Drug-induced tubulointerstitial nephritis in a retrospective study using spontaneous reporting system database

Figures & data

Table 1 Numbers of all ADRs and TIN from 2004 to 2016

	Year
	2004	2005	2006	2007	2008	2009	2010	2011	2012	2013	2014	2015	2016
All ADRs
Total number of reports	86,287	109,049	111,224	120,135	133,760	127,469	157,672	184,380	212,583	160,534	194,853	211,587	174,589
Death due to all	6,841	8,296	8,081	9,128	10,247	10,133	10,603	11,397	10,122	10,130	13,928	13,557	11,678
ADRs	(7.9%)	(7.6%)	(7.3%)	(7.6%)	(7.7%)	(7.9%)	(6.7%)	(6.2%)	(4.8%)	(6.3%)	(7.1%)	(6.4%)	(6.7%)
Nonrecovery from	8,178	10,234	10,534	10,846	12,773	12,425	16,549	18,647	24,031	15,025	20,838	22,709	15,183
ADRs	(9.5%)	(9.4%)	(9.5%)	(9.0%)	(9.5%)	(9.7%)	(10.5%)	(10.1%)	(11.3%)	(9.4%)	(10.7%)	(10.7%)	(8.7%)
TIN
Total number of reports	159	174	122	150	266	140	143	214	351	241	395	428	305
Death due to	0	2	0	0	1	0	0	2	0	0	1	4	0
drug-induced TIN	(0%)	(1.2%)	(0%)	(0%)	(0.4%)	(0%)	(0%)	(0.9%)	(0%)	(0%)	(0.3%)	(0.9%)	(0%)
Nonrecovery from	31	19	12	4	67	35	10	37	30	18	46	36	28
drug-induced TIN	(19.5%)	(10.9%)	(9.8%)	(2.7%)	(25.2%)	(25.0%)	(7.0%)	(17.3%)	(8.5%)	(7.5%)	(11.6%)	(8.4%)	(9.2%)

Abbreviations: ADR, adverse drug reaction; TIN, tubulointerstitial nephritis.

Table 2 Characteristics of the patients with drug-induced TIN

Variables	N	Percent
Sex
Men	1,766	57.2
Women	1,301	42.1
Unknown	21	0.7
Age (years)
Under 10	137	4.5
10s	270	8.7
20s	153	5.0
30s	239	7.7
40s	271	8.8
50s	415	13.4
60s	668	21.6
70s	510	16.5
80s	335	10.9
90s	37	1.2
Unknown	53	1.7
Period for treatment at the episode
1 week	371	12.0
2 weeks	110	3.6
4 weeks	36	1.2
12 weeks	422	13.7
24 weeks	63	2.0
1 year	212	6.9
After 1 year	211	6.8
Unknown	1,663	53.8

Abbreviation: TIN, tubulointerstitial nephritis.

Table 3 Most frequently reported drugs that induce TIN

Suspected drug	Cases (n)	ROR	95% CI
Gliclazide	13	30.5	17.4–53.2
Tosufloxacin tosilate hydrate	38	29.5	21.3–41.0
Piperacillin–tazobactam	80	24.3	19.4–30.5
Cefteram pivoxil	10	23.5	12.5–44.2
Mefenamic acid	15	22.5	13.4–37.7
Cefotaxime sodium	10	21.5	11.5–40.5
Mesalazine	85	20.1	16.1–25.0
Piperacillin sodium	97	19.6	16.0–24.1
Polaprezinc	10	19.3	10.3–36.2
Teneligliptin hydrobromide hydrate	11	17.8	9.8–32.4
Benidipine hydrochloride	14	17.4	10.2–29.6
Loxoprofen sodium hydrate	205	15.8	13.7–18.2
Ketoprofen	11	15.5	8.5–28.3
Loratadine	10	14.4	7.7–27.0
Cefdinir	21	14.1	9.2–21.8
Tretinoin	12	13.6	7.7–24.2
Cefditoren pivoxil	23	12.8	8.5–19.4
Ibuprofen	14	12.7	7.5–21.5
Ursodeoxycholic acid	17	11.6	7.2–18.8
Pyrazinamide	17	11.6	7.2–18.8
Acetaminophen	116	11.5	9.6–13.9
Limaprost alfadex	13	11.5	6.7–20.0
Atazanavir sulfate	11	10.3	5.7–18.8
Omeprazole	39	10.2	7.4–14.1
Rebamipide	43	10.2	7.5–13.8
Enalapril maleate	20	10.2	6.5–15.9
Rifampicin	35	9.6	6.9–13.5
Cefcapene pivoxil hydrochloride hydrate	33	9.4	6.6–13.2
Montelukast sodium	10	8.3	4.4–15.5
Abacavir sulfate	14	7.2	4.2–12.1
Eldecalcitol	14	7.1	4.2–12.0
Vancomycin hydrochloride	40	7.1	5.2–9.7
Ethambutol hydrochloride	20	6.9	4.4–10.7
Moxifloxacin hydrochloride	10	6.7	3.6–12.6
Levofloxacin hydrate	58	6.7	5.1–8.7
Diclofenac sodium	66	6.6	5.2–8.5
Famotidine	50	6.2	4.7–8.2
Isoniazid	21	5.5	3.6–8.5
Candesartan cilexetil	24	5.2	3.5–7.7
Minocycline hydrochloride	18	5.1	3.2–8.1
Risedronate sodium hydrate	13	5.1	2.9–8.8
Clarithromycin	40	5.0	3.6–6.8
Ceftriaxone sodium hydrate	27	4.9	3.4–7.2
Cefazolin sodium	15	4.6	2.8–7.7
Lansoprazole	45	4.5	3.3–6.0
Allopurinol	42	4.4	3.2–5.9
Rosuvastatin calcium	14	4.2	2.5–7.2
Sodium rabeprazole	13	4.1	2.4–7.2
Ampicillin–sulbactam	11	4.1	2.3–7.5
Meropenem hydrate	22	4.1	2.7–6.3
Carbocisteine	12	4.0	2.3–7.1
Amoxicillin hydrate	25	3.9	2.7–5.9
Adefovir pivoxil	11	3.9	2.2–7.1
Garenoxacin mesilate hydrate	15	3.8	2.3–6.3
Atorvastatin calcium hydrate	18	3.1	1.9–4.9
Lamivudine	18	2.9	1.8–4.7
Glimepiride	15	2.9	1.7–4.8
Amlodipine besilate	25	2.9	1.9–4.3
Sodium valproate	30	2.6	1.8–3.8
Aspirin	32	2.3	1.7–3.3
Trimethoprim-Sulfamethoxazole	17	2.2	1.3–3.5
Celecoxib	12	1.9	1.1–3.3
Valaciclovir hydrochloride	17	1.7	1.1–2.7
Pregabalin	27	1.7	1.2–2.5
Carbamazepine	29	1.5	1.1–2.2

Abbreviations: ROR, reporting odds ratio; TIN, tubulointerstitial nephritis.