Table 2.
PMRs by dosing category and type of information provided to inform dosing over time (2012–2022).
| Years of approval | |||||
|---|---|---|---|---|---|
| Dosing category | Type of information | All years | 2012–2015 | 2016–2019 | 2020–2022 |
| Intrinsic factors | Hepatic impairment | 45 (58.4) | 15 (33.3) | 14 (31.1) | 16 (35.6) |
| Renal impairment | 21 (27.3) | 9 (42.9) | 5 (23.8) | 7 (33.3) | |
| Age (pediatric) | 7 (9.1) | — | — | 7 (100) | |
| Genetic subgroup | 2 (2.6) | 1 (50) | — | 1 (50) | |
| Renal and hepatic impairment | 1 (1.3) | — | 1 (100) | — | |
| Low body weight | 1 (1.3) | — | — | 1 (100) | |
| Subtotal | 77 (46.7) | 25 (32.5) | 20 (26) | 32 (41.6) | |
| Extrinsic factors | Drug interaction | 42 (87.5) | 11 (26.2) | 7 (16.7) | 24 (57.1) |
| Drug–drug interaction | 5 (10.4) | 4 (80) | — | 1 (20) | |
| Food effect | 1 (2.1) | — | 1 (100) | — | |
| Subtotal | 48 (29.1) | 15 (31.3) | 8 (16.7) | 25 (52.1) | |
| Dosing variation | Evaluate safety and efficacy of lower dose(s) | 9 (31) | 2 (22.2) | 2 (22.2) | 5 (55.6) |
| Evaluate alternative dose(s)/dosage(s) | 9 (31) | 6 (66.7) | 1 (11.1) | 2 (22.2) | |
| Inform dose modifications/monitoring | 8 (27.6) | 4 (50) | 4 (50) | — | |
| Inform long-term use/chronic administration | 2 (6.9) | 1 (50) | 1 (50) | — | |
| Determine if additional dosing trial needed | 1 (3.5) | 1 (100) | — | — | |
| Subtotal | 29 (17.6) | 14 (48.3) | 8 (27.6) | 7 (24.1) | |
| Miscellaneous | Long-term follow-up | 5 (45.5) | 2 (40) | 2 (40) | 1 (20) |
| QT/QTc assessment | 4 (36.4) | 3 (75) | — | 1 (25) | |
| Animal toxicology study | 2 (18.2) | 1 (50) | — | 1 (50) | |
| Subtotal | 11 (6.7) | 6 (36.4) | 2 (18.2) | 3 (27.3) | |
| Total | 165 | 60 (36.4) | 38 (23) | 67 (40.6) | |