Yes

Vasodilator

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)

C

Hypersensitivity to organic nitrates; hypersensitivity to isosorbide, nitroglycerin, or any component of the product; concurrent use with sildenafil; angle-closure glaucoma (intraocular pressure may be increased); head trauma or cerebral hemorrhage (increase intracranial pressure); severe anemia; allergy to adhesive (transdermal product)

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. Alcohol 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.

Spray or patch:

>10%: Central nervous system: Headache (patch 63%, spray 50%)

1% to 10%:

Cardiovascular: Hypotension (patch 4%), increased angina (patch 2%)

Central nervous system: Lightheadedness (patch 6%), syncope (patch 4%)

<1% (Limited to important or life-threatening symptoms): Allergic reactions, application site irritation (patch), rash, dizziness, weakness, restlessness, pallor, perspiration, collapse, exfoliative dermatitis, vertigo, palpitations, methemoglobinemia (rare, overdose)

Topical, sublingual, intravenous: Incidence of reactions are not reported:

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™).

Symptoms of overdose include hypotension, flushing, syncope, throbbing headache with reflex tachycardia, methemoglobinemia with extremely large overdoses; I.V. overdose may be additionally associated with increased intracranial pressure, confusion, vertigo, palpitation, nausea, vomiting, dyspnea, diaphoresis, heartblock, bradycardia, coma, seizures, and death

After gastric decontamination, treatment is supportive and symptomatic; hypotension is treated with positioning, fluids, and careful use of low-dose pressors, if needed; methylene blue may treat methemoglobinemia

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 potentiates the hypotensive effects of nitrates; concurrent use is contraindicated.

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

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

Reduces cardiac oxygen demand by decreasing left ventricular pressure and systemic vascular resistance; dilates coronary arteries and improves collateral flow to ischemic regions

Onset and duration of action is dependent upon dosage form administered

Onset of effect:

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 metabolism

Half-life: 1-4 minutes

Elimination: Excretion of inactive metabolites in urine

Note: Hemodynamic and antianginal tolerance often develop within 24-48 hours of continuous nitrate administration

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

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

May need to use nitrate-free interval (10-12 hours/day) to avoid tolerance development; gradually decrease dose in patients receiving NTG for prolonged period to avoid withdrawal reaction

Blood pressure, heart rate

Concomitant use of sildenafil (Viagra®) 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.

May cause dizziness

None reported, but monitor for hypotension if receiving a psychotropic

No information available to require special precautions

No effects or complications reported

Oral: Take as directed. Do not chew or swallow sublingual tablets; allow to dissolve under tongue. Do not chew or crush extended release capsules; swallow with 8 oz of water.

Spray. Spray directly on mucous members; do not inhale.

Topical: Spread prescribed amount thinly on applicator; rotate application sites.

Transdermal: Place on hair-free area of skin, rotate sites.

Do not change brands without consulting prescriber. Do not discontinue abruptly. Keep medication in original container, tightly closed. Take medication while sitting down and use caution when changing position (rise from sitting or lying position slowly). May cause dizziness; use caution when driving or engaging in hazardous activities until response to drug is known. If chest pain is unresolved in 15 minutes, seek emergency medical help at once. Report acute headache, rapid heartbeat, unusual restlessness or dizziness, muscular weakness, or blurring vision. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

I.V. must be prepared in glass bottles and use special sets intended for nitroglycerin; transdermal patches labeled as mg/hour; do not crush sublingual drug product; NTG infusions should be administered only via a pump that can maintain a constant infusion rate

Capsule, sustained release: 2.5 mg, 6.5 mg, 9 mg, 13 mg

Injection: 0.5 mg/mL (10 mL); 0.8 mg/mL (10 mL); 5 mg/mL (1 mL, 5 mL, 10 mL, 20 mL); 10 mg/mL (5 mL, 10 mL)

Injection, solution in D₅W: 25 mg (250 mL), 50 mg (250 mL, 500 mL), 100 mg (250 mL), 200 mg (500 mL)

Ointment, topical (Nitrol®): 2% [20 mg/g] (30 g, 60 g)

Patch, transdermal, topical: Systems designed to deliver 0.1 mg/hr, 0.2 mg/hr, 0.4 mg/hr, 0.6 mg/hr, 2.5, 5, 7.5, 10, or 15 mg NTG over 24 hours

Spray, translingual: 0.4 mg/metered spray (5.7, 12 g)

Tablet:

Buccal, controlled release: 1 mg, 2 mg, 3 mg

Sublingual (Nitrostat®): 0.3 mg, 0.4 mg, 0.6 mg

Sustained release: 2.6 mg, 6.5 mg, 9 mg

Buckley R and Roberts R, "Symptomatic Bradycardia Following the Administration of Sublingual Nitroglycerin," Am J Emerg Med, 1993, 11(3):253-5.

Ehrenpreis ED, Young MA, and Leikin JB, "Symptomatic Nitroglycerin Toxicity From Erroneous Use of Topical Nitroglycerin," Vet Hum Toxicol, 1990, 32(2):138-9.

Elkayam U, "Tolerance to Organic Nitrates: Evidence, Mechanisms, Clinical Relevance, and Strategies for Prevention," Ann Intern Med, 1991, 114(8):667-77.

Khan AH and Carleton RA, "Nitroglycerin-Induced Hypotension and Bradycardia," Arch Intern Med, 1981, 141(8):984.

Marshall JB and Ecklund RE, "Methemoglobinemia From Overdose of Nitroglycerin," JAMA, 1980, 244(4):330.