Prevalence and Severity of Potential Drug–Drug Interactions in Patients with Multiple Sclerosis with and without Polypharmacy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Gathered Data
2.3. Drug Characterization
2.4. Polypharmacy
2.5. Identification of Drug–Drug Interactions
2.6. Composite Rating of pDDI Severity Levels
2.7. Statistics
3. Results
3.1. Sociodemographic and Clinical Patient Profile
3.2. Polypharmacy
3.3. Comorbidities
3.4. Drug Profile
3.5. Drug–Drug Interactions
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Total Polypharmacy | Rx Polypharmacy | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
All Patients | PwP | Pw/oP | p | PwP | Pw/oP | p | ||||||
N | 627 | 334 (53.3%) | 293 (46.7%) | 242 (38.6%) | 385 (61.4%) | |||||||
Sociodemographic data | ||||||||||||
Sex | 0.793 Fi | 0.720 Fi | ||||||||||
Male | 186 (29.7%) | 101 (30.2%) | 85 (29.0%) | 74 (30.6%) | 112 (29.1%) | |||||||
Female | 441 (70.3%) | 233 (69.8%) | 208 (71.0%) | 168 (69.4%) | 273 (70.9%) | |||||||
Age (years) | 19–86 R | 48.6 (13.3) a | 20–86 R | 53.0 (12.7) a | 19–74 R | 43.6 (12.2) a | <0.001 t | 24–86 R | 54.8 (12.1) a | 19–75 R | 44.7 (12.5) a | <0.001 t |
School years | 6–18 R | 10.5 (1.3) a | 6–14 R | 10.3 (1.2) a | 8–18 R | 10.7 (1.3) a | <0.001 t | 6–14 R | 10.2 (1.2) a | 8–18 R | 10.7 (1.3) a | <0.001 t |
Educational level | 0.019 Chi | 0.002 Chi | ||||||||||
No training | 19 (3.0%) | 8 (2.4%) | 11 (3.8%) | 7 (2.9%) | 12 (3.1%) | |||||||
Skilled worker | 398 (63.5%) | 229 (68.6%) | 169 (57.7%) | 173 (71.5%) | 225 (58.4%) | |||||||
Technical college | 89 (14.2%) | 46 (13.8%) | 43 (14.7%) | 33 (13.6%) | 56 (14.5%) | |||||||
University | 121 (19.3%) | 51 (15.3%) | 70 (23.9%) | 29 (12.0%) | 92 (23.9%) | |||||||
Employment status | <0.001 Chi | <0.001 Chi | ||||||||||
In training | 7 (1.1%) | 1 (0.3%) | 6 (2.0%) | 0 (0.0%) | 7 (1.8%) | |||||||
In studies | 6 (1.0%) | 0 (0.0%) | 6 (2.0%) | 0 (0.0%) | 6 (1.6%) | |||||||
Employed | 269 (42.9%) | 92 (27.5%) | 177 (60.4%) | 53 (21.9%) | 216 (56.1%) | |||||||
Unemployed | 25 (4.0%) | 10 (3.0%) | 15 (5.1%) | 7 (2.9%) | 18 (4.7%) | |||||||
Disability-pensioned | 304 (48.5%) | 225 (67.4%) | 79 (27.0%) | 178 (73.6%) | 126 (32.7%) | |||||||
Other | 16 (2.6%) | 6 (1.8%) | 10 (3.4%) | 4 (1.7%) | 12 (3.1%) | |||||||
Partnership | 1.000 Fi | 0.305 Fi | ||||||||||
No | 162 (25.8%) | 86 (25.7%) | 76 (25.9%) | 68 (28.1%) | 94 (24.4%) | |||||||
Yes | 465 (74.2%) | 248 (74.3%) | 217 (74.1%) | 174 (71.9%) | 291 (75.6%) | |||||||
Place of Residence | 0.288 Chi | 0.962 Chi | ||||||||||
Rural community | 224 (35.7%) | 119 (35.6%) | 105 (35.8%) | 89 (36.8%) | 135 (35.1%) | |||||||
Provincial town | 108 (17.2%) | 63 (18.9%) | 45 (15.4%) | 42 (17.4%) | 66 (17.1%) | |||||||
Medium-sized town | 112 (17.9%) | 64 (19.2%) | 48 (16.4%) | 43 (17.8%) | 69 (17.9%) | |||||||
City | 183 (29.2%) | 88 (26.3%) | 95 (32.4%) | 68 (28.1%) | 115 (29.9%) | |||||||
Number of children | 0–4 R | 1 b | 0–4 R | 1 b | 0–4 R | 1 b | 0.089 U | 0–4 R | 1 b | 0–4 R | 1 b | 0.056 U |
0 | 169 (27.0%) | 77 (23.1%) | 92 (31.4%) | 54 (22.3%) | 115 (29.9%) | |||||||
1 | 170 (27.1%) | 98 (29.3%) | 72 (24.6%) | 68 (28.1%) | 102 (26.5%) | |||||||
≥2 | 288 (45.9%) | 159 (47.6%) | 129 (44.0%) | 120 (49.6%) | 168 (43.6%) | |||||||
Number of siblings | 0–13 R | 1 b | 0–13 R | 1 b | 0–11 R | 1 b | 0.081 U | 0–13 R | 1 b | 0–11 R | 1 b | 0.018 U |
0 | 71 (11.3%) | 33 (9.9%) | 38 (13.0%) | 26 (10.7%) | 45 (11.7%) | |||||||
1 | 305 (48.6%) | 160 (47.9%) | 145 (49.5%) | 103 (42.6%) | 202 (52.5%) | |||||||
≥2 | 251 (40.0%) | 141 (42.2%) | 110 (37.5%) | 113 (46.7%) | 138 (35.8%) | |||||||
Clinical data | ||||||||||||
EDSS | 0–9 R | 3.5 b | 0–9 R | 4.5 b | 0–7.5 R | 2.0 b | <0.001 U | 0–9 R | 5.0 b | 0–7.5 R | 2.5 b | <0.001 U |
Disease duration (years) | 0–52 R | 10 b | 0–50 R | 12.5 b | 0–52 R | 9 b | <0.001 U | 0–50 R | 14 b | 0–52 R | 9 b | <0.001 U |
Age at MS onset | 9–75 R | 35 b | 9–75 R | 38 b | 12–62 R | 32 b | <0.001 U | 9–75 R | 39 b | 12–69 R | 33 b | <0.001 U |
Disease course | <0.001 Chi | <0.001 Chi | ||||||||||
CIS/RRMS | 415 (66.2%) | 158 (47.3%) | 257 (87.7%) | 91 (37.6%) | 324 (84.2%) | |||||||
SPMS | 154 (24.6%) | 125 (37.4%) | 29 (9.9%) | 109 (45.0%) | 45 (11.7%) | |||||||
PPMS | 58 (9.3%) | 51 (15.3%) | 7 (2.4%) | 42 (17.4%) | 16 (4.2%) | |||||||
Comorbidities | 0–9 R | 1 b | 0–9 R | 2 b | 0–5 R | 1 b | <0.001 U | 0–9 R | 3 b | 0–7 R | 1 b | <0.001 U |
0 | 184 (29.3%) | 46 (13.8%) | 138 (47.1%) | 24 (9.9%) | 160 (41.6%) | |||||||
1 | 150 (23.9%) | 60 (18.0%) | 90 (30.7%) | 39 (16.1%) | 111 (28.8%) | |||||||
2 | 122 (19.5%) | 76 (22.8%) | 46 (15.7%) | 50 (20.7%) | 72 (18.7%) | |||||||
3 | 82 (13.1%) | 71 (21.3%) | 11 (3.8%) | 58 (24.0%) | 24 (6.2%) | |||||||
4 | 50 (8.0%) | 44 (13.2%) | 6 (2.0%) | 35 (14.5%) | 15 (3.9%) | |||||||
≥5 | 39 (6.2%) | 37 (11.1%) | 2 (0.7%) | 36 (14.9%) | 3 (0.8%) | |||||||
Pharmaceutical data | ||||||||||||
Number of total drugs taken | 0–19 R | 5.3 (3.3) c | 5–19 R | 7.8 (2.7) c | 0–4 R | 2.6 (1.1) c | <0.001 t | 5–19 R | 8.5 (2.7) c | 0–9 R | 3.3 (1.7) c | <0.001 t |
0–4 | 293 (46.7%) | 0 (0.0%) | 293 (100.0%) | 0 (0.0%) | 293 (76.1%) | |||||||
5–9 | 261 (41.6%) | 261 (78.1%) | 0 (0.0%) | 169 (69.8%) | 92 (23.9%) | |||||||
≥10 | 73 (11.6%) | 73 (21.9%) | 0 (0.0%) | 73 (30.2%) | 0 (0.0%) | |||||||
Duration of use | ||||||||||||
Long-term drugs | 0–16 R | 4.6 (3.1) c | 1–16 R | 6.7 (2.7) c | 0–4 R | 2.2 (1.1) c | <0.001 t | 1–16 R | 7.4 (2.7) c | 0–9 R | 2.8 (1.7) c | <0.001 t |
PRN drugs | 0–7 R | 0.8 (1.2) c | 0–7 R | 1.1 (1.4) c | 0–4 R | 0.4 (0.7) c | <0.001 t | 0–7 R | 1.2 (1.4) c | 0–6 R | 0.6 (0.9) c | <0.001 t |
Rx vs. OTC | ||||||||||||
Rx drugs | 0–18 R | 4.2 (3.0) c | 1–18 R | 6.2 (2.8) c | 0–4 R | 1.9 (1.0) c | <0.001 t | 5–18 R | 7.3 (2.4) c | 0–4 R | 2.2 (1.2) c | <0.001 t |
OTC drugs | 0–8 R | 1.1 (1.3) c | 0–8 R | 1.6 (1.4) c | 0–3 R | 0.6 (0.8) c | <0.001 t | 0–6 R | 1.2 (1.3) c | 0–8 R | 1.1 (1.3) c | 0.206 t |
Drug purpose | ||||||||||||
DMD | 0–2 R | 0.9 (0.4) c | 0–2 R | 0.9 (0.4) c | 0–2 R | 0.8 (0.4) c | 0.004 t | 0–2 R | 0.9 (0.4) c | 0–2 R | 0.8 (0.4) c | <0.001 t |
Symptomatic drugs | 0–9 R | 2.0 (2.0) c | 0–9 R | 3.1 (2.0) c | 0–3 R | 0.7 (0.9) c | <0.001 t | 0–9 R | 3.3 (2.0) c | 0–9 R | 1.2 (1.4) c | <0.001 t |
Comorbidity drugs | 0–14 R | 2.5 (2.4) c | 0–14 R | 3.8 (2.6) c | 0–4 R | 1.0 (0.9) c | <0.001 t | 0–14 R | 4.3 (2.7) c | 0–7 R | 1.3 (1.3) c | <0.001 t |
Total Polypharmacy | Rx Polypharmacy | ||||||
---|---|---|---|---|---|---|---|
Drug Category | Total Number of Drugs | PwP | Pw/oP | p | PwP | Pw/oP | p |
All | 3341 (100%) | 2591 (77.6%) | 750 (22.4%) | 2060 (61.7%) | 1281 (38.3%) | ||
Duration of use | 0.176 Fi | 0.013 Fi | |||||
Long-term drugs | 2855 (85.5%) | 2226 (85.9%) | 629 (83.9%) | 1785 (86.7%) | 1070 (83.5%) | ||
PRN drugs | 486 (14.5%) | 365 (14.1%) | 121 (16.1%) | 275 (13.3%) | 211 (16.5%) | ||
Rx vs. OTC | 0.011 Fi | <0.001 Fi | |||||
Rx drugs | 2630 (78.7%) | 2065 (79.7%) | 565 (75.3%) | 1766 (85.7%) | 864 (67.4%) | ||
OTC drugs | 711 (21.3%) | 526 (20.3%) | 185 (24.7%) | 294 (14.3%) | 417 (32.6%) | ||
Drug purpose | <0.001 Chi | <0.001 Chi | |||||
DMD | 530 (15.9%) | 297 (11.5%) | 233 (31.1%) | 223 (10.8%) | 307 (24.0%) | ||
Symptomatic drugs | 1253 (37.5%) | 1035 (39.9%) | 218 (29.0%) | 796 (38.6%) | 457 (35.7%) | ||
Comorbidity drugs | 1558 (46.6%) | 1259 (48.6%) | 299 (39.9%) | 1041 (50.6%) | 517 (40.3%) |
Total Polypharmacy | Rx Polypharmacy | ||||||
---|---|---|---|---|---|---|---|
All Patients | PwP | Pw/oP | pFi | PwP | Pw/oP | pFi | |
N | 627 | 334 (53.3%) | 293 (46.7%) | 242 (38.6%) | 385 (61.4%) | ||
Most used non-DMDs | |||||||
Cholecalciferol | 261 (41.6%) | 178 (53.3%) | 83 (28.3%) | <0.001 | 125 (51.7%) | 136 (35.3%) | <0.001 |
Pantoprazole | 178 (28.4%) | 155 (46.4%) | 23 (7.8%) | <0.001 | 144 (59.5%) | 34 (8.8%) | <0.001 |
Enoxaparin | 127 (20.3%) | 114 (34.1%) | 13 (4.4%) | <0.001 | 105 (43.3%) | 22 (5.7%) | <0.001 |
Ibuprofen | 105 (16.7%) | 61 (18.3%) | 44 (15.0%) | 0.286 | 41 (16.9%) | 64 (16.6%) | 0.913 |
Baclofen | 78 (12.4%) | 72 (21.6%) | 6 (2.0%) | <0.001 | 68 (28.1%) | 10 (2.6%) | <0.001 |
Levothyroxine | 75 (12.0%) | 51 (15.3%) | 24 (8.2%) | 0.007 | 41 (16.9%) | 34 (8.8%) | 0.003 |
Cyanocobalamin | 66 (10.5%) | 46 (13.8%) | 20 (6.8%) | 0.006 | 27 (11.2%) | 39 (10.1%) | 0.690 |
Zopiclone | 65 (10.4%) | 58 (17.4%) | 7 (2.4%) | <0.001 | 53 (21.9%) | 12 (3.1%) | <0.001 |
Magnesium | 60 (9.6%) | 45 (13.5%) | 15 (5.1%) | <0.001 | 21 (8.7%) | 39 (10.1%) | 0.580 |
Acetylsalicylic acid | 55 (8.8%) | 48 (14.4%) | 7 (2.4%) | <0.001 | 41 (16.9%) | 14 (3.6%) | <0.001 |
DMDs (all, incl. methylprednisolone) | |||||||
Methylprednisolone | 123 (19.6%) | 110 (32.9%) | 13 (4.4%) | <0.001 | 101 (41.7%) | 22 (5.7%) | <0.001 |
Interferon beta-1a | 64 (10.2%) | 25 (7.5%) | 39 (13.3%) | 0.018 | 14 (5.8%) | 50 (13.0%) | 0.004 |
Glatiramer acetate | 57 (9.1%) | 21 (6.3%) | 36 (12.3%) | 0.012 | 14 (5.8%) | 43 (11.2%) | 0.023 |
Natalizumab | 47 (7.5%) | 18 (5.4%) | 29 (9.9%) | 0.034 | 9 (3.7%) | 38 (9.9%) | 0.005 |
Fingolimod | 41 (6.5%) | 21 (6.3%) | 20 (6.8%) | 0.872 | 15 (6.2%) | 26 (6.8%) | 0.869 |
Teriflunomide | 36 (5.7%) | 19 (5.7%) | 17 (5.8%) | 1.000 | 11 (4.5%) | 25 (6.5%) | 0.379 |
Dimethyl fumarate | 32 (5.1%) | 10 (3.0%) | 22 (7.5%) | 0.011 | 8 (3.3%) | 24 (6.2%) | 0.135 |
Mitoxantrone | 28 (4.5%) | 15 (4.5%) | 13 (4.4%) | 1.000 | 11 (4.5%) | 17 (4.4%) | 1.000 |
Ocrelizumab | 27 (4.3%) | 25 (7.5%) | 2 (0.7%) | <0.001 | 19 (7.9%) | 8 (2.1%) | 0.001 |
Interferon beta-1b | 23 (3.7%) | 9 (2.7%) | 14 (4.8%) | 0.203 | 7 (2.9%) | 16 (4.2%) | 0.515 |
Alemtuzumab | 20 (3.4%) | 5 (1.5%) | 15 (5.1%) | 0.012 | 2 (0.8%) | 18 (4.7%) | 0.009 |
Immunoglobulin G | 7 (1.1%) | 3 (0.3%) | 4 (1.4%) | 0.711 | 0 (0.0%) | 7 (1.8%) | 0.047 |
Cladribine | 6 (1.0%) | 2 (0.6%) | 4 (1.4%) | 0.426 | 2 (0.8%) | 4 (1.0%) | 1.000 |
Azathioprine | 4 (0.6%) | 2 (0.6%) | 2 (0.7%) | 1.000 | 1 (0.4%) | 3 (0.8%) | 1.000 |
Rituximab | 2 (0.3%) | 1 (0.3%) | 1 (0.3%) | 1.000 | 0 (0.0%) | 2 (0.5%) | 0.525 |
Total Polypharmacy | Rx Polypharmacy | ||||||
---|---|---|---|---|---|---|---|
All Patients | PwP | Pw/oP | pFi | PwP | Pw/oP | pFi | |
N | 627 | 334 (53.3%) | 293 (46.7%) | 242 (38.6%) | 385 (61.4%) | ||
Severity level | |||||||
Mild | 363 (57.9%) | 297 (88.9%) | 66 (22.5%) | <0.001 | 225 (93.0%) | 138 (35.8%) | <0.001 |
Mildly moderate | 195 (31.1%) | 175 (52.4%) | 20 (6.8%) | <0.001 | 157 (64.9%) | 38 (9.9%) | <0.001 |
Moderate | 174 (27.8%) | 155 (46.4%) | 19 (6.5%) | <0.001 | 140 (57.9%) | 34 (8.8%) | <0.001 |
Moderately severe | 69 (11.0%) | 64 (19.2%) | 5 (1.7%) | <0.001 | 61 (25.2%) | 8 (2.1%) | <0.001 |
Severe | 7 (1.1%) | 6 (1.8%) | 1 (0.3%) | 0.129 | 5 (2.1%) | 2 (0.5%) | 0.114 |
No pDDI at all | 227 (36.2%) | 22 (6.6%) | 205 (70.0%) | <0.001 | 7 (2.9%) | 220 (57.1%) | <0.001 |
Total Number of pDDIs Recorded | Rx-Rx | Rx-OTC | OTC-OTC | pChi | |
---|---|---|---|---|---|
N | 2887 | 2231 (77.3%) | 549 (19.0%) | 107 (3.7%) | |
Severity level | <0.001 | ||||
Mild | 1889 (65.4%) | 1469 (65.8%) | 327 (59.6%) | 93 (86.9%) | |
Mildly moderate | 511 (17.7%) | 417 (18.7%) | 85 (15.5%) | 9 (8.4%) | |
Moderate | 373 (12.9%) | 249 (11.2%) | 120 (21.9%) | 4 (3.7%) | |
Moderately severe | 107 (3.7%) | 89 (4.0%) | 17 (3.1%) | 1 (0.9%) | |
Severe | 7 (0.2%) | 7 (0.3%) | 0 (0.0%) | 0 (0.0%) |
Total Amount (N = 627) | Total Polypharmacy | Rx Polypharmacy | |||||
---|---|---|---|---|---|---|---|
Drug 1 | Drug 2 | pDDI Severity | Amount in PwP (N = 334) | Amount in Pw/oP (N = 293) | Amount in PwP (N = 242) | Amount in Pw/oP (N = 385) | |
pDDIs of non-DMDs | |||||||
Cholecalciferol | Magnesium | mild | 36 (5.7%) | 30 (9.0%) | 6 (2.0%) | 15 (6.2%) | 21 (5.5%) |
Cyanocobalamin | Pantoprazole | mild | 27 (4.3%) | 25 (7.5%) | 2 (0.7%) | 23 (9.5%) | 4 (1.0%) |
Calcium | Cholecalciferol | mild | 26 (4.1%) | 25 (7.5%) | 1 (0.3%) | 22 (9.1%) | 4 (1.0%) |
Levothyroxine | Pantoprazole | mildly moderate | 23 (3.7%) | 22 (6.6%) | 1 (0.3%) | 22 (9.1%) | 1 (0.3%) |
Acetylsalicylic acid | Enoxaparin | moderate | 21 (3.3%) | 20 (6.0%) | 1 (0.3%) | 19 (7.9%) | 2 (0.5%) |
Cholecalciferol | Simvastatin | mild | 20 (3.2%) | 19 (5.7%) | 1 (0.3%) | 19 (7.9%) | 1 (0.3%) |
Baclofen | Fampridine | mild | 20 (3.2%) | 19 (5.7%) | 1 (0.3%) | 17 (7.0%) | 3 (0.8%) |
Cholecalciferol | Prednisolone | mild | 18 (2.9%) | 18 (5.4%) | 0 (0.0%) | 15 (6.2%) | 3 (0.8%) |
Pantoprazole | Torasemide | mild | 18 (2.9%) | 18 (5.4%) | 0 (0.0%) | 18 (7.4%) | 0 (0.0%) |
Cyanocobalamin | Folic acid | mild | 17 (2.7%) | 12 (3.6%) | 5 (1.7%) | 8 (3.3%) | 9 (2.3%) |
pDDIs of DMDs incl. methylprednisolone | |||||||
Acetylsalicylic acid | Methylprednisolone | moderate | 21 (3.3%) | 20 (6.0%) | 1 (0.3%) | 19 (7.9%) | 2 (0.5%) |
Ibuprofen | Methylprednisolone | mildly moderate | 14 (2.2%) | 13 (3.9%) | 1 (0.3%) | 13 (5.4%) | 1 (0.3%) |
Methylprednisolone | Ramipril | mild | 12 (1.9%) | 12 (3.6%) | 0 (0.0%) | 12 (5.0%) | 0 (0.0%) |
Citalopram | Methylprednisolone | moderately severe | 10 (1.6%) | 10 (3.0%) | 0 (0.0%) | 10 (4.1%) | 0 (0.0%) |
Methylprednisolone | Torasemide | mild | 10 (1.6%) | 10 (3.0%) | 0 (0.0%) | 10 (4.1%) | 0 (0.0%) |
Dipyrone | Methylprednisolone | moderate | 9 (1.4%) | 9 (2.7%) | 0 (0.0%) | 9 (3.7%) | 0 (0.0%) |
Methylprednisolone | Solifenacin | mildly moderate | 9 (1.4%) | 9 (2.7%) | 0 (0.0%) | 8 (3.3%) | 1 (0.3%) |
Citalopram | Fingolimod | moderately severe | 7 (1.1%) | 5 (1.5%) | 2 (0.7%) | 3 (1.2%) | 4 (1.0%) |
Mitoxantrone | Ondansetron | mildly moderate | 7 (1.1%) | 4 (1.2%) | 3 (1.0%) | 3 (1.2%) | 4 (1.0%) |
Interferon beta-1a | Ramipril | mildly moderate | 7 (1.1%) | 5 (1.5%) | 2 (0.7%) | 4 (1.7%) | 3 (0.8%) |
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Bachmann, P.; Frahm, N.; Debus, J.L.; Mashhadiakbar, P.; Langhorst, S.E.; Streckenbach, B.; Baldt, J.; Heidler, F.; Hecker, M.; Zettl, U.K. Prevalence and Severity of Potential Drug–Drug Interactions in Patients with Multiple Sclerosis with and without Polypharmacy. Pharmaceutics 2022, 14, 592. https://doi.org/10.3390/pharmaceutics14030592
Bachmann P, Frahm N, Debus JL, Mashhadiakbar P, Langhorst SE, Streckenbach B, Baldt J, Heidler F, Hecker M, Zettl UK. Prevalence and Severity of Potential Drug–Drug Interactions in Patients with Multiple Sclerosis with and without Polypharmacy. Pharmaceutics. 2022; 14(3):592. https://doi.org/10.3390/pharmaceutics14030592
Chicago/Turabian StyleBachmann, Paula, Niklas Frahm, Jane Louisa Debus, Pegah Mashhadiakbar, Silvan Elias Langhorst, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Michael Hecker, and Uwe Klaus Zettl. 2022. "Prevalence and Severity of Potential Drug–Drug Interactions in Patients with Multiple Sclerosis with and without Polypharmacy" Pharmaceutics 14, no. 3: 592. https://doi.org/10.3390/pharmaceutics14030592
APA StyleBachmann, P., Frahm, N., Debus, J. L., Mashhadiakbar, P., Langhorst, S. E., Streckenbach, B., Baldt, J., Heidler, F., Hecker, M., & Zettl, U. K. (2022). Prevalence and Severity of Potential Drug–Drug Interactions in Patients with Multiple Sclerosis with and without Polypharmacy. Pharmaceutics, 14(3), 592. https://doi.org/10.3390/pharmaceutics14030592