Millis

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Medically reviewed

Laura Arias

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Millis

Property Description
Active ingredient Nitroglycerin (Glyceryl trinitrate, GTN)
Form Oromucosal Spray (Sublingual)
Pharmacological class Organic Nitrate, Vasodilator
Common use Rapid management of acute circulatory discomfort
Origin Synthetic chemical compound

What is Millis and Its Pharmacological Classification?

Millis is a prescription medicinal product defined by its single active ingredient, Nitroglycerin, accurately identified as Glyceryl trinitrate (GTN). This compound belongs to the Organic Nitrate pharmacological class, established for its powerful function as a Vasodilator. As a synthetic agent, it is chemically manufactured to consistently deliver a precise therapeutic amount of the active component. Its classification confirms its primary purpose: to induce the relaxation and widening of the smooth muscle in blood vessel walls throughout the circulatory system. Nitroglycerin acts directly on vascular smooth muscle to cause vasodilation, which works by expanding the body’s blood vessels.


Composition and Rapid-Action Oromucosal Spray Form

The Millis product is characterized by its formulation as an Oromucosal Spray, a specific liquid solution delivered via a metered dose. It is a Single-Active Ingredient Product, containing Nitroglycerin dissolved in a carrier vehicle, typically including dehydrated alcohol and specific triglycerides. This Sublingual or Oromucosal route of administration is essential, as it ensures the substance is absorbed rapidly through the oral lining, gaining immediate entry into the bloodstream. This specific spray delivery system provides extremely quick pharmacological effects, a feature that distinguishes it from slower delivery formats. Sublingual Nitroglycerin preparations are designed for the acute management of circulatory discomfort due to this rapid-acting nature. This fast-acting characteristic allows the medicine to provide swift relief when needed.


General Therapeutic Role of Nitroglycerin

The general therapeutic role of Nitroglycerin is intrinsically linked to its potent vasodilatory action. By relaxing veins and arteries, the medicine immediately reduces the circulatory pressure and strain on the heart. Specifically, it substantially decreases the amount of blood returning to the heart (preload), which subsequently lowers the heart's overall workload. This mechanism promotes the widening of the coronary arteries, enhancing the supply of oxygenated blood to the heart muscle itself, thereby addressing the underlying issue of an oxygen supply imbalance. Millis is often utilized in scenarios requiring a rapid reduction in cardiac workload to restore circulatory balance.

What side effects are possible with Millis?

Possible Side Effects and Safety Information

This section outlines the officially documented adverse effects and safety characteristics for Millis (Nitroglycerin Oromucosal Spray), based strictly on government regulatory documents such as the FDA Prescribing Information and the European Summary of Product Characteristics (SmPC).

Frequency-Classified Adverse Reactions

The following are side effects documented in regulatory labeling, categorized by frequency:

  • Very Common (Affects 1 in 10 or more): Headache.
  • Common (Affects 1 in 10 to 1 in 100): Dizziness, Vertigo, Facial Flushing, Nausea, Asthenia (Weakness).
  • Uncommon (Affects 1 in 100 to 1 in 1,000): Syncope (Fainting), Application site discomfort (e.g., Burning, Stinging).
  • Rare to Very Rare: Orthostatic Hypotension, Circulatory Collapse, Angina Pectoris aggravated, Allergic Dermatitis, Exfoliative Dermatitis, and decreased heart rate (Bradycardia).

Serious Safety Considerations

The most clinically significant adverse reaction listed is the potential for severe hypotension (extremely low blood pressure), which may lead to circulatory collapse or shock. Other serious effects documented include Methemoglobinemia (associated with higher doses) and Exfoliative Dermatitis.

Safety Constraints and Special Populations

Official labeling defines strict limitations for the use of Millis:

  • Contraindications: The medicine must not be used in individuals with conditions such as Severe Anemia, Pronounced Hypotension, Circulatory Failure, or conditions involving Increased Intracranial Pressure.
  • Time-Related Patterns: Headaches are very common when treatment is initiated but frequently decrease with continued use. Hypotension is also more likely upon initial use or dose increase.
  • Pediatric Use: Use in children and adolescents under 18 years of age is contraindicated as safety and efficacy have not been established by regulatory agencies.

Overdose and Emergency Response

Overdose and When to Seek Help

Official regulatory information describes overdose with Millis (Nitroglycerin) as an exaggerated extension of its vasodilatory action, which requires immediate medical intervention.

Overdose is primarily characterized by severe cardiovascular manifestations and central nervous system effects. Documented signs include severe hypotension (very low blood pressure), circulatory collapse, and reflex tachycardia. Additional clinical signs documented in official labeling include severe throbbing headache, dizziness, vertigo, vomiting, and flushing.

Severe Outcomes and Emergency Actions

The most severe and potentially life-threatening outcomes documented in regulatory sources are shock, seizures, coma, and methaemoglobinaemia (a condition affecting the blood's oxygen-carrying capacity).

Authorities uniformly state that individuals must seek immediate medical attention or contact a Poison Help line when overdose is suspected. This immediate action is mandated because no specific antidote is known for the medicine's vasodilatory effects, meaning treatment must be symptomatic and supportive in a clinical setting.

Management procedures described in official labels focus on treating hypotension through volume replacement and addressing methaemoglobinaemia with appropriate counter-agents, while continuous monitoring of vital signs is required.

Therapeutic Uses of Millis

Millis is relevant for symptomatic relief in patients whose discomfort is associated with conditions marked by increased physiological stress. This medication is commonly used across conditions presenting with acute episodes of angina pectoris, a condition for which this medication is commonly indicated.

Rapid Relief for Acute Anginal Chest Pain

Millis is applied in clinical settings that involve acute symptom patterns and is relevant for easing symptoms related to physical discomfort, such as the sudden onset of pressure, tightness, or squeezing in the chest. This medicine assists with the management of symptom clusters that may become intense or disruptive. The medication plays a role in managing acute distress, contributing to improved comfort and stability when symptoms become more noticeable.

Managing Exertion-Induced Symptoms (Acute Prophylaxis)

This approach is relevant when supportive symptom management is appropriate, applied in scenarios where additional management of discomfort is needed for conditions marked by increased physiological stress. Millis may assist with the management of symptom clusters that appear suddenly, contributing to improved comfort by easing anticipated chest discomfort, and supports general well-being during symptomatic phases.


Quick Fact: Relief for Anginal Chest Pain

Millis is primarily used for symptomatic relief of angina, supportive management during episodes of heightened symptoms, and easing discomfort and pressure in the chest.

Regulatory References

  1. NIH MedlinePlus overview of Nitroglycerin Spray

Eligibility and Restrictions for Use

The eligibility for using Millis (Nitroglycerin Oromucosal Spray) is strictly defined by regulatory documents, which establish the permitted age group and list several conditions and co-administered medications that prohibit its use.

Official Eligibility and Contraindications

Classification Eligible Population/Prohibited Conditions
Established Use Adults are the standard population for the acute relief and prophylaxis of the indicated condition.
Absolute Contraindications Use is strictly forbidden in patients taking Phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) or Soluble Guanylate Cyclase (sGC) stimulators (e.g., riociguat).
Prohibitive Conditions Patients with severe anemia, increased intracranial pressure (e.g., cerebral hemorrhage or head trauma), acute circulatory failure or shock, or known hypersensitivity to nitrates must not use this medicine.
Pediatric Restriction Not recommended for children and adolescents, as the safety and effectiveness of the spray in the pediatric population have not been established by regulators.
Pregnancy and Lactation Safety data are insufficient to determine risk in pregnancy; use is conditional. It is unknown if the drug is excreted in human milk.
Conditional Use Caution is advised for geriatric patients and those with conditions like hypertrophic cardiomyopathy or severe hypotension due to volume depletion.

The regulatory profile clearly defines Millis as an adult-use medicine, with the most severe eligibility restriction being the absolute prohibition against its use with other vasodilatory medications that may cause life-threatening hypotension.

What should I know about interactions with other medicines?

Millis Interactions with Other Medicines and Products

Millis, which contains Nitroglycerin, has a defined interaction profile centered on its potent vasodilatory action, as documented in official government regulatory sources.


Formally Contraindicated Combinations

Co-administration of Millis with certain drug classes is strictly prohibited due to the high risk of severe, life-threatening hypotension and cardiovascular collapse. This restriction is based on the amplification of the drug's effects. The contraindicated classes are:

  • Phosphodiesterase Type 5 (PDE-5) Inhibitors (e.g., Sildenafil, Tadalafil, Vardenafil).
  • Soluble Guanylate Cyclase (sGC) Stimulators (e.g., Riociguat).

Documented Pharmacodynamic and Exposure Interactions

Other clinically significant interactions are documented in regulatory labeling, primarily concerning additive effects or changes in drug levels:

Interacting Product Category Official Interaction Description
Antihypertensive Medicines Additive hypotensive effects can occur with other blood pressure-lowering agents (e.g., Beta-Blockers, Calcium Channel Blockers).
Aspirin May reduce clearance and increase plasma concentrations ( C max and AUC) of Nitroglycerin.
Ergotamine and related drugs Nitroglycerin increases the oral bioavailability of Ergotamine; co-administration is advised against.
Heparin Nitroglycerin may reduce the anticoagulant effect of Heparin, requiring aPTT monitoring.
Alcohol May enhance sensitivity to the hypotensive effects of nitrates.

These interactions are formally documented to prevent enhanced effects, reduced efficacy of co-administered drugs, or severe drops in blood pressure.

Mechanism of Action

Enzymatic Activation of the NO-cGMP Pathway

The mechanism begins with the biotransformation of Nitroglycerin (GTN), which acts as a prodrug. This process requires specific enzymes, primarily Mitochondrial Aldehyde Dehydrogenase ( ALDH2), to metabolize the molecule and release Nitric Oxide ( NO). This NO then quickly activates the enzyme Soluble Guanylate Cyclase ( sGC) inside vascular smooth muscle cells. The resulting rapid increase in the second messenger cyclic Guanosine Monophosphate ( cGMP) initiates the cellular pathway leading to relaxation.

Modulation of Vascular Smooth Muscle Tone

The elevated cGMP levels initiate a sequence that ultimately causes the dephosphorylation of proteins responsible for muscle contraction, leading to widespread vascular smooth muscle relaxation (vasodilation). This effect is most pronounced in the systemic veins, dramatically increasing their capacity. The resulting shift in blood volume significantly lowers the volume of blood returning to the heart, a key hemodynamic parameter known as preload, leading to a reduction in cardiac workload.

Mechanistic Constraints (Tolerance)

The mechanism is constrained by its requirement for the enzyme and cofactors involved in NO generation. Continuous or repeated use can lead to the saturation or depletion of these upstream components, a limitation known as pharmacological tolerance. This constraint implies that the mechanism is optimally suited for acute, intermittent pathway modulation rather than sustained, continuous pathway engagement.

Dosage and Administration Information

How Millis is Used: Official Administration Guidelines

Millis, a nitroglycerin product, is formulated as an Oromucosal Spray and is strictly administered via the sublingual route (onto or under the tongue) for rapid absorption into the bloodstream. This method is designated for the acute, as-needed management of circulatory discomfort or its prophylaxis.

Official Dosing and Frequency

Official prescribing information outlines precise dosing and frequency constraints for adult use:

Use Scenario Starting Dose Repetition Schedule Maximum Limit
Acute Event 1 or 2 metered sprays (400 - 800 mug) Repeat every 5 minutes if symptoms persist No more than 3 metered sprays (total 1200 mug) within 15 minutes
Acute Prophylaxis 1 or 2 metered sprays 5 to 10 minutes before activity As directed by a healthcare provider

If symptoms are not relieved after the third spray within the 15-minute period, immediate medical attention is required.

Key Administration Procedures

To ensure proper use, the device must be primed before the first use (and after periods of non-use) to ensure a full dose is delivered. During use, the container should be held upright, and the spray must be directed onto or under the tongue; the dose is not to be inhaled. Following administration, the user should not swallow, expectorate, or rinse the mouth for a period of 5 to 10 minutes to allow the medicine to be absorbed efficiently through the oral mucosa. The use of Millis is not recommended for children or adolescents under the age of 18.

Recent Clinical Evidence

Research Evidence / Overview of Studies for Millis

This overview summarizes the official research conducted on the active ingredient in Millis (Nitroglycerin Oromucosal Spray), focusing on the types of studies available and the nature of the findings described in regulatory and scientific literature. The research described contributes to the broader evidence landscape but does not provide individual predictions or clinical recommendations.


1. Research Exploring Acute Angina Outcomes

Research has extensively explored the use of the spray for managing episodic or acute changes associated with chest discomfort. These investigations have primarily relied on short-term Randomized Controlled Trials (RCTs), often designed as crossover studies comparing the active spray to placebo in adults diagnosed with Chronic Stable Angina Pectoris. Studies monitored changes in patient-reported discomfort over very short time intervals. Findings describing patterns where the active spray reported a shorter Time to Onset of Change in Patient-Reported Discomfort compared to placebo have been documented.


2. Research Exploring Prophylactic Outcomes Before Exertion

Research also explored the application of the spray shortly before planned physical exertion. These studies involved controlled settings, such as functional tests, using placebo-controlled RCTs. Studies monitored outcomes reflecting daily functioning or activity level, specifically the time a participant could exercise before the onset of chest discomfort. Findings indicated that when the spray was used preemptively, participants appeared to have changes in the measured time to symptom onset during the exercise test compared to placebo.


3. Uncertainty and Research Gaps

Research in specific groups, such as older adults or populations with various concurrent conditions (comorbidities), is still insufficient. The overall certainty remains low for long-term effects, as primary studies feature limited follow-up durations restricted to acute use. Furthermore, research comparing this spray formulation against other nitroglycerin formulations in larger, specialized trials is still developing.

Key Studies & References

  1. Nitroglycerin Spray: MedlinePlus Drug Information

Frequently Asked Questions (FAQ)

Common questions about Millis (FAQ)

Q: How quickly should I expect to feel the effects of Millis?

A: Official prescribing information indicates that the active ingredient in Millis is absorbed very quickly through the oral lining. Clinical studies show that the maximum concentration of the medication in the bloodstream is typically reached within 5 to 7.5 minutes following administration, leading to a rapid pharmacological effect.

Q: Can Millis be taken with other maintenance medications for chronic conditions?

A: Regulatory documents advise caution when Millis is used with any medication that lowers blood pressure, such as Beta-Blockers or Calcium Channel Blockers. This is due to the potential for additive effects, which could cause blood pressure to drop too low. Information about all other medicines should be reviewed by a healthcare provider.

Q: What should I do if the side effects from Millis feel too strong?

A: If you experience severe side effects like extreme dizziness, feeling faint, or lightheadedness, these may be signs of a dangerously low blood pressure drop. Official guidance recommends sitting or lying down immediately to help prevent fainting. If symptoms persist or are concerning, consult with a healthcare professional.

Q: How does Millis compare to older treatments for the same condition?

A: Clinical studies comparing the spray formulation to older sublingual tablets indicate that the spray generally provides a similar anti-anginal effect. Some data suggests that this formulation may be associated with a different side effect profile, including potentially fewer reports of headache.

Q: Is Millis safe for people with high blood pressure?

A: Millis is a vasodilator, which means it is designed to lower blood pressure. Therefore, caution is required when it is used by individuals with existing high blood pressure or those taking blood pressure medications. Official product information stresses the need to avoid use with certain other medications due to the risk of severe hypotension (very low blood pressure).

Q: How should Millis be stored (temperature, light, etc.)?

A: Regulatory requirements state that Millis must be stored at controlled room temperature and protected from heat and light. Because the product is a pressurized, flammable canister, it must never be frozen, punctured, or incinerated, and should be kept out of the sight and reach of children.

Q: What is the biggest difference between Millis and other similar medications?

A: The key distinction is the specific formulation as an oromucosal spray and the sublingual (under the tongue) route of administration. This delivery method is designed for very rapid absorption directly into the bloodstream. This provides a quick pharmacological effect, setting it apart from slower-acting nitrate medications or different formulations.

Q: Is a metallic taste in the mouth normal when starting Millis?

A: Official adverse reaction reports do not explicitly list a metallic taste as a common side effect. However, a small number of patients have reported general taste disturbances. These sensations, when reported, are often described as mild and temporary.

Q: Can taking Millis make you feel dizzy or lightheaded?

A: Yes, dizziness, vertigo, and lightheadedness are common side effects documented in the official product information. These effects are often related to the primary action of the drug, which involves lowering blood pressure. Patients are informed about these potential effects.

Q: How long does Millis typically stay in your system?

A: The half-life of the active ingredient, which is a measure of how quickly the drug is cleared, is reported to be very short, typically between 1 and 4 minutes. This rapid clearance is consistent with its use as a fast-acting, short-duration medication for acute events.

Q: Why do some people feel very tired after taking Millis?

A: Official labeling lists asthenia, a medical term referring to a lack of energy or weakness, as a common adverse reaction. This feeling of generalized weakness can be interpreted by users as tiredness after administration.

Q: Are there any mood changes that can happen while taking Millis?

A: While significant mood changes are not listed as common side effects, some reports have included mild psychiatric adverse reactions, such as feelings of restlessness or apprehension. This information comes from official safety surveillance reports.

Q: What were the major findings from the clinical trials for Millis?

A: Key findings from clinical trials established the spray’s rapid effectiveness. Studies demonstrated a statistically significant reduction in the time patients took to report relief compared to a placebo. Additionally, the medicine appeared to change the measured time participants could exercise before symptoms began during controlled exercise tests.

Q: Can Millis be crushed or split if it's a tablet?

A: Millis is not manufactured as a tablet or capsule. It is supplied as an oromucosal spray within a specialized canister. Therefore, there are no instructions provided for crushing or splitting the medication, as it is only intended for administration via spray onto or under the tongue.

Q: Can taking Millis affect my ability to drive or operate machinery?

A: Yes. Official safety information advises caution because side effects like dizziness, vertigo, and lightheadedness are common. These symptoms may impair your ability to safely drive or operate machinery, particularly when you first start treatment or after a dose is administered.

Q: Is there a maximum time someone can safely take Millis?

A: There is no fixed limit on the total duration of use for Millis. However, for continuous, long-term use of nitrate medications, official guidance recommends incorporating a daily nitrate-free interval, typically 10 to 12 hours, to help prevent pharmacological tolerance from developing.

Q: Can Millis cause temporary changes in vision?

A: Although it is not a common side effect, official adverse event reports have listed blurred vision as a rare adverse reaction. This suggests that some temporary visual changes may occur in a small number of users.

How should Millis be stored and disposed of?

Official Storage and Handling Requirements

Millis (Nitroglycerin oromucosal spray) must be stored at Controlled Room Temperature, defined as 20 C to 25 C (68 F to 77 F), with permitted fluctuations. The product must not be frozen or exposed to extreme heat, moisture, or direct light. It should be kept in its tightly closed original container and stored securely out of the sight and reach of children.

Disposal

Due to the pressurized and flammable nature of the canister, regulatory labeling states that the product must not be punctured, incinerated, or used near a flame. Unused or expired medicine must be properly discarded according to local guidelines; it is not to be flushed down the toilet or poured into a drain unless specifically instructed by a healthcare professional.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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