Does Tizanidine Cause Acute Pancreatitis?
Tizanidine is not established as a cause of acute pancreatitis based on current evidence, but there is one documented case report suggesting a possible association in the setting of severe hypertriglyceridemia, making it a Class IV drug (weakest evidence category) for drug-induced pancreatitis.
Evidence Classification
Tizanidine falls into Class IV drug classification for drug-induced pancreatitis, meaning only a single case report exists without rechallenge data or consistent latency patterns 1.
The evidence-based classification system for drug-induced pancreatitis requires either rechallenge data (Class I), consistent latency in ≥75% of cases (Class II), or multiple case reports (Class III) to establish stronger causality 1, 2.
Only 31 drugs have definite causality established for pancreatitis, and tizanidine is not among them 3.
The Single Case Report
One 2019 case report described a 55-year-old man who developed pancreatitis after being prescribed tizanidine, but this patient had untreated severe hypertriglyceridemia, which is itself a well-established independent cause of acute pancreatitis 4.
The proposed mechanism in this case involved tizanidine's alpha-2 agonist effects slowing gastrointestinal motility and potentially contracting the hepato-pancreatic sphincter, which could theoretically obstruct pancreatic enzyme flow 4.
This case demonstrates confounding by indication rather than definitive causality, as hypertriglyceridemia alone accounts for the pancreatitis risk 4.
Clinical Context from Guidelines
The 2021 Mayo Clinic/SPAQI consensus statement on perioperative management extensively discusses tizanidine's adverse effects—including dose-dependent sedation, hypotension, bradycardia, and drug interactions with CYP1A2 inhibitors—but makes no mention of pancreatitis risk 5.
Drug-induced pancreatitis has an overall incidence of only 0.1-2% of all pancreatitis cases, making it a relatively rare cause 3, 2.
Established High-Risk Medications (For Comparison)
The medications with the strongest evidence for causing pancreatitis include 6, 3, 7:
- Azathioprine/6-mercaptopurine: 4% incidence in IBD patients, typically within 3-4 weeks of initiation
- Mesalazine: Hazard ratio 3.5
- GLP-1 receptor agonists (semaglutide, liraglutide): Association reported but causality not definitively established
- DPP-4 inhibitors: Should be discontinued if pancreatitis suspected
Clinical Recommendation
Do not avoid tizanidine based on pancreatitis risk alone, as the evidence is insufficient to establish causality 1, 2.
However, exercise caution in specific scenarios:
Patients with severe hypertriglyceridemia (>12 mmol/L or >1000 mg/dL) should have their lipid disorder aggressively managed before starting tizanidine, as this combination may theoretically increase risk 4.
Monitor for pancreatitis symptoms (epigastric pain radiating to back, nausea, vomiting) in any patient on tizanidine who has additional risk factors including gallstones, alcohol use, or hypertriglyceridemia 8.
If acute pancreatitis develops in a patient taking tizanidine, consider discontinuing the medication and avoid rechallenge, particularly if no other clear etiology is identified 1, 2.
Key Pitfall to Avoid
Do not attribute pancreatitis to tizanidine without thoroughly excluding common causes (gallstones 45-60%, alcohol 20-25%, hypertriglyceridemia) 8. The single case report involved a patient with severe untreated hypertriglyceridemia, which alone explains the pancreatitis 4.