American Academy of Pediatrics

TABLE 3

Variation in Clinically Significant DDI Exposure Stratified by Risk Grade

Risk Grade and DDI No.	Drug 1	Drug 2	Total Patient-Days of Exposure	DDI Exposure Rate per 1000 Days	DDI Description
Risk Grade and DDI No.	Drug 1	Drug 2	Total Patient-Days of Exposure	DDI Exposure Rate per 1000 Days	Δ [Drug]	Δ Drug Metabolism	↑ADE
X
33	Fentanyl	Linezolid+	14 306	1.52	—	—	X^a
41	Methadone+	Voriconazole	8053	0.86	↓	—	—
18	Sirolimus	Voriconazole	3133	0.33	↑	—	X^a
7	Citalopram+	Linezolid+	1349	0.14	—	—	—
17	Rifampin+	Voriconazole	666	0.07	↑	—	—
15	Phenobarbital+	Voriconazole	438	0.05	↓	—	X^b
52	Voriconazole+	Ziprasidone+	258	0.03	—	—	X^b
31	Erythromycin	Sotalol+	245	0.03	—	—	—
45	Nifedipine	Phenytoin	101	0.01	↑ and ↓	—	—
12	Linezolid+	Sumatriptan+	16	<0.01	—	X	—
39	Levofloxacin+	Sotalol+	79	0.01	—	—	X^b
10	Fosamprenavir	Rifampin+	0	0.00	↓	—	—
D
11	Lamotrigine+	Valproic acid	13 769	1.46	—	—	X^c
51	Tacrolimus	Voriconazole	26 068	2.77	↑	—	—
43	Methotrexate	Sulfamethoxazole/trimethoprim	2324	0.25	—	—	X^d
29	Cyclosporine	Voriconazole+	22 268	2.37	—	X	—
20	Amlodipine+	Erythromycin+	8772	0.93	—	X	—
1	Amiodarone	Digoxin	4669	0.50	↑	—	—
38	Ibuprofen+	Methotrexate	625	0.07	↑	—	—
8	Clopidogrel+	Omeprazole+	3182	0.34	↓	—	—
13	Meropenem+	Valproic acid	2217	0.24	↓	—	—
2	Amiodarone	Methadone	5145	0.55	—	—	X^b
3	Amiodarone	Warfarin	4248	0.45	↑	—	—
37	Ibuprofen+	Lithium	1416	0.15	↑	—	—
30	Doxycycline	Phenobarbital+	999	0.11	↓	—
50	Tacrolimus	Rifampin+	1422	0.15	↓	—
47	Quetiapine	Voriconazole+	1335	0.14	—	—	X^b
21	Aspirin+	Methotrexate	181	0.02	↑	—	—
25	Carbamazepine	Erythromycin	825	0.09	↑	—	—
14	Metronidazole	Warfarin	452	0.05	↑	—	—
49	Sotalol+	Voriconazole+	745	0.08	—	—	X^b
48	Rifampin+	Sirolimus	1247	0.13	↓	—	—
6	Ciprofloxacin+	Theophylline+	304	0.03	—	X	—
9	Clopidogrel	Fluconazole	708	0.08	↓	—	—
34	Fluconazole+	Sotalol+	316	0.03	—	—	X^b
28	Cyclosporine+	Rifampin+	381	0.04	—	X	—
27	Caspofungin	Rifampin	122	0.01	↓	—	—
46	Phenytoin	Warfarin+	45	<0.01	↑	—	—
24	Carbamazepine	Cyclosporine	35	<0.01	↓	—	—
16	Rifampin+	Tacrolimus	0	0.00	↓	—	—
C
44	Nicardipine+	Tacrolimus	111 427	11.84	↑	—	—
36	Haloperidol	Quetiapine+	6951	0.74	—	—	X^b
35	Furosemide+	Risperidone	19 882	2.11	—	—	X^e
42	Methotrexate	Penicillin+	2749	0.29	↑	—	—
4	Amitriptyline+	Sertraline+	7806	0.83	↑	—	X^a
19	Amiodarone+	Ciprofloxacin+	12 638	1.34	—	—	X^b
40	Methadone	Phenobarbital	23 044	2.45	↓	—	—
53	Warfarin+	Rifampin+	5883	0.63	↓	—	—
32	Erythromycin	Tacrolimus	2995	0.32	↑	—	—
5	Amitriptyline+	Trazodone+	1682	0.18	—	—	X
23	Atorvastatin	Fluconazole	496	0.05	↑	—	—
26	Carbamazepine	Fluoxetine	341	0.04	↑	—	—
22	Atorvastatin	Erythromycin	227	0.02	↑	—	—

Risk Grade and DDI No.	Drug 1	Drug 2	Total Patient-Days of Exposure	DDI Exposure Rate per 1000 Days	DDI Description
Risk Grade and DDI No.	Drug 1	Drug 2	Total Patient-Days of Exposure	DDI Exposure Rate per 1000 Days	Δ [Drug]	Δ Drug Metabolism	↑ADE
X
33	Fentanyl	Linezolid+	14 306	1.52	—	—	X^a
41	Methadone+	Voriconazole	8053	0.86	↓	—	—
18	Sirolimus	Voriconazole	3133	0.33	↑	—	X^a
7	Citalopram+	Linezolid+	1349	0.14	—	—	—
17	Rifampin+	Voriconazole	666	0.07	↑	—	—
15	Phenobarbital+	Voriconazole	438	0.05	↓	—	X^b
52	Voriconazole+	Ziprasidone+	258	0.03	—	—	X^b
31	Erythromycin	Sotalol+	245	0.03	—	—	—
45	Nifedipine	Phenytoin	101	0.01	↑ and ↓	—	—
12	Linezolid+	Sumatriptan+	16	<0.01	—	X	—
39	Levofloxacin+	Sotalol+	79	0.01	—	—	X^b
10	Fosamprenavir	Rifampin+	0	0.00	↓	—	—
D
11	Lamotrigine+	Valproic acid	13 769	1.46	—	—	X^c
51	Tacrolimus	Voriconazole	26 068	2.77	↑	—	—
43	Methotrexate	Sulfamethoxazole/trimethoprim	2324	0.25	—	—	X^d
29	Cyclosporine	Voriconazole+	22 268	2.37	—	X	—
20	Amlodipine+	Erythromycin+	8772	0.93	—	X	—
1	Amiodarone	Digoxin	4669	0.50	↑	—	—
38	Ibuprofen+	Methotrexate	625	0.07	↑	—	—
8	Clopidogrel+	Omeprazole+	3182	0.34	↓	—	—
13	Meropenem+	Valproic acid	2217	0.24	↓	—	—
2	Amiodarone	Methadone	5145	0.55	—	—	X^b
3	Amiodarone	Warfarin	4248	0.45	↑	—	—
37	Ibuprofen+	Lithium	1416	0.15	↑	—	—
30	Doxycycline	Phenobarbital+	999	0.11	↓	—
50	Tacrolimus	Rifampin+	1422	0.15	↓	—
47	Quetiapine	Voriconazole+	1335	0.14	—	—	X^b
21	Aspirin+	Methotrexate	181	0.02	↑	—	—
25	Carbamazepine	Erythromycin	825	0.09	↑	—	—
14	Metronidazole	Warfarin	452	0.05	↑	—	—
49	Sotalol+	Voriconazole+	745	0.08	—	—	X^b
48	Rifampin+	Sirolimus	1247	0.13	↓	—	—
6	Ciprofloxacin+	Theophylline+	304	0.03	—	X	—
9	Clopidogrel	Fluconazole	708	0.08	↓	—	—
34	Fluconazole+	Sotalol+	316	0.03	—	—	X^b
28	Cyclosporine+	Rifampin+	381	0.04	—	X	—
27	Caspofungin	Rifampin	122	0.01	↓	—	—
46	Phenytoin	Warfarin+	45	<0.01	↑	—	—
24	Carbamazepine	Cyclosporine	35	<0.01	↓	—	—
16	Rifampin+	Tacrolimus	0	0.00	↓	—	—
C
44	Nicardipine+	Tacrolimus	111 427	11.84	↑	—	—
36	Haloperidol	Quetiapine+	6951	0.74	—	—	X^b
35	Furosemide+	Risperidone	19 882	2.11	—	—	X^e
42	Methotrexate	Penicillin+	2749	0.29	↑	—	—
4	Amitriptyline+	Sertraline+	7806	0.83	↑	—	X^a
19	Amiodarone+	Ciprofloxacin+	12 638	1.34	—	—	X^b
40	Methadone	Phenobarbital	23 044	2.45	↓	—	—
53	Warfarin+	Rifampin+	5883	0.63	↓	—	—
32	Erythromycin	Tacrolimus	2995	0.32	↑	—	—
5	Amitriptyline+	Trazodone+	1682	0.18	—	—	X
23	Atorvastatin	Fluconazole	496	0.05	↑	—	—
26	Carbamazepine	Fluoxetine	341	0.04	↑	—	—
22	Atorvastatin	Erythromycin	227	0.02	↑	—	—

[Drug], serum drug concentration; Δ, altered; —, not applicable.

Serotonin syndrome.

Prolonged QT syndrome.

Lamotrigine-specific ADE.

Methotrexate-specific ADEs.

Risperidone-specific ADEs.

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