Table 3.
Incidence of diarrhea as adverse drug reactions by patient background and treatment factors
| Background and treatment factors | Patients (n/total) | Proportion (%) | 95% CI | P value |
|---|---|---|---|---|
| All cases | 107/1177 | 9.09 | 7.510 to 10.880 | – |
| Patient background | ||||
| Age group | ||||
| 15–64 years | 35/352 | 9.94 | 7.024 to 13.557 | 0.5065 |
| ≥ 65 years | 72/825 | 8.73 | 6.891 to 10.864 | |
| Sex | ||||
| Male | 57/672 | 8.48 | 6.487 to 10.850 | 0.4020 |
| Female | 50/505 | 9.90 | 7.438 to 12.845 | |
| Eastern Cooperative Oncology Group performance status | ||||
| 0 | 10/119 | 8.40 | 4.103 to 14.911 | 0.52711 |
| 1 | 38/356 | 10.67 | 7.665 to 14.356 | |
| 2 | 30/320 | 9.38 | 6.415 to 13.113 | |
| 3 | 25/298 | 8.39 | 5.503 to 12.135 | |
| 4 | 4/83 | 4.82 | 1.329 to 11.882 | |
| Unknown | 0/1 | 0.00 | ||
| Hepatic function abnormalities present | 11/114 | 9.65 | 4.916 to 16.609 | 0.8273 |
| Hepatic function abnormalities absent | 96/1063 | 9.03 | 7.376 to 10.917 | |
| Renal impairment present | 9/74 | 12.16 | 5.715 to 21.836 | 0.3424 |
| Renal impairment absent | 98/1103 | 8.88 | 7.272 to 10.721 | |
| Complications (except cancer) present | 80/755 | 10.60 | 8.492 to 13.014 | 0.0163 |
| Complications (except cancer) absent | 27/422 | 6.40 | 4.258 to 9.173 | |
| History of gastrointestinal disease present | 25/220 | 11.36 | 7.490 to 16.317 | 0.1930 |
| History of gastrointestinal disease absent | 81/946 | 8.56 | 6.858 to 10.530 | |
| Treatment factors | ||||
| Duration of naldemedine treatment | ||||
| < 2 weeks | 35/220 | 15.91 | 11.338 to 21.425 | 0.00402 |
| 2– < 4 weeks | 20/215 | 9.30 | 5.775 to 14.001 | |
| 4– < 6 weeks | 8/142 | 5.63 | 2.463 to 10.799 | |
| 6– < 8 weeks | 8/81 | 9.88 | 4.361 to 18.536 | |
| 8– < 10 weeks | 4/83 | 4.82 | 1.329 to 11.882 | |
| 10– < 12 weeks | 6/53 | 11.32 | 4.270 to 23.029 | |
| ≥ 12 weeks | 26/383 | 6.79 | 4.482 to 9.789 | |
| Time from opioid administration to starting naldemedine treatment | ||||
| 1–2 days | 13/219 | 5.94 | 3.198 to 9.937 | 0.2471 |
| 3–4 days | 14/105 | 13.33 | 7.485 to 21.358 | |
| 5–6 days | 7/69 | 10.14 | 4.177 to 19.792 | |
| 7–13 days | 11/134 | 8.21 | 4.169 to 14.213 | |
| ≥ 14 days | 62/634 | 9.78 | 7.580 to 12.361 | |
| Unknown | 0/16 | 0.00 | - | |
| Opioid analgesics used when naldemedine was started | ||||
| Weak | 12/91 | 13.19 | 7.004 to 21.902 | 0.2384 |
| Strong | 89/1032 | 8.62 | 6.983 to 10.506 | |
| Weak + strong | 6/47 | 12.77 | 4.832 to 25.741 | |
| Unknown | 0/7 | 0.00 | - | |
| Previous use of laxatives (including prophylactic): yes | 86/854 | 10.07 | 8.134 to 12.287 | 0.0574 |
| Previous use of laxatives (including prophylactic): no | 21/323 | 6.50 | 4.069 to 9.767 | |
| Concomitant laxatives: yes | 91/950 | 9.58 | 7.782 to 11.630 | 0.2335 |
| Concomitant laxatives: no | 16/227 | 7.05 | 4.082 to 11.194 | |
| Concomitant drugs other than opioids or laxatives: yes | 100/996 | 10.04 | 8.244 to 12.077 | 0.0079 |
| Concomitant drugs other than opioids or laxatives: no | 7/181 | 3.87 | 1.569 to 7.806 | |
1Ptrend = 0.2287; 2 Ptrend 0.0036; 3 Ptrend = 0.3189. All ptrend results were calculated using the Cochran-Armitage test