Note: Safety: Contraindicated in patients taking a phosphodiesterase 5 (PDE5) inhibitor for any indication or a soluble guanylate cyclase inhibitor (eg, riociguat) due to potentially severe hypotension. In general, if a patient who has taken a PDE5 inhibitor for erectile dysfunction develops chest pain, delay nitrate therapy for ≥12 hours after taking avanafil, ≥24 hours after taking sildenafil or vardenafil, and ≥48 hours after taking tadalafil (Khera 2020; Stendra [avanafil] prescribing information). Consult drug interactions database for more information. In addition, avoid or use with caution in patients likely to develop hypotension or in whom hypotension could result in serious decompensation, including those with hypertrophic cardiomyopathy, severe aortic stenosis, or right ventricular infarction.
Acute decompensated heart failure (adjunctive therapy): 
Note: Consider in patients with volume overload and without symptomatic hypotension to help relieve dyspnea when response to IV diuretics is not adequate (ACCF/AHA [Yancy 2013]).
Continuous IV infusion: Initial: 5 to 10 mcg/minute; titrate as needed based on response and tolerability in increments of 5 to 10 mcg/minute every 3 to 5 minutes up to a maximum of 200 mcg/minute. Lower doses produce venous dilation; however, arterial vasodilation may occur at high doses (Colucci 2020; Coons 2011; Mebazaa 2016). Tachyphylaxis develops within 24 to 48 hours of continuous administration. Hemodynamic control after this initial period can be maintained by transitioning to long-term oral therapy for heart failure (Colucci 2020).
Anal fissure (alternative agent):
Note: Administer topically as a local vasodilator in conjunction with supportive measures. A 0.2% ointment is not commercially available and must be prepared by a licensed compounding facility (Bleday 2020).
Peri-anal 0.2% or 0.4% ointment: After cleansing, apply around fissure(s) twice daily as directed for 4 weeks; if symptoms persist, continue treatment for another 4 weeks for a total duration of 8 weeks (Bacher 1997; Bleday 2020; Kennedy 1999; Lund 1997; Zuberi 2000).
Angina: 
Note: Recommended for acute angina. For prevention of recurrent angina, may use in combination with other anti-anginal therapy (eg, a beta-blocker) (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).
Acute angina: 
Note: If pain is not relieved or worsens 3 to 5 minutes after 1 sublingual or translingual dose, seek immediate emergency medical attention (eg, call 911) (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).
Sublingual powder (0.4 mg/packet): Initial: 1 or 2 packets at onset; repeat every 5 minutes if angina persists; may administer up to 3 packets in a 15-minute period (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).
Sublingual tablet: Initial: 0.3 or 0.4 mg at onset; repeat every 5 minutes if angina persists; may administer up to 3 tablets in a 15-minute period (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]). For patients with refractory angina in the emergency department, up to 0.6 mg as a single dose may be considered (Reeder 2020).
Translingual 0.4 mg/spray: Initial: 1 or 2 sprays at onset; repeat every 5 minutes if angina persists; may administer up to 3 sprays in a 15-minute period (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).
Continuous IV infusion:
Note: Consider IV therapy if angina is not relieved with other dosage forms. Avoid in patients with hypotension (eg, systolic BP <90 mm Hg or >30 mm Hg below baseline), marked bradycardia (eg, <50 beats per minute) or tachycardia (eg, >100 beats per minute), and/or suspected right ventricular infarction (ACCF/AHA [O'Gara 2013]; Reeder 2020).
Initial: 5 to 10 mcg/minute with continuous cardiac monitoring; titrate as needed to relieve angina symptoms in increments of 5 mcg/minute every 5 to 10 minutes up to 20 mcg/minute; if angina persists at a dose of 20 mcg/minute, may increase by 10 to 20 mcg/minute every 3 to 5 minutes to a maximum dose of 400 mcg/minute (ACCF/AHA [O'Gara 2013]; Reeder 2020; manufacturer's labeling). Tachyphylaxis develops within 24 to 48 hours of continuous nitrate administration.
Prevention of angina (adjunctive therapy):
Sublingual powder (0.4 mg/packet): Initial: 1 packet 5 to 10 minutes prior to activities that may provoke angina.
Sublingual tablet: Initial: 0.3 or 0.4 mg 5 to 10 minutes prior to activities that may provoke angina.
Translingual 0.4 mg/spray: Initial: 1 or 2 sprays 5 to 10 minutes prior to activities that may provoke angina.
Topical 2% ointment: Initial: Apply ½ inch upon rising and apply another ½ inch 6 hours later; if necessary, the dose may be doubled to 1 inch and subsequently doubled again to 2 inches if response is inadequate. Recommended maximum frequency of administration is 2 doses/day. Include a nitrate-free interval of ~10 to 12 hours each day to minimize the risk of tolerance.
Topical patch, transdermal: Initial: 0.2 to 0.4 mg/hour; increase dose as needed based on response and tolerability to a maximum of 0.8 mg/hour. Use a patch-on period of 12 to 14 hours/day and patch-off period (nitrate-free interval) of 10 to 12 hours/day to minimize the risk of tolerance. Alternatively, some experts recommend applying patch 30 to 45 minutes prior to activities that may provoke angina and removing patch after activity is complete (Chaudhary 2020).
ER capsule, oral: Initial: 2.5 to 6.5 mg 3 to 4 times daily; increase dose as needed based on response and tolerability to 26 mg 4 times daily. Include a nitrate-free interval of ~10 to 12 hours each day to minimize the risk of tolerance.
Extravasation management, sympathomimetic vasopressors (alternative agent) (off-label use):
Note: Nitroglycerin is an alternative if phentolamine is not available (Reynolds 2014).
Topical 2% ointment: Apply a 1-inch strip to site of ischemia; may repeat every 8 hours if needed (Reynolds 2014).
Hypertension, perioperative (alternative agent):
Note: For patients with chronic hypertension prior to surgery, restart oral therapies as soon as appropriate once hemodynamically stable. Address underlying causes (eg, pain, agitation, withdrawal, hypervolemia) prior to initiating antihypertensive therapy. Generally used for patients with hypervolemia who are not responsive to IV diuretic therapy, particularly if there is known or suspected ischemic heart disease or heart failure (Broussard 2020; London 2020).
Continuous IV infusion: Initial: 5 to 10 mcg/minute; increase based on BP response and tolerability in increments of 5 mcg/minute every 3 to 5 minutes up to 20 mcg/minute; if no response at a dose of 20 mcg/minute, may increase by 10 to 20 mcg/minute every 3 to 5 minutes to a maximum dose of 200 mcg/minute. Lower doses primarily produce venous dilation; however, arterial vasodilation may occur at high doses (Broussard 2020; London 2020; manufacturer's labeling). Tachyphylaxis develops within 24 to 48 hours of continuous nitrate administration; if vasodilator requirements continue longer than 24 to 48 hours, transition to an alternative IV or oral vasodilator.
Hypertensive emergency (alternative agent) (off-label use):
Note: Limitations of use include variable efficacy compared to other agents (eg, inconsistent and transient BP response), possible reflex tachycardia, and possible reduced cardiac output. May be used as adjunctive therapy for patients with acute coronary syndrome or acute pulmonary edema. In general, goal of therapy is to reduce mean arterial pressure ~10% to 20% over the first hour, then 5% to 15% further over the next 23 hours, unless there is a compelling indication (eg, acute aortic dissection, severe preeclampsia, eclampsia) for more rapid BP and heart rate control (ACC/AHA [Whelton 2018]; Elliot 2020a; Marik 2011).
Continuous IV infusion: Initial: 5 mcg/minute; increase based on BP response and tolerability in increments of 5 mcg/minute every 3 to 5 minutes up to 20 mcg/minute; if no response at a dose of 20 mcg/minute, may increase by 10 to 20 mcg/minute every 3 to 5 minutes to a maximum dose of 200 mcg/minute. Lower doses produce venous dilation; however, arterial vasodilation may occur at high doses (ACC/AHA [Whelton 2018]; Elliot 2020b; Marik 2011). Tachyphylaxis develops within 24 to 48 hours of continuous nitrate administration; if vasodilator requirements continue longer than 24 to 48 hours, transition to an alternative IV or oral vasodilator.
Uterine relaxation (off-label use):
Note: May be used for obstetric emergencies (eg, uterine inversion, difficult fetal extraction due to uterine contraction, internal podalic version of a second twin) or to facilitate extraction of a trapped placenta, external cephalic version, or replacement of deeply prolapsed fetal membranes before placement of a cerclage (Hofmeyr 2020; Macones 2020; Weeks 2020). Dosing provided is an example and may vary based on indication.
IV: 50 mcg once; may repeat at 1-minute intervals as needed to sufficiently relax the uterus; maximum total dose: 250 mcg (Altabef 1992; Bayhi 1992; Chedraui 2003; Dayan 1996; Hofmeyr 2020; Macones 2020; Weeks 2020). If urgent uterine relaxation is required (eg, for fetal extraction), may use initial bolus of 100 to 200 mcg (Axemo 1998).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
 Detailed Nitroglycerin dosage information
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Nitronal IV solution has been discontinued in the US for more than 1 year.
Note: Continuous IV infusion dosing units vary by age (mcg/kg/minute or mcg/minute); extra precautions should be taken. Tolerance to the hemodynamic and antianginal effects can develop within 24 to 48 hours of continuous use. Nitrate-free interval (10 to 12 hours/day) is recommended to avoid tolerance development; gradually decrease dose in patients receiving nitroglycerin for prolonged periods to avoid withdrawal reaction.
Heart failure; cardiogenic shock: Limited data available:
Infants and Children: Continuous IV infusion: Initial: 0.25 to 0.5 mcg/kg/minute; titrate by 1 mcg/kg/minute every 15 to 20 minutes as needed; faster titration may be necessary in some patients; in adolescents, titration every 3 to 5 minutes has been suggested; usual dose range: 1 to 5 mcg/kg/minute; usual maximum dose: 10 mcg/kg/minute (AHA [Chameides 2011]; Artman 1987; Ilbawi 1985; Park 2014); doses up to 20 mcg/kg/minute may be used (Friedman 1985)
Adolescents: Continuous IV infusion: Initial: 5 to 10 mcg/minute; titrate every 3 to 5 minutes as needed to maximum rate of 200 mcg/minute (AHA [Chameides 2011]; Park 2014)
Extravasation (sympathomimetic vasopressors), treatment (alternative to phentolamine): Very limited data available; dosing based on experience in neonatal patients; optimal dosing has not been established: Infants, Children, and Adolescents: Topical: 2% ointment: 4 mm/kg applied as a thin ribbon to the affected areas; after 8 hours if no improvement, the dose may be repeated at the affected site (Wong 1992). The maximum reported dose is application of a 1-inch strip to the affected site in a neonate (Denkler 1989); however, this is greater than the usual initial adult dose (1/2 inch) for angina; hypotension may occur; carefully monitor blood pressure (Reynolds 2014). Note: Minimal data available from clinical trials/case reports; however, use has been described in reviews of extravasation treatment (Reynolds 2014; Treadwell 2012).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Reconstitution
Vials: Dilute in D5W or NS; maximum concentration not to exceed 400 mcg/mL; prepare in glass bottles, EXCEL, or PAB containers (adsorption occurs to soft plastic (eg, PVC). Also available in premixed glass containers.
Administration
IV: Prepare in glass bottles, EXCEL or PAB containers. Adsorption occurs to soft plastic (eg, PVC); use administration sets intended for nitroglycerin. Avoid in-line IV filters that adsorb nitroglycerin. Administer via infusion pump.
Intra-anal ointment: Using a finger covering (eg, plastic wrap, surgical glove, finger cot), place finger beside 1 inch measuring guide on the box and squeeze ointment the length of the measuring line directly onto covered finger. Insert ointment into the anal canal using the covered finger up to first finger joint (do not insert further than the first finger joint) and apply ointment around the side of the anal canal. If intra-anal application is too painful, may apply the ointment to the outside of the anus. Wash hands following application.
ER capsule: Swallow whole. Do not chew, break, or crush. Administer with a full glass of water.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Topical ointment and transdermal formulations are available. If safety and efficacy of nitroglycerin can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of ointment, transdermal, or alternative therapy should be considered in high-risk patients.
Sublingual powder: Empty the contents of packet under the tongue, close mouth, and breathe normally. Allow powder to dissolve without swallowing. Do not rinse or spit for 5 minutes after dosing.
Sublingual tablet: Do not chew, crush, or swallow sublingual tablet. Place under tongue and allow to dissolve. Alternately, may be placed in the buccal pouch. May take small sip of water prior to placing tablet under the tongue to aid dissolution.
Topical ointment: Wash hands prior to and after use. Application site should be clean, dry, and hair free. Apply to chest or back with the applicator or dose-measuring paper. Spread in a thin layer over a 2.25 x 3.5 inch area. Do not rub into skin. Tape applicator into place.
Extravasation management, sympathomimetic vasopressors (alternative agent) (off-label use): Stop vesicant infusion immediately and disconnect IV line (leave needle/cannula in place); gently aspirate extravasated solution from the IV line (do NOT flush the line); remove needle/cannula; elevate extremity. Apply nitroglycerin ointment as a thin ribbon to site of ischemia (Reynolds 2014; Wong 1992). May also apply dry warm compresses (Hurst 2004; Reynolds 2014).
Topical patch, transdermal: Application site should be clean, dry, and hair free. Remove patch after 12 to 14 hours. Rotate patch sites. Dispose of any used of unused patches by folding adhesive ends together, replace in pouch or sealed container and discard properly in trash, away from children and pets.
Translingual spray: Do not shake container. Prior to initial use, the pump must be primed by spraying 5 times (Nitrolingual) or 10 times (Nitromist) into the air. Priming sprays should be directed away from patient and others. Release spray onto or under tongue. Close mouth immediately after administration; do not inhale spray. Do not expectorate or rinse the mouth for 5 to 10 minutes following administration. Content of the container should be checked periodically; when the container is held upright, the end of the pump should be covered by the fluid in the bottle or the remaining sprays will not deliver the intended dose. If pump is unused for 6 weeks, a single priming spray (Nitrolingual) or 2 priming sprays (Nitromist) should be completed. If pump is unused for 3 months, re-prime with up to 5 sprays (Nitrolingual).
