Role of medicines of unknown identity in adverse drug reaction-related s in developing countries: evidence from a cross-sectional study in a teaching hospital in the Lao PDR Drug Safety Céline Caillet*, Chanvilay Sichanh, Gaëtan ssemat, Myriam Malet-Martino, gnès Sommet, Haleh Bagheri, Noudy Sengxeu, Niphonh Mongkhonmath, Mayfong Mayxay, Lamphone Syhakhang, Maryse Lapeyre-Mestre, Paul N. Newton, nne Roussin *Pharmacoépidémiologie, UMR 1027 INSERM-Université Toulouse III, Faculté de Médecine, Toulouse, France and Infectious Diseases Data Observatory WorldWide ntimalarial Resistance Network, Centre for Tropical Medicine and Global Health, CCVTM, University of Oxford, Churchill Hospital, Oxford, United Kingdom E-mail address: celine.caillet@iddo.org 1
Electronic Supplementary Material 5. Description of the 23 adverse drug reactions-related s N Gender - ge (Years) WHO-RT Preferred term Gastro-intestinal disorders 1 M-50 2 M-65 3 F-68 4 F-65 nemia 5 M-54 Diarrhoea 6 M-33 7 M-60 Haemorrhoidal hemorrhage Outcome Comorbidities Hepatitis C, Nodular hepatocellular carcinoma H.pylori PI(s) - Known Identity in tablets/capsules used during the 2 weeks before moxicillin Gemfibrozil,cetyl leucine, -orphenadrine( ) Unknown nguillulosis Prednison** trial fibrillation Dysrythmia Carbamazepine**, cetylsalicylic acid**, Diclofenac injection**,enalapril, Omeprazole, injection, Vitamins and minerals combination, Carvedilol, cetylsalicylic acid**, Doxycycline Diclofenac**, luminium magnesium( ), hyoscine butylbromide, ofloxacine PI(s) - Unkown identity in tablets/capsules used during the 2 weeks before Identification by 1 H NMR/MS Identification No look-alike Look-alike Tablet/capsule not with in the in the available in the medicines medicines collection medicines medicines collection collection collection photographs only a Omeprazole or esomeprazole (undifferenciable by NMR/MS) Folic acid Piroxicam**, Tetracycline, -Orphenadrin, Herbal medicine (Berberin) Prednison**, Thiamin Likely serratiopeptidase (PI not identifiable by NMR/MS), Flunarizine Thiamin, Heptaminol Ibuprofen**, Medicine not available at the time of interview Origin of DR Thiamine Diclofenac** +B cetylsalicylic acid** Dextromethorphanchlorpheniramin, Cloxacillin Indometacin**, Thiamin-nicotinic acid-scorbic acid, Digoxin, Thiaminnicotinic acid- scorbic acid,omeprazole or esomeprazole (undifferenciable by NMR/MS) +B dditional information pain. Ibuprofen was used after the first symptom (melena) Yaa chud use (6 medicines). Patient alcohol dependent Yaa chud use (3 medicines) +B - Sulfamethox azoletrimethoprim +B - Had also drunk large amount of alcohol during the two days preceding pain; History of alcoholism; Current tabagism; Diclofenac given after the first 2
8 F-78 Diarrhoea 9 F-62 10 F-56 11 F-52 12 F-53 Metabolic and nutritional disorders 13 M-69 Coma hypoglycaemic 14 F-77 Hypoglycaemia 15 F-75 Hypoglycaemia 16 F-67 Hypokalaemia, Dyspnea Unknown Fatal Hypertension diabetes Caecal mycobacterial granuloma diabetes Microcytic anemia, Diarrhea of unknown etiology Hypertension cute pulmonary oedema Colchicine***, Carvedilol**, Enalapril, Gliclazide, Eperisone, mitryptylin, Pregabalin, Mecobalamin, Furosemide, Simvastatin, Haloperidol, Diazepam, Ferrous sulfate-folic acid cetylsalicylic acid**,, Metformin, Glimepiride, Enalapril, mlodipine, Ceftriaxone, Tranexamic acid, Omeprazole Mefenamic acid** ( ), Ibuprofen**, Betamethasoneneomycin cream, Clarithromycin, Terpin, scorbic acid, Diazepam Piroxicam***, Magnesium salicylate-phenyltoloxamine***, Diclofenac cream, B-vitamin complex cetylsalicylic acid**, Topical diclofenac, Carvedilol Gliclazide**, Combination of vitamins and minerals, Eperisone Glibenclamide***, Sulfamethoxazole- Trimethoprim**, Enalapril, scorbic acid,furosemide, Bacillus subtilis,, Diazepam, Omeprazole, Magnesium trisilicate-dried aluminium hydroxide kaolin, -Chlorpheniramine- Phenylephrin( ) Furosemide***, Sodium polystyrene sulfonate***,insulin**, Dobutamine, Omeprazole, Glibenclamide*** B symptoms Negative stool analysis cetylsalicylic acid continued after the first symptoms +B - C+B C High dose of piroxicam (60 mg per day) pain High dose (20 mg per day) of glibenclamide - +B - +B Before starting medicines, kaliemia =3.98 mmol/l. t arrival at Mahosot(4 3
17 F-55 18 M-63 Hypokalaemia, Dyspnea Hyperkalaemia, Hypotension, Renal deficiency Skin and appendages disorders 19 F-22 20 M-25 21 F-45 Rash erythematous Pruritus Toxic epidermal necrolysis Toxic epidermal necrolysis, llergy to seafood Liver and biliary disorders 22 F-17 Vision disorders 23 F-42 Hepatitis Jaundice Visual acuity reduced Unknown Not fully Kidney insufficiency, type 2 dyslipidemia Diarrhea,Cirrh osis Epilepsy Domperidone, Phloroglucinol, Calcium gluconate, Ceftriaxone, Cimetidine, Hyoscine butylbromide, Noramidopyrine, Vitamins combination, Unidentified active ingredient Furosemide***, miloride- Hydrochlorothiazide**, Insulin**, Ferrous ascorbate, Calcium carbonate, Gliclazide, Folic acid, Mecobalamin Enalapril**, Metformin Roxythromycine, Vitamins combinatin, Lysosyme, Dexchlorpheniramine Phenobarbital***, Norfloxacine**, Diclofenac**, Hydrocortisone, Promethazine, Chlorpheniramine, Erythromycin Levofloxacine***, Tramadol***, Omeprazole***, Noramidopyrine***, Cefuroxime, Phloroglucinol, paracetamoldexchlorpheniramine ***( ) (3 different brand products), - Chlorpheniramine- Phenylephrin*** ( ), Silymarin, Biphenyl dimethyl dicarboxylate Rifampicin-Isoniazid- Pyrazinamide- Ethambutol** Clarithromycin***, Cephalexin***, Unidentifiable***, Thiamin- Pyridoxine*** +B days later) kaliemia=2.0 mmol/l. Recent increase of the dose of furosemide (double dose) The patient had recently doubled his dose of enalapril. Kaliemia=6.3 mmol/l Had a generalized oedema after a perfusion during her childhood (don't know the name of the culprit medicine) - - C+B Patient weight : 41 kg - * Unassessable, ** Possible, *** Probable a : The pharmaceutical unit was not given to the research team at the time of interview and 1 H NMR/MS identification was thus not performed : dverse Drug Reaction, B:Drug-Drug interaction, C:Unintentional overdose In bold: Pharmaceutical unit that is part of a Yaa Chud ( ) Self-medication PI, ctive Pharmaceutical Ingredient; WHO-RT, World Health Organization-dverse reaction Terminology; 1 H NMR, Proton Nuclear Magnetic Resonance; MS, Mass Spectrometry 4
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