Additional contraindications for I.V. product: Hypotension; uncorrected hypovolemia; inadequate cerebral circulation; constrictive pericarditis; pericardial tamponade

Spray or patch:

>10%: Central nervous system: Headache (patch 63%, spray 50%)

1% to 10%:

Cardiovascular: Hypotension (patch 4%), increased angina (patch 2%), syncope (patch 4%)

Central nervous system: Lightheadedness (patch 6%)

<1% (Limited to important or life-threatening): Allergic reactions, application site irritation (patch), rash, dizziness, weakness, restlessness, pallor, perspiration, collapse, exfoliative dermatitis, vertigo, palpitation, methemoglobinemia (rare, overdose)

Topical, sublingual, intravenous: Frequency not defined:

Cardiovascular: Hypotension (infrequent), postural hypotension, crescendo angina (uncommon), rebound hypertension (uncommon), pallor, cardiovascular collapse, tachycardia, shock, flushing, peripheral edema

Central nervous system: Headache (most common), lightheadedness (related to blood pressure changes), syncope (uncommon), dizziness, restlessness

Gastrointestinal: Nausea, vomiting, bowel incontinence, xerostomia

Genitourinary: Urinary incontinence

Hematologic: Methemoglobinemia (rare, overdose)

Neuromuscular & skeletal: Weakness

Ocular: Blurred vision

Miscellaneous: Cold sweat

The incidence of hypotension and adverse cardiovascular events may be increased when used in combination with sildenafil (Viagra®).

Alteplase (tissue plasminogen activator) has a lesser effect when used with I.V. nitroglycerin; avoid concurrent use.

Ergot alkaloids may cause an increase in blood pressure and decrease in antianginal effects; avoid concurrent use.

Ethanol can cause hypotension when nitrates are taken 1 hour or more after ethanol ingestion.

Heparin's effect may be reduced by I.V. nitroglycerin. May affect only a minority of patients.

Sildenafil, tadalafil, vardenafil: Significant reduction of systolic and diastolic blood pressure with concurrent use (contraindicated). Do not administer sildenafil, tadalafil, or vardenafil within 24 hours of a nitrate preparation.

Nitroglycerin diluted in D5W or NS in glass containers is physically and chemically stable for 48 hours at room temperature and 7 days under refrigeration; in D5W or NS in Excell®/PAB® containers is physically and chemically stable for 24 hours at room temperature and 14 days under refrigeration

Premixed bottles are stable according to the manufacturer's expiration dating

Standard diluent: 50 mg/250 mL D5W; 50 mg/500 mL D5W

Minimum volume: 100 mg/250 mL D5W; concentration should not exceed 400 mcg/mL

Store sublingual tablets and ointment in tightly closed containers at 15°C to 30°C

Stable in D5LR, D5¹/2NS, D5NS, LR, ¹/2NS; variable stability (consult detailed reference) in D5W, NS

Y-site administration: Compatible: Alatrofloxacin, amiodarone, amphotericin B cholesteryl sulfate complex, atracurium, cisatracurium, diltiazem, dobutamine, dobutamine with dopamine, dobutamine with lidocaine, dobutamine with sodium nitroprusside, dopamine, dopamine with lidocaine, dopamine with sodium nitroprusside, epinephrine, esmolol, famotidine, fentanyl, fluconazole, furosemide, gatifloxacin, haloperidol, heparin, hydromorphone, inamrinone, insulin (regular), labetalol, lidocaine, lidocaine with sodium nitroprusside, linezolid, lorazepam, midazolam, milrinone, morphine, nicardipine, norepinephrine, pancuronium, propofol, ranitidine, remifentanil, sodium nitroprusside, streptokinase, tacrolimus, theophylline, thiopental, vecuronium, warfarin. Incompatible: Alteplase, levofloxacin. Variable (consult detailed reference): Hydralazine

Compatibility in syringe: Compatible: Heparin

Compatibility when admixed: Dose is variable and may require titration, therefore it is not advisable to mix with other agents. Compatible: Alteplase, aminophylline, dobutamine, dopamine, enalaprilat, furosemide, lidocaine, verapamil. Incompatible: Hydralazine, phenytoin. Variable (consult detailed reference): Bretylium, dobutamine with sodium nitroprusside

Onset of action: Sublingual tablet: 1-3 minutes; Translingual spray: 2 minutes; Buccal tablet: 2-5 minutes; Sustained release: 20-45 minutes; Topical: 15-60 minutes; Transdermal: 40-60 minutes; I.V. drip: Immediate

Peak effect: Sublingual tablet: 4-8 minutes; Translingual spray: 4-10 minutes; Buccal tablet: 4-10 minutes; Sustained release: 45-120 minutes; Topical: 30-120 minutes; Transdermal: 60-180 minutes; I.V. drip: Immediate

Duration: Sublingual tablet: 30-60 minutes; Translingual spray: 30-60 minutes; Buccal tablet: 2 hours; Sustained release: 4-8 hours; Topical: 2-12 hours; Transdermal: 18-24 hours; I.V. drip: 3-5 minutes

Protein binding: 60%

Metabolism: Extensive first-pass effect

Half-life elimination: 1-4 minutes

Excretion: Urine (as inactive metabolites)

Children: Pulmonary hypertension: Continuous infusion: Start 0.25-0.5 mcg/kg/minute and titrate by 1 mcg/kg/minute at 20- to 60-minute intervals to desired effect; usual dose: 1-3 mcg/kg/minute; maximum: 5 mcg/kg/minute

Adults:

Buccal: Initial: 1 mg every 3-5 hours while awake (3 times/day); titrate dosage upward if angina occurs with tablet in place

Oral: 2.5-9 mg 2-4 times/day (up to 26 mg 4 times/day)

I.V.: 5 mcg/minute, increase by 5 mcg/minute every 3-5 minutes to 20 mcg/minute; if no response at 20 mcg/minute increase by 10 mcg/minute every 3-5 minutes, up to 200 mcg/minute

Ointment: ¹/2" upon rising and ¹/2" 6 hours later; the dose may be doubled and even doubled again as needed

Patch, transdermal: Initial: 0.2-0.4 mg/hour, titrate to doses of 0.4-0.8 mg/hour; tolerance is minimized by using a patch-on period of 12-14 hours and patch-off period of 10-12 hours

Sublingual: 0.2-0.6 mg every 5 minutes for maximum of 3 doses in 15 minutes; may also use prophylactically 5-10 minutes prior to activities which may provoke an attack

Esophageal spastic disorders (unlabeled use): 0.3-0.4 mg 5 minutes before meals

Translingual: 1-2 sprays into mouth under tongue every 3-5 minutes for maximum of 3 doses in 15 minutes, may also be used 5-10 minutes prior to activities which may provoke an attack prophylactically

Hemodialysis: Supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

Elderly: In general, dose selection should be cautious, usually starting at the low end of the dosing range

Oral: Take as directed. Do not chew or swallow sublingual tablets; allow to dissolve under tongue. Sit down before using sublingual or buccal tablet or spray form. Do not chew or crush extended release capsules; swallow with 8 oz of water.

Spray: Spray directly on mucous membranes; do not inhale.

Topical: Spread prescribed amount thinly on applicator; rotate application sites.

Transdermal: Use as directed; place on hair-free area of skin, rotate sites (usually, patches will be removed for a period each day)

Concomitant use of sildenafil (Viagra®) or other phosphodiesterase-5 enzyme inhibitors (PDE-5) may precipitate acute hypotension, myocardial infarction, or death. Nitrates used in right ventricular infarction may induce acute hypotension. Nitrate use in severe pericardial effusion may reduce cardiac filling pressure and precipitate cardiac tamponade. In the management of heart failure, the combination of isosorbide dinitrate and hydralazine confers beneficial effects on disease progression and cardiac outcomes.

In the treatment of unstable angina/non-ST-segment elevation MI, nitroglycerin (sublingual tablet or spray), followed by intravenous administration, is recommended for immediate relief of ischemia and associated symptoms. Note that nitrate use may result in significant hypotension in individuals who are volume depleted.

Nitrate use in right ventricular infarction may induce acute hypotension. Nitrate use in severe pericardial effusion may reduce cardiac filling pressure and precipitate cardiac tamponade.

The 2004 STEMI guidelines suggest that healthcare providers should instruct patients, with sublingual nitroglycerin on hand, to take one dose sublingually in response to chest discomfort/pain. If chest pain is unimproved or worsening 5 minutes after the dose has been taken, the patient or family should call an ambulance. Use I.V. nitroglycerin for relief of ongoing ischemic discomfort (if S.L. nitroglycerin has been ineffective), control of hypertension, or management of pulmonary congestion. Nitrates should not be used if hypotension limits the addition of a beta-blocker.

Aerosol, translingual spray (Nitrolingual®): 0.4 mg/metered spray (12 g) [contains alcohol 20%; 200 metered sprays]

Capsule, extended release (Nitro-Time®): 2.5 mg, 6.5 mg, 9 mg

Infusion [premixed in D5W]: 0.1 mg/mL (250 mL, 500 mL); 0.2 mg/mL (250 mL); 0.4 mg/mL (250 mL, 500 mL)

Injection, solution: 5 mg/mL (5 mL, 10 mL) [contains alcohol and propylene glycol]

Ointment, topical:

Nitro-Bid®: 2% [20 mg/g] (30 g, 60 g)

Nitrol® [DSC]: 2% [20 mg/g] (3 g, 60 g)

Tablet, buccal, extended release (Nitrogard®): 2 mg, 3 mg

Tablet, sublingual (NitroQuick®, Nitrostat®, Nitro-Tab®): 0.3 mg, 0.4 mg, 0.6 mg

Transdermal system [once daily patch]: 0.1 mg/hour (30s); 0.2 mg/hour (30s); 0.4 mg/hour (30s); 0.6 mg/hour (30s)

Minitran™: 0.1 mg/hour (30s); 0.2 mg/hour (30s); 0.4 mg/hour (30s); 0.6 mg/hour (30s)

Nitrek®: 0.2 mg/hour (30s); 0.4 mg/hour (30s); 0.6 mg/hour (30s)

Nitro-Dur®: 0.1 mg/hour (30s); 0.2 mg/hour (30s); 0.3 mg/hour (30s); 0.4 mg/hour (30s); 0.6 mg/hour (30s); 0.8 mg/hour (30s)

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction),"Circulation, 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed August 26, 2004.

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),"J Am Coll Cardiol, 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Cheitlin MD, Hutter AM Jr, Brindis RG, et al, "ACC/AHA Expert Consensus Document. Use of Sildenafil (Viagra) in Patients With Cardiovascular Disease. American College of Cardiology/American Heart Association,"J Am Coll Cardiol, 1999, 33(1):273-82.

Erstad BL and Barletta JF, "Treatment of Hypertension in the Perioperative Patient,"Ann Pharmacother, 2000, 34(1):66-79.

Gibbons RJ, Abrams J, Chatterjee K, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina),"J Am Coll Cardiol, 2003, 41(1):159-68. Available at: http://http://www.acc.org/clinical/guidelines/stable/stable_clean.pdf. Accessed May 5, 2004.