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.

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

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 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

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.

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.

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

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]

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.

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.

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

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 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

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.

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.

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

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]

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.

Specific Drugs or Laboratory Tests