Nitroglycerin (Nitrostat) is also called as Glyceryl Trinitrate. It belongs to the class of medicines called nitrates. It is a vasodilator and primarily used in the symptomatic treatment of angina.

Nitroglycerin (Nitrostat)  Uses:

• Treatment or prevention of angina pectoris Intravenous (IV) administration:

  • Angina pectoris treatment or prevention.
  • Acute decompensated heart failure (especially when associated with acute myocardial infarction).
  • Perioperative hypertension (especially during cardiovascular surgery).
  • Induction of intraoperative hypotension Intra-anal administration (Rectiv ointment):
    • Associated with chronic anal fissure, treatment of moderate-to-severe pain

• Off Label Use of Nitroglycerin in Adults:

  • Esophageal spastic disorders
  • Gastroesophageal variceal hemorrhage
  • Sympathomimetic vasopressor extravasation injury (alternative to phentolamine)
  • Uterine relaxation (for uterine inversion)

Nitroglycerin (Nitrostat) Dose in Adults

Note:

• In the US, Nitronal IV solution has been discontinued for more than 1 year.

Note:

• Within 24 to 48 hours of continuous nitrate administration, Hemodynamic and antianginal tolerance often develop.
• To avoid tolerance development, Nitrate-free interval (10 to 12 hours/day) is recommended.
• In patients receiving nitroglycerin for prolonged period, gradually decrease dose to avoid withdrawal reaction.

Nitroglycerin (Nitrostat) Dose in the treatment of acute decompensated heart failure (off-label dose):

• IV:
• Initial:
  • 10-20 mcg/min, with subsequent titration (eg, 10-20 mcg/min every 5-15 mins) up to 200 mcg/min or
  • 0.3-0.5 mcg/kg/min with titration (if SBP ≥90 mm Hg) in increments of 20 mcg/min every 1-3 mins up to 400 mcg/min.
  • Patients who do not respond hemodynamically with doses of ~200 mcg/min should be considered nonresponders.

Nitroglycerin (Nitrostat) Dose in the treatment of Angina/coronary artery disease:

• Per Oral:
  • Initial:
    • Daily 2.5-6.5 mg orally 3 to 4 times.
    • May titrate up to 26 mg 4 times daily
• IV:
  • Initial:
    • 10 mcg/min, with subsequent titration to desired blood pressure effect.
  • Manufacturer's labeling:
    • Dosing in the prescribing information may not reflect current clinical practice.
    • 5 mcg/min, increase by 5 mcg/min every 3-5 mins to 20 mcg/min.
    • If no response at 20 mcg/min, may increase by 10-20 mcg/min every 3-5 min (generally accepted max dose: 400 mcg/min)

• Sublingual powder (0.4 mg/packet):

  • 4 mg every 5 mins up to 3 doses.
  • In response to chest pain, patients should be advised to take 1 dose promptly.
  • If after 1 dose, pain is unrelieved or worsened 3-5 mins, the patient or caregiver should call 9-1-1 immediately.
  • Manufacturer's labeling:
    • Dosing in the prescribing information may not reflect current clinical practice.
    • 1-2 packets under tongue every 5 mins as needed for max of 3 packets in 15 mins.
    • It may also use be used prophylactically 5-10 mins prior to activities that may provoke an angina attack, .

• Sublingual tablet:

  • 0.3-0.4 mg every 5 mins for up to three doses.
  • In response to chest pain, patients should be advised to take 1 dose promptly.
  • If pain is unrelieved or worsened 3-5 mins after 1 dose, the patient or caregiver should call 9-1-1 immediately.
  • Manufacturer's labeling:
    • Dosing in the prescribing information may not reflect current clinical practice.
    • For max of 3 tablets in 15 minutes, 0.3-0.6 mg every 5 mins.
    • May also use prophylactically 5-10 mins prior to activities that may provoke an attack.

• Topical 2% ointment:

  • 1/2 ” upon rising and 1/2 ” 6 hours later.
  • If necessary, the dose may be doubled to 1” and subsequently doubled again to 2” if response is inadequate.
  • Doses of 1/2 ”  to 2” were used in clinical trials.
  • Recommended max:
    • 2 doses/day.
    • Include a nitrate free-interval ~10-12 hours/day.

• Topical transdermal patch:

  • 2-0.4 mg/hour initially and titrate to doses of 0.4-0.8 mg/hour.
  • Tolerance is minimized by using a patch-on period of 12-14 hours/day and patch-off period of 10-12 hours/day.

• Translingual 0.4 mg/spray:

  • Up to 3 doses, 4 mg every 5 mins.
  • Patients should be advised to take 1 dose promptly in response to chest pain.
  • If pain is unrelieved or worsened 3 to 5 mins after 1 dose, the patient or caregiver should call 9-1-1 immediately.
  • Manufacturer's labeling:
    • Dosing in the prescribing information may not reflect current clinical practice.
    • 1-2 sprays onto or under tongue approximately every 5 mins for max of 3 sprays in 15 minutes.
    • It may also be used prophylactically 5-10 mins prior to activities which may provoke an angina attack,

Nitroglycerin (Nitrostat) Dose in the treatment of chronic Anal fissure (0.4% ointment):

• Intra-anal:
  • 1 inch (equals 1.5 mg of nitroglycerin) every 12 hours for up to three weeeks.

Nitroglycerin (Nitrostat) Dose in the treatment of Esophageal spastic disorders (off-label):

• Sublingual:
  • 0.3-0.6 mg.
  • Additional data may be necessary to further define the role of nitroglycerin in this condition.

Nitroglycerin (Nitrostat) Dose in the treatment of Gastroesophageal variceal hemorrhage (off-label):

• IV infusion:
• Initial:
  • 40 mcg/min, increase by 40 mcg/min every 15 mins if systolic blood pressure is >90 to 100 mm Hg, up to a max of 400 mcg/min.
  • Coadminister with vasopressin and use at the highest effective dose for a max of 24 hours to minimize the development of adverse effects.

Nitroglycerin (Nitrostat) Dose in the treatment of Sympathomimetic vasopressor extravasation injury (alternative to phentolamine):

• Topical 2% ointment:
  • Apply a 1-inch strip to site of ischemia.
  • May repeat every 8 hours if needed.
  • To further define the role of topical nitroglycerin in this condition, additional data may be necessary.

Nitroglycerin (Nitrostat) Dose in the treatment of Uterine relaxation (for uterine inversion):

• IV:
  • Following delivery, 50 mcg to relax the uterus when uterine inversion occurs.
  • If needed, dose may be repeated.
• Max total dose:
  • 200 mcg.

Nitroglycerin (Nitrostat) Dose in Childrens

Note:

• For more than 1 year, Nitronal IV solution has been discontinued in the US.

Note:

• Continuous IV infusion dosing units vary by age (mcg/kg/min or mcg/min).
• Extra precautions should be taken.
• Within 24 to 48 hours of continuous use, tolerance to the hemodynamic & antianginal effects can develop.
• To avoid tolerance development, Nitrate-free interval (10 to 12 hours/day) is recommended.
• To avoid withdrawal reaction, gradually decrease dose in patients receiving nitroglycerin for prolonged periods.

Nitroglycerin (Nitrostat) Dose in the treatment of Heart failure and cardiogenic shock:

• Infants and Children:

  • Continuous IV infusion:

    • Initial:
    • 0.25-0.5 mcg/kg/min.
    • Titrate by 1 mcg/kg/minute every 15-20 minutes as needed.'
    • In some patients, faster titration may be necessary.
    • In adolescents, titration every 3-5 mins has been suggested.
  • Usual dose range:
    • 1-5 mcg/kg/min.
  • Usual max dose:
    • 10 mcg/kg/min (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:
      • 5-10 mcg/min.
      • Titrate every 3-5 mins as needed to the maximum rate of 200 mcg/min.

Nitroglycerin (Nitrostat) Dose in the treatment of Extravasation (sympathomimetic vasopressors), (alternative to phentolamine):

• Infants, Children, and Adolescents:

  • Topical: 2% ointment:
    • 4 mm/kg, Apply a thin ribbon to the affected areas.
    • If no improvement after 8 hours, the dose may be repeated at the affected site.
    • The max reported dose is the application of a 1-inch strip to the affected site in a neonate.
    • However, this is greater than the usual initial adult dose ( 1/2 inch) for angina.
    • Hypotension may occur.
    • Carefully examine blood pressure.
  • Note:
    • Minimal data are available from clinical trials/case reports.
    • However, use has been described in reviews of extravasation treatment.

Pregnancy Risk Category: C

• The placenta is crossed by Nitroglycerin
• Prior to cesarean delivery the concentrations of nitroglycerin in the umbilical cord at birth (1 minute after the dosing) was significantly lower than that in the maternal plasma.
• We observed a wide range in the maternal plasma concentrations.
• After applying a transdermal patch of 0.4 mg/hour for pregnant women between 20 and 36 weeks gestation, concentrations in nitroglycerin were low.
• However, they were detectable in the Fetal Serum within 1 to 4 Hours (fetal/Matern ratio: 0.23).
• When preeclampsia is accompanied by pulmonary edema, intravenous nitroglycerin should be used.
• In cases of uterine inversion, Nitroglycerin can be helpful after delivery.
• To further understand the role of nitroglycerin in other conditions that require uterine relaxation such as preterm labor, external cephalic version, retained feta or retained placenta, additional data may be required.

Nitroglycerin use during breastfeeding:

• It is unknown if breast milk contains nitroglycerin or not.
• There is not much information available on breastfeeding and nitroglycerin use.
• Breastfeeding infants from mothers who used topical nitroglycerin to treat anal fissures did not experience adverse events.
• A case report reveals that nitroglycerin cream was used to treat Raynaud phenomenon.
• Breastfeeding was stopped prior to the start of therapy.
• In a matter of weeks, signs and symptoms will disappear.
• According to the manufacturer, when deciding whether to continue or stop breastfeeding during therapy, it is important to consider the risks to infants, the benefits to the mother and the benefits to the mother.

Nitroglycerin (Nitrostat) Dose in Kidney Disease:

• In the manufacturer's labeling, there are no dosage adjustments provided.

Nitroglycerin Dose in Liver disease:

• In the manufacturer's labeling, there are no dosage adjustments provided.

Common Side Effects of Nitroglycerin (Nitrostat):

• Central Nervous System:

  • Headache

Less Common Side Effects of Nitroglycerin (Nitrostat):

• Cardiovascular:

  • Hypotension
  • Syncope
  • Peripheral Edema

• Central Nervous System:

  • Dizziness
  • Paresthesia

• Gastrointestinal:

  • Abdominal Pain

• Neuromuscular & Skeletal:

  • Weakness

• Respiratory:

  • Dyspnea
  • Pharyngitis
  • Rhinitis

Rare Side effects of Nitroglycerin (Nitrostat):

• Cardiovascular:

  • Bradycardia
  • Exacerbation Of Angina Pectoris
  • Flushing
  • Orthostatic Hypotension

• Dermatologic:

  • Diaphoresis

• Gastrointestinal:

  • Vomiting

• Miscellaneous:

  • Drug Tolerance

Contraindications to Nitroglycerin (Nitrostat):

• Hypersensitivity to nitroglycerin or other nitrates/nitrites or any component (includes adhesives that are used in transdermal products).
• Concurrent use of phosphodiesterase-5 inhibitors (avanafil sildenafil or vardenafil), concurrent use with soluble guanylate cyclase stimulators (eg riociguat).

Additional contraindications to IV products:

• Hypersensitivity to corn and corn products (solutions containing Dextrose)
• Constrictive pericarditis.
• Increased intracranial pressure
• Pericardial tamponade.
• Restrictive cardiomyopathy.
• Uncorrected hypovolemia.

Additional contraindications to sublingual product or rectal ointment

• Acute circulatory failure (sublingual tablets or powder).
• Sublingual tablet only for early myocardial injury; See Note
• Increased intracranial pressure
• Severe anemia

Additional contraindications to the translingual product

• Increased intracranial pressure
• Severe anemia.
• Acute circulatory failure (Nitrolingual only).

Canadian labeling:Additional contraindications to translingual products (not listed in the US labeling)

• Glaucoma with closed-angle vision
• Myocardial Infarction.
• Heart failure can be caused by constrictive pericarditis, heart stenosis (aortic and mitral stenosis), hypertrophic obstructive cardiomyopathy or constrictive pericarditis.

Canadian labeling:Additional contraindications to the transdermal patch (not on US labeling)

• Acute circulatory failure accompanied by marked hypotension (shock or states of collapse).
• Orthostatic hypotension
• Myocardial insufficiency caused by obstruction (eg, presence aortic or mitral stasis or constrictive pericarditis).
• Increased intracranial pressure
• An increase in intraocular pressure
• Severe anemia.

Notice:

• The American College of Cardiology Foundation/American Heart Association (ACCF/AHA), guidelines for managing ST-elevation myocardial Infarction (STEMI), and the ACC/AHA guidelines to manage patients with non-ST elevation acute coronary syndromes, (NSTE-ACS), recommend that you avoid nitrates under the following conditions:
  • Hypotension (SBP 90mm Hg or >=30mm Hg below baseline), marked bradycardia, tachycardia and right ventricular infarction.
  • Sublingual nitroglycerin can be used to treat persistent chest pain in patients with STEMI and NSTE-ACS.

Warnings and precautions

• Headache

  • Dose-related headaches can occur, especially during the initial dose.

• Hypotension and bradycardia

  • Even with low doses, severe hypotension and shock can occur.
  • Hypotension may be accompanied by paradoxical bradycardia and increased angina pectoris.
  • Orthostatic hypotension can also be a possibility.
  • This may be accentuated by ethanol.
  • Be cautious in cases of volume depletion, hypotension, constrictive or mitralstenosis, preexisting hypotension, volume loss, volume depletion, constrictive and constrictive pericarditis, aortic stenosis, aortic stenosis, and extreme caution when there is suspected right ventricular involvement.
  • The ACCF/AHA recommends that patients with severe hypotension (SBP >90 mm Hg, or >=30mm Hg below baseline), bradycardia, tachycardia, or right ventricular MI, be avoided.

• Increased intracranial pressure

  • Patients with neurologic injuries (eg intracranial hemorhage, trauma brain injury) may experience increased intracranial pressure.
  • Some products may not be used in patients who have high intracranial pressure.

• Hypertrophic cardiomyopathy, (HCM)

  • Patients with HCM and outflow tract obstruction should be avoided.
  • Preload may be reduced, which can lead to obstruction and hypotension.

Nitroglycerin (glyceryl trinitrate): Drug Interaction

Monitoring parameters:

• Blood pressure, heart rate.
• Consult individual institutional policies & procedures

How to administer Nitroglycerin (Nitrostat)?

• 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 an 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 & squeeze ointment the length of the measuring line directly onto the 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) & apply ointment around the side of the anal canal.
  • May apply the ointment to the outside of the anus if an intra-anal application is too painful.
  • Wash hands following application.

• Extended-release capsule:

  • swallow whole.
  • Do not chew, break, or crush.
  • Administer with a full glass of water.

• Sublingual powder:

  • Empty the contents of the packet under the tongue, close mouth, and breathe normally.
  • Allow the powder to dissolve without swallowing.
  • Do not rinse or spit for 5 mins after dosing.

• Sublingual tablet:

  • Do not chew, crush, or swallow sublingual tablets.
  • Place under tongue & allow to dissolve.
  • Alternately, it may be placed in the buccal pouch.
  • May take a small sip of water prior to placing the tablet under the tongue to aid dissolution.

• Topical ointment:

  • Wash hands prior to & after use.
  • The 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.

• Sympathomimetic vasopressors extravasation injury (alternative to phentolamine) (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 the site of ischemia.
  • May also apply dry warm compresses.

• Topical transdermal patch:

  • The application site should be clean, dry, and hair-free.
  • Remove patch after 12 to 14 hours.
  • Rotate patch sites.
  • Dispose of any use of unused patches by folding adhesive ends together, replace in a pouch or sealed container, and discard properly in trash, away from children and pets.

• Translingual spray:

  • Do not shake the 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 the patient & others.
  • Release spray onto or under the tongue.
  • After administration, close mouth immediately.
  • Do not inhale the spray.
  • Following administration, do not expectorate or rinse the mouth for 5-10 mins.
  • The 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.
  • A single priming spray (Nitrolingual) or 2 priming sprays (Nitromist) should be completed if the pump is unused for 6 weeks.
  • Re-prime with up to 5 sprays if the pump is unused for 3 months (Nitrolingual).

Mechanism of action of Nitroglycerin (Nitrostat):

• Nitroglycerin is a free radical of nitric dioxide.
• Smooth muscle is activated by nitric oxygen. This increases guanylate cyclease, which leads to cGMP (guanosine 3’5’ monophosphate) and dephosphorylation myosin light chain.
• Produces a vasodilator action on the peripheral veins, and arteries that have more prominent effects on veins.
• Preload (left ventricular ejection pressure) reduces the cardiac oxygen demand and primarily lowers cardiac oxygen need.
• Afterload may be slightly reduced
• It dilates the coronary arteries and increases collateral flow to ischemic areas.
• Intra-anal administration is recommended for rectal fissures. It results in decreased sphincter tone, and intra-anal tension.

The onset of action:

• Sublingual tablet:
  • 1-3 mins.
• Translingual spray:
  • Similar to the sublingual tablets.
• Extended-release:
  • ~60 mins.
• Topical:
  • 15-30 mins.
• Transdermal:
  • ~30 mins.
• IV:
  • Immediate

Peak effect:

• Sublingual powder:
  • 7 minutes.
• Sublingual tablet:
  • 5 mins.
• Translingual spray:
  • 4-15 mins.
• Extended-release:
  • 2.5-4 hours.
• Topical:
  • ~60 mins.
• Transdermal:
  • 120 mins.
• IV:
  • Immediate

Duration:

• Sublingual tablet:
  • At least 25 minutes.
• Translingual spray:
  • Similar to the sublingual tablets.
• Extended-release:
  • 4-8 hours (Gibbons 2003).
• Topical:
  • 7 hours.
• Transdermal:
  • 10-12 hours.
• IV:
  • 3-5 mins

Protein binding:

• 60%

Metabolism:

• Extensive first-pass effect.
• Metabolized hepatically to glycerol di- and mononitrate metabolites via liver reductase enzyme.
• Subsequent metabolism to glycerol and organic nitrate.
• Nonhepatic metabolism via red blood cells and vascular walls also occurs

Half-life elimination:

• ~1-4 mins

Excretion:

• Urine (as inactive metabolites)

International Brands of Nitroglycerin:

• GoNitro
• Minitran
• Nitro-Bid
• Nitro-Dur
• Nitro-Time
• Nitrolingual
• NitroMist
• Nitronal
• Nitrostat
• Rectiv
• APO-Nitroglycerin
• Minitran
• MYLAN-Nitro
• Nitro-Dur
• Nitroject
• Nitrol [DSC]
• Nitrolingual
• RHO-Nitro
• Transderm-Nitro
• Trinipatch 0.2
• Trinipatch 0.4
• Trinipatch 0.6
• Angiderm Patch
• Anginine
• Angised
• Cardiocare
• Cardiplast
• Cardispray
• Cardnit
• Deponit
• Deponit NT
• Dermatrans
• Diafusor
• Domitral
• Enetege
• Epinitril
• Glytrin
• Glytrin Spray
• Herzer
• Lycinate
• Millisrol
• Minitran
• Myonit Insta
• Myovin
• Natispray
• Niglinar
• Nit-Ret
• Nitracor
• Nitradisc
• Nitradisc TTS
• Nitral
• Nitriderm TTS
• Nitril
• Nitro
• Nitro Mack
• Nitro Mack Retard
• Nitro Pohl
• Nitro-Dur
• Nitro-Dur 10
• Nitro-Mack
• Nitro-Pflaster
• Nitro-Pflaster-ratiopharm
• Nitrobaat
• Nitrocard
• Nitrocerin
• Nitrocine
• Nitrocine 5
• Nitrocontin
• Nitrocontin Continus
• Nitrocor
• Nitroderm
• Nitroderm TTS
• Nitroderm TTS Ext
• Nitroderm TTS-5
• Nitrodisc
• Nitrodom
• Nitrodyl
• Nitrodyl TTS
• Nitrogesic
• Nitroglycerinum
• Nitroglycerinum prolongatum
• Nitroject
• Nitrol
• Nitrolingual
• Nitrolingual Pumpspray
• Nitrolingual Spray
• Nitromack Retard
• Nitromax
• Nitromex
• Nitromint
• Nitromint Aerosol
• Nitromint Khi dung
• Nitromint Retard
• Nitronal
• Nitronal Aqueous
• Nitronal Spray
• Nitrong
• Nitrong Retard
• Nitroplast
• Nitroplus
• Nitrosol Spray
• Nitrostat
• Nitrovas
• Nitrozell Retard
• NTG
• Nysconitrine
• Nyserin
• Perlinganit
• Ratiopharm
• Rectogesic
• Rectogesic Ointment
• Sustac
• Sustonit
• Transiderm Nitro
• Tridil
• Trimonit
• Trinipatch
• Venitrin
• Willlong

Nitroglycerin Brand Names in Pakistan: