivers about 230 metered sprays.806

Prime (but do not shake) the spray pump or aerosol container prior to first use or after a period of nonuse (i.e., ≥6 weeks) according to the manufacturers' instructions.806 807

To administer the lingual aerosol or solution, hold the container or spray pump upright with the valve head uppermost and the spray orifice as close to the opened mouth as possible.806 807 To release a spray, press valve head with the forefinger.806 807 Spray lingual aerosol or solution onto or under tongue and immediately close mouth; do not inhale spray.806 807

Do not expectorate the drug nor rinse the mouth for 5–10 minutes following administration.806 807

Sublingual Administration

Sublingual tablets are dissolved under the tongue or in the buccal pouch.809 Do not swallow sublingual tablets.

Sublingual powder is dissolved under the tongue; do not swallow sublingual powder.823

Topical Administration (Transdermal System)

Apply nitroglycerin transdermal system topically to the skin as directed by manufacturer.811

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.b

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

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.205 206 207 210

Topical Administration (Ointment)

Apply topically using manufacturer-supplied applicator paper to measure dose.b

Spread on any non-hairy skin area (usually the chest or back) in a thin, uniform layer without massaging or rubbing; use applicator to prevent absorption through the fingers.b Tape applicator into place on skin.600

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

Some clinicians suggest avoiding placement of ointment on areas of chest where defibrillation paddles typically are placed due to potential for altered electrical conductivity.206

IV Administration

Administer via a controlled-infusion device that maintains a constant infusion rate.b

Because nitroglycerin readily migrates into many plastics, the manufacturers’ specific instructions for dilution, dosage, and administration must be carefully followed. 208

About 40–80% of the total amount of nitroglycerin in a diluted solution for IV infusion may be absorbed by the PVC tubing of IV administration sets in general use.b Special non-PVC plastic IV administration sets available that cause minimal drug absorption; when such sets are used, nearly all of the calculated dose of nitroglycerin is delivered to the patient.b

Administration through the same infusion set as blood can result in pseudoagglutination and hemolysis.208

Do not admix with other drugs.b

Dilution

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

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

Dosage

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

For IV administration, must consider the type of IV administration set used (PVC or non-PVC) in dosage estimations.b 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.b

Relative hemodynamic and antianginal tolerance may develop during prolonged infusions, contributing to the need for careful dosage titration.b

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

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.b

Adults

Chronic Stable 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.806 807

May give additional single sprays at intervals of approximately every 5 minutes as necessary if relief is not attained after initial spray(s);806 807 do not exceed 3 sprays in a 15-minute period.806 807

If pain persists after a total of 3 doses within a 15-minute period, seek prompt medical attention.806 807

If used prophylactically, may administer 5–10 minutes before situations likely to provoke angina attacks.806 807

Sublingual

Sublingual tablets: 0.3–0.6 mg at the first sign of an acute anginal attack.809 If relief not attained after a single dose, may give additional doses at 5-minute intervals.809 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.809

Sublingual powder: 1 or 2 packets (0.4 or 0.8 mg, respectively) at the onset of an attack.823 If relief is not attained after the initial dose, may administer an additional packet (0.4 mg) every 5 minutes as needed up to a total of 3 packets within a 15-minute period.823 If pain persists after a total of 3 packets within a 15-minute period, seek prompt medical attention.823

If used prophylactically, may administer a dose of nitroglycerin (as sublingual tablets or powder) 5–10 minutes before engaging in activities likely to provoke angina attacks.809 823

Long-term Prophylactic Management of Angina
Oral

Extended-release capsules: In clinical studies, initial dosage of 2.5–6.5 mg 3–4 times daily as an extended-release formulation has been administered, with subsequent titration based on patient response and adverse effects.810

To minimize occurrence of tolerance, a nitrate-free interval is recommended; however, minimum nitrate-free interval necessary with the extended-release capsules not known.810 Studies with other nitroglycerin formulations suggest that 10–14 hours may be sufficient.601

Do not use an extended-release formulation to treat acute attacks of angina; onset of action not sufficiently rapid.810

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.b

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.601 (See Tolerance and Dependence Under Cautions.)

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

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

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.600 601 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.601

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.600

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

Amount of nitroglycerin reaching the circulation varies directly with the size of application area and amount of ointment applied.b 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).600

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.601 (See Tolerance and Dependence Under Cautions.)

Do not use ointment to treat acute attacks of angina.600

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.1100 Assess need for IV nitroglycerin, if not contraindicated.1100

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.1100

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.812 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.812 Higher dosages generally required when a PVC administration set is used; manufacturer states usual initial dosage is 25 mcg/minute with such administration sets.812 Titrate dosage according to patient's response.812

Continuously monitor BP and heart rate during administration.812

Acute MI
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.527 Dosage will vary considerably among patients; adjust based on individual requirements, BP response, and adverse effects.527 812

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.812 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.812 Higher dosages generally required when a PVC administration set is used; manufacturer states usual initial dosage is 25 mcg/minute with such administration sets.812 Titrate dosage according to patient's response.812

Continuously monitor BP and heart rate during administration.812

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.812 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.812 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.812 Titrate dosage according to patient's response and possible adverse effects.812

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.1200

Always consider the risks of overly aggressive therapy in any hypertensive crisis.542 1200

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment.b

Renal Impairment

No dosage adjustments necessary for renal impairment.809

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.809

Detailed Nitroglycerin dosage information

Cautions for Nitroglycerin

Contraindications

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.809 c

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,262 or nitric oxide donors since severe, potentially fatal hypotensive episodes can occur.260 261 262 263 266 271 272 282 284 285 288

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.260 264 271

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),281 or illicitly.260 281 282

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.260 282

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.804 807 823 Such concomitant use is contraindicated.804 807 823 Time course and dose dependence of this interaction not established; use of these drugs within a few days of one another not recommended.823

Cardiovascular Effects

Severe hypotension, particularly in upright position, can occur even with low nitroglycerin doses, particularly in the elderly.807 809 811

Use with caution in patients who are volume depleted or have preexisting hypotension.807 809 811

Paradoxical bradycardia and angina exacerbation may accompany hypotension.807 809 811

Benefits in acute MI and CHF not established.811 If used in these conditions, careful clinical or hemodynamic monitoring for possible hypotension or tachycardia is recommended.811

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.c

Sensitivity Reactions

Allergic reactions reported rarely.811 Contact dermatitis or fixed drug eruptions reported in patients receiving nitroglycerin ointment or transdermal system.811 Anaphylactoid reaction reported; possibly may occur with any route.811

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.809 c

Carefully individualize nitrate dosage to minimize the risk of tolerance; also consider potential risks of nitrate withdrawal.c

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.601 Consider the possibility of increased frequency or severity of angina during the nitrate-free interval.c

Possible cross-tolerance to sublingual nitroglycerin during long-term nitrate use.c

Nitrate dependence is possible (documented in daily industrial exposures); withdrawal manifestations (e.g., ischemic symptoms, MI, sudden death) can occur.c

Specific Populations

Pregnancy

Sublingual tablets: Category B.809 Sublingual nitroglycerin has been used for the treatment of angina during pregnancy without fetal harm.825

Lingual aerosol, lingual solution, ointment, transdermal system: Category C.600 806 807 811

Extended-release capsules, injection, sublingual powder: Data regarding pregnancy lacking.810 812 823

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.809 823 825 Use during pregnancy only if clearly needed.806 807 809

Lactation

Not known whether nitroglycerin is distributed into milk.809 The low molecular weight of nitroglycerin suggests that some distribution into milk may occur.825 Caution if used in nursing women.809

Pediatric Use

Safety and efficacy not established in pediatric patients.807 809 811

Geriatric Use

Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether they respond different than younger adults.809 811

Severe hypotension, particularly in upright position, can occur even with low nitroglycerin doses, particularly in the elderly.811 Geriatric patients may be more susceptible to hypotension and may be at greater risk of falling.811 Use with caution in geriatric patients who may be volume-depleted, are on multiple medications, or who, for whatever reason, already are hypotensive.811

May aggravate angina caused by hypertrophic cardiomyopathy, particularly in the elderly.807 811

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.809 811

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.807 809 811 c

Drug Interactions

Specific Drugs or Laboratory Tests

Drug or Test

Interaction

Comments

Alcohol

Concomitant use may cause hypotensionc

Use concomitantly with cautionc

Aspirin

High-dose aspirin (1 g) may increase exposure to nitroglycerin and enhance its vasodilatory and hemodynamic effects806 823

Antihypertensive drugs

Possible additive hypotensive effectsc

Dosage adjustment of either the nitrate/nitrite or the other agent with hypotensive activity may be necessary to avoid orthostatic hypotension during concomitant usec

Ergot alkaloids (dihydroergotamine)

Dihydroergotamine may counteract the coronary vasodilatory effect of nitrates303 316

Risk of angina precipitation316 806 807 823

Concomitant use not recommended316 806 807 823

Heparin

Because some,203 204 237 245 247 but not all,246 evidence indicates that IV nitroglycerin may antagonize the anticoagulant effect of heparin when these drugs are administered concomitantly, exercise caution203 204 237 245 247 812

Closely monitor patients receiving heparin and IV nitroglycerin concomitantly (e.g., measure APTT) to avoid inadequate anticoagulation203 204 236 237 245 246 247

If IV nitroglycerin therapy is discontinued in patients receiving heparin, reduction in heparin dosage may be necessary204 263 245 246 247

Nitrites

Observe patients receiving nitrates or nitrites concomitantly for possible additive hypotensive effectsc

Dosage adjustment of either the nitrate/nitrite or the other agent with hypotensive activity may be necessary to avoid orthostatic hypotension during concomitant usec

Phenothiazines

Possible additive hypotensive effectsc

Use concomitantly with caution; may need to adjust dosage to avoid orthostatic hypotension c

Phosphodiesterase (PDE) type 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)

Selective PDE type 5 inhibitors profoundly potentiate the vasodilatory effects (e.g., a >25-mm Hg decrease in SBP) of organic nitrates and nitrites (e.g., nitroglycerin, isosorbide dinitrate), and potentially life-threatening hypotension and/or hemodynamic compromise can result259 260 261 262 263 264 266 271 272 274 275 282 284 285

Combined use is contraindicated259 260 261 262 282 287

Some experts state that coadministration of PDE type 5 inhibitors with long-acting nitrates should be strictly avoided within 24 hours of nitrate administration; nitrates should not be taken for 24 hours after use of sildenafil or 48 hours after tadalafil1101

If a nitrate or nitrite is administered after a PDE inhibitor (e.g., >24 hours after sildenafil use), carefully monitor response to the initial doses and ensure proper facilities for fluid and vasopressor (e.g., α-adrenergic agonists) support are readily available260 289 334

Riociguat

Possible additive hypotensive effect804 807 823

Concomitant use contraindicated804 807 823

Test, Zlatkis-Zak color reaction

Nitrates and nitrites may interfere with the Zlatkis-Zak color reaction causing a false report of decreased serum cholesterolc

Thrombolytic agents

Concomitant administration of tissue-type plasminogen activator (t-PA) and IV nitroglycerin reduces plasma levels of t-PA and its thrombolytic effect806 823

Use concomitantly with caution806
Nitroglycerin drug interactions (more detail)

Nitroglycerin Pharmacokinetics

Absorption

Bioavailability

Absorbed percutaneously through skin and oral mucosa.c

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

Rates of delivery and absorption of nitroglycerin from transdermal systems vary depending on the specific preparation; consult the individual manufacturers’ information.b Preparations usually labeled in terms of the approximate rate of drug delivery per hour.b

Onset and Duration

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

Antianginal Effects

Dosage Form

Onset

Duration

Sublingual

within 2 min

up to 30 min

Topical ointment

30 min

3 h

Oral extended-release

1 h327

up to 12 h327
Hemodynamic Effects

Dosage Form

Onset

Duration

Sublingual

2 min

up to 30 min

Topical ointment

within 1 h

3–6 h

Plasma Concentrations

Following topical application of transdermal system, steady-state plasma concentrations attained by about 2 hours;811 prolonged onset compared with other currently available dosage forms.b

Distribution

Extent

Widely distributed in the body.b

Unknown if nitroglycerin is distributed into milk.807 809 811

Plasma Protein Binding

Nitroglycerin: about 60% bound.b

Elimination

Metabolism

Metabolized to 1,3-glyceryl dinitrate, 1,2-glyceryl dinitrate, and glyceryl mononitrate.811 b

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

Dinitrate metabolites are metabolized further to inactive mononitrates and are metabolized ultimately to glycerol and carbon dioxide.208

Extrahepatic sites of metabolism include red blood cells and vascular walls.208

Half-life

Nitroglycerin: 1–4 minutes.811 b

Stability

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

Storage

Oral

Extended-release Capsules

Store at 25°C (may be exposed to 15–30°C); protect from moisture.810

Dispense in a tight container.810

Sublingual Powder

Store at 20–25°C (may be exposed to 5–40°C).823

Sublingual Tablets

Store in original glass container at 20–25°C.809

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.b

Lingual Aerosol

Store at 25°C (may be exposed to 15–30°C).806

Contains a highly flammable propellant (butane); do not forcefully open container, spray toward a flame, or place into a fire for disposal.806

Lingual Solution in Spray Pump

Store at 25°C (may be exposed to 15–30°C).807

Contains 20% alcohol; do not forcefully open container, spray toward a flame, or place into a fire or incinerator for disposal.807

Topical

Ointment

Tight containers at 20–25°C.600

Advise patients to tightly close multiple-dose containers of nitroglycerin ointment immediately after each use.600

Transdermal System

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

Parenteral

IV Solutions

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

Premixed solution in 5% dextrose injection: 25°C; avoid freezing and excessive heat.812

Compatibility

Parenteral

Consult specialized references and the manufacturers’ labeling for specific stability and compatibility information, including IV containers and administration sets.b

Solution CompatibilityHID

Compatible

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M
Drug Compatibility
Admixture CompatibilityHID

Compatible

Alteplase

Aminophylline

Dobutamine HCl

Dopamine HCl

Enalaprilat

Furosemide

Lidocaine HCl

Verapamil HCl

Incompatible

Hydralazine HCl

Phenytoin sodium

Variable

Bretylium tosylate

Dobutamine HCl with sodium nitroprusside
Y-Site CompatibilityHID

Compatible

Amiodarone HCl

Amphotericin B cholesteryl sulfate complex

Argatroban

Atracurium besylate

Bivalirudin

Dexmedetomidine HCl

Diltiazem HCl

Dobutamine HCl

Dobutamine HCl with dopamine HCl

Dobutamine HCl with lidocaine HCl

Dobutamine HCl with sodium nitroprusside

Dopamine HCl

Dopamine HCl with dobutamine HCl

Dopamine HCl with lidocaine HCl

Dopamine HCl with sodium nitroprusside

Drotrecogin alfa (activated)

Epinephrine HCl

Esmolol HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Fluconazole

Furosemide

Haloperidol lactate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydromorphone HCl

Inamrinone lactate

Labetalol HCl

Lidocaine HCl

Lidocaine HCl with dobutamine HCl

Lidocaine HCl with dopamine HCl

Lidocaine HCl with sodium nitroprusside

Linezolid

Lorazepam

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nicardipine HCl

Norepinephrine bitartrate

Pancuronium bromide

Pantoprazole sodium

Propofol

Ranitidine HCl

Remifentanil HCl

Sodium nitroprusside

Sodium nitroprusside with dobutamine HCl

Sodium nitroprusside with dopamine HCl

Sodium nitroprusside with lidocaine HCl

Tacrolimus

Theophylline

Thiopental sodium

Tirofiban HCl

Vasopressin

Vecuronium bromide

Warfarin sodium

Incompatible

Alteplase

Lansoprazole

Levofloxacin

Variable

Hydralazine HCl

Actions

Advice to Patients

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

Nitroglycerin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Lingual

Aerosol

0.4 mg/spray*

Nitroglycerin Aerosol

NitroMist

Mist

Solution

0.4 mg/spray*

Nitroglycerin Spray

Nitrolingual Pumpspray

Arbor

Oral

Capsules, extended-release

2.5 mg*

Nitroglycerin Capsules ER

Nitro-Time

Time-Cap

6.5 mg*

Nitroglycerin Capsules ER

Nitro-Time

Time-Cap

9 mg*

Nitroglycerin Capsules ER

Nitro-Time

Time-Cap

Parenteral

For injection concentrate, for IV infusion

5 mg/mL (50 mg)

Nitroglycerin Injection

Sublingual

Powder

0.4 mg/packet

GoNitro

Espero

Tablets

0.3 mg*

Nitroglycerin Tablets

Nitrostat

Pfizer

0.4 mg*

Nitroglycerin Tablets

Nitrostat

Pfizer

0.6 mg*

Nitroglycerin 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)*

Minitran

Valeant

Nitro-Dur

Merck

Nitroglycerin Transdermal System

0.2 mg/hour (total nitroglycerin content and transdermal system size may vary by manufacturer)*

Minitran

Valeant

Nitro-Dur

Merck

Nitroglycerin Transdermal System

0.3 mg/hour (60 mg/15 cm2)

Nitro-Dur

Merck

0.4 mg/hour (total nitroglycerin content and transdermal system size may vary by manufacturer)*

Minitran

Valeant

Nitro-Dur

Merck

Nitroglycerin Transdermal System

0.6 mg/hour (total nitroglycerin content and transdermal system size may vary by manufacturer)*

Minitran

Valeant

Nitro-Dur

Merck

Nitroglycerin Transdermal System

0.8 mg/hour (160 mg/40 cm2)

Nitro-Dur

Merck

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

Nitroglycerin in Dextrose

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

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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. http://www.ncbi.nlm.nih.gov/pubmed/577507?dopt=AbstractPlus

102. Whitworth CG, Grant WM. Use of nitrate and nitrite vasodilators by glaucomatous patients. Arch Ophthalmol. 1964; 71:492-6. http://www.ncbi.nlm.nih.gov/pubmed/14109031?dopt=AbstractPlus

103. Zah K. Vliv nitroglyceriner na krevni obeh u sitnici: X pokuane farmakologicka studie. Cesk Ofthalmol. 1957; 13:146-9.

104. Peczon JD, Grant WM, Lambert BW. Systemic vasodilators, intraocular pressure, and chamber depth in glaucoma. Am J Ophthalmol. 1971; 72:74-8. http://www.ncbi.nlm.nih.gov/pubmed/5571214?dopt=AbstractPlus

200. Wyeth Laboratories Inc. Isordil (isosorbide dinitrate) prescribing information. In: Physicians’ desk reference. 54th ed. Montvale NJ: Medical Economics Company Inc; 2000:3260-1.

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. http://www.ncbi.nlm.nih.gov/pubmed/3574424?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3925740?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3107486?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6806492?dopt=AbstractPlus

207. Kuhnen R, Nitsch J, Lüderitz B. Explosion von Nitropflastern bei Defibrillation. Dtsch Med Wochenschr. 1985; 110:37.

208. Marion Laboratories, Inc. Nitro-Bid Plateau CAPS (nitroglycerin) prescribing information. In: Huff BB, ed. Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997(Suppl A):A205-7.

209. Rorer Pharmaceuticals. Nitrospan (nitroglycerin) sustained-release capsules prescribing information. In: Huff BB, ed. Physicians’ desk reference. 42nd ed. Oradell, NJ: Medical Economics Company Inc; 1988:1807.

210. Summit Pharmaceuticals. Transderm-Nitro (nitroglycerin) transdermal prescribing information. Summit, NJ; 1996 May.

211. Geneva Generics. Nitroglycerin S.R. capsules prescribing information. Broomfield, CO; 1982 Aug.

212. Robertson D, Stevens RM. Nitrates and glaucoma. JAMA. 1977; 237:117. http://www.ncbi.nlm.nih.gov/pubmed/576138?dopt=AbstractPlus

213. Wizemann AJS, Wizemann V. Organic nitrate therapy in glaucoma. Am J Ophthalmol. 1980; 90:106-9. http://www.ncbi.nlm.nih.gov/pubmed/6772033?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/4248312?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3139326?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2896919?dopt=AbstractPlus

219. Sreebny LM, Valdini A. Xerostomia: a neglected symptom. Arch Intern Med. 1987; 147:1333-7. http://www.ncbi.nlm.nih.gov/pubmed/3300589?dopt=AbstractPlus

220. Rasler FE. Ineffectiveness of sublingual nitroglycerin in patients with dry mucous membranes. N Engl J Med. 1986; 314:181. http://www.ncbi.nlm.nih.gov/pubmed/3079881?dopt=AbstractPlus

221. Straehl P, Galeazzi RL. Isosorbide dinitrate bioavailability, kinetics, and metabolism. Clin Pharmacol Ther. 1985; 38:140-9. http://www.ncbi.nlm.nih.gov/pubmed/4017416?dopt=AbstractPlus

222. Thadani U, Whitsett T. Relationship of pharmacokinetic and pharmacodynamic properties of organic nitrates. Clin Pharmacokinet. 1988; 15:32-43. http://www.ncbi.nlm.nih.gov/pubmed/3135973?dopt=AbstractPlus

223. Bogaert MG. Clinical pharmacokinetics of organic nitrates. Clin Pharmacokinet. 1983; 8:410-21. http://www.ncbi.nlm.nih.gov/pubmed/6414751?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2681004?dopt=AbstractPlus

228. Fung HL. Pharmacokinetics and pharmacodynamics of isosorbide dinitrate. Am Heart J. 1985; 110(1 Part 2):213-6. http://www.ncbi.nlm.nih.gov/pubmed/4013997?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/4005392?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6642789?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6851405?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1976063?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3987768?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8422206?dopt=AbstractPlus

235. Warner Lambert. Nitrostat (nitroglycerin) tablets prescribing information. In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:1981-2.

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. http://www.cardiosource.org/Science-And-Quality/Practice-Guidelines-and-Quality-Standards.aspx

237. Baxter Healthcare. Nitroglycerin in 5% dextrose injection prescribing information. Deerfield, IL; 1995 Jun.

238. 3M Pharmaceuticals. Minitran (nitroglycerin) transdermal delivery system prescribing information. Northridge, CA; 1995 Mar.

240. Come PC, Pitt B. Nitroglycerin-induced severe hypotension and bradycardia in patients with acute myocardial infarction. Circulation. 1976; 54:624-8. http://www.ncbi.nlm.nih.gov/pubmed/822962?dopt=AbstractPlus

241. Kinch JW, Ryan TJ. Right ventricular infarction. N Engl J Med. 1994; 330:1211-7. http://www.ncbi.nlm.nih.gov/pubmed/8139631?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6780232?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7910229?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2112878?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2121114?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1482804?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3925741?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6783307?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6794931?dopt=AbstractPlus

254. Needleman P, Jakschik B, Johnson EM Jr. Sulfhydryl requirement for relaxation of vascular smooth muscle. J Pharmacol Exp Ther. 1973; 187:324-31. http://www.ncbi.nlm.nih.gov/pubmed/4201275?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3520315?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2057035?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10073779?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9916601?dopt=AbstractPlus

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]. http://www.fda.gov

267. Aldridge J, Measham F. Sildenafil (Viagra) is used as a recreational drug in England. BMJ. 1999; 318:669. http://www.ncbi.nlm.nih.gov/pubmed/10066221?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1115104&blobtype=pdf

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]. https://www.vitality3.net)

270. Anon. Viagra. From the 4nRx Web Site. https://www.4nrx.com)

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. http://www.fda.gov

272. Kloner RA. Erectile dysfunction and sildenafil citrate and cardiologists. Am J Cardiol. 1999; 83:576-82. http://www.ncbi.nlm.nih.gov/pubmed/10073864?dopt=AbstractPlus

273. Pfizer, New York, NY. Personal communication on sildenafil.

274. Steers WD. Viagra-after one year. Urology. 1999; 54:12-7. http://www.ncbi.nlm.nih.gov/pubmed/10414719?dopt=AbstractPlus

275. Langtry HD, Markham A. Sildenafil: a review of its use in erectile dysfunction. Drugs. 1999; 57:967-89. http://www.ncbi.nlm.nih.gov/pubmed/10400408?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8987969?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10536133?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10422958?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9580646?dopt=AbstractPlus

285. Anon. Sildenafil: an oral drug for impotence. Med Lett Drugs Ther. 1998; 40:51-52. http://www.ncbi.nlm.nih.gov/pubmed/9599594?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10404845?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10348610?dopt=AbstractPlus

290. Wyeth-Ayerst. Ismo (isosorbide mononitrate) tablets prescribing information. In: Physicians’ desk reference. 54th ed. Montvale, NJ: Medical Economics Company Inc; 2000:3258-60.

291. Schwarz. Monoket (isosorbide mononitrate) tablets prescribing information (dated 1999 Jul). Milwaukee, WI; 1999 Jul.

292. Key Pharmaceuticals. Imdur (isosorbide mononitrate) extended-release tablets prescribing information (dated 1998 Sept). In: Physicians’ desk reference. 54th ed. Montvale, NJ: Medical Economics Company Inc; 2000:1467-9.

293. USP DI: drug information for the health care provider. Johnson KW, ed. 20th ed. Englewood, CO: Micromedex, Inc; 2000:2269-70.

294. Parfitt K, ed. Martindale: the complete drug reference. 32nd ed. London, UK: The Pharmaceutical Press; 1999:893-4.

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. http://www.ncbi.nlm.nih.gov/pubmed/3113910?dopt=AbstractPlus

297. Jonsson UE. Various administration forms of nitrates and their possibilities. Drugs. 1987; 33(Suppl 4):23-31. http://www.ncbi.nlm.nih.gov/pubmed/3304960?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10188765?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6529537?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1463671&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/7751425?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3360048?dopt=AbstractPlus

302. Wyeth-Ayerst. Isordil Titradose (isosorbide dinitrate) tablets prescribing information. In: Physicians’ desk reference. 54th ed. Montvale, NJ: Medical Economics Company Inc; 2000:3261-2.

303. Kirsten R, Nelson K, Kirsten D et al. Clinical pharmacokinetics of vasodilators: part II. Clin Pharmacokinet. 1998; 35:9-36. http://www.ncbi.nlm.nih.gov/pubmed/9673832?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2354713?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10499557?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8806342?dopt=AbstractPlus

307. Jonsson UE. Development of long-acting nitrate delivery systems. Eur J Clin Pharmacol. 1990; 38(Suppl 1):S15-9. http://www.ncbi.nlm.nih.gov/pubmed/2113000?dopt=AbstractPlus

308. Key Pharmaceuticals, Kenilworth, NJ. Personal communication on Imdur.

309. Prakash A, Markham A. Long-acting isosorbide mononitrate. Drugs. 1999; 57:93-9. http://www.ncbi.nlm.nih.gov/pubmed/9951954?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7957516?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6733004?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1463459&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/6364805?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/10664923?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3622599?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7729327?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2661197?dopt=AbstractPlus

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.

327. Eon Laboratories. Nitroglycerin slowcaps (nitroglycerin sustained-release) capsules prescribing information. Laurelton, NY; 2000 Mar.

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. http://www.ncbi.nlm.nih.gov/pubmed/8422206?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/15533851?dopt=AbstractPlus

338. Anon. BiDil for heart failure. Med Lett Drugs Ther. 2005; 47:77-8. http://www.ncbi.nlm.nih.gov/pubmed/16186789?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/23817082?dopt=AbstractPlus

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. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3695607&blobtype=pdf

542. Marik PE, Varon J. Hypertensive crises: challenges and management. Chest. 2007; 131:1949-62. http://www.ncbi.nlm.nih.gov/pubmed/17565029?dopt=AbstractPlus

600. Fougera. Nitro-Bid (nitroglycerin 2%) ointment prescribing information. Melville, NY; 2011 Sep

601. Thadani U. Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance. Am J Cardiovasc Drugs. 2014; 14:287-301. http://www.ncbi.nlm.nih.gov/pubmed/24664980?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/22528319?dopt=AbstractPlus

696. Vanden Hoek TL, Morrison LJ, Shuster M et al. Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010; 122(18 Suppl 3):S829-61.

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; :. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4946749&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/26992459?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/24902977?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4083844&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/26316714?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4548722&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/20061507?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/27502078?dopt=AbstractPlus

806. Mist Pharmaceuticals. NitroMist (nitroglycerin) lingual aerosol prescribing information. Cranford, NJ; 2016 Jun.

807. Arbor Pharmaceuticals. Nitrolingual Pumpspray (nitroglycerin) lingual spray prescribing information. Atlanta, GA; 2015 Jan.

808. Anderson JL, Morrow DA. Acute Myocardial Infarction. N Engl J Med. 2017; 376:2053-2064. http://www.ncbi.nlm.nih.gov/pubmed/28538121?dopt=AbstractPlus

809. Pfizer. NitroStat (nitroglycerin) sublingual tablet prescribing information. New York, NY; 2017 Jan.

810. AvKARE, Inc. Nitroglycerin ER capsule prescribing information. Pulaski, TN; 2016 Jan.

811. Valeant Pharmaceuticals. Minitran (nitroglycerin) transdermal infusion system prescribing information. Bridgewater, NJ; 2014 Dec.

812. Baxter. Nitroglycerin in 5% dextrose injection prescribing information. Deerfield, IL; 2016 Aug.

813. James Alexander Corporation. Amyl nitrite inhalant prescribing information. Blairstown, NJ; 2010 Jul.

814. Par Pharmaceutical. Isosorbide dinitrate tablet prescribing information. Chestnut Ridge, NY; 2016 Feb.

815. Lannett Company Inc. Isosorbide mononitrate tablet prescribing information. Philadelphia, PA; 2016 Oct.

816. Mallinckrodt Pharmaceuticals. Nitric oxide gas prescribing information. Port Allen, LA; 2016 Feb.

817. . Sublingual nitroglycerin powder (GoNitro). Med Lett Drugs Ther. 2016; 58:156-157. http://www.ncbi.nlm.nih.gov/pubmed/27906151?dopt=AbstractPlus

823. Espero Pharmaceuticals. GoNitro (nitroglycerin) sublingual powder prescribing information. Jacksonville, FL; 2016 Jun.

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. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4676081&blobtype=pdf

1101. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.

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. http://www.ncbi.nlm.nih.gov/pubmed/29133356?dopt=AbstractPlus

b. AHFS drug information 2019. McEvoy GK, ed. Nitroglycerin. Bethesda, MD: American Society of Health-System Pharmacists; 2018.

c. AHFS drug information 201. McEvoy GK, ed. Nitrates and Nitrites General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2018.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1217-29.

Frequently asked questions

Medical Disclaimer