Nitroglycerin (Systemic) Monograph for Professionals - Drugs.com

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# Nitroglycerin (Systemic)

Brand names: GoNitro, Minitran, Nitro-Bid, Nitro-Dur, Nitrolingual, ... show all 8 brands NitroMist, Nitrostat, Nitro-Time
Drug class: Nitrates and Nitrites
VA class: CV250
Chemical name: Trinitrate 1,2,3-propanetriol
Molecular formula: C3H5N3O9
CAS number: 55-63-0

Medically reviewed by Drugs.com on Mar 3, 2022. Written by ASHP.

### Warning

Special Alerts:

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 (Systemic)

### Chronic Stable Angina

Management of angina pectoris secondary to CAD.

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

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.

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

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.

### 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).

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. Topical or oral nitrates may be an acceptable alternative to IV therapy in patients who do not have refractory or recurrent ischemia.

### Acute MI

Management of patients with acute MI.

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.

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

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

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

### 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.

### Heart Failure and Low-output Syndromes

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

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

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

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

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

### 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.

## Related/similar drugs

amlodipine, aspirin, lisinopril, metoprolol, losartan, furosemide, carvedilol

## Nitroglycerin (Systemic) Dosage and Administration

### General

#### Hypertensive Emergency

- Adults with a compelling indication—severe preeclampsia or eclampsia or pheochromocytoma crisis: Reduce SBP to <140 mm Hg during the first hour.

- Adults with a compelling indication—acute aortic dissection: Reduce SBP to <120 mm Hg within the first 20 minutes.

- Initial goal of IV therapy in adults without a compelling indication is to reduce SBP by ≤25% within the first hour, followed by further reduction if stable to 160/110 or 160/100 mm Hg within the next 2–6 hours, avoiding excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia. If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal BP in the next 24–48 hours.

### Administration

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

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

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

#### Lingual Administration

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

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

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.

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. To release a spray, press valve head with the forefinger. Spray lingual aerosol or solution onto or under tongue and immediately close mouth; do not inhale spray.

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

#### Sublingual Administration

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

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

#### Topical Administration (Transdermal System)

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

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

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

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

#### Topical Administration (Ointment)

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

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. Tape applicator into place on skin.

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

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

#### IV Administration

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

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

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. 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.

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

Do not admix with other drugs.

##### Dilution

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

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

### Dosage

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

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

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

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

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

#### Adults

##### 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.

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

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

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

Sublingual

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

Sublingual powder: 1 or 2 packets (0.4 or 0.8 mg, respectively) at the onset of an attack. 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. If pain persists after a total of 3 packets within a 15-minute period, seek prompt medical attention.

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.

###### 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.

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

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

Topical (Transdermal System)

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

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

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

Topical (Ointment)

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

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

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

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

To minimize the occurrence of tolerance to the effects of nitroglycerin, a nitrate-free interval of 10–14 hours has been recommended; however, the minimum nitrate-free interval necessary has not been determined. (See Tolerance and Dependence Under Cautions.)

Do not use ointment to treat acute attacks of angina.

##### NSTE ACS

###### Sublingual, then IV (if necessary)

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

###### IV

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

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

Continuously monitor BP and heart rate during administration.

##### 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. Dosage will vary considerably among patients; adjust based on individual requirements, BP response, and adverse effects.

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

Continuously monitor BP and heart rate during administration.

##### Hypertension

###### Perioperative Hypertension or Induction of Intraoperative Hypotension

IV

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

###### Hypertensive Emergency† [off-label]

IV

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

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

### Special Populations

#### Hepatic Impairment

No specific dosage recommendations for hepatic impairment.

#### Renal Impairment

No dosage adjustments necessary for renal impairment.

#### Geriatric Patients

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

Detailed Nitroglycerin dosage information

## Cautions for Nitroglycerin (Systemic)

### Contraindications

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

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

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

  Use of extended-release oral nitrate preparations in patients with functional or organic GI hypermotility or malabsorption syndrome.

- Concomitant use of selective phosphodiesterase (PDE) inhibitors (e.g., sildenafil, tadalafil, vardenafil). (See Selective Phosphodiesterase (PDE) Inhibitors under Cautions)

- Concomitant use of soluble guanylate cyclase (sGC) stimulators (e.g., riociguat). (See Concomitant Use with sGC Stimulators under Cautions.)

### Warnings/Precautions

#### Warnings

##### Concomitant Use with Selective Phosphodiesterase (PDE) Inhibitors

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

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

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

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

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

##### Concomitant Use with sGC Stimulators

Concomitant use of nitrates (e.g., nitroglycerin) or nitrites (e.g., amyl nitrite) with a sGC stimulator (e.g., riociguat) can cause additive hypotensive effects. Such concomitant use is contraindicated. Time course and dose dependence of this interaction not established; use of these drugs within a few days of one another not recommended.

##### Cardiovascular Effects

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

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

Paradoxical bradycardia and angina exacerbation may accompany hypotension.

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

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

#### Sensitivity Reactions

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

#### General Precautions

##### Tolerance and Dependence

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

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

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

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

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

#### Specific Populations

##### Pregnancy

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

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

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

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

##### Lactation

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

##### Pediatric Use

Safety and efficacy not established in pediatric patients.

##### Geriatric Use

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

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

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

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

### Common Adverse Effects

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

## Interactions for Nitroglycerin (Systemic)

### Specific Drugs or Laboratory Tests

Drug or Test | Interaction | Comments
--- | --- | ---
Alcohol | Concomitant use may cause hypotension | Use concomitantly with caution
Aspirin | High-dose aspirin (1 g) may increase exposure to nitroglycerin and enhance its vasodilatory and hemodynamic effects |
Antihypertensive drugs | Possible additive hypotensive effects | Dosage adjustment of either the nitrate/nitrite or the other agent with hypotensive activity may be necessary to avoid orthostatic hypotension during concomitant use
Ergot alkaloids (dihydroergotamine) | Dihydroergotamine may counteract the coronary vasodilatory effect of nitrates Risk of angina precipitation | Concomitant use not recommended
Heparin | Because some, but not all, evidence indicates that IV nitroglycerin may antagonize the anticoagulant effect of heparin when these drugs are administered concomitantly, exercise caution | Closely monitor patients receiving heparin and IV nitroglycerin concomitantly (e.g., measure APTT) to avoid inadequate anticoagulation If IV nitroglycerin therapy is discontinued in patients receiving heparin, reduction in heparin dosage may be necessary
Nitrites | Observe patients receiving nitrates or nitrites concomitantly for possible additive hypotensive effects | Dosage adjustment of either the nitrate/nitrite or the other agent with hypotensive activity may be necessary to avoid orthostatic hypotension during concomitant use
Phenothiazines | Possible additive hypotensive effects | Use concomitantly with caution; may need to adjust dosage to avoid orthostatic hypotension

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 result

Combined use is contraindicated

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 tadalafil

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 available

Riociguat | Possible additive hypotensive effect | Concomitant use contraindicated
Test, Zlatkis-Zak color reaction | Nitrates and nitrites may interfere with the Zlatkis-Zak color reaction causing a false report of decreased serum cholesterol |
Thrombolytic agents | Concomitant administration of tissue-type plasminogen activator (t-PA) and IV nitroglycerin reduces plasma levels of t-PA and its thrombolytic effect | Use concomitantly with caution

Nitroglycerin drug interactions (more detail)

## Nitroglycerin (Systemic) Pharmacokinetics

### Absorption

#### Bioavailability

Absorbed percutaneously through skin and oral mucosa.

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

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

#### Onset and Duration

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

Antianginal Effects
Dosage Form | Onset | Duration
--- | --- | ---
Sublingual | within 2 min | up to 30 min
Topical ointment | 30 min | 3 h
Oral extended-release | 1 h | up to 12 h

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; prolonged onset compared with other currently available dosage forms.

### Distribution

#### Extent

Widely distributed in the body.

Unknown if nitroglycerin is distributed into milk.

#### Plasma Protein Binding

Nitroglycerin: about 60% bound.

### Elimination

#### Metabolism

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

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

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

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

#### Half-life

Nitroglycerin: 1–4 minutes.

## Stability

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

### Storage

#### Oral

##### Extended-release Capsules

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

Dispense in a tight container.

##### Sublingual Powder

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

##### Sublingual Tablets

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

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

##### Lingual Aerosol

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

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

##### Lingual Solution in Spray Pump

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

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

#### Topical

##### Ointment

Tight containers at 20–25°C.

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

##### Transdermal System

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

#### Parenteral

##### IV Solutions

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

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

### Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

#### Parenteral

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

##### 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

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

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

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

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

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

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

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

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

## Advice to Patients

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

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

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

- Importance of instructing patients to discard cotton from tablet bottle once the original container is opened.

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

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

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

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

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

- Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

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

- Importance of informing patients of other important precautionary information. (See Cautions.)

## 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 2023, Selected Revisions March 3, 2022. 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.

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## Frequently asked questions

- What is the shelf life of nitroglycerin tablets?
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