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Special Alerts
Transdermal Patches: Risk of Burns During MRI - March 2009
The U.S. Food and Drug Administration (FDA) has issued a public health advisory regarding the risk of burns associated with the use of transdermal medication patches containing aluminum or other metals during MRI screening. The package labeling for certain metal-containing patches includes a warning related to the risk of burns if the patches are not removed prior to MRI procedures. However, not all transdermal medication patches with metallic backings have this warning in the labeling. Although metal materials are present in certain patches, it may not be visible. The FDA is currently reviewing the components of all transdermal medication systems to ensure that proper warnings are present in the labeling of those patches that do contain metal materials. In the interim, the FDA recommends that healthcare professionals who refer patients to have an MRI procedure should identify patients who are wearing a transdermal medication patch prior to the scan. Those patients who are wearing a transdermal medication patch should be advised on the proper removal of the patch prior to the procedure as well as reapplication following the scan.
Additional information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm111493.htm
Medication Safety Issues
Sound-alike/look-alike issues:
Nitroglycerin may be confused with nitrofurantoin, nitroprusside
Nitro-Bid® may be confused with Macrobid®, Nicobid®
Nitroderm may be confused with NicoDerm®
Nitrol® may be confused with Nizoral®
Nitrostat® may be confused with Nilstat®, nystatin
Nitroglycerin transdermal patches should be removed prior to defibrillation or MRI study.
International issues:
Nitrocor® [Chile and Italy] may be confused with Natrecor® which is a brand name for nesiritide in the U.S.
Nitrocor® [Chile and Italy] may be confused with Nutracort® which is a brand name for hydrocortisone in the U.S.
Nitro-Dur® may be confused with Nitrocor® [Chile and Italy]
Pronunciation
(nye troe GLI ser in)
U.S. Brand Names
Index Terms
Generic Available
Yes: Capsule, injection, patch, tablet
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of angina pectoris; I.V. for congestive heart failure (especially when associated with acute myocardial infarction); pulmonary hypertension; perioperative hypertension (especially during cardiovascular surgery); induction of intraoperative hypotension
Use: Unlabeled/Investigational
Esophageal spastic disorders (sublingual)
Pregnancy Risk Factor
C
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to organic nitrates; hypersensitivity to isosorbide, nitroglycerin, or any component of the formulation; concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, or vardenafil); angle-closure glaucoma (intraocular pressure may be increased); head trauma or cerebral hemorrhage (increase intracranial pressure); severe anemia; allergy to adhesive (transdermal product)
Additional contraindications for I.V. product: Hypotension; uncorrected hypovolemia; inadequate cerebral circulation; constrictive pericarditis; pericardial tamponade
Warnings/Precautions
Concerns related to adverse effects:
• Hypotension/bradycardia: Severe hypotension can occur; paradoxical bradycardia and increased angina pectoris can accompany hypotension. Orthostatic hypotension can also occur; ethanol can accentuate this. Use with caution in volume depletion, hypotension, and right ventricular infarctions.
Disease-related concerns:
• Hypertrophic cardiomyopathy: Use with caution in patients with hypertrophic cardiomyopathy; nitrates may reduce preload, exacerbating obstruction and cause hypotension and/or worsening of heart failure.
Concurrent drug therapy issues:
• PDE-5 inhibitors: Avoid concurrent use with PDE-5 inhibitors (eg, sildenafil, tadalafil, vardenafil).
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues:
• Long-acting agents: Avoid use of long-acting agents in acute MI or HF; cannot easily reverse if adverse events develop.
• Transdermal patches: Patches should be removed prior to defibrillation or MRI study.
Other warnings/precautions:
• Tolerance: Appropriate dosing is needed to minimize tolerance development.
Adverse Reactions
Frequency not always defined:
Cardiovascular: Hypotension (4%), crescendo angina (2%), flushing, peripheral edema, postural hypotension, tachycardia
Central nervous system: Headache (most common; 50% to 63%), lightheadedness (6%), syncope (4%), dizziness
Gastrointestinal: Bowel incontinence, nausea, vomiting, xerostomia
Genitourinary: Urinary incontinence
Ocular: Blurred vision
Miscellaneous: Diaphoresis
<1% (Limited to important or life-threatening): Allergic reactions, application site irritation (patch), cardiovascular collapse, exfoliative dermatitis, methemoglobinemia (rare; overdose), pallor, palpitation, rash, rebound hypertension, restlessness, shock, vertigo, weakness
Drug Interactions
Alteplase: Nitroglycerin may decrease the serum concentration of Alteplase. Risk C: Monitor therapy
Heparin: Nitroglycerin may diminish the anticoagulant effect of Heparin. Nitroglycerin may decrease the serum concentration of Heparin. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination
Rosiglitazone: Vasodilators (Organic Nitrates) may enhance the adverse/toxic effect of Rosiglitazone. Specifically, a greater risk of myocardial ischemia was reported for users of this combination in a meta-analysis. Management: Consider alternatives to this combination when possible. Rosiglitazone prescribing information states that the combination of rosiglitazone and a nitrate is not recommended. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase the hypotensive effects of nitroglycerin). Monitor.
Herb/Nutraceutical: Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (american), kola, licorice (may worsen hypertension). Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse (may cause hypotension).
Storage
Doses should be made in glass bottles, Excel® or PAB® containers. Adsorption occurs to soft plastic (eg, PVC). 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 Excel®/PAB® containers it 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. Store sublingual tablets and ointment in tightly closed containers at 15°C to 30°C. Store spray and transdermal patch at 25°C; excursions permitted to 15°C to 30°C (59°F to 86°F).
Reconstitution
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.
Compatibility
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.
Mechanism of Action
Works by relaxation of smooth muscle, producing a vasodilator effect on the peripheral veins and arteries with more prominent effects on the veins. Primarily reduces cardiac oxygen demand by decreasing preload (left ventricular end-diastolic pressure); may modestly reduce afterload; dilates coronary arteries and improves collateral flow to ischemic regions
Pharmacodynamics/Kinetics
Onset of action: Sublingual tablet: 1-3 minutes; Translingual spray: 2 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; 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; 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)
Dosage
Note: Hemodynamic and antianginal tolerance often develop within 24-48 hours of continuous nitrate administration. Nitrate-free interval (10-12 hours/day) is recommended to avoid tolerance development; gradually decrease dose in patients receiving NTG for prolonged period to avoid withdrawal reaction.
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:
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
Administration: Oral
Sublingual: Do not crush sublingual product (tablet). Place under tongue and allow to dissolve.
Translingual spray: Do not shake container. Release spray onto or under tongue. Do not rinse the mouth for at least 5-10 minutes. Priming sprays should be directed away from patient and others. The end of the pump should be covered by the fluid in the bottle.
Nitrolingual®: Prime prior to first use (5 sprays into the air). If unused for 6 weeks, a single priming spray should be completed.
Administration: I.V.
I.V. must be prepared in glass bottles and use special sets intended for nitroglycerin. Glass I.V. bottles and administration sets provided by manufacturer.
Administration: I.V. Detail
Nitroglycerin can be absorbed by plastic (polyvinyl chloride) tubing or containers. Infusion pump may not infuse accurately with different tubing. Be alert to potential for unregulated flow.
pH: 3.0-6.5
Monitoring Parameters
Blood pressure, heart rate
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take as per directions (see below). Do not change brands without consulting prescriber. Do not discontinue abruptly. Keep medication in original container, tightly closed. If anginal chest pain is unresolved in 15 minutes, seek emergency medical help at once. Daily use may cause dizziness or lightheadedness (use caution when driving or engaging in hazardous activities until response to drug is known); headache (consult prescriber for approved analgesic); hypotension (use care when changing position from sitting or lying to standing, when climbing stairs or when engaging in tasks that are potentially hazardous until response to drug is known); GI disturbances (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report acute headache, rapid heartbeat, unusual restlessness or dizziness, muscular weakness, or blurred vision or seeing abnormal colors. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
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: Follow exact instructions in product insert. 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 and rotate sites (usually, patches will be removed for a period each day). Remove patch while having MRI scan; can cause burns.
Geriatric Considerations
Caution should be used when using nitrate therapy in the elderly due to hypotension. Hypotension is enhanced in the elderly due to decreased baroreceptor response, decreased venous tone, and often hypovolemia (dehydration) or other hypotensive drugs.
Additional Information
I.V. preparations contain alcohol and/or propylene glycol; may need to use nitrate-free interval (10-12 hours/day) to avoid tolerance development. Tolerance may possibly be reversed with acetylcysteine; gradually decrease dose in patients receiving NTG for prolonged period to avoid withdrawal reaction.
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.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: 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.
Cardiovascular Considerations
Nitrates improve the balance between myocardial oxygen supply and demand, primarily by decreasing oxygen demand. Nitrates decreases myocardial oxygen demand by reducing preload via dilation of peripheral veins. Nitrates improve myocardial oxygen supply by dilating epicardial coronary arteries and collateral vessels, leaving resistance vessels alone. Nitrates are unlikely to induce a coronary steal syndrome. Nitrates improve exercise tolerance in stable angina patients. An adequate nitroglycerin-free period must be provided with all nitrate products to prevent nitrate tolerance from developing. In the treatment of unstable angina/non-ST-segment elevation MI, I.V. NTG is indicated for immediate relief of ischemia when sublingual nitroglycerin (tablet or spray) and intravenous beta-blocker have failed. I.V. NTG may also be of benefit in nonhypotensive high-risk patients. Caution should be observed if administering nitrates to individuals who are volume-depleted or are experiencing a right ventricular infarction. Additionally, nitrates should not be given to an individual who has received a phosphodiesterase-5 enzyme inhibitor within the past 24 hours. In a stabilized patient, intravenous nitroglycerin should be converted within 24 hours to a nonparenteral alternative in a regimen that is designed to prevent tolerance.
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.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
None reported, but monitor for hypotension if receiving a psychotropic
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other pharmacological agents patient may be taking (eg, heparin, ergot alkaloids, sildenafil, tadalafil, or vardenafil). See Administration specifics for different formulations. Evaluate therapeutic effectiveness (cardiac status) and adverse response (eg, hypotension, arrhythmias, CNS changes, GI disturbances). Dose should be reduced gradually when discontinuing after long-term therapy. Teach patient proper use (according to purpose and formulation), possible side effects/appropriate interventions (eg, drug-free intervals; removes transdermal patches for specific period of time), and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, extended release: 2.5 mg, 6.5 mg, 9 mg
Nitro-Time®: 2.5 mg, 6.5 mg, 9 mg
Infusion [premixed in D5W]: 25 mg (250 mL) [0.1 mg/mL]; 50 mg (250 mL) [0.2 mg/mL]; 50 mg (500 mL) [0.1 mg/mL]; 100 mg (250 mL) [0.4 mg/mL]; 200 mg (500 mL) [0.4 mg/mL]
Injection, solution: 5 mg/mL (5 mL, 10 mL) [contains ethanol and propylene glycol]
Ointment, topical:
Nitro-Bid®: 2% [20 mg/g] (1 g, 30 g, 60 g)
Solution, translingual [spray]:
Nitrolingual®: 0.4 mg/metered spray (4.9 g) [contains ethanol 20%; 60 metered sprays]; (12 g) [contains ethanol 20%; 200 metered sprays]; (16.9 g) [contains ethanol 20%; 260 metered sprays]
Tablet, sublingual: 0.3 mg, 0.4 mg, 0.6 mg
NitroQuick® [DSC], Nitrostat®: 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)
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)
Pricing: U.S. (www.drugstore.com)
Capsule, controlled release (Nitroglycerin CR)
2.5 mg (30): $13.99
6.5 mg (30): $49.70
9 mg (30): $35.99
Ointment (Nitro-Bid)
2% (60): $22.99
2% (60): $24.99
Patch, 24-hour (Minitran)
0.1 mg/hour (30): $78.98
0.2 mg/hour (30): $79.09
0.4 mg/hour (30): $87.72
0.6 mg/hour (30): $94.88
Patch, 24-hour (Nitro-Dur)
0.1 mg/hour (30): $88.28
0.2 mg/hour (30): $99.72
0.3 mg/hour (30): $98.77
0.4 mg/hour (30): $110.57
0.6 mg/hour (30): $109.47
0.8 mg/hour (30): $110.56
Patch, 24-hour (Nitroglycerin)
0.1 mg/hour (30): $25.99
0.2 mg/hour (30): $28.99
0.4 mg/hour (30): $36.99
0.6 mg/hour (30): $39.99
Solution (Nitrolingual)
0.4 mg/spray (4.9): $125.04
0.4 mg/spray (12): $203.05
Sublingual (Nitroglycerin)
0.3 mg (100): $20.99
0.4 mg (100): $37.99
0.6 mg (100): $22.84
Sublingual (Nitrostat)
0.3 mg (100): $27.76
0.4 mg (25): $19.31
0.4 mg (100): $29.89
0.6 mg (100): $24.99
References
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(5):588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 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.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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