Nitroglycerin (Topical) (Monograph)

Brand name: Rectiv
Drug class: Basic Ointments and Protectants

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Organic nitrate; vasodilating agent.

Uses for Nitroglycerin (Topical)

Chronic Anal Fissure

Intra-anal treatment of moderate to severe pain associated with chronic anal fissure.

Chronic anal fissure is thought to be related to sustained high resting anal sphincter tone and associated anodermal ischemia. Lateral internal sphincterotomy generally has been used to treat anal fissures that do not respond to conservative therapy (e.g., sitz baths, increased dietary fiber); however, minor incontinence, which may be persistent, may develop after surgery. Botulinum toxin type A injections or topical therapy with nitrates (e.g., nitroglycerin rectal ointment) or calcium-channel blocking agents (e.g., diltiazem gel, not commercially available in US) has been used to reduce anal sphincter tone and circumvent potential complications of surgery.

Nitroglycerin (Topical) Dosage and Administration

Administration

Rectal Administration

0.4% ointment: apply rectally into the anal canal; do not administer orally, vaginally, or topically to the eye.

Apply using a finger covering (e.g., plastic wrap, disposable surgical glove, finger cot). Squeeze a line of ointment equaling the length of the measuring line on the dosage guide on the ointment carton onto the covered finger.

Gently insert ointment into the anal canal no further than to the first finger joint using the covered finger; also apply around the side of the anal canal. If pain prevents insertion, apply directly to the outside of the anus.

Discard the used finger covering and wash hands after application of the ointment.

Dosage

Adults

Chronic Anal Fissure

Rectal

375 mg (1 inch) of 0.4% ointment (equivalent to 1.5 mg nitroglycerin) every 12 hours for ≤3 weeks.

Improved outcomes (e.g., healing rates, reduction in pain) reported after extension of treatment duration to 6 weeks^{† [off-label]}.

Special Populations

No special population dosage recommendations at this time.

Cautions for Nitroglycerin (Topical)

Contraindications

Known hypersensitivity to nitroglycerin, other nitrates or nitrites, or any ingredient in the formulation.
Concomitant or recent (within a few days) treatment with selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil).
Severe anemia or increased intracranial pressure.

Warnings/Precautions

Sensitivity Reactions

Flushing, allergic reactions, and application site reactions (including drug rash and exfoliative dermatitis) reported rarely.

Cardiovascular Effects

May cause venous and arterial dilation, which can decrease venous blood returning to the heart and reduce arterial vascular resistance and systolic pressure.

Use with caution in patients with blood volume depletion, hypotension, cardiomyopathies, CHF, acute MI, or poor cardiac function; monitor cardiovascular status and clinical condition in such patients.

More pronounced adverse cardiovascular effects likely in geriatric patients.

Risk of transient lightheadedness, occasionally related to BP changes. Hypotension (including orthostatic hypotension), in some cases requiring discontinuance of nitroglycerin ointment, reported infrequently.

Headache

Risk of dose-related headaches, which may be severe; headaches typically are of short duration and respond to analgesics (e.g., acetaminophen). Tolerance occurs but headache may recur after each dose. Prophylactic acetaminophen recommended by some clinicians.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether nitroglycerin is distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Increased sensitivity to nitrates (e.g., more frequent or severe hypotension and related dizziness or fainting) reported in geriatric patients; may be related to higher frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.

Common Adverse Effects

Headache, dizziness.

Drug Interactions

Specific Drugs

Drug	Interaction	Comments
Alcohol	Additive vasodilating effects, possibly resulting in hypotension	Avoid concomitant use
Aspirin	Possible increase in nitroglycerin concentrations and pharmacologic effects
β-Adrenergic blocking agents	Possible additive hypotensive effects	Monitor for possible additive effects (e.g., orthostatic hypotension)
Calcium-channel blocking agents	Possible additive hypotensive effects	Monitor for possible additive effects (e.g., orthostatic hypotension)
Ergot alkaloids (e.g., dihydroergotamine, ergotamine)	Possible reduced first-pass metabolism and increased bioavailability of dihydroergotamine; may result in ergotism Ergotamine is known to precipitate angina pectoris	Consider possibility of ergotism if used concomitantly
Heparin	Possible decreased anticoagulant effect of IV heparin	Monitor anticoagulation status if used concomitantly
Hypotensive agents	Possible additive hypotensive effects	Monitor for possible additive effects (e.g., orthostatic hypotension)
Nitrates	Possible additive hypotensive effects	Monitor for possible additive effects (e.g., orthostatic hypotension)
PDE5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)	Potentiated hypotensive effects of organic nitrates	Use of nitroglycerin ointment within a few days of PDE5 inhibitors is contraindicated
Tissue-type plasminogen activator (t-PA)	Possible reduced plasma concentrations and thrombolytic effects of t-PA	Use concomitantly with caution

Nitroglycerin (Topical) Pharmacokinetics

Absorption

Bioavailability

Mean absolute bioavailability approximately 50% of a 0.75-mg dose applied to the anal canal as nitroglycerin 0.2% ointment (not commercially available in US).

Distribution

Extent

Not known whether nitroglycerin is distributed into milk.

Plasma Protein Binding

Approximately 60%.

Elimination

Metabolism

Metabolized by a liver reductase enzyme to glycerol dinitrate and mononitrate metabolites and then to glycerol and organic nitrate. Also metabolized in extrahepatic sites, including red blood cells and vascular walls.

The 2 major metabolites of nitroglycerin are 1,2-dinitroglycerol and 1,3-dinitroglycerol; the contribution of metabolites to the pharmacologic effect on the anal sphincter is not known.

Elimination Route

Metabolism is the primary route of elimination.

Half-life

1.5–7.5 minutes.

Stability

Storage

Rectal

Ointment

20–25°C (may be exposed to 15–30°C). Keep tightly closed; discard 8 weeks after first opened.

Actions

Principal pharmacologic property is relaxation of vascular smooth muscle, resulting in generalized vasodilation.
Nitroglycerin forms free radical nitric oxide, which activates guanylate cyclase; activation of guanylate cyclase results in an increase of guanosine-3′,5′-monophosphate (cyclic GMP) in smooth muscle and other tissues, leading to dephosphorylation of myosin light chains and vasodilation.
Intra-anal application of nitroglycerin reduces sphincter tone and resting intra-anal pressure. The reduction in anal pressure may result in increased anal blood flow.

Advice to Patients

Importance of providing patient a copy of manufacturer’s patient information.
Importance of advising patients to discard ointment 8 weeks after it is first opened.
Importance of advising patients not to use nitroglycerin 0.4% rectal ointment within a few days of use of selective PDE5 inhibitors (e.g., sildenafil, tadalafil, vardenafil).
Importance of advising patients to stop using nitroglycerin 0.4% rectal ointment and to seek immediate medical attention if symptoms of a severe allergic reaction (e.g., difficulty breathing, swelling of the face, lips, tongue, or throat) occur.
Risk of lightheadedness and hypotension on standing, especially just after rising from a supine or seated position; may occur more frequently when alcohol is consumed. Importance of advising patients to stand up slowly from a supine or seated position and to avoid consuming alcohol while using nitroglycerin 0.4% rectal ointment.
Risk of dizziness; importance of advising patients not to drive or use machinery immediately after applying nitroglycerin 0.4% rectal ointment.
Risk of headache; tolerance to headaches develops. Importance of advising patients not to alter the schedule of nitroglycerin 0.4% rectal ointment treatment to avoid headaches. Headaches may be prevented or relieved by use of an analgesic (e.g., acetaminophen).

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.