Nitroglycerin 0.4% Ointment
It is used to treat anal pain.
Drug Class
Agent for anal fissure
Pharmacologic Class
Organic Nitrate
Pregnancy Category
Category C
FDA Approved
Jun 2011
DEA Schedule
Not Controlled
Overview
What is this medicine?
Nitroglycerin ointment is a medication applied around the anus to help heal anal fissures. It works by relaxing the muscles in the anal area and improving blood flow, which helps the fissure to heal and reduces pain.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Before and after applying the medication, wash your hands thoroughly.
To apply the ointment:
1. Cover your finger with plastic wrap, a surgical glove, or a finger cot.
2. Use the dosing guide on the packaging to apply the correct amount of ointment to your covered finger.
3. Gently insert the finger with the ointment into the anal canal, up to the first finger joint.
4. Smear the ointment inside the anus. You can also apply the ointment to the outside of the anus if needed.
Remember to avoid getting the ointment in your mouth, nose, vagina, or eyes, as it may cause burning.
Storage and Disposal
Store this medication at room temperature in a dry place, avoiding bathrooms. Keep the tube tightly closed and use the medication within 8 weeks of opening. Store all medications in a safe location, out of the reach of children and pets.
Missed Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or extra doses.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Before and after applying the medication, wash your hands thoroughly.
To apply the ointment:
1. Cover your finger with plastic wrap, a surgical glove, or a finger cot.
2. Use the dosing guide on the packaging to apply the correct amount of ointment to your covered finger.
3. Gently insert the finger with the ointment into the anal canal, up to the first finger joint.
4. Smear the ointment inside the anus. You can also apply the ointment to the outside of the anus if needed.
Remember to avoid getting the ointment in your mouth, nose, vagina, or eyes, as it may cause burning.
Storage and Disposal
Store this medication at room temperature in a dry place, avoiding bathrooms. Keep the tube tightly closed and use the medication within 8 weeks of opening. Store all medications in a safe location, out of the reach of children and pets.
Missed Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or extra doses.
Lifestyle & Tips
- Maintain good bowel habits to avoid constipation and straining during bowel movements (e.g., adequate fiber and fluid intake).
- Avoid prolonged sitting or standing if experiencing dizziness.
- Use a finger cot or disposable glove for application to prevent absorption through the fingers.
Available Forms & Alternatives
Available Strengths:
- Nitroglycerin 0.2 Mg/hr Patch
- Nitroglycerin 0.6 Mg/hr Patch
- Nitroglycerin 0.4 Mg/hr Patch
- Nitroglycerin 0.1 Mg/hr Patch
- Nitroglycerin 400mcg Spray 60 Doses
- Nitroglycerin 400mcg Spray 200 Dose
- Nitroglycerin 0.6mg Sub Tabs 100
- Nitroglycerin 0.4mg Sub Tab 25s
- Nitroglycerin 0.3mg Sl Tabs 100
- Nitroglycerin 0.4mg Sub Tabs 100s
- Nitroglycerin 0.3mg Sl Tabs 100
- Nitroglycerin 0.4% Ointment
Dosing & Administration
Adult Dosing
Standard Dose:
Approximately 375 mg of ointment (containing 1.5 mg nitroglycerin) applied perianally every 12 hours
Condition-Specific Dosing:
chronic_anal_fissure:
Apply 1 inch of ointment (approx. 375 mg) perianally every 12 hours, using a finger cot or glove.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment recommended due to low systemic absorption.
Moderate:
No specific adjustment recommended due to low systemic absorption.
Severe:
No specific adjustment recommended due to low systemic absorption.
Dialysis:
No specific considerations due to low systemic absorption.
Hepatic Impairment:
Mild:
No specific adjustment recommended due to low systemic absorption.
Moderate:
No specific adjustment recommended due_to low systemic absorption.
Severe:
No specific adjustment recommended due to low systemic absorption.
Pharmacology
Mechanism of Action
Nitroglycerin is an organic nitrate that is converted to nitric oxide (NO) in vascular smooth muscle cells. NO activates guanylate cyclase, increasing intracellular cyclic guanosine monophosphate (cGMP), which leads to dephosphorylation of myosin light chains and subsequent relaxation of smooth muscle. In the context of anal fissures, this action primarily relaxes the internal anal sphincter, reducing anal canal pressure and improving blood flow to the anoderm, thereby promoting healing.
Pharmacokinetics
Absorption:
Bioavailability:
Low and variable (extensive first-pass metabolism)
Tmax:
Variable, typically within 30-60 minutes for topical effect
FoodEffect:
Not applicable for topical administration
Distribution:
Vd:
Large (approximately 3 L/kg for IV, but systemic distribution is limited with topical)
ProteinBinding:
Approximately 60%
CnssPenetration:
Limited
Elimination:
HalfLife:
1-4 minutes (parent drug); metabolites have longer half-lives (up to several hours)
Clearance:
High systemic clearance
ExcretionRoute:
Renal (primarily as glucuronide conjugates of metabolites)
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Within minutes (for local sphincter relaxation)
PeakEffect:
Variable, typically within 30-60 minutes for local effect
DurationOfAction:
Approximately 6-8 hours (for sphincter relaxation)
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Severe dizziness or fainting
Abnormal heartbeat (fast, slow, or irregular)
Flushing
Blurred vision
Dry mouth
Excessive sweating
Pale skin
Severe nausea or vomiting
Restlessness
Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they persist, contact your doctor:
Dizziness or headache (note: headaches may occur when starting this medication, but they often improve over time; do not adjust your dosage without consulting your doctor)
* If you experience any other side effects that concern you or do not go away, discuss them with your doctor.
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor for guidance. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Severe dizziness or fainting
Abnormal heartbeat (fast, slow, or irregular)
Flushing
Blurred vision
Dry mouth
Excessive sweating
Pale skin
Severe nausea or vomiting
Restlessness
Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they persist, contact your doctor:
Dizziness or headache (note: headaches may occur when starting this medication, but they often improve over time; do not adjust your dosage without consulting your doctor)
* If you experience any other side effects that concern you or do not go away, discuss them with your doctor.
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor for guidance. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe or persistent headache (common, but report if debilitating)
- Dizziness or lightheadedness upon standing (orthostatic hypotension)
- Fainting (syncope)
- Blurred vision
- Unusual sweating or clamminess
- Chest pain (rare with topical, but seek immediate medical attention if occurs)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction and its symptoms.
Certain health conditions, including:
+ Anemia
+ Increased pressure in the head, which may be caused by bleeding in the brain or a head injury
+ Recent heart attack
+ Heart problems
+ Low blood volume
If you are currently taking any of the following medications:
+ Avanafil
+ Riociguat
+ Sildenafil
+ Tadalafil
+ Vardenafil
+ Dihydroergotamine
+ Ergonovine
+ Ergotamine
+ Methylergonovine
Note that this is not an exhaustive list of all potential interactions. Therefore, it is crucial to disclose all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you may have.
Your doctor and pharmacist need to be aware of all your medications and health conditions to ensure it is safe for you to take this medication. Never start, stop, or adjust the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction and its symptoms.
Certain health conditions, including:
+ Anemia
+ Increased pressure in the head, which may be caused by bleeding in the brain or a head injury
+ Recent heart attack
+ Heart problems
+ Low blood volume
If you are currently taking any of the following medications:
+ Avanafil
+ Riociguat
+ Sildenafil
+ Tadalafil
+ Vardenafil
+ Dihydroergotamine
+ Ergonovine
+ Ergotamine
+ Methylergonovine
Note that this is not an exhaustive list of all potential interactions. Therefore, it is crucial to disclose all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you may have.
Your doctor and pharmacist need to be aware of all your medications and health conditions to ensure it is safe for you to take this medication. Never start, stop, or adjust the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, be cautious when performing tasks that require alertness and clear vision, such as driving, until you understand how it affects you. To minimize the risk of dizziness or fainting, stand up slowly after sitting or lying down, and exercise caution when navigating stairs.
Follow your healthcare provider's instructions for monitoring your blood pressure. Additionally, be aware that this medication may interfere with certain laboratory tests, so it is crucial to notify all your healthcare providers and laboratory personnel that you are taking this drug.
Avoid consuming alcohol while on this medication, as it may interact with the drug. If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
When starting this medication, be cautious when performing tasks that require alertness and clear vision, such as driving, until you understand how it affects you. To minimize the risk of dizziness or fainting, stand up slowly after sitting or lying down, and exercise caution when navigating stairs.
Follow your healthcare provider's instructions for monitoring your blood pressure. Additionally, be aware that this medication may interfere with certain laboratory tests, so it is crucial to notify all your healthcare providers and laboratory personnel that you are taking this drug.
Avoid consuming alcohol while on this medication, as it may interact with the drug. If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Severe hypotension (low blood pressure)
- Reflex tachycardia (fast heart rate)
- Flushing
- Persistent throbbing headache
- Dizziness
- Syncope
- Palpitations
- Nausea and vomiting
- Diaphoresis
- Methemoglobinemia (rare, but serious, characterized by cyanosis, shortness of breath, fatigue)
What to Do:
If overdose is suspected, seek immediate medical attention or call a poison control center (1-800-222-1222). Lay the patient down with legs elevated. Administer intravenous fluids. If severe hypotension persists, consider alpha-adrenergic agonists (e.g., phenylephrine) in patients without cardiac contraindications. For methemoglobinemia, methylene blue may be administered.
Drug Interactions
Contraindicated Interactions
- Phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil) due to potentiation of hypotensive effects.
- Riociguat (soluble guanylate cyclase stimulator) due to potentiation of hypotensive effects.
Major Interactions
- Other vasodilators (e.g., hydralazine, minoxidil)
- Antihypertensive agents (e.g., beta-blockers, calcium channel blockers, ACE inhibitors, ARBs, diuretics) due to additive hypotensive effects.
- Alcohol (ethanol) due to additive hypotensive effects.
Moderate Interactions
- Tricyclic antidepressants (TCAs)
- Phenothiazines (may cause orthostatic hypotension)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Blood pressure
Rationale: To establish baseline cardiovascular status and assess risk of hypotension.
Timing: Prior to initiation of therapy.
Heart rate
Rationale: To establish baseline and monitor for reflex tachycardia.
Timing: Prior to initiation of therapy.
Routine Monitoring
Blood pressure
Frequency: Periodically, especially during initial treatment or dose adjustments.
Target: Maintain within patient's normal range, avoiding symptomatic hypotension.
Action Threshold: Significant drop in systolic BP (>20 mmHg) or symptomatic hypotension (dizziness, lightheadedness, syncope).
Headache severity
Frequency: Daily, especially during initial treatment.
Target: Not applicable
Action Threshold: Severe or debilitating headache that is not manageable with analgesics.
Symptom Monitoring
- Headache (common)
- Dizziness
- Lightheadedness
- Flushing
- Nausea
- Blurred vision
- Syncope (fainting)
- Palpitations
Special Patient Groups
Pregnancy
Category C. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown adverse effects at doses higher than human therapeutic doses.
Trimester-Specific Risks:
First Trimester:
Limited human data; theoretical risk based on animal studies at high doses.
Second Trimester:
Limited human data.
Third Trimester:
Limited human data.
Lactation
It is unknown whether nitroglycerin is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Low systemic absorption suggests low risk.
Infant Risk:
Low risk due to low systemic absorption, but monitor infant for signs of hypotension, flushing, or headache.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Use with caution in elderly patients, as they may be more susceptible to the hypotensive effects of nitrates. Consider starting with lower doses if systemic effects are a concern, and monitor blood pressure closely.
Clinical Information
Clinical Pearls
- Headache is a very common side effect and often indicates that the medication is working. It typically lessens with continued use.
- Patients should be instructed to apply the ointment externally around the anus, not internally into the rectum.
- Always use a finger cot or disposable glove for application to prevent absorption through the fingers of the person applying the ointment.
- Patients should be advised to sit or lie down if they experience dizziness or lightheadedness after application.
- Avoid abrupt discontinuation, although less critical for topical than systemic forms, to prevent potential rebound symptoms.
Alternative Therapies
- Botulinum toxin injection (e.g., Botox) for internal anal sphincter relaxation
- Topical calcium channel blockers (e.g., diltiazem ointment, nifedipine ointment)
- Surgical lateral internal sphincterotomy (for refractory cases)
Cost & Coverage
Average Cost:
Price range varies, typically $100-$300 per 30g tube of 0.4% ointment
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (for generic), Tier 3 or Tier 4 (for brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.