Nitroglycerin (Monograph)
Brand names: GoNitro, Minitran, Nitro-Bid, Nitro-Dur, Nitrolingual,
... show all 8 brands
Drug class: beta-Adrenergic Blocking Agents
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
Related/similar drugs
amlodipine, lisinopril, metoprolol, losartan, aspirin, furosemide, carvedilol
Nitroglycerin 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.1200
-
Adults with a compelling indication—acute aortic dissection: Reduce SBP to <120 mm Hg within the first 20 minutes.1200
-
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.1200 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.1200
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
Lingual1 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
SublingualSublingual 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
OralExtended-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
IVInitially, 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]
IVInitially, 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
Cautions for Nitroglycerin
Contraindications
-
Known hypersensitivity to nitroglycerin, other nitrates or nitrites, or any ingredient in the formulation.806 807 809
-
Use of topical nitroglycerin (transdermal system) in those allergic to adhesives used in the system.811
-
Use of sublingual nitroglycerin tablets in patients with early MI, severe anemia, or increased intracranial pressure.809
Use of extended-release oral nitrate preparations in patients with functional or organic GI hypermotility or malabsorption syndrome.c
-
Concomitant use of selective phosphodiesterase (PDE) inhibitors (e.g., sildenafil, tadalafil, vardenafil).809 c (See Selective Phosphodiesterase (PDE) Inhibitors under Cautions)
-
Concomitant use of soluble guanylate cyclase (sGC) stimulators (e.g., riociguat).806 807 823 (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.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 |
|
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 |
||
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 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
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 |
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
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 |
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.c
-
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.c
-
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.c
-
By decreasing myocardial oxygen consumption, nitrates and nitrites alter the imbalance of myocardial oxygen supply and consumption which is thought to cause angina pectoris.236 250
-
Because of hemodynamic profile, nitrates and nitrites are particularly beneficial in patients with left ventricular systolic dysfunction or CHF.236 250
-
Both direct vasodilatory effects on the coronary bed and drug-induced prevention of episodic coronary artery vasoconstriction increase total coronary blood flow.236
-
After therapeutic doses, cardiac output may increase transiently and then decrease.c
-
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.c
Advice to Patients
-
Advise patients of the likelihood of headache, particularly with initial nitrate therapy.c
-
Advise patients to take nitrates as directed, particularly since tolerance can occur.c
-
Advise patients to tightly close multiple-dose containers of nitroglycerin ointment immediately after each use.b
-
Importance of instructing patients to discard cotton from tablet bottle once the original container is opened.b
-
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.b
-
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,527 817 1100 1101 because inability to relieve chest pain may indicate acute MI.c
-
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.260 264 271
-
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),281 or illicitly.260 281 282
-
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.260 282
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.809
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.809
-
Importance of informing patients of other important precautionary information.809 (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
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
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
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