Nitroglycerin

Pronunciation

U.S. Brand Names

Minitran™; Nitrek®; Nitro-Bid®; Nitro-Dur®; Nitrogard®; Nitrol® [DSC]; Nitrolingual®; NitroQuick®; Nitrostat®; Nitro-Tab®; NitroTime®

Synonyms

Glyceryl Trinitrate; Nitroglycerol; NTG

Generic Available

Yes: Capsule, injection, patch, tablet

Canadian Brand Names

Gen-Nitro; Minitran™; Nitro-Dur®; Nitrol®; Nitrostat™; Rho-Nitro; Transderm-Nitro®

Use

Treatment of angina pectoris; I.V. for congestive heart failure (especially when associated with acute myocardial infarction); pulmonary hypertension; hypertensive emergencies occurring perioperatively (especially during cardiovascular surgery)

Use - Unlabeled/Investigational

Esophageal spastic disorders (sublingual)

Pregnancy Risk Factor

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

Severe hypotension can occur. Use with caution in volume depletion, hypotension, and right ventricular infarctions. Paradoxical bradycardia and increased angina pectoris can accompany hypotension. Orthostatic hypotension can also occur. Ethanol can accentuate this. Tolerance does develop to nitrates and appropriate dosing is needed to minimize this (drug-free interval). Safety and efficacy have not been established in pediatric patients. Avoid use of long-acting agents in acute MI or CHF; cannot easily reverse. Nitrate may aggravate angina caused by hypertrophic cardiomyopathy. Nitroglycerin transdermal patches should be removed prior to defibrillation or MRI study.

Adverse Reactions

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®).

Overdosage/Toxicology

Symptoms of overdose include hypotension, throbbing headache, palpitations, bloody diarrhea, bradycardia, cyanosis, tissue hypoxia, metabolic acidosis, clonic convulsions, circulatory collapse, and methemoglobinemia with extremely large overdoses. Treatment is supportive and symptomatic. Methemoglobinemia should be treated with methylene blue (1-2 mg/kg over 5 minutes). Additional doses may be necessary (0.5-1 mg/kg) based on follow-up methemoglobin levels (obtained after 30 minutes).

Drug Interactions

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.

Stability

Doses should be made in glass bottles, Excell® or PAB® containers; adsorption occurs to soft plastic (ie, 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 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

Compatibility

Dose is variable and may require titration, therefore it is not advisable to mix with other agents.

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; 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)

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:

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

Monitoring Parameters

Blood pressure, heart rate

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. 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: 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)

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

Nitroglycerin 5 mg/mL contains propylene glycol 518 mg/mL (30% v/v).

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, and moderately reducing afterload by dilating peripheral arteries. 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

No significant effects or complications reported

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

Dosage Forms

[DSC] = Discontinued product

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)

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, 110:588-636. 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.

International Brand Names

Adesitrin® (IT); Amitacon® (TH); Anginine® (AU, NZ); Angiolingual® (CL); Angised® (BD, CY, HK, HR, IL, IN, JO, KW, LB, SI, SY, TH, ZA); Anglix® (MX); Aquo-Trinitrosan® (DE, RO); Buccard® (DK); Cardinit® (MX); Corangin® (DE); Cordipatch® (FR); Cordiplast® (AT, ES); Coro-Nitro® (DE); Coro Nitro Pump Spray® (GB); Dauxona® (AR); DBL Glyceryl Trinitrate® (TH); Deponit 5® (GB); Deponit 10® (GB); Deponit® (AT, BE, CH, CZ, DE, FI, GB, HK, IE, IL, IT, LU, NL, RU, SG); Dermatrans® (ES, IT); Diafusor® (BE, ES, FR, LU); Discotrine® (DK, FR); Enetege® (AR); Epinitril® (ES, FR); Estaro® (NL); Gen-Nitro (CA); Gepan Nitroglycerin® (DE); Glycerylnitrat® (NO); Glyceryl Trinitrate® (AU, GB, ID, NZ); Glytrin® (DK, GB, IE, NL, SE); Glytrin Spray® (GB, NZ, TH); GTN® (GB); Herzer® (JP); Lénitral® (FR); Lenitral® (RO); Maycor Nitrospray® (CZ, RO); Millisrol® (IN, JP); Minitran® (AR, AT, AU, BE); Minitran™ (CA); Minitran® (CH, CR, ES, FI, GB, GT, HN, IT, LU, MX, NL, NO, NZ, PA, RO, SE, SV); MinitranS® (DE); Myonit® (IN); Natispray® (FR, IT, LU); Neos nitro OPT® (DE); Niglinar® (AR); Nirmin® (PL, RU, YU); Nitracor® (PL); Nitradisc® (AR, AU, BR, ES, LU, MX, PT, ZA); Nitrangin® (DE); Nitrangin Isis® (DE); Nit-Ret® (CZ, RU); Nitriderm TTS® (FR); Nitrilex® (CZ); Nitro-Bid® (AU); Nitrocard® (PL); Nitrocine® (GB, HK, ID, IE, IL, SG, TH, ZA); Nitroclyn® (BR); Nitrocontin® (BD, IN); Nitrocor® (CL, IT); Nitroderm Matrix® (ES); Nitroderm TTS® (AR, AT, BE, BR, CH, CL, CR, DE, DO, ES, GT, HK, HN, HR, HU, IL, IN, IT, LU, MT, MX, NZ, PA, PL, PT, RO, SI, SV, TH, TR); Nitrodom® (AR); Nitro Dur® (AR, AT, AU, CA, CH, ES, GB, HK, HU, IT, NL, NO, PL, PT, SI, YU); Nitrodyl® (BE, LU); Nitro® (FI, HK, HU, RO, RU); Nitrogesic® (IN); Nitroglicerina® (CL, RO); Nitroglicerina L.CH.® (CL); Nitroglicerina PH&T® (IT); Nitroglicerina Richmond® (AR); Nitroglicerin® (YU); Nitroglycerin AstraZeneca® (SE); Nitroglycerin Bioren® (CH); Nitroglycerin Dak® (DK); Nitroglycerine Amps® (IL); Nitroglycerine Pohl® (NL); Nitroglycerin "Lannacher"® (AT); Nitroglycerin NM Pharma® (SE); Nitroglycerin® (NO, RU, TR); Nitroglycerin Nycomed® (RU); Nitroglycerin Slovakofarma® (CZ); Nitroglycerin Streuli® (CH); Nitroglycerinum® (PL); Nitroglycerinum prolongatum® (PL); Nitroglycerin Wander® (CH); Nitroject® (RU, TH); Nitrol® (CA); Nitrolingual® (AT, AU, BE, CH, DE, DK, GB, HK, HR, HU, IE, IL, LU, NL, NO, NZ, SE, SI, TR, YU, ZA); Nitro Mack® (CH, CZ, DE, HK, LU); Nitro-Mack® (PL); Nitro Mack Retard® (AT, CH, CY, EG, ID, JO, KW, LB, RO, RU, SG, TH); Nitro Mack® (RO, RU); Nitro-M-Bid® (BE); Nitromex® (DK, FI, NO, SE); Nitromin® (GB, IE); Nitromint® (BD, CZ, EG, HU, PL, PT, RO, RU, SY); Nitromint NT® (HU); Nitronal-A® [inf.] (CH); Nitronal® (CH, GB, HR, IL, NZ, SI); Nitrong® (LU, RU, SI); Nitro-Pflaster-ratiopharm® (DE, LU); Nitroplast® (ES); Nitro Pohl® (AT, CZ); Nitro-Pohl® (HU); Nitro Pohl® (NL); Nitroprontan® (AR); Nitroretard® (RO); Nitro Solvay® (DE); Nitrostat™ (CA); Nitrostat® (HK, NL); Nitrosylon® (IT); Nitroven® (NO); Nitrovis® (IL); Nitrovital L® (RO); Nysconitrine® (BE, LU); Oxycardin® (AR); Percutol® (GB); Perganit® (IT); Perlinganit® (AT, CH, CZ, DE, FI, HU, LU, PL, RU, TR); Plastranit® (PT); Polnitrin® (PL); Rectogesic® (AU); Rho-Nitro (CA); Solinitrina® (ES); Solinitrina TS® (ES); Suscard Buccal® (CY, GB, IE, JO, KW, MT); Suscard® (GB, HK, IE, SE); Sustac® (CY, GB, HU, IE, JO, KW, MT, RU, SI); Sustonit® (PL); Top-Nitro® (IT); Transderm-Nitro® (CA); Transiderm Nitro® (AU, FI, GB, IE, NL, NO, SE); Tridil® (BR, HK); Trimonit® (PL); Trinipatch® (BE, ES, FR, IL, LU, NL, PT); Triniplas® (IT); Trinispray® (ES); Trinitrina® (IT); Trinitrine Merck® (FR); Trinitrine Simple Laleuf® (FR); Trinitrin Simplex Laleuf® (CH); Trinitroglicerina Fabra® (AR); Trinitron® (AR); Trinitrosan® (DE, HR, RO); Trintek® (GB); Venitrin® (IT); Vernies® (ES); Willlong® (BE, LU)

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