Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use

Honma, Takeshi; Onda, Kenji; Masuyama, Koichi

doi:10.1186/s40360-024-00738-6

Table 3 Potential drug-drug interaction analysis based on adverse event reports of renal failure 1

From: Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use

MTX + Drug	n₁₁₁	n₁₁₊	E₁₁₁	Ω shrinkage model		Additive model		Multiplicative model		CRR model
Acetaminophen	266	15,488	255.28	0.06 (-0.11–0.23)	N	0	N	1.02	P	1.02	N
Celecoxib	136	8,481	143.42	-0.08 (-0.32–0.17)	N	0	N	0.92	N	0.99	N
Acetylsalicylic acid	134	9,119	192.73	-0.52 (-0.77– -0.28)	N	-0.01	N	0.66	N	0.81	N
Diclofenac	115	6,579	172.27	-0.58 (-0.84– -0.32)	N	-0.01	N	0.64	N	0.82	N
Ibuprofen	59	4,255	64.66	-0.13 (-0.5–0.24)	N	0	N	0.89	N	0.98	N
Naproxen	49	5,598	110.08	-1.16 (-1.56– -0.76)	N	-0.01	N	0.43	N	0.65	N
Meloxicam	47	4,569	72.32	-0.62 (-1.03– -0.2)	N	-0.01	N	0.63	N	0.82	N
Loxoprofen	33	1,280	44.85	-0.44 (-0.93–0.06)	N	-0.01	N	0.7	N	0.89	N
Rofecoxib	31	1,265	59.72	-0.93 (-1.44– -0.43)	N	-0.02	N	0.48	N	0.64	N
Indometacin	28	869	33.43	-0.25 (-0.79–0.28)	N	-0.01	N	0.79	N	0.93	N
Ketoprofen	19	829	28.2	-0.56 (-1.21–0.09)	N	-0.01	N	0.64	N	0.83	N
Etodolac	14	906	20.59	-0.54 (-1.3–0.22)	N	-0.01	N	0.65	N	0.83	N
Piroxicam	12	431	4.69	1.27 (0.45–2.08)	P	0.02	P	9.21	P	1.69	N
Sulindac	9	439	7.56	0.24 (-0.7–1.18)	N	0	N	1.16	P	1.1	N
Zaltoprofen	6	55	1.57	1.65 (0.5–2.8)	P	0.08	P	3.63	P	1.42	N
Ketorolac	4	219	5.82	-0.49 (-1.9–0.92)	N	-0.01	N	0.65	N	0.84	N
Flurbiprofen	4	181	3.07	0.33 (-1.08–1.75)	N	0.01	P	1.27	P	1.12	N
Lornoxicam	4	93	1.02	1.57 (0.16–2.98)	P	0.04	P	–	N	1.79	N
Fenoprofen	3	8	0.09	2.58 (0.94–4.21)	P	0.37	P	–	N	2.38	P
Mefenamic acid	2	129	2.82	-0.41 (-2.41–1.59)	N	-0.01	N	0.68	N	0.87	N
Tenoxicam	2	40	1.98	0.01 (-1.99–2.01)	N	0	N	0.95	N	1.01	N
Oxaprozin	1	159	1.74	-0.58 (-3.41–2.25)	N	0	N	1.02	P	0.56	N
Aceclofenac	1	134	4.58	-1.76 (-4.59–1.07)	N	-0.03	N	0.21	N	0.42	N
Acemetacin	1	46	0.5	0.58 (-2.25–3.41)	N	0.02	P	–	N	1.94	N
Bromfenac	1	12	0.76	0.25 (-2.58–3.08)	N	0.02	P	1.23	P	1.17	N
Suprofen	1	1	0.01	1.55 (-1.27–4.38)	N	1	P	–	N	2	N

Methotrexate (MTX) was concomitantly used with acetaminophen (APAP) or non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis (RA) patients. n₁₁₁, the number of adverse event cases where MTX and the analgesic were used concomitantly; n₁₁₊, the number of cases where MTX and the analgesic were used concomitantly; E₁₁₁, the expected value in the Ω shrinkage measure model; CRR, combination risk ratio; P, positive signal; N, non-positive signal

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