Pronunciation: NYE-troe-GLIS-er-in
Class: Vasodilator, Nitrate

Trade Names

Minitran
- Patch, transdermal 9 mg
- Patch, transdermal 18 mg
- Patch, transdermal 36 mg
- Patch, transdermal 54 mg

Nitrek
- Patch, transdermal 22.4 mg
- Patch, transdermal 44.8 mg
- Patch, transdermal 67.2 mg

Nitro-Bid
- Ointment, transdermal 2% in a lanolin-petrolatum base

Nitro-Dur
- Patch, transdermal 20 mg
- Patch, transdermal 40 mg
- Patch, transdermal 60 mg
- Patch, transdermal 80 mg
- Patch, transdermal 100 mg
- Patch, transdermal 120 mg
- Patch, transdermal 160 mg

Nitro-Time
- Capsules, sustained-release, oral 2.5 mg
- Capsules, sustained-release, oral 9 mg

Nitroglycerin
- Injection, solution, concentrate 5 mg/mL
- Capsules, sustained-release, oral 6.5 mg

Nitroglycerin in 5% Dextrose
- Injection 100 mcg/mL
- Injection 200 mcg/mL
- Injection 400 mcg/mL

Nitrolingual
- Aerosol spray, sublingual 0.4 mg/metered dose

Nitrostat
- Tablets, sublingual 0.3 mg
- Tablets, sublingual 0.4 mg
- Tablets, sublingual 0.6 mg

Rectiv
- Ointment, rectal 0.4%

Gen-Nitro (Canada)
Nitrol (Canada)
Nitrolingual Pumpspray (Canada)
Rho-Nitro Pumpspray (Canada)
Transderm-Nitro (Canada)
Trinipatch (Canada)

Pharmacology

Relaxation of vascular smooth muscle and dilation of peripheral arteries and veins.

Slideshow: Can Prescription Drugs Lead to Weight Gain?

Pharmacokinetics

Absorption

Rapid. The bioavailability of the rectal ointment is approximately 50% of the dose.

Distribution

Vd is 3 L/kg. Protein binding is approximately 60% (parent); 1,2 dinitroglycerin is 60%; 1,3 dinitroglycerin is 30%.

Metabolism

Primarily metabolized in the liver by nitrate reductase; known sites of extrahepatic metabolism include red blood cells and vascular walls. Metabolized to inorganic nitrate and the active 1,2 and 1,3 dinitroglycerols.

Elimination

Serum half-life is 3 min ( Minitran ) and 1 to 8 min (sublingual). Cl is 1 L/kg/min ( Minitran ).

Onset

1 to 2 min (IV), 1 to 3 min (sublingual), and 1 h (ER).

Peak

1 to 4 h (immediate-release tablet), 6 to 7 min (sublingual), and 2 h (transdermal).

Duration

3 to 5 min (IV), 30 to 60 min (sublingual), 5 h (ER), and up to 12 h (transdermal ointment).

Indications and Usage

Aerosol spray, sublingual tablets

Acute relief of an attack or prophylaxis of angina pectoris caused by coronary artery disease.

ER capsules, transdermal ointment, transdermal patch

Prevention of angina pectoris caused by coronary artery disease.

IV

Treatment of perioperative hypertension; control of CHF in the setting of acute MI; treatment of angina pectoris in patients not responding to sublingual nitroglycerin and beta-blockers; induction of intraoperative hypotension.

Rectal ointment

Treatment of moderate to severe pain associated with chronic anal fissures.

Unlabeled Uses

IV

Management of acute MI; treatment of hypertensive emergencies; in combination with vasopressin to treat variceal bleeding, cocaine-induced acute coronary syndrome; management of Prinzmetal angina occurring in patients without coronary heart disease; management of sympathomimetic-induced cardiopulmonary toxicities.

Sublingual

Management of acute MI; management of Prinzmetal angina occurring in patients without coronary heart disease.

Transdermal

Management of acute MI; treatment of Prinzmetal angina occurring in patients without coronary heart disease; treatment of chronic anal fissure pain (ointment); erectile dysfunction; Raynaud disease.

Contraindications

IV, aerosol spray, sublingual tablets, transdermal patch

Allergy to organic nitrates; patient using phosphodiesterase type 5 inhibitors (PDE5) (eg, sildenafil, tadalafil, vardenafil).

IV

Pericardial tamponade; restrictive cardiomyopathy; constrictive pericarditis; solutions containing dextrose in patients with known allergy to corn or corn products.

Transdermal ointment, ER

Allergy to organic nitrates.

Sublingual tablets

Early MI; severe anemia; increased intracranial pressure.

Transdermal patch

Allergy to adhesives used in transdermal patches.

Rectal ointment

Hypersensitivity to organic nitrates, other nitrates, or nitrites; concurrent use with PDE5 inhibitors; severe anemia; increased intracranial pressure.

Dosage and Administration

Anal Fissure
Adults

Rectal Apply 1 inch of ointment intra-anally every 12 h for up to 3 wk.

Angina
Adults Aerosol spray

1 or 2 sprays onto or under tongue at first sign of acute angina attack; repeat every 5 min (do not exceed 3 sprays in 15 min). Also may be used 5 to 10 min before activity that might precipitate an anginal attack.

ER capsules

2.5 to 6.5 mg 3 to 4 times daily initially, titrate to response.

Sublingual tablets

0.3 to 0.6 mg dissolved under the tongue or in buccal pouch at first sign of acute angina attack; repeat every 5 min (do not exceed 3 tablets in 15 min). Also may be used as a single dose 5 to 10 min before activity that might precipitate an anginal attack.

Transdermal ointment

Initially, ½-inch dose applied twice daily (upon arising in the morning and 6 h later). May double dose in patients tolerating this dose but failing to respond to it.

Transdermal patch

Initially, 0.2 to 0.4 mg/h patch applied once daily; titrate dose to response. Remove patch after 12 to 14 h to provide nitroglycein-free interval.

Perioperative Hypertension, Induction of Intraoperative Hypotension, Refractory Angina, CHF Secondary to Acute MI
Adults

IV 5 mcg/min initially using nonabsorbing infusion set or 25 mcg/min using a polyvinyl chloride (PVC) administration set; titrate to response. Initial dose (non-PVC set) titration should be in 5 mcg/min increments every 3 to 5 min until some response is observed. If no response occurs at 20 mcg/min, increments of 10 to 20 mcg/min can be used. Once a partial BP response is observed, reduce dose and lengthen interval between dose increases.

General Advice

• To minimize development of tolerance, ensure daily nitroglycerin-free interval of 10 to 12 h is provided.

• Aerosol spray
• Do not shake container before administering dose.
• Prime aerosol unit initially with 1 spray. Reprime with 1 spray if unit has not been used for 6 or more weeks.
• Hold container upright as close to open mouth as possible; press button firmly to release spray onto or under the tongue; caution patient not to inhale spray. Have patient avoid swallowing immediately after administering spray. The patient should not expectorate medicine or rinse mouth for 5 to 10 min following administration.
• During administration of sublingual spray, patient should rest, preferably in the sitting position.
• Contains alcohol. Do not spray toward flames.

• Capsules
• Caution patient not to chew, crush, or open ER capsules.

• Injection
• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, intra-arterial, or intracoronary administration.
• Several preparations of nitroglycerin injection are available. They differ in concentration and/or volume per container. When switching from one product to another, pay attention to the dilution and dosage and administration instructions.
• Nitroglycerin solution for injection is concentrated and must be diluted prior to administration. Transfer contents of 1 vial (25 or 50 mg) into 500 mL glass bottle of dextrose 5% or sodium chloride 0.9% to provide final concentrations of 50 mcg/mL or 100 mg/mL. After initial titration, concentration of solution may be increased, if necessary, to a max concentration of 400 mcg/mL to limit fluids given to patient.
• Nitroglycerin in dextrose 5% is premixed and requires no further dilution.
• Use only with glass bottles and non-PVC infusions sets provided by manufacturer, or use non-PVC infusion sets.
• Administer only via infusion pump that can maintain constant infusion rate.
• Do not administer if container has lost vacuum, or if solution is discolored or cloudy or contains particulate matter.
• Avoid use of in-line filters that absorb nitroglycerin.
• When changing concentrations, disconnect tubing from patient and flush with new solution before continuing therapy.
• Do not mix nitroglycerin infusions through the same infusion set as blood to avoid pseudoagglutination and hemodialysis.
• Do not mix nitroglycerin solutions with any other medication.

• Rectal ointment
• For intra-anal use only; not for oral, ophthalmic, or intravaginal use.
• A finger covering (eg, plastic wrap, disposable surgical glove, finger cot) should be used for application.
• To obtain a 1 inch dose, the covered finger is laid alongside the 1 inch dosing line on the carton and the tube is gently squeezed until a line of ointment the length of the measuring line on the carton is expressed onto the finger.
• Gently insert the ointment into the anal canal using the covered finger no further than to the first finger joint and apply the ointment around the side of the anal canal. If this cannot be done because of pain, the ointment can be applied directly to the outside of the anus.
• Hands should be washed after application of the ointment.

• Sublingual tablets
• Caution patient not to crush, chew, or swallow sublingual tablets.
• During administration of sublingual tablets, patient should rest, preferably in the sitting position.

• Transdermal ointment
• Measure prescribed dose of ointment using measuring applicator supplied with tube. Squeeze necessary amount of ointment onto applicator and place applicator (ointment side down) on desired area of skin. Spread ointment using dose-measuring applicator, then tape applicator into place. Do not rub ointment into skin.
• Keep ointment tube tightly wrapped; cover dose-measuring applicator with plastic kitchen wrap to prevent staining of clothing by ointment.

• Transdermal patch
• Remove patch from foil pouch immediately prior to application.
• Remove protective liner from patch and apply to any area of the body except the extremities below the knee or elbow; the chest is preferred site. Press the patch on the skin and smooth down.
• Apply only to area that is clean, dry, and hairless. If hair is likely to interfere with patch adherence, clip, do not shave, the area before application.
• Do not apply patch to skin areas with cuts or irritation or immediately after showering or bathing.
• If the patch falls off, discard it and put a new one on at a different skin site.
• Do not discharge cardioverter/defibrillator through paddle electrode that overlies a transdermal patch. Doing so may damage the paddles and burn the patient.

Storage/Stability

Store ER capsules, aerosol spray, transdermal ointment, transdermal patch, solution for injection, and rectal ointment at controlled room temperature (59° to 86°F). Protect from freezing and light. Discard any unused solution. The rectal ointment should be discarded after 8 weeks of first opening. Store premixed nitroglycerin with dextrose at room temperature of 77°F (brief exposure up to 104°F does not affect product). Protect from freezing. Avoid excessive heat. Store sublingual tablets at controlled room temperature (68° to 77°F). Protect sublingual tablets from moisture.

Drug Interactions

Alcohol

Severe hypotension and CV collapse may occur.

Alteplase

Coadministration decreases plasma concentrations and thrombolytic effects of alteplase.

Beta-blockers (eg, propranolol)

Beta-blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. Additional hypotensive effects may occur.

Calcium channel blockers

Symptomatic orthostatic hypotension may occur.

Ergot alkaloids (eg, dihydroergotamine)

May increase systolic BP and decrease antianginal effects.

Heparin

May decrease anticoagulation effect when used in conjunction with IV nitroglycerin. Monitor the patient's anticoagulation status.

PDE5 inhibitors (eg, sildenafil, tadalafil, vardenafil)

Because the hypotensive effects of nitrates may be potentiated, concomitant use of any form of organic nitrates is contraindicated in patients receiving PDE5 inhibitors.

Salicylates (eg, aspirin)

Vasodilatory and hemodynamic effects of nitroglycerin may be enhanced.

Laboratory Test Interactions

May cause false report of reduced serum cholesterol with Zlatkis-Zak color reaction. May cause falsely elevated results of serum triglyceride assays (IV).

Adverse Reactions

Cardiovascular

Crescendo angina, hypotension, palpitations, rebound hypertension, syncope, vasodilation.

CNS

Asthenia, dizziness, headache, light-headedness, paresthesia, restlessness, vertigo, weakness.

Dermatologic

Allergic reactions including contact dermatitis or fixed drug eruptions (ointment or patches), drug rash, exfoliative dermatitis, flushing, perspiration.

EENT

Pharyngitis.

GI

Abdominal pain, burning or tingling in the oral cavity (sublingual), nausea, vomiting.

Hematologic-Lymphatic

Methemoglobinemia.

Local

Application-site irritation (transdermal).

Respiratory

Dyspnea.

Miscellaneous

Collapse, pallor, peripheral edema.

Precautions

Monitor Continuously monitor BP and heart rate while administering IV nitroglycerin; monitor pulmonary capillary wedge pressure when indicated.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Make dose selection with caution, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of comorbidity. Adverse reactions are likely to be more pronounced.

Acute MI/Heart failure

Benefits of oral and transdermal nitroglycerin not established; use with caution and with close clinical and hemodynamic monitoring in these settings to avoid hypotension and tachycardia. Use of ER nitroglycerin in these settings is not recommended because effects of nitroglycerin are difficult to terminate rapidly.

Angina

May aggravate angina caused by hypertrophic cardiomyopathy.

CNS effects

Produces dose-related headaches, which may be severe. Tolerance to headache occurs.

Diabetes mellitus

Use nitroglycerin solutions containing dextrose with caution.

Methemoglobinemia

High doses may produce methemoglobinemia, especially in patients with methemoglobin reductase deficiency.

Severe hypotension

Severe hypotension and shock may occur even with small doses, particularly with an upright posture. Use with caution in patients who are hypotensive or volume depleted; alcohol accentuates this reaction.

Tolerance

May develop with repeated use for prolonged periods of time; minimize tolerance by ensuring daily nitroglycerin-free intervals of 10 to 12 h are provided.

Overdosage

Symptoms

Air hunger, bloody diarrhea, coma, confusion, death, diaphoresis with flushed or cold and clammy skin, dyspnea followed later by reduced ventilatory effort, heart block and bradycardia, increased intracranial pressure, methemoglobinemia, moderate fever, nausea, palpitations, paralysis, seizures, syncope, throbbing headache, vertigo, visual disturbances, vomiting.

Patient Information

• Advise patients to carefully review the patient information leaflets and booklets supplied with each product before starting therapy, and to read and check for new information each time the medication is refilled.
• Review with patients and families the signs and symptoms of angina (eg, acute onset of pressure-like chest pain that may radiate down the left arm and/or into the neck or jaw, often associated with sweating and shortness of breath or difficulty breathing).
• Ensure patients using ER capsules, transdermal ointment, or transdermal patch to prevent angina attacks have sublingual nitroglycerin tablets or aerosol spray available at all times. Ensure patients know when and how to use sublingual nitroglycerin or aerosol spray and what to do if angina pain worsens or fails to respond to sublingual nitroglycerin.
• Caution patients that antianginal effectiveness of nitroglycerin is strongly related to the dosing regimen and not to stop taking or change the dose or frequency of administration unless advised by their health care provider.
• Advise patients that headaches are a common adverse reaction of therapy and are also a marker of effectiveness. Advise patients that acetaminophen can be used to relieve headache without reducing the medication's effectiveness. Caution patients not to reduce the dose or change the frequency of administration to avoid medication-induced headache.
• Advise patients to notify their health care provider if angina symptoms increase in frequency or severity, or if there is a sudden increase in the frequency of use of sublingual nitroglycerin or aerosol spray.
• Caution patients that medication may cause dizziness, light-headedness, or fainting, especially while standing or following consumption of alcohol.
• Caution patients to avoid sudden position changes to prevent orthostatic hypotension.
• Instruct patients to notify their health care provider if any of the following occur: frequent episodes of dizziness or light-headedness; fainting; intolerable headache; episodes of sweating; nausea and/or vomiting; any unusual or unexplained feeling or sensation.

• Aerosol spray
• Ensure patients know when and how to use aerosol spray: Sit down before using spray. Do not shake container before administering dose. Prime aerosol unit initially with 1 spray. Reprime with 1 spray if unit has not been used for 6 or more weeks. Hold container upright as close to open mouth as possible; press button firmly to release spray onto or under the tongue. Caution patient not to inhale spray. Have patient avoid swallowing immediately after administering spray or expectorating or rinsing the mouth for 5 to 10 min following administration. If pain remains, dose may be repeated every 5 min until 3 sprays are taken. Instruct patients to call 911 if pain becomes more intense or persists after a total of 3 sprays.
• Caution patients that aerosol spray contains alcohol and not to spray toward flames or forcefully open or burn container after use.
• Advise patients to discard aerosol and replace with new unit when end of pump is no longer covered by fluid.

• ER capsules
• Instruct patients using ER capsules to swallow whole and not to crush, chew, or open capsules.

• Injection
• Advise patients, families, or caregivers that medication will be prepared and administered by a health care provider in the intensive care center with close monitoring.

• Sublingual tablets
• Instruct patients to carry the tablets with them at all times and to keep the tablets in the original glass container and tightly capped.
• Instruct patients to sit down and dissolve 1 tablet under the tongue or between the cheek and gum at the first sign of an anginal attack. If pain remains, dose may be repeated every 5 min until 3 tablets are taken. Instruct patients to call 911 if pain becomes more intense or persists after a total of 3 tablets.
• Caution patients not to crush, chew, or swallow sublingual tablets.
• Instruct patients to lie down if dizziness or light-headedness occurs.
• Advise patients that tablets may produce a burning or tingling sensation but that the ability to cause burning or tingling is not considered a reliable method for determining potency of the tablets.
• Advise patients to discontinue nitroglycerin and notify their health care provider if vision is blurred or dry mouth occurs.

• Transdermal ointment
• Ensure patients know how to use transdermal ointment: Measure prescribed dose of ointment using measuring applicator supplied with tube by squeezing necessary amount of ointment onto applicator and placing applicator (ointment side down) on desired area of skin. Spread ointment using dose-measuring applicator, then tape applicator into place. Caution patients not to rub ointment into skin.
• Advise patients to cover dose-measuring applicator with plastic kitchen wrap to prevent staining of clothing by ointment.
• Instruct patients to remove first applicator 6 h after application and apply a second applicator. Instruct patients to remove second applicator after 6 h to provide a nitrate-free dosing interval.

• Transdermal patch
• Ensure patients know how to use transdermal patch: Remove patch from foil pouch immediately prior to application and remove protective liner from patch and apply to any area of the body except the extremities below the knee or elbow. Advise patient that the chest is the preferred site. Press the patch on the skin and smooth down.
• Advise patients to apply only to area that is clean, dry, and hairless. If hair is likely to interfere with patch adherence, instruct patient to clip, not shave, the area before application.
• Caution patients not to apply patch to skin areas with cuts or irritation, or immediately after showering or bathing.
• Advise patients that if the patch falls off, discard it and put a new one on at a different skin site.
• Caution patients to remove and discard patch after 12 to 14 h, as instructed by their health care provider, to provide a nitroglycerin-free interval.

Copyright © 2009 Wolters Kluwer Health.