Drug induced acute pancreatitis: Does it exist?

Table 1 Classification of drug induced pancreatitis

Class Ia drugs At least 1 case report with positive rechallenge, excluding all other causes, such as alcohol, hypertriglyceridemia, gallstones, and other drugs

Class Ib drugs At least 1 case report with positive rechallenge; however, other causes, such as alcohol, hypertriglyceridemia, gallstones, and other drugs were not ruled out

Class II drugs At least 4 cases in the literature Consistent latency (75% of cases)

Class III drugs At least 2 cases in the literature No consistent latency among cases No rechallenge

Class IV drugs Drugs not fitting into the earlier-described classes, single case report published in medical literature, without rechallenge

Table 2 Summary of drug-induced acute pancreatitis

Class 1a Azodisalicylate; Bezafibrate; Cannabis; Carbimazole; Codeine; Cytosine; Arabinoside; Dapsone; Enalapril; Furosemide; Isoniazid; Mesalamine; Metronidazole; Pentamidine; Pravastatin; Procainamide; Pyritonol; Simvastatin; Stibogluconate; Sulfamethoxazole; Sulindac; Tetracycline; Valproic acid

Class 1b All trans-retinoic acid; Amiodarone; Azathioprine; Clomiphene; Dexamethasone; Ifosfamide; Lamivudine; Losartan; Lynesterol/methoxyethinylestradiol; 6-MP; Meglumine; Methimazole; Nelfinavir; Norethindronate/mestranol; Omeprazole; Premarin; Sulfamethazole; Trimethoprimsulfamethazole

Class 2 Acetaminophen; Chlorthiazide; Clozapine; DDI; Erythromycin; Estrogen; L-asparaginase; Pegasparagase; Propofol; Tamoxifen

Table 3 Methods of causal inference

Randomized controlled trials

Controlled trials without randomization

Cohort studies

Case-control studies

Ecologic studies

Case reports and case series

Table 4 Bradford Hill criteria for causation

Temporality - causal factor must precede effect

Strength of association - magnitude of the relative risk estimates observed

Consistency of the association - extent to which scientific results are similar across the entire body of evidence

Biologic gradient (dose-response) - the extent to which the relative risk estimates increase in magnitude as the dose of the exposure increases

Biologic plausibility - the extent to which a mechanism of action has been proposed, studied and demonstrated in toxicological or other laboratory based studies

Specificity - refers to the precision with which the exposure and the outcome can be defined

Coherence - the extent to which the evidence and hypotheses for the results fit together into a reasonable and well-tested explanation

Experimentation - the extent to which a randomized clinical trials or cohort studies are available

Analogy - the extent that the purported exposure-disease relationship under consideration is similar to other relationships