Nitroglycerin (Sublingual tablet)

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Nitroglycerin (Sublingual tablet)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

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Overview

Nitroglycerin (Sublingual tablet) is an anti-anginal vasodilator that is FDA approved for the treatment of angina pectoris due to coronary artery disease. Common adverse reactions include hypotension, flushing, dizziness, headache, and lightheadedness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Acute Relief of Angina Pectoris
  • Dosing Information
  • One tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack.
  • The dose may be repeated approximately every 5 minutes until relief is obtained. If the pain persists after a total of 3 tablets in a 15-minute period, or if the pain is different than is typically experienced, prompt medical attention is recommended. Nitrostat may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.
  • During administration the patient should rest, preferably in the sitting position.
  • No dosage adjustment is required in patients with renal failure.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Congestive Heart Failure, Myocardial Infarction with Complication
  • Developed by: ACC/AHA
  • Class of Recommendation: Class IIa
  • Strength of Evidence: Category B
  • Dosing Information

Non–Guideline-Supported Use

Postoperative Pain
  • Dosing Information
  • Addition of transdermal nitroglycerin 5 mg/24 hours to intrathecal sufentanil in patients receiving knee surgery decreases the 24-hour analgesic requirement. However, transdermal nitroglycerin alone did not demonstrate a significant analgesic effect.[7]
Chronic Anal Fissure
  • Dosing Information
  • Nitroglycerin 0.2% ointment was effective for healing chronic anal fissures compared with placebo with no significant difference in fissure recurrence after 9 months.[8]
Biliary Tract Disorder
  • Dosing Information
  • Sublingual doses of 0.3 to 0.6 mg administered at the beginning of the procedure aided successful cannulation of the common bile duct, insertion of the Dormia basket, and removal of stones 4 to 11 mm in diameter.[9]
Dysmenorrhea
  • Dosing Information
  • Pain intensity was reduced and fewer analgesics were used compared with placebo, but headache incidence was increased in women with primary dysmenorrhea who received nitroglycerin patch 0.1 mg/hr for 24 hours on days 1, 2, and 3 of each cycle.[10]
External Cephalic Version with Tocolysis
  • Dosing Information
  • IV nitroglycerin improved the success rate of external cephalic version in nulliparous and multiparous women.[11]
Gastrointestinal Hemorrhage
  • Dosing Information
  • Combined therapy with vasopressin and nitroglycerin was more effective than vasopressin alone in controlling acute variceal hemorrhage, and nitroglycerin prevented cardiotoxic effects of vasopressin infusions.[12]
Prophylaxis of Post-ERCP Pancreatitis
  • Dosing Information
Preeclampsia
  • Dosing Information
  • Transdermal nitroglycerin 5 mg/24 hours initiated at 24 to 26 weeks gestation and continued for an average of 60 days increased the likelihood of a complication-free outcome with no significant effect on maternal blood pressure, uterine artery resistance index, or umbilical artery and middle cerebral artery pulsatility indices.[14]
Pulmonary Edema
  • Dosing Information
  • Sublingual nitroglycerin (0.4 to 2.4 mg at 5- to 10-minute intervals) was beneficial in the emergency treatment of pulmonary edema.[15]
Retained Placenta
  • Dosing Information
  • IV bolus nitroglycerin 500 mcg resulted in spontaneously uterine relaxation and placentas were extracted without complications.[16]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

  • The safety and effectiveness of nitroglycerin in pediatric patients have not been established.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Nitroglycerin (Sublingual tablet) in pediatric patients.

Non–Guideline-Supported Use

Chronic Anal Fissure
  • Dosing Information
  • Nitroglycerin ointment applied topically healed chronic anal fissures in 8 weeks without evidence of fissure recurrence on follow-up and was more effective in healing of the fissure than lidocaine or placebo.[17][18]

Contraindications

Warnings

Precautions

  • Only the smallest dose required for effective relief of the acute anginal attack should be used. Excessive use may lead to the development of tolerance. Nitrostat tablets are intended for sublingual or buccal administration and should not be swallowed.
  • Severe hypotension, particularly with upright posture, may occur with small doses of nitroglycerin. This drug should therefore be used with caution in patients who may be volume-depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris.
  • Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.
  • As tolerance to other forms of nitroglycerin develops, the effects of sublingual nitroglycerin on exercise tolerance, although still observable, is blunted.
  • In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance rarely occurs. Chest pain, acute myocardial infarction and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence.
  • Several clinical trials of nitroglycerin patches or infusions in patients with angina pectoris have evaluated regimens that incorporated a 10- to 12-hour nitrate free interval. In some of these trials, an increase in the frequency of anginal attack during the nitrate free interval was observed in a small number of patients. In one trial, patients had decreased exercise tolerance at the end of the nitrate interval. Hemodynamic rebound has been observed only rarely; on the other hand, few studies were so designed that rebound, if it had occurred, would have been detected.
  • Nitrate tolerance as a result of sublingual nitroglycerin administration is probably possible, but only in patients who maintain high continuous nitrate levels for more than 10 or 12 hours daily. Such use of sublingual nitroglycerin would entail administration of scores of tablets daily and is not recommended.
  • The drug should be discontinued if blurring of vision or drying of the mouth occurs. Excessive dosage of nitroglycerin may produce severe headaches.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Nitroglycerin (Sublingual tablet) in the drug label.

Postmarketing Experience

Drug Interactions

  • Nitrates may interfere with the Zlatkis-Zak color reaction, causing a false report of decreased serum cholesterol.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category B
  • Animal reproduction and teratogenicity studies have not been conducted with nitroglycerin sublingual tablets. However, teratology studies conducted in rats and rabbits with topically applied nitroglycerin ointment at dosages up to 80 mg/kg/day and 240 mg/kg/day, respectively revealed no toxic effects on dams or fetuses.
  • There are no adequate and well-controlled studies in pregnant women. Nitroglycerin should be given to a pregnant woman only if clearly needed.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Nitroglycerin (Sublingual tablet) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Nitroglycerin (Sublingual tablet) during labor and delivery.

Nursing Mothers

  • It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitroglycerin is administered to a nursing woman.

Pediatric Use

  • The safety and effectiveness of nitroglycerin in pediatric patients have not been established.

Geriatic Use

  • Clinical studies of Nitrostat did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Gender

There is no FDA guidance on the use of Nitroglycerin (Sublingual tablet) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Nitroglycerin (Sublingual tablet) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Nitroglycerin (Sublingual tablet) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Nitroglycerin (Sublingual tablet) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Nitroglycerin (Sublingual tablet) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Nitroglycerin (Sublingual tablet) in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous
  • Transdermal patch
  • Ointment

Monitoring

IV Compatibility

There is limited information regarding IV Compatibility of Nitroglycerin (Sublingual tablet) in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Hemodynamic Effects
  • The effects of nitroglycerin overdose are generally the results of nitroglycerin's capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; tachycardia; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.
  • No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the hypotension associated with nitroglycerin overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.
  • The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good.
  • In patients with renal disease or congestive heart failure therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin overdose in these patients may be subtle and difficult, and invasive monitoring may be required.
  • Methemoglobinemia has been rarely reported in association with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial PO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.
  • If methemoglobinemia is present, intravenous administration of methylene blue, 1 to 2 mg/kg of body weight, may be required.

Chronic Overdose

There is limited information regarding Chronic Overdose of Nitroglycerin (Sublingual tablet) in the drug label.

Pharmacology

There is limited information regarding Nitroglycerin (Sublingual tablet) Pharmacology in the drug label.

Mechanism of Action

  • The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload). Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.
  • Therapeutic doses of nitroglycerin may reduce systolic, diastolic, and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively, or increased heart rate decreases diastolic filling time.
  • Elevated central venous and pulmonary capillary wedge pressures, and pulmonary and systemic vascular resistance are also reduced by nitroglycerin therapy. Heart rate is usually slightly increased, presumably due to a compensatory response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged. Myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased and a more favorable supply-demand ratio can be achieved. Patients with elevated left ventricular filling pressures and increased systemic vascular resistance in association with a depressed cardiac index are likely to experience an improvement in cardiac index. In contrast, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced following nitroglycerin administration.

Structure

  • Nitrostat is a stabilized sublingual compressed nitroglycerin tablet that contains 0.3 mg, 0.4 mg , or 0.6 mg nitroglycerin; as well as lactose monohydrate, NF; glyceryl monostearate, NF; pregelatinized starch, NF; calcium stearate, NF powder; and silicon dioxide, colloidal, NF.
  • Nitroglycerin, an organic nitrate, is a vasodilating agent. The chemical name for nitroglycerin is 1, 2, 3 propanetriol trinitrate and the chemical structure is:
This image is provided by the National Library of Medicine.

Pharmacodynamics

  • Consistent with the symptomatic relief of angina, digital plethysmography indicates that onset of the vasodilatory effect occurs approximately 1 to 3 minutes after sublingual nitroglycerin administration and reaches a maximum by 5 minutes postdose. Effects persist for at least 25 minutes following Nitrostat administration.

Pharmacokinetics

  • Nitroglycerin is rapidly absorbed following sublingual administration of Nitrostat tablets. Mean peak nitroglycerin plasma concentrations occur at a mean time of approximately 6 to 7 minutes postdose (Table 1). Maximum plasma nitroglycerin concentrations (Cmax) and area under the plasma concentration-time curves (AUC) increase dose-proportionally following 0.3 to 0.6 mg Nitrostat. The absolute bioavailability of nitroglycerin from Nitrostat tablets is approximately 40% but tends to be variable due to factors influencing drug absorption, such as sublingual hydration and mucosal metabolism.
This image is provided by the National Library of Medicine.
  • Distribution
  • The volume of distribution (VArea) of nitroglycerin following intravenous administration is 3.3 L/kg. At plasma concentrations between 50 and 500 ng/mL, the binding of nitroglycerin to plasma proteins is approximately 60%, while that of 1,2- and 1,3-dinitroglycerin is 60% and 30%, respectively.
  • Metabolism
  • A liver reductase enzyme is of primary importance in the metabolism of nitroglycerin to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. Known sites of extrahepatic metabolism include red blood cells and vascular walls. In addition to nitroglycerin, 2 major metabolites 1,2- and 1,3-dinitroglycerin, are found in plasma. Mean peak 1,2- and 1,3-dinitroglycerin plasma concentrations occur at approximately 15 minutes postdose. The elimination half-life of 1,2- and 1,3-dinitroglycerin is 36 and 32 minutes, respectively. The 1,2- and 1,3-dinitroglycerin metabolites have been reported to possess approximately 2% and 10%, respectively, of the pharmacological activity of nitroglycerin. Higher plasma concentrations of the dinitro metabolites, along with their nearly 10-fold longer elimination half-lives, may contribute significantly to the duration of pharmacologic effect. Glycerol mononitrate metabolites of nitroglycerin are biologically inactive.
  • Elimination
  • Nitroglycerin plasma concentrations decrease rapidly, with a mean elimination half-life of 2 to 3 minutes. Half-life values range from 1.5 to 7.5 minutes. Clearance (13.6 L/min) greatly exceeds hepatic blood flow. Metabolism is the primary route of drug elimination.

Nonclinical Toxicology

  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Animal carcinogenesis studies with sublingually administered nitroglycerin have not been performed.
  • Carcinogenicity potential of nitroglycerin was evaluated in rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years. Rats developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes. At high dose, the incidences of hepatocellular carcinomas in males was 48% and in females was 33%, compared to 0% in untreated controls. Incidences of testicular tumors were 52% vs. 8% in controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice.
  • Nitroglycerin was mutagenic in Ames tests performed in 2 different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, PO, or in ex vivo cytogenetic tests in rat and dog cells.
  • In a 3-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for 6 months prior to mating of the F0 generation, with treatment continuing through successive F1 and F2 generations. The high dose was associated with decreased feed intake and body weight gain in both sexes at all matings. No specific effect on the fertility of the F0 generation was seen. Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high-dose males. In this 3-generation study, there was no clear evidence of teratogenicity.

Clinical Studies

There is limited information regarding Clinical Studies of Nitroglycerin (Sublingual tablet) in the drug label.

How Supplied

  • Nitrostat is supplied as white, round, flat-faced tablets in 3 strengths (0.3 mg, 0.4 mg, and 0.6 mg) in bottles containing 100 tablets each, with color-coded labels, and in color-coded Patient Convenience Packages of 4 bottles of 25 tablets each.
This image is provided by the National Library of Medicine.

Storage

There is limited information regarding Nitroglycerin (Sublingual tablet) Storage in the drug label.

Images

Drug Images

Package and Label Display Panel

This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.

Patient Counseling Information

  • Nitrostat is a sublingual tablet and should not be chewed, crushed, or swallowed.
  • If possible, patients should sit down when taking Nitrostat tablets and should use caution when returning to a standing position. This eliminates the possibility of falling due to lightheadedness or dizziness.
  • One tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack. The dose may be repeated approximately every 5 minutes until relief is obtained.
  • If chest pain persists after a total of 3 tablets in a 15-minute period, or if the pain is different than is typically experienced, prompt medical attention is recommended.
  • Nitrostat may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.
  • Nitroglycerin may produce a burning or tingling sensation when administered sublingually; however, the ability to produce a burning or tingling sensation should not be considered a reliable method for determining the potency of the tablets.
  • Headaches can sometimes accompany treatment with nitroglycerin. In patients who get these headaches, the headaches may be a marker of the activity of the drug.
  • Treatment with nitroglycerin may be associated with lightheadedness upon standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol.
  • Nitroglycerin should be kept in the original glass container and must be tightly capped after each use to prevent loss of tablet potency.
This image is provided by the National Library of Medicine.

Precautions with Alcohol

  • Treatment with nitroglycerin may be associated with lightheadedness upon standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol.
  • Concomitant use of nitrates and alcohol may cause hypotension.

Brand Names

  • Minitran®
  • Nitro-Bid®
  • Nitro-Dur®
  • Nitrolingual®
  • Nitrostat®
  • Nitrotab®
  • Nitrek®
  • NitroMist®
  • Nitrostat®[19]

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. American College of Emergency Physicians (2013-01-29). "2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Journal of the American College of Cardiology. 61 (4): –78-140. doi:10.1016/j.jacc.2012.11.019. ISSN 1558-3597. PMID 23256914. Unknown parameter |coauthors= ignored (help)
  2. Jugdutt, B. I. (1992-09-24). "Role of nitrates after acute myocardial infarction". The American Journal of Cardiology. 70 (8): 82–87B. ISSN 0002-9149. PMID 1529930.
  3. Schneider, W. (1991). "Nitrate therapy in heart failure". Cardiology. 79 Suppl 2: 5–13. ISSN 0008-6312. PMID 1760830. Unknown parameter |coauthors= ignored (help)
  4. Jugdutt, B. I. (1988-10). "Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications. Effect of timing, dosage, and infarct location". Circulation. 78 (4): 906–919. ISSN 0009-7322. PMID 3139326. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  5. Awan, N. A. (1983-07). "Effect of combined nitroglycerin and dobutamine infusion in left ventricular dysfunction". American Heart Journal. 106 (1 Pt 1): 35–40. ISSN 0002-8703. PMID 6408917. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  6. Loeb, H. S. (1983-10). "Beneficial effects of dopamine combined with intravenous nitroglycerin on hemodynamics in patients with severe left ventricular failure". Circulation. 68 (4): 813–820. ISSN 0009-7322. PMID 6413087. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  7. Lauretti, G. R. (1999-03). "Transdermal nitroglycerine enhances spinal sufentanil postoperative analgesia following orthopedic surgery". Anesthesiology. 90 (3): 734–739. ISSN 0003-3022. PMID 10078674. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  8. Carapeti, E. A. (1999-05). "Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate". Gut. 44 (5): 727–730. ISSN 0017-5749. PMC 1727506. PMID 10205213. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  9. Uchida, N. (1997-09). "Endoscopic lithotomy of common bile duct stones with sublingual nitroglycerin and guidewire". The American Journal of Gastroenterology. 92 (9): 1440–1443. ISSN 0002-9270. PMID 9317059. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  10. Moya, R. A. (2000-05). "Transdermal glyceryl trinitrate in the management of primary dysmenorrhea". International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics. 69 (2): 113–118. ISSN 0020-7292. PMID 10802078. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  11. Hilton, Jennifer (2009-09). "Intravenous nitroglycerin for external cephalic version: a randomized controlled trial". Obstetrics and Gynecology. 114 (3): 560–567. doi:10.1097/AOG.0b013e3181b05a19. ISSN 0029-7844. PMID 19701035. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  12. Gimson, A. E. (1986-06). "A randomized trial of vasopressin and vasopressin plus nitroglycerin in the control of acute variceal hemorrhage". Hepatology (Baltimore, Md.). 6 (3): 410–413. ISSN 0270-9139. PMID 3086204. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  13. Bai, Y. (2009-08). "Glyceryl trinitrate for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: a meta-analysis of randomized, double-blind, placebo-controlled trials". Endoscopy. 41 (8): 690–695. doi:10.1055/s-0029-1214951. ISSN 1438-8812. PMID 19670137. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  14. Lees, C. (1998-11). "The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial". Ultrasound in Obstetrics & Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 12 (5): 334–338. doi:10.1046/j.1469-0705.1998.12050334.x. ISSN 0960-7692. PMID 9819872. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  15. Bussmann, W. D. (1978-05-01). "Effect of sublingual nitroglycerin in emergency treatment of severe pulmonary edema". The American Journal of Cardiology. 41 (5): 931–936. ISSN 0002-9149. PMID 417614. Unknown parameter |coauthors= ignored (help)
  16. Peng, A. T. (1989-07). "Intravenous nitroglycerin for uterine relaxation in the postpartum patient with retained placenta". Anesthesiology. 71 (1): 172–173. ISSN 0003-3022. PMID 2502047. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  17. Simpson, John (2003-10). "The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children". Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 9 (10): –123-126. ISSN 1234-1010. PMID 14523338. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  18. Tander, B. (1999-12). "A prospective, randomized, double-blind, placebo-controlled trial of glyceryl-trinitrate ointment in the treatment of children with anal fissure". Journal of Pediatric Surgery. 34 (12): 1810–1812. ISSN 0022-3468. PMID 10626860. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  19. "Nitrostat (nitroglycerin) tablet".
  20. "http://www.ismp.org". External link in |title= (help)

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