Overview of Evicel

Evicel is a Fibrin Sealant categorized as a specialized biological medicinal product used in surgical settings to support the body's natural bleeding control process, known as haemostasis.

Quick Facts

Property	Description
Active Ingredients	Human Fibrinogen, Human Thrombin
Form	Solution for Sealant (Dual-Component Kit)
Pharmacological Class	Hemostatic Agent, Blood Coagulation Factor
General Purpose	Adjuvant to surgical haemostasis and tissue sealing
Origin	Plasma-derived (from pooled human plasma)

What Type of Medicine is Evicel Fibrin Sealant?

Evicel is classified as a hemostatic agent belonging to the pharmacological group of Blood Coagulation Factors. It is explicitly identified as a plasma-derived therapeutic, meaning its active substances originate from pooled human plasma. The use of fibrin sealants provides a localized, active method of achieving haemostasis, which is clinically recognized for reducing the duration of surgical procedures. This product is strictly intended for topical application, serving as an adjuvant to conventional surgical techniques such as sutures.

Composition and Form: What is Evicel Made Of?

Evicel is a combination product containing two essential active ingredients: Human Fibrinogen (Clottable Protein) and Human Thrombin (a serine protease). It is supplied as a Solution for Sealant within a dual-component system, a key differentiating feature that ensures the active components remain separate until the moment of application. The components, prepared in an aqueous base, are designed to react instantly upon mixing to facilitate immediate and robust clot formation.

What is the General Purpose of Evicel?

This product's general purpose is to provide supportive treatment by enhancing the localized control of bleeding and acting as an aid for sealing tissues during various surgical operations. When applied, the two primary components rapidly mimic the last steps of the physiological blood coagulation cascade, causing the Fibrinogen to be converted instantly into insoluble Fibrin threads. This rapid, on-demand conversion creates a tenacious, localized Fibrin Clot that helps to reinforce and seal the treated soft tissues, often used when controlling broad surface bleeding is a challenge.

Regulatory References

What side effects are possible with Evicel ?

Possible Side Effects and Safety Information

Evicel is a plasma-derived biological medicinal product, and its risk profile is formally documented in government regulatory sources, establishing its adverse reactions and safety constraints.

Documented Adverse Reactions and Frequency

Side effects are officially classified by the frequency with which they were reported in clinical studies, as documented in regulatory labeling.

Frequency	Common Examples
Common	Abdominal abscess, Coagulopathy, Intracranial hypotension (CSF leakage), Headache, Pyrexia
Uncommon	Graft infection, Haematoma, Decreased haemoglobin, Vascular graft occlusion, Meningitis, Hydrocephalus, Post-operative wound complication
Rare	Hypersensitivity or allergic reactions, Anaphylaxis, Formation of antibodies to product components

Serious Safety Restrictions

Official labeling defines specific, life-threatening risks that require strict adherence to safety constraints:

Intravascular Injection is Prohibited: The product must not be applied intravascularly (into a blood vessel). Inadvertent injection can lead to life-threatening thromboembolic events (clotting) and Disseminated Intravascular Coagulation (DIC).
Risk of Embolism: Using a spray applicator with a pressure regulator at incorrect pressures or distances may result in life-threatening air or gas embolism.
Infectious Risk: As a plasma-derived medicine, there is a theoretical risk of transmitting infectious agents, such as certain viruses, despite manufacturing safety measures.

Population-Specific Notes

Regulatory documents state that safety is not established for use during pregnancy and lactation, and data are too limited to support safety and effectiveness in children (pediatric population).

Overdose and Emergency Response

Official regulatory documentation states that no case of overdose has been reported for Evicel Fibrin Sealant in clinical studies or post-marketing experience. Due to its intended topical use as a surgical hemostatic agent, the official warnings focus on severe, acute complications related to misapplication or immunological response.

Documented Acute Risks

The product’s regulatory profile identifies life-threatening risks associated with unintended systemic exposure. Inadvertent intravascular injection (into a blood vessel) carries the potential to lead to a thromboembolic event or Disseminated Intravascular Coagulation (DIC), affecting the coagulation and cardiovascular systems. A separate documented risk is life-threatening air or gas embolism, which is associated with the use of high-pressure spray devices. Immediate medical attention is required for signs of these severe complications, as well as for evidence of a severe hypersensitivity reaction or anaphylaxis.

Emergency Actions and Monitoring

Regulatory instructions mandate that administration must be discontinued immediately if signs of acute events, such as hypersensitivity, are observed. Management involves symptomatic and supportive treatment. Furthermore, close monitoring of blood pressure, pulse, and oxygen saturation is specifically required during spray application to detect potential signs of embolism.

Therapeutic Uses of Evicel

What Evicel Treats: Main Uses and Benefits

Evicel is a therapeutic sealant generally used during surgery to address specific types of bleeding and tissue challenges, providing supportive treatment when conventional methods may be insufficient. The medicine is used by surgeons to help reduce local bleeding during operations when standard techniques are not sufficient.

It is commonly used to help with acute symptomatic episodes such as mild-to-moderate diffuse surgical oozing and to assist with tissue reinforcement in compromised surgical closures, including dural repair in neurosurgery. This product is considered relevant in clinical settings marked by anatomical complexity, or when operating on patients whose systemic clotting may be temporarily impaired.

The sealant provides support that helps ease the overall symptom burden in these contexts by creating localized support for control of bleeding. This action assists with maintaining functional stability at the operative site and may help manage the risk of post-operative fluid leakage.

“This application supports the localized control of persistent oozing, which contributes to easing the overall symptom load (blood loss).”

Uses and Supportive Role: Intraoperative Oozing

Context	Symptom Management	Therapeutic Benefit
Complex Surgery	Control of persistent, mild-to-moderate surface bleeding	Supports the stability of the operative field
Tissue Reinforcement	Management of potential fluid leakage risk	Supports the reinforcement of tissue closure

Eligibility and Restrictions for Use

Evicel's eligibility profile is strictly defined by regulatory authorities and based on patient history, age, and the manner of application.

Contraindications and Restrictions

Classification	Rule	Constraint Details
Absolute Contraindication	Known severe systemic reactions to human blood products.	Patients with a history of anaphylactic or severe systemic hypersensitivity to blood-derived components must not use Evicel.
Prohibited Application	Intravascular Injection.	The product must not be injected directly into the circulatory system due to the risk of life-threatening thromboembolic events.
Use Limitation	Severe or Brisk Bleeding.	The product is not indicated for the treatment of brisk arterial bleeding or massive venous hemorrhage.

Age and Physiological Status

Adults: Approved for general use as an adjunct to haemostasis during surgery.
Pediatric Patients: Use is supported for children ge 6 months of age. Safety and effectiveness are not established for infants younger than 6 months.
Pregnancy and Lactation: Use is conditional. Evicel should be administered only if clearly needed, as safety in controlled clinical trials has not been established for pregnant or breastfeeding women.

What should I know about interactions with other medicines?

Interactions with other medicines and products

The official regulatory profile for Evicel Fibrin Sealant addresses interactions primarily through local physicochemical incompatibility and the absence of systemic drug interaction data.

Interaction Scope

Category	Official Regulatory Documentation
Systemic Drug Interactions	None known. Formal interaction studies have not been performed with co-administered medicinal products, which is consistent with the product's strictly topical application.
Mechanistic Basis	None documented for systemic pharmacokinetic or pharmacodynamic interactions.
Incompatible Substances	Alcohol, Iodine, or Heavy Metals (e.g., antiseptic solutions) are identified as presenting a risk of physicochemical denaturation to the product.
Timing Restriction	Must not be mixed with any other medicinal products before application.

Official Interaction Profile

Official regulatory statements confirm that no drug interactions are known. The primary focus of the interaction profile is on procedural constraints and local compatibility.

The product may be denatured after exposure to solutions containing alcohol, iodine, or heavy metals.
Incompatible solutions should be removed to the greatest possible extent from the application site before the sealant is applied.
The medicinal product must not be mixed with other medicinal products.

This structure reflects the product's classification as a locally applied sealant, emphasizing administrative separation and local substance incompatibility over systemic drug interactions.

Mechanism of Action

Evicel is a two-component fibrin sealant that initiates the final stages of the coagulation cascade upon application. The mechanism relies on the controlled interaction between the two constituent solutions: the fibrinogen component and the thrombin component. When these two solutions mix, the human thrombin solution acts as a highly specific serine protease. Thrombin cleaves the A and B fibrinopeptides from the human fibrinogen molecule. This proteolytic action converts soluble fibrinogen monomers into fibrin monomers. These fibrin monomers then spontaneously self-assemble through hydrogen bonding and end-to-end interactions to form a network of insoluble, cohesive, cross-linked fibrin polymer strands.

The Factor XIII (Fibrin Stabilizing Factor) present in the fibrinogen component is activated by the thrombin. Activated Factor XIIIa then catalyzes the formation of covalent varepsilon-(gamma-glutamyl)lysine bonds between the fibrin monomers. This enzymatic cross-linking stabilizes the initial fibrin polymer structure, resulting in a cohesive matrix formation. The resultant fibrin network is structurally and functionally analogous to the final polymer created during the natural physiological hemostasis pathway.

Dosage and Administration Information

How to Use Evicel

Evicel is administered strictly by topical application (applied to the surface of the tissue) and must never be injected into blood vessels or directly into the tissue itself. Its use is restricted to experienced surgeons trained in the procedure.

Official Administration Protocol

Administration Scope	Instructions
Route of Administration	Topical use only (epilesional).
Dosing	Must be individualized by the treating physician based on the size of the area, type of surgery, and application method. The initial volume must be sufficient to entirely cover the target area.
Frequency	A single application during the surgical procedure, with re-application permitted if the initial effect is not complete.
Preparation	The frozen components must be thawed and warmed to 20 C to 30 C before use. Thawed product can be refrigerated for up to 30 days or kept at room temperature (up to 25 C) for up to 24 hours.

Procedural Steps

Preparation and Warming: The two components are thawed and warmed to the required temperature range before the procedure begins.
Site Preparation: The surface of the wound or tissue must be dried as much as possible using standard surgical techniques, such as swabs or suction.
Application: The product must be applied as a thin, even layer using the dedicated application device, either via the drip method or by spraying in short bursts (0.1–0.2 mL). Excessive clot thickness may negatively affect its performance.

These official instructions define the standardized procedure for using the medicine. The process focuses on precise preparation and delivery of the product to the surgical site, ensuring it is applied topically to a dry surface to maximize the intended effect while strictly prohibiting injection.

Recent Clinical Evidence

Research Evidence / Overview of Studies for Evicel

Evidence for Use as an Adjunct to Hemostasis in Abdominal Surgery

Research on this sealant includes large, Phase III randomized controlled trials (RCTs) conducted in adult patients. These studies were designed to evaluate the sealant's use as supportive treatment for bleeding that was studied during abdominal or retroperitoneal procedures.

What researchers studied in these trials was whether the sealant was associated with achieving the hemostasis endpoint, defined as the absence of bleeding at the target site at a short, defined time point, typically 10 minutes. Findings describe patterns observed in the studies related to the proportion of patients achieving the endpoint within that interval. Patient outcomes extending beyond the immediate surgical period were not the primary focus of these short-term studies.

Evidence for Use in Dural Closure and Neuro-Surgical Sealing

Research explored the application of the sealant in neurosurgery as an adjunct to suturing for repairing the dura mater. What researchers studied in these trials were outcomes related to functional measures, including the achievement of the closure endpoint during surgery. Studies also monitored the incidence of post-operative complications like cerebrospinal fluid (CSF) leakage tracked for approximately 30 days.

What remains uncertain involves long-term effects, which are not fully established. While data are available for the 30-day post-operative period, there is limited information for outcomes beyond that timeframe. Some earlier research was not designed to establish a definitive outcome, and study findings have been mixed regarding the rate of post-operative CSF leakage, suggesting evidence quality varies across studies.

Research Evidence in Special Populations

Dedicated research has examined the use of the sealant in pediatric subjects (children and adolescents). These trials monitored acute changes, specifically the time required for bleeding to stop (Time-to-Hemostasis), when the sealant was used versus an active comparator. However, data for certain groups remain insufficient, particularly for infants under 0.6 years old, meaning outcomes for this very young population are not fully established.

Key Studies & References A multicentre, prospective, randomized, controlled study to evaluate the use of a fibrin sealant as an adjunct to sutured dural repair in cranial surgery (Adult Neurosurgery RCT)

Frequently Asked Questions (FAQ)

Common questions about Evicel (FAQ)

Q: Is Evicel the same as other 'fibrin sealants' I've heard about?

A: Evicel is formally classified in official documents as a specialized Fibrin Sealant or hemostatic agent. This product class is used in surgical settings to help the body control bleeding. It works by supporting the natural process of blood clotting at the site of application.

Q: Is it true that Evicel is made from human blood components?

A: Yes, according to official documentation, Evicel is a plasma-derived product. This means its key active substances are separated and prepared from pooled human plasma, which is a component of blood.

Q: What happens to Evicel in the body after it has done its job?

A: The fibrin network that forms is temporary. Official documents state that as wound healing progresses, the body induces a process called fibrinolytic activity that gradually breaks down the fibrin into harmless degradation products.

Q: Can Evicel be used in pregnant patients?

A: Official regulatory documents state that the safety of Evicel for use during pregnancy and lactation is not established in controlled clinical trials. The product information indicates that its use should be reserved for situations where the treating physician determines it is clearly needed, based on a risk assessment.

Q: How does the concentration of the product relate to its effectiveness?

A: Official application instructions note that Evicel should be applied as a thin, even layer. Regulatory documents state that excessive clot thickness may negatively interfere with the product's intended performance.

Q: Can Evicel be used in areas where there is a lot of fluid or bleeding?

A: Regulatory application instructions indicate the importance of a dry surgical site. The surface area of the tissue is to be dried to the greatest extent possible using standard surgical techniques, such as swabs or suction, before Evicel is applied.

Q: How quickly does Evicel 'set' or start working during a procedure?

A: The product’s mechanism involves the two components mixing to form a fibrin clot immediately upon application. Clinical studies often define the achievement of hemostasis (stopping bleeding) at a short, specific time point, with results commonly reported at 10 minutes following application.

Q: Is Evicel meant to replace sutures (stitches) entirely?

A: Evicel is indicated as an adjunct, meaning a supportive treatment, to conventional surgical techniques like sutures or ligation. It is not intended to be used as the sole treatment for massive venous hemorrhage or brisk arterial bleeding.

Q: Do researchers know if Evicel affects future wound healing long-term?

A: Regulatory documents state that long-term effects beyond the initial 30-day post-operative period are not fully established. Due to the product's human origin, long-term animal studies to evaluate potential safety have not been performed.

Q: Is Evicel approved in countries outside of the US?

A: Yes, official product information confirms that the sealant has regulatory approvals in several major global jurisdictions. This includes the European Union (EMA), Canada, and Australia (TGA), in addition to the US Food and Drug Administration (FDA).

Q: Do patients generally feel any discomfort or pain when Evicel is applied?

A: The product is applied strictly to the surface of the tissue and its use is restricted to experienced surgeons during a procedure. Since the patient is typically under anesthesia during application, the feeling of the sealant being applied is not expected.

Q: Is there a maximum amount of Evicel that can be used in one procedure?

A: Regulatory instructions state that the dose must be individualized by the treating physician based on the patient and the surgical site. However, clinical trial data noted that individual dosages used were reported to be up to 10 mL for some specific types of procedures.

Q: Can Evicel be used on surface cuts or external injuries?

A: Regulatory data supports the use of Evicel as an aid to hemostasis and tissue sealing during surgery (e.g., abdominal, vascular, neurosurgery). It is not indicated for general use on simple surface cuts or external injuries outside of the controlled surgical setting.

Q: Does Evicel contain any synthetic (non-natural) materials?

A: The active components of the product are listed in official documents as being human plasma-derived. Evicel is formally classified as a biological medicinal product, suggesting the active ingredients are not synthetic.

Q: If I have a known protein allergy, can I still receive Evicel?

A: Official product information states that Evicel is formally contraindicated (must not be used) in patients with a known severe systemic reaction or hypersensitivity to the active substances or any of the excipients (inactive ingredients).

Q: What should a patient do if they think they're having a reaction to Evicel after surgery?

A: Official patient information indicates that if signs of a severe reaction are noticed after the procedure, such as difficulty breathing, rash, or swelling, the doctor or healthcare provider must be informed.

Q: Is Evicel considered a drug or a medical device?

A: Evicel is a combination product regulated by government agencies. It is licensed by the FDA as a Biological Product License Application (BLA) and is regulated in Europe (EMA) as a Biological Medicinal Product.

Q: How does Evicel compare to a traditional blood clot?

A: The product's mechanism of action is described in official documentation as creating a fibrin network. This network is structurally and functionally analogous (similar in structure and function) to the final polymer that is created during the body's natural physiological clotting pathway.

Q: Does the application of Evicel require special training for the surgeon?

A: Yes, regulatory documents clearly state that the use of Evicel is restricted to experienced surgeons who have been trained in its use. This restriction ensures the product is applied correctly using the proper techniques.

Q: Why is the application process of Evicel usually described as 'quick'?

A: The product’s mechanism involves the two separate components mixing at the surgical site, leading to the formation of a fibrin clot immediately upon application. This instantaneous reaction, combined with the application method of quick, controlled bursts, contributes to the process being described as quick.

Q: Can patients who are vegetarian or vegan receive Evicel?

A: Evicel is manufactured from human plasma-derived components. This means its active substances originate from pooled human plasma, which is a biological material of human origin.

How should Evicel be stored and disposed of?

Storage and Disposal Instructions for Evicel

Evicel solutions must be stored strictly according to regulatory specifications to maintain product stability and must be kept out of the reach and sight of children.

Required Storage Conditions

Storage State	Temperature Requirement	Stability Limit
Frozen	le -18^° C	24 months (shelf life)
Thawed, Refrigerated	2^° C to 8^° C	Up to 30 days
Thawed, Room Temp	Up to 25^° C	Up to 24 hours

Handling and Disposal Rules

Protection: Vials must be stored in the original outer carton in order to protect from light and kept in an upright position. The product must not be re-frozen once thawed, nor should it be refrigerated after having been stored at room temperature.

Disposal: Evicel is for single use only. Any unused medicinal product or residue must be discarded in accordance with local requirements for pharmaceutical waste.

Evicel