Brand name: Rectiv
Drug class: Skin and Mucous Membrane Agents, Miscellaneous

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

Introduction

Organic nitrate; vasodilating agent.¹

Uses for Nitroglycerin (Topical)

Chronic Anal Fissure

Intra-anal treatment of moderate to severe pain associated with chronic anal fissure.^{1 3 6 7 8 9}

Chronic anal fissure is thought to be related to sustained high resting anal sphincter tone and associated anodermal ischemia.⁷ 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.^{3 5 7} 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.^{3 5 9}

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.¹

Apply using a finger covering (e.g., plastic wrap, disposable surgical glove, finger cot).¹ Squeeze a line of ointment equaling the length of the measuring line on the dosage guide on the ointment carton onto the covered finger.¹

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.¹ If pain prevents insertion, apply directly to the outside of the anus.¹

Discard the used finger covering and wash hands after application of the ointment.¹

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.¹

Improved outcomes (e.g., healing rates, reduction in pain) reported after extension of treatment duration to 6 weeks^{† [off-label]}.^{3 5 6}

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Nitroglycerin (Topical)

Contraindications

• Known hypersensitivity to nitroglycerin, other nitrates or nitrites, or any ingredient in the formulation.¹

• Concomitant or recent (within a few days) treatment with selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil).¹

• Severe anemia or increased intracranial pressure.¹

Warnings/Precautions

Sensitivity Reactions

Flushing, allergic reactions, and application site reactions (including drug rash and exfoliative dermatitis) reported rarely.¹

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.¹

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.¹

More pronounced adverse cardiovascular effects likely in geriatric patients.¹

Risk of transient lightheadedness, occasionally related to BP changes.¹ Hypotension (including orthostatic hypotension), in some cases requiring discontinuance of nitroglycerin ointment, reported infrequently.¹

Headache

Risk of dose-related headaches, which may be severe; headaches typically are of short duration and respond to analgesics (e.g., acetaminophen).^{1 8} Tolerance occurs but headache may recur after each dose.^{1 8} Prophylactic acetaminophen recommended by some clinicians.³

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether nitroglycerin is distributed into milk.¹ Caution if used in nursing women.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

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.¹

Common Adverse Effects

Headache,^{1 6 7} dizziness.^{1 6}

Drug Interactions

Specific Drugs

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).¹

Distribution

Extent

Not known whether nitroglycerin is distributed into milk.¹

Plasma Protein Binding

Approximately 60%.¹

Elimination

Metabolism

Metabolized by a liver reductase enzyme to glycerol dinitrate and mononitrate metabolites and then to glycerol and organic nitrate.¹ Also metabolized in extrahepatic sites, including red blood cells and vascular walls.¹

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.¹

Elimination Route

Metabolism is the primary route of elimination.¹

Half-life

1.5–7.5 minutes.¹

Stability

Storage

Rectal

Ointment

20–25°C (may be exposed to 15–30°C).¹ Keep tightly closed; discard 8 weeks after first opened.¹

Actions

• Principal pharmacologic property is relaxation of vascular smooth muscle, resulting in generalized vasodilation.¹

• 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.¹

• Intra-anal application of nitroglycerin reduces sphincter tone and resting intra-anal pressure.^{1 4 5 7} The reduction in anal pressure may result in increased anal blood flow.^{4 7}

Advice to Patients

• Importance of providing patient a copy of manufacturer’s patient information.²

• Importance of advising patients to discard ointment 8 weeks after it is first opened.²

• 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).¹

• 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.²

• 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.¹ Importance of advising patients to stand up slowly from a supine or seated position¹ and to avoid consuming alcohol while using nitroglycerin 0.4% rectal ointment.²

• Risk of dizziness; importance of advising patients not to drive or use machinery immediately after applying nitroglycerin 0.4% rectal ointment.¹

• Risk of headache; tolerance to headaches develops.¹ Importance of advising patients not to alter the schedule of nitroglycerin 0.4% rectal ointment treatment to avoid headaches.¹ Headaches may be prevented or relieved by use of an analgesic (e.g., acetaminophen).¹

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.

Frequently asked questions

• How do you take GoNitro to treat an angina attack (chest pain)?
• What is the shelf life of nitroglycerin tablets?

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