nitroglycerin topical

Nitroglycerin topical is a medication that belongs to the nitrates class of drugs, used for the long-term prevention of chest pain (angina pectoris) associated with coronary artery disease. It is used off-label in the treatment of congestive heart failure.

Nitroglycerin topical is an ointment applied on the skin, usually on the chest, abdomen, or thighs.

Nitroglycerin relaxes the smooth muscles around blood vessels, dilating the veins and arteries, which reduces the heart’s workload and prevents angina pectoris. Dilatation of the veins causes peripheral venous pooling of blood which reduces the venous return of blood to the heart and consequently, the cardiac preload. Dilatation of arteries reduces systemic vascular resistance and the mean arterial pressure, which reduces the cardiac afterload, making it easier for the heart to pump out blood. Dilation of coronary arteries increases blood flow to the heart muscles.

Nitroglycerin is absorbed through the skin and is converted into nitric oxide in the vascular smooth muscle cells. Nitric oxide molecules bind to soluble guanylate cyclase (sGC), an enzyme in the cardiovascular smooth muscles, and activate the synthesis of a signaling molecule known as cyclic guanosine monophosphate (cGMP). An increase in cGMP concentration leads to the relaxation of the vascular smooth muscles.

• Do not use nitroglycerin topical in patients with hypersensitivity to nitroglycerin, other nitrites or nitrates, or any of the components in the formulation.
• Do not use nitroglycerin concurrently with or after recent use of phosphodiesterase-5 (PDE-5) inhibitors such as avanafil, sildenafil, tadalafil, or vardenafil, it can cause severe hypotension.
• Do not use concurrently with soluble guanylate cyclase (sGC) stimulators such as riociguat, it may cause hypotension.
• Do not interchange brands, they may not be bioequivalent.
• Headache is a marker of the drug’s activity. Drug-induced headache should be treated with aspirin or acetaminophen. Absence of headache is likely to be associated with loss of antianginal efficacy of the drug. 
• Nitroglycerin topical is primarily used for long-term prevention of angina, and not to treat an acute episode of angina, because its onset of action is not sufficiently rapid.
• There should be a nitrate-free interval of 10-12 hours to avoid the development of nitroglycerin tolerance.
• In some clinical trials, anginal attacks have been more easily provoked during nitrate-free intervals than before treatment. Patients have demonstrated hemodynamic rebound and decreased exercise tolerance. The importance of these observations to routine, clinical use of transdermal nitroglycerin is not known.
• Tolerance to other forms of nitroglycerin also may develop and blunt the effect of nitrate therapy on exercise tolerance. Physical dependence may develop; chest pains, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from patients who have developed tolerance.
• Use with caution in patients who drink alcohol, it can enhance the vasodilatory effects of nitroglycerin.
• Use with caution in patients with increased intracranial pressure due to head trauma. Cerebral hemorrhage is a potential contraindication.
• Use with caution in the following conditions:
  • Hyperthyroidism
  • Increased intraocular pressure
  • Hypertrophic cardiomyopathy
  • Hypotension
  • Blood volume depletion
  • Low systolic blood pressure
• Nitrate therapy may aggravate angina caused by hypertrophic cardiomyopathy.
• Severe hypotension, particularly with upright posture, may occur with even small doses. Use nitroglycerin with caution in patients who may be volume depleted or who are already hypotensive, it can cause paradoxical bradycardia and increased angina.
• Benefits of topical nitroglycerin in patients with acute myocardial infarction or congestive heart failure are not established. If used in these conditions, monitor the patient carefully to avoid the hazards of hypotension and tachycardia.

Common side effects of nitroglycerin topical include:

• Headache
• Lightheadedness
• Dizziness
• Blurred vision
• Rapid heart rate (tachycardia)
• Low blood pressure (hypotension)
• Flushing
• Excessive sweating (diaphoresis)
• Nervousness
• Nausea
• Vomiting
• Dry mouth (xerostomia)
• Allergic reactions
• Contact dermatitis

Less common side effects of nitroglycerin topical include:

• Fainting (syncope)
• Coronary artery disease-associated chest pain (unstable or crescendo angina)
• Rebound high blood pressure (hypertension)
• Prolonged bleeding time
• Low platelet count (thrombocytopenia)
• Severe skin reaction with peeling (exfoliative dermatitis)
• Serious allergic reaction (anaphylaxis)
• Methemoglobinemia, a condition with high blood level of methemoglobin, a form of hemoglobin that cannot carry and deliver oxygen (rare)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Ointment

• 2%

Adult:

Angina Pectoris (Long-Term Prophylaxis)

• 0.5-2 inches applied in am and 6 hours later to truncal skin

Congestive Heart Failure (Off-label)

• 1.5 inches, increase by 0.5-1 inch up to 4 inches, every 4 hours

Pediatric:

• Safety and efficacy not established

Overdose

• The adverse effects of nitroglycerin overdose are primarily because of its vasodilatory effects, which can cause venous pooling, hypotension and reduced cardiac output.
• The hemodynamic changes due to overdose can have many systemic effects including an increase in intracranial pressure with associated symptoms such as headache, confusion, vertigo, and fever; visual disturbances, nausea and vomiting, palpitations, slow heart rate, fainting, shortness of breath, seizures, paralysis, coma, and death.
• There is no specific antidote for nitroglycerin overdose. Overdose treatment includes increasing the central fluid volume, which may be achieved by elevation of the patient’s legs, and intravenous infusion of normal saline if required.
• Treatment of nitroglycerin overdose with central fluid volume increase may be more difficult and hazardous in patients with kidney disease or congestive heart failure, who may require invasive monitoring.
• In some patients, nitroglycerin overdose may cause methemoglobinemia, which may be treated with intravenous methylene blue.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of nitroglycerin topical include:
  • avanafil
  • bromocriptine
  • cabergoline
  • dihydroergotamine
  • dihydroergotamine intranasal
  • ergoloid mesylates
  • ergotamine
  • methylergonovine
  • sildenafil
  • tadalafil
  • vardenafil
• Serious interactions of nitroglycerin topical include:
  • cabergoline
  • ergoloid mesylates
  • ergotamine
  • lofexidine
  • methylergonovine
• Moderate interactions of nitroglycerin topical include:
  • arginine
  • bretylium
  • bupivacaine implant
  • tetracaine
• Mild interactions of nitroglycerin topical include:
  • acetylcysteine
  • acetylcysteine (Antidote)
  • ethanol

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on the safety of nitroglycerin topical use during pregnancy. Nitroglycerin topical should be used in pregnant women only if benefits to the mother outweigh potential risks to the fetus.
• It is not known if nitroglycerin is present in breast milk, use with caution in nursing mothers.

• Use nitroglycerin topical exactly as prescribed.
• Do not apply with your fingers, use the applicator provided with the medication. Do not rub or massage.
• Discontinue if you develop blurred vision, and contact your healthcare provider.
• Avoid alcohol while on nitroglycerin therapy, it may increase the vasodilatory effects.
• Notify your physician immediately if you experience faintness, flushing and dizziness. These symptoms are more likely when getting up suddenly from a lying position.
• Store safely out of reach of children.
• Nitroglycerin topical is for external use only. In case of accidental ingestion or overdose, seek immediate medical help or contact Poison Control.