General

Pronunciation:
nye-tro-gli-ser-in

nitroglycerin extended-release capsules

Trade Name(s)

• Nitro-Time

nitroglycerin intravenous

Trade Name(s)

• Nitro-Bid IV
• Nitroject 
• Tridil

nitroglycerin sublingual tablets

Trade Name(s)

• Nitrostat

nitroglycerin transdermal ointment

Trade Name(s)

• Nitro-Bid

nitroglycerin transdermal patch

Trade Name(s)

• Nitro-Dur
• Trinipatch 

nitroglycerin translingual spray

Trade Name(s)

• Nitrolingual

Ther. Class.

antianginals

Pharm. Class.

nitrates

Indications

• Acute (translingual, SL, ointment) and long-term prophylactic (oral, transdermal) management of angina pectoris.
• PO Adjunct treatment of HF.
• IV Adjunct treatment of acute MI.
• Production of controlled hypotension during surgical procedures.
• Treatment of HF.

Action

• Increases coronary blood flow by dilating coronary arteries and improving collateral flow to ischemic regions.
• Produces vasodilation (venous greater than arterial).
• Decreases left ventricular end-diastolic pressure and left ventricular end-diastolic volume (preload).
• Reduces myocardial oxygen consumption.

Therapeutic Effect(s):

• Relief or prevention of anginal attacks.
• Increased cardiac output.
• Reduction of BP.

Pharmacokinetics

Absorption: Well absorbed after oral, buccal, and sublingual administration. Also absorbed through skin. Orally administered nitroglycerin is rapidly metabolized, leading to ↓ bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Undergoes rapid and almost complete metabolism by the liver; also metabolized by enzymes in bloodstream.

Half-life: 1–4 min.

TIME/ACTION PROFILE (cardiovascular effects)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• ↑ intracranial pressure;
• Severe anemia;
• Pericardial tamponade;
• Constrictive pericarditis;
• Uncorrected hypovolemia;
• Alcohol intolerance (large IV doses only);
• Acute circulatory failure/shock;
• Black Box:  Concurrent use of PDE-5 inhibitor (avanafil, sildenafil, tadalafil, vardenafil) or riociguat.

Use Cautiously in:

• Head trauma or cerebral hemorrhage;
• Glaucoma;
• Hypertrophic cardiomyopathy;
• Severe hepatic impairment;
• Malabsorption or hypermotility (PO);
• Cardioversion (remove transdermal patch before procedure);
• OB:  May compromise maternal/fetal circulation;
• Lactation:  Safety not established in breastfeeding;
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: hypotension, tachycardia, syncope

Derm: contact dermatitis (transdermal), flushing

EENT: blurred vision

GI: abdominal pain, nausea, vomiting

Neuro: dizziness, headache, apprehension, restlessness, weakness.

Misc: alcohol intoxication (large IV doses only), tolerance

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Avanafil,  sildenafil,  tadalafil, or  vardenafil  may result in severe hypotension (do not use within 24 hr of isosorbide dinitrate or mononitrate); concurrent use contraindicated.
•  Riociguat  may result in severe hypotension; concurrent use contraindicated.
• Additive hypotension with  antihypertensives, acute ingestion of  alcohol,  beta blockers,  calcium channel blockers,  haloperidol, or  phenothiazines.
• Agents having anticholinergic properties ( tricyclic antidepressants,  antihistamines,  phenothiazines ) may ↓ absorption of translingual or sublingual nitroglycerin.

Route/Dosage

SL (Adults): Tablets:  0.3–0.6 mg; may repeat every 5 min for 2 additional doses for acute attack; may also be used prophylactically 5–10 min before activities that may precipitate an acute attack.

 Translingual Spray: (Adults): 1–2 sprays; may be repeated every 5 min for 2 additional doses for acute attack; may also be used prophylactically 5–10 min before activities that may precipitate an acute attack.

PO (Adults): 2.5–9 mg every 8–12 hr.

IV (Adults): 5 mcg/min; ↑ by 5 mcg/min every 3–5 min to 20 mcg/min; if no response, ↑ by 10–20 mcg/min every 3–5 min (dosing determined by hemodynamic parameters; max: 200 mcg/min).

Transdermal (Adults): Ointment:  1–2 in. every 6–8 hr.  Transdermal patch:  0.2–0.4 mg/hr initially; may titrate up to 0.4–0.8 mg/hr. Patch should be worn 12–14 hr/day and then taken off for 10–12 hr/day.

Availability (generic available)

Extended-release capsules: 2.5 mg, 6.5 mg, 9 mg

Sublingual tablets: 0.3 mg, 0.4 mg, 0.6 mg

Translingual spray: 0.4 mg/spray in 4.9-g bottle (60 doses) or 14.6-g bottle (200 doses)

Transdermal patch: 0.1 mg/hr, 0.2 mg/hr, 0.3 mg/hr, 0.4 mg/hr, 0.6 mg/hr, 0.8 mg/hr

Transdermal ointment: 2%

Solution for injection: 5 mg/mL

Premixed infusion: 25 mg/250 mL D5W, 50 mg/250 mL D5W, 100 mg/250 mL D5W

Assessment

• Assess location, duration, intensity, and precipitating factors of patient's anginal pain.
• Monitor BP and HR before and after administration. Patients receiving IV nitroglycerin require continuous ECG and BP monitoring. Additional hemodynamic parameters may be monitored.

Lab Test Considerations:

May cause ↑ urine catecholamine and urine vanillylmandelic acid concentrations.

• Excessive doses may cause ↑ methemoglobin concentrations.
• May cause falsely ↑ serum cholesterol levels.

Implementation

• PO Administer dose 1 hr before or 2 hr after meals with a full glass of water for faster absorption.  DNC: Sustained-release preparations should be swallowed whole; do not break, crush, or chew. 
• SL Tablet should be held under tongue until dissolved. Avoid eating, drinking, or smoking until tablet is dissolved.
• Translingual spray: Spray  Nitrolingual  under tongue.

• Topical 

  Rotate sites of topical application to prevent skin irritation. Remove patch or ointment from previous site before application.

  • Doses may be ↑ to the highest dose that does not cause symptomatic hypotension.
  • Apply ointment by using dose-measuring application papers supplied with ointment. Squeeze ointment onto measuring scale printed on paper. Use paper to spread ointment onto nonhairy area of skin (chest, abdomen, thighs; avoid distal extremities) in a thin, even layer, covering a 2–3-in. area. Do not allow ointment to come in contact with hands. Do not massage or rub in ointment; this will ↑ absorption and interfere with sustained action. Apply occlusive dressing if ordered.
  • Transdermal patches may be applied to any hairless site (avoid distal extremities or areas with cuts or calluses). Apply firm pressure over patch to ensure contact with skin, especially around edges. Apply a new dose unit if the first one becomes loose or falls off. Units are waterproof and not affected by showering or bathing. Do not cut or trim system to adjust dosage. Do not alternate between brands of transdermal products; dose may not be equivalent. Remove patches before MRI, cardioversion, or defibrillation to prevent patient burns. Patch may be worn for 12–14 hr and removed for 10–12 hr at night to prevent development of tolerance.

Patient/Family Teaching

• Instruct patient to take medication as directed, even if feeling better. Take missed doses as soon as remembered unless next dose is scheduled within 2 hr (6 hr with extended-release preparations). Do not double doses. Do not discontinue abruptly; gradual dose ↓ may be necessary to prevent rebound angina.

  • Caution patient to change positions slowly to minimize orthostatic hypotension. 1st dose should be taken while in a sitting or reclining position, especially in older adults.
  • Advise patient to avoid concurrent use of alcohol with this medication. Patient should also consult health care provider before taking OTC medications while taking nitroglycerin.
  • Inform patient that headache is a common side effect that should decrease with continuing therapy. Aspirin or acetaminophen may be ordered to treat headache. Notify health care provider if headache is persistent or severe.
  • Advise patient to notify health care provider if dry mouth or blurred vision occurs.
• Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.
• Acute Anginal Attacks: Advise patient to sit down and use medication at 1st sign of attack. Relief usually occurs within 5 min. Dose may be repeated if pain is not relieved in 5–10 min. Call health care provider or go to nearest emergency room if anginal pain is not relieved by 3 tablets in 15 min.
• SL Inform patient that tablets should be kept in original glass container or in specially made metal containers, with cotton removed to prevent absorption. Tablets lose potency in containers made of plastic or cardboard or when mixed with other capsules or tablets. Exposure to air, heat, and moisture also causes loss of potency. Instruct patient not to open bottle frequently, handle tablets, or keep bottle of tablets next to body (e.g., shirt pocket) or in automobile glove compartment. Advise patient that tablets should be replaced 6 mo after opening to maintain potency.
• Lingual Spray: Instruct patient to lift tongue and spray dose under tongue.

Evaluation/Desired Outcomes

• Decrease in frequency and severity of anginal attacks.

  • Increase in activity tolerance. During long-term therapy, tolerance may be minimized by intermittent administration in 12–14 hr or 10–12 hr off intervals.
• Controlled hypotension during surgical procedures.
• Treatment of HF associated with acute MI.