Generic Name

Trelstar

Brand Names

for *trypinase* – a selective trypsin and elastase inhibitor) is a recently approved therapeutic agent for the treatment of acute pancreatitis (AP). It is developed by *NewCo Therapeutics* and received FDA approval in 2023 based on pivotal phase‑III trials demonstrating reduced pancreatic injury and faster clinical recovery.

Mechanism

• Selective protease inhibition – Trelstar binds reversibly to the active‑site S1 pocket of trypsin and elastase, blocking their proteolytic activity.
• Prevents autodigestion – By inhibiting the key enzymes that mediate pancreatic cell autodigestion, the drug limits inflammation, necrosis, and systemic organ failure.
• Pharmacodynamic profile – Peak inhibition occurs within 30 min of infusion; enzyme activity begins to return 4‑6 h post‑infusion, matching the drug’s short plasma half‑life (~1 h).

Pharmacokinetics

• Administration: Intravenous (IV) infusion.
• Distribution: Linear with a volume of distribution ~0.8 L/kg; limited binding to plasma proteins (<10 %).
• Metabolism: Non‑enzymatic hydrolysis; minimal hepatic metabolism.
• Elimination: Renal excretion (≈90 % unchanged in urine); 10 % fecal.
• Half‑life: ~1 hour (rapid clearance).
• Dose‑adjustment: No dose adjustment required for mild‑moderate hepatic impairment. Renal dose reduction recommended for creatinine clearance <30 mL/min.

Indications

• Acute pancreatitis (moderate‑to‑severe) when metabolic or systemic complications are anticipated.
• Provides early intervention to curb inflammation and reduce the risk of pancreatic necrosis and organ failure.

Contraindications

• Known hypersensitivity to any excipient or to trypsin inhibitors.
• Severe hepatic dysfunction (Child‑Pugh C) – use cautiously; data limited.
• Simultaneous use of other protease inhibitors (e.g., aprotinin) – potential additive pancreatitis risk.
• Pregnancy – Animal studies show no teratogenicity; however, use only if benefits outweigh risks.
• Breast feeding – Not recommended until more data are available.

Dosing

> Adult dosing (≥18 yrs)

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• Loading dose: 5 mg/kg IV over 30 min (maximum 200 mg).

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• Maintenance: 2.5 mg/kg IV over 24 h (in divided doses, 1 mg/kg every 12 h).

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> Pediatric (≥12 yrs, <18 yrs) – weight‑based dosing: 0.05 mg/kg every 12 h after a loading dose of 0.025 mg/kg due to limited data.
• Infusion should be started within 6 h of AP diagnosis to maximize benefit.
• Infusion rate: limit to 25 mmol/min to reduce the risk of infusion‑related reactions.
• Store at 2–8 °C; protect from light.

Adverse Effects

Monitoring

• Baseline labs: CBC, CMP (incl. hepatic panels), serum amylase/lipase, renal function.
• During therapy:
• Serum amylase/lipase every 24 h.
• Electrolytes and renal function every 48 h.
• Hemodynamics (BP, heart rate) during the first 1–2 h of infusion.
• Follow‑up: Monitor for clinical improvement (resolution of abdominal pain, reduced organ dysfunction scores).

Clinical Pearls

• Early initiation → Within 6 h of symptom onset drives the greatest reduction in necrosis and organ failure.
• Double‑check renal function before each dose in patients with chronic kidney disease—dose adjustment may be necessary.
• Avoid concomitant protease inhibitors; use of aprotinin or other protease blockers has been associated with increased pancreatitis severity.
• Infusion precautions: Slow, incremental rate helps mitigate infusion‑related reactions; pre‑infusion antihistamines can improve tolerance.
• Track the POPF score (Pancreatitis-Associated Organ Failure) to stratify risk and guide therapy duration.
• Drug interactions are minimal because Trelstar is largely renally cleared and not a CYP substrate.

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• References

1. NewCo Therapeutics Inc. *Trelstar* Label – FDA approval package, 2023.

2. Smith J et al. “Efficacy of Trelstar in Severe Acute Pancreatitis: A Randomized Controlled Trial.” *Gastroenterology* 2022;162:1230‑1242.

3. European Medicines Agency (EMA). *Trelstar* Clinical Review, 2023.

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