Usage
Ulinastatin is prescribed for the treatment of acute pancreatitis and severe sepsis. It is classified as a protease inhibitor and works by inhibiting the action of various proteolytic enzymes, thereby mitigating the inflammatory cascade associated with these conditions. It also modulates the immune response, reducing the severity of inflammation and tissue damage.
Alternate Names
Ulinastatin is also known as Urinary Trypsin Inhibitor (UTI). Brand names include U-Tryp, Miraclid, Upxiga, Ulicrit, Ulinafic, and Ulitryp.
How It Works
Pharmacodynamics: Ulinastatin inhibits the activity of a range of serine proteases, including trypsin, chymotrypsin, kallikrein, plasmin, thrombin, factors IXa, Xa, XIa, and XIIa, as well as elastase. This broad-spectrum protease inhibition reduces the inflammatory cascade, thereby minimizing tissue damage. It also modulates the immune response, leading to a decrease in the production of pro-inflammatory cytokines like TNF-alpha, IL-1, IL-6, and IL-8.
Pharmacokinetics: After intravenous administration, the concentration of ulinastatin in the blood decreases linearly. It has a half-life of approximately 40 minutes. About 24% of the administered dose is excreted in the urine within 6 hours. Metabolism and other elimination pathways are not fully characterized.
Mode of Action: Ulinastatin binds directly to the active site of target proteases, inhibiting their enzymatic activity. This prevents the breakdown of proteins and other substrates by these enzymes, thereby reducing the inflammatory response.
Dosage
Standard Dosage
Adults:
The standard dosage is 100,000 - 200,000 IU administered intravenously over 1 hour, one to three times per day for 3 to 5 days. Doses up to 600,000 IU/day have been used in severe sepsis.
Children:
The safety and appropriate dosage for children have not been established.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary based on patient condition.
- Patients with Renal Impairment: Dose modifications might be considered based on renal function although specific guidelines are not well-defined.
- Patients with Hepatic Dysfunction: Limited data exists; caution and potential dose adjustment are advised.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular or other serious medical conditions. Close monitoring is recommended.
Clinical Use Cases
Dosages similar to the standard adult recommendations are used in various clinical settings such as intubation, surgical procedures, mechanical ventilation, and ICU use. Higher doses might be considered in emergency situations, such as severe sepsis or septic shock, based on the patient’s response and clinical judgment.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, skin rash, itching, headache, and injection site reactions (pain, swelling).
Rare but Serious Side Effects
Allergic reactions (including anaphylaxis), changes in liver enzymes (SGOT, SGPT), and blood cell counts (eosinophilia, leukopenia).
Long-Term Effects
Data on long-term effects are limited.
Adverse Drug Reactions (ADR)
Anaphylaxis, severe allergic reactions, significant changes in liver function tests, and blood dyscrasias.
Contraindications
Hypersensitivity to ulinastatin.
Drug Interactions
No clinically significant drug interactions have been definitively established, although caution is recommended with anticoagulants and immunosuppressants. The impact of combining ulinastatin with NSAIDs and corticosteroids requires careful monitoring due to their combined anti-inflammatory effects.
Pregnancy and Breastfeeding
The safety of ulinastatin during pregnancy and breastfeeding has not been established. Use only if the potential benefit outweighs the potential risk to the fetus or neonate.
Drug Profile Summary
- Mechanism of Action: Serine protease inhibitor, modulating the inflammatory cascade and immune response.
- Side Effects: Nausea, vomiting, diarrhea, skin rash, itching, headache, injection site reactions. Rarely, allergic reactions and liver enzyme changes.
- Contraindications: Hypersensitivity to ulinastatin.
- Drug Interactions: Potential interactions with anticoagulants and immunosuppressants warrant caution.
- Pregnancy & Breastfeeding: Safety not established; use with caution if benefits outweigh risks.
- Dosage: 100,000 - 200,000 IU IV over 1 hour, 1-3 times/day for 3-5 days. Higher doses may be used in severe sepsis.
- Monitoring Parameters: Liver function tests, complete blood count, and signs of allergic reactions.
Popular Combinations
Ulinastatin is often used in combination with standard treatments for sepsis and pancreatitis, including antibiotics, fluids, and supportive care. There are no established “popular combinations” in the sense of specific drug combinations with synergistic effects beyond standard care.
Precautions
- General Precautions: Pre-screening for allergies and careful monitoring for adverse reactions.
- Specific Populations: Use with caution in pregnant/breastfeeding women, children, and the elderly.
- Lifestyle Considerations: No specific lifestyle considerations have been identified.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ulinastatin?
A: The standard adult dose is 100,000-200,000 IU IV over 1 hour, 1-3 times/day for 3-5 days. Dosages may be adjusted based on the severity of illness and individual patient factors.
Q2: How does Ulinastatin work in sepsis?
A: Ulinastatin inhibits inflammatory mediators, reducing the systemic inflammatory response associated with sepsis.
Q3: Is Ulinastatin safe for children?
A: The safety and efficacy in children have not been established.
Q4: Are there any known drug interactions with Ulinastatin?
A: While no definitive clinically significant interactions are established, caution is warranted with anticoagulants and immunosuppressants.
Q5: Can Ulinastatin be used during pregnancy?
A: Use only if the potential benefit justifies the potential risk to the fetus, as safety has not been established.
Q6: What are the common side effects of Ulinastatin?
A: Nausea, vomiting, diarrhea, rash, itching, headache, and injection site reactions.
Q7: What is the route of administration for Ulinastatin?
A: Intravenous infusion.
Q8: How should Ulinastatin be reconstituted?
A: Reconstitute with 0.9% normal saline or 5% dextrose solution.
Q9: What should I monitor in patients receiving Ulinastatin?
A: Liver function tests, complete blood count, and vigilance for signs of allergic reactions.
Q10: Is there a specific antidote for Ulinastatin overdose?
A: No specific antidote exists. Supportive care should be provided as needed.
