Xigris, Drotrecogin-ALFA liquid

Introduction to Xigris (Drotrecogin-ALFA Liquid)

Xigris, known generically as Drotrecogin-ALFA, is a recombinant human activated protein C used primarily in critical care settings. Developed to combat severe sepsis and septic shock, it functions as an anticoagulant and anti-inflammatory agent. Despite its controversial history, Xigris remains a subject of interest in medical research.

Xigris was initially approved by the FDA for severe sepsis with high risk of death. However, it was later withdrawn due to inconclusive efficacy results. Understanding its mechanisms, uses, and side effects is crucial for healthcare professionals considering its application in critical care.

Composition and Formulation

Xigris contains Drotrecogin-ALFA, a recombinant form of human activated protein C. It is produced using genetically engineered mammalian cells, ensuring a high degree of similarity to endogenous human protein C. This precision enhances its efficacy and safety profile in modulating coagulation and inflammation.

• Active Ingredient: Drotrecogin-ALFA
• Excipients: Sodium chloride, Polysorbate 80, Citric acid
• Formulation: Lyophilized powder for intravenous infusion

The lyophilized form requires reconstitution before administration. This allows for stability during storage and precise dosing during administration.

Uses of Xigris (Drotrecogin-ALFA)

Primary Indications

Xigris is primarily indicated for:

• Severe sepsis with multiple organ failure
• Septic shock requiring vasopressor support

Its use is generally reserved for critically ill patients with a high risk of mortality. Its anticoagulant and anti-inflammatory properties are particularly beneficial in mitigating disseminated intravascular coagulation (DIC).

Off-Label Uses

• Acute Respiratory Distress Syndrome (ARDS)
• Coagulopathy related conditions
• Multi-Organ Dysfunction Syndrome (MODS)
• Experimental use in severe COVID-19 cases

Although off-label use remains controversial, ongoing clinical trials are exploring its efficacy in treating other severe inflammatory conditions.

How Xigris Works

Drotrecogin-ALFA exerts its effects through complex pathways:

• Inhibits coagulation by inactivating Factors Va and VIIIa
• Promotes fibrinolysis by reducing plasminogen activator inhibitor-1
• Modulates inflammation by inhibiting pro-inflammatory cytokines

By balancing coagulation and inflammation, Xigris helps prevent organ dysfunction in septic patients.

Dosage and Administration

Administered as an intravenous infusion, the recommended dosage is:

• 24 mcg/kg/hour for a duration of 96 hours

Dosage adjustments may be required for patients with renal or hepatic impairment. Close monitoring is essential to minimize bleeding risks.

Side Effects of Xigris

Common Side Effects

• Bleeding and hemorrhage
• Gastrointestinal symptoms like nausea and diarrhea
• Allergic reactions including rash and itching

Serious Adverse Effects

• Intracranial hemorrhage
• Anaphylactic reactions
• Thrombocytopenia

Regular monitoring of coagulation parameters is recommended to detect adverse effects early.

Interactions with Other Medications

Drug-Drug Interactions

• Anticoagulants such as Warfarin and Heparin
• Thrombolytic agents like Alteplase
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Concurrent use with other anticoagulants increases the risk of bleeding complications. It is crucial to evaluate patient medication history before administration.

Contraindications and Warnings

Absolute Contraindications

• Active internal bleeding
• Recent surgery or trauma
• Severe thrombocytopenia

Due to its potent anticoagulant effects, Xigris is contraindicated in patients with active bleeding or conditions predisposing to hemorrhage.

Relative Contraindications

• Recent ischemic stroke
• Severe liver disease
• End-stage renal disease

Important Precautions and Careful Administration

• Monitor for signs of bleeding and coagulation abnormalities
• Use with caution in patients with coagulopathy
• Discontinue if severe adverse reactions occur

Administration in Special Populations

Administration to Elderly Patients

In elderly patients, careful dose adjustment is required due to age-related changes in pharmacokinetics and increased risk of bleeding complications.

Administration to Pregnant Women and Nursing Mothers

Limited data on safety in pregnancy. Use only if benefits justify the potential risks. Caution is advised during breastfeeding due to the unknown excretion in human milk.

Administration to Children and Adolescents

Not routinely recommended for pediatric patients due to insufficient safety and efficacy data. Pediatric dosage guidelines remain experimental and should be used with caution.

Overdosage and Toxicity

Symptoms of overdose include excessive bleeding, hypotension, and anaphylaxis. In case of overdose:

• Discontinue infusion immediately
• Initiate supportive care and symptomatic treatment
• Monitor coagulation parameters closely

Storage and Handling Precautions

• Store at 2°C to 8°C (36°F to 46°F)
• Protect from light and moisture
• Reconstitute under sterile conditions
• Dispose of unused product as per biohazard regulations

Clinical Trials and Evidence-Based Research

Several clinical trials have evaluated the efficacy and safety of Xigris, including:

• PROWESS Study: Demonstrated reduced mortality in severe sepsis
• ADDRESS Study: No benefit in patients with low risk of death
• ENHANCE Trial: Provided insights into safety and bleeding risks

Despite mixed results, research continues to explore its role in inflammatory and coagulative disorders.

Conclusion and Summary

Xigris (Drotrecogin-ALFA) is a potent anticoagulant and anti-inflammatory agent initially used for severe sepsis and septic shock. Although controversial, it remains an important topic in critical care research. Careful patient selection, monitoring, and adherence to contraindications are vital for safe administration.

Ongoing research may redefine its applications and effectiveness, particularly in emerging inflammatory diseases. Its complex pharmacology and potential benefits warrant continued exploration in evidence-based medicine.