Class Ia

Acetaminophen Acetaminophen was documented as the cause of AP in total of 9 cases, most secondary to overdose or suicidal attempt.1– 9 Moderate to severe pancreatitis was reported in 5 cases.2,4,5,7,9

5-Aminosalicylate Oral 5-aminosalcylate compounds that was implicated in AP.10–20

Amiodarone All reported cases, showed favorable outcome with only mild pancreatitis.21–24

Androgenic Anabolic Steroids Liane and Magee, in addition to, Rosenfeld et al described cases of other steroids types, with severe pancreatitis in one of them.25,26

Cannabis A total of 11 case reports of cannabis induced AP27–34

Cimetidine and Ranitidine Cimetidine was reported as a probable cause of AP in total of 5 cases.35–38

Clomiphene Three case reports had implicated clomiphene as a cause of AP.39–41

Enalapril and Perindopril Literature review revealed other 8 case of mild/moderate pancreatitis with favorable outcome.42–46

Estrogen and Related Products Acute pancreatitis secondary to exogenous estrogen exposure, has been described in many forms. Two cases of AP with favorable outcomes were reported, after exposure to estradiol valerate in preparation to cryo-thawed embryo transfer.47,48 Further cases were described after exposure to oral contraceptive pills (OCP),49–55 estrogen replacement therapy,56–58 and in preparation of gender reassignment surgery.59

Furosemide Furosemide was incriminated in 7 cases of AP,60–66 with positive rechallenge in 4 cases.62–65

Isoniazid Isoniazid was associated with pancreatitis in multiple patients, either during chemoprophylaxis67,68 or treatment of tuberculosis.69–75 Positive rechallenge was described in total of 6 patients,69–71,73–75 with exclusion of other causes in 4 patients.69,70,74,75

α-Methyldopa Another case described by Van der Heide et al in addition to a case described by Warren et al were excluded due to absence of abdominal pain or confirmatory imaging studies.76,77

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Metronidazole Multiple case reports implicated in AP.78–88

Statins Atorvastatin (Class III)89–91, and Fluvastatin (Class IV),92 are also other statins that have also been implicated with DIAP.

Sulindac Multiple reports has implicated Sulindac with mild DIAP.93–98

Tamoxifen A total of 8 case reports, fulfilling inclusion criteria, had implicated tamoxifen as the cause of AP99–106

Class Ib

Total of 26 had at least 1 case report with positive rechallenge, but these case reports failed to document exclusion of other causes or other possible etiologies were available. These drugs are Azathioprine,107–114 Bortezomib,115–120 Carbamazepine,121–123 Clonidine,124 Clozapine,125–133 Cytosine arabinoside,134–136 Dapsone,137–139 Dexamethasone,140,141 Fenofibrate,142 Hydrocortisone,143,144 6-Mercaptopurine,145,146 Methimazole,147–151 Mirtazapine,152–155 Nelfinavir,156 Nitrofurantoin,157 Omeprazole,158 Paclitaxel,159–163 ,164–180 Prednisone,144,181–184 Propofol,185–193 Quetiapine,194–201 ,202–205 Sorafenib,206–212 Tigecycline,286–292 Valproic acid,220–233 and Valsartan.234

Azathioprine Total of 11 cases in 8 case reports had implicated azathioprine in DIAP.107–114

Bortezomib DIAP was described in patients receiving treatment for multiple myeloma with bortezomib.115–120

Methimazole Five case reports implicated methimazole in DIAP favorable outcome in all cases.147–151

Mirtazapine Multiple case reported described DIAP.152–155

Pentamidine Multiple case reports had implicated pentamidine in all of its forms, intravenous, intramuscular and aerosolized.236-252

Prednisone Total of 8 cases in 5 case reports was described in literature.144,181–184

Propofol Propofol was implicated in 10 cases.185–193

Sodium Stibogluconate Four case reports described DIAP in patients receiving sodium stibogluconate for treatment of leishmaniasis202–205

Valproic Acid Total of 18 cases in 13 case reports described DIAP in patients receiving valproic acid293-304

Class II

Total of 17 medications had at least 4 cases in the literature with consistent latency. These drugs are All Trans Retinoic acid,235–242 L-Asparaginase/Peg-Asparaginase,243–246 Canagliflozin,247–250 Chlorothiazide,251–253 Codeine,254,255 Dideoxy inosine (Didanosine),256–266 Gold therapy,267–269 Hydrochlorothiazide,270–274 Interferon Alpha 2b/Ribavirin,275–282 Lisinopril,339- 350 Liraglutide,295–299 Meglumine antimonite,300–303 Nilotinib,304–306 Olanzapine,307–315 Prednisolone,316–319 Riluzole,320–323 and Sitagliptin.324–327 Please see the supplementary material for a complete list of cases references.

30 | Class III

Total of 30 medications had at least 2 cases in the literature with no consistent latency among cases and no rechallenge. These medications included Aspirin,328 Atorvastatin,89–91 Capecitabine,329,330 Captopril,331–333 Ceftrixone,334,335 Celecoxib,336– 338 Chlorthalidone,339,340 Ciprofloxacin,341,342 Clarithromycin,343–345 Cocaine,346–349 Cyclosporine,350,351 ,352–354 Erythromycin,355–357 Everolimus,358,359 Exenatide,360–362 Indomethacin,363,364 Interferon Alpha 2b,282,365 Irbesartan,366,367 Ketorolac,368,369 Metformin,370–372 Metolazone,373,374 Minocycline,375 Naproxen,376–378 Orlistat,379 Pazopanib,380,381 Phenformin,382–386 Ritonavir,387–389 Saw palmetto,390,391 Tacrolimus,392,393 and Vildagliptin.394,395 Please see the supplementary material for a complete list of cases references.

Class IV

Class IV drugs included drugs not fitting into the earlier described classes, single case report published in medical literature, without rechallenge. Total of 78 medications were described in this group, including L-Arginine,396 Adefovir,397 Ado-trastuzumab Emtansine,398 Albiglutide,399 Allopurinol,400 Amitriptyline,401 Amoxicillin/Clavulanate,402 Ampicillin,403 Anagrelide hydrochloride,404 Artesunate,405 Atenolol,406 Axitinib,407 Benazepril,408 Bendroflumethiazide,409 Bezafibrate,410 Boceprevir,411 Brentuximab vendontin,412 Calcium carbonate,413 Ceramium Kondoi,414 Danazol,415 Diclofenac,416 Dideoxycytidine,417 Dimethyl fumarate,418 Entecavir,419 Ergotamine tartrate,420 Estramustine phosphate,421 Ethacrynic acid,422 Ezetimibe,423 Famciclovir,424 Fluconazole,425 Fluvastatin,92 Gadobenate dimeglumine (MULTIHANCE),426 Glimepiride,427 Horsetail infusions (Equisetum arvense),428 Ibuprofen,429 Icodextrin,430 Ifosfamide,431 Imatinib,432 Interferon Alpha-2a,433 Interferon Beta-1a,434 Interleukin-2,435 Ketoprofen,436 Lacosamide,437 Lamivudine,438 Lamotrigine,439 Lanreotide autogel,440 Levetircetam,441 Mefenamic acid,442 Micafungin,443 ,444 Montelukast,445 Motesanib,446 Mycophenolate mofetil,447 Naltrexone,448 Nifuroxazide,449 Nivolumab,450 Octreotide,451 Oxacalcitriol,452 Oxyphenbutazone,453 ,454 Phenolphthalein,455 Ramipril,456 Risperidone,457 Roxithromycin,458 Secnidazole,459 Sertraline,460 Stavudine,461 Sunitinib,462 Tacalcitol,463 Telmisartan,464 Theophylline,465 ,466 Tocilizumab,467 Vedolizumab,468 Vemurafenib,469 Venlafaxine,470 Vinblastine,471 and Ziprasidone.472 Cases reporting combination of medications make it difficult to determine the exact causative drugs. These combinations included Mifepristone/Gemeprost/Acetaminophen-Codeine,473 Lovastatin/Gemfibrozil,474 Infliximab/Adalimumab,475 Diphenoxylate/atropine,476 Dabigatran/lamotrigine,477 and Ezetimibe/simvastatin.478 Combination chemotherapy was also reported as a possible cause of AP. These combinations include Docetaxel/Carboplatin,479 Lobaplatin/Etoposide,480 Vinblastine/Cisplatin,471 and Vincristine/Doxorubicin/Cyclophosphamide/Ifosfamide/Asparaginase.481–484

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