Table 3.
Concomitant medication use (> 10% of total patient population; full analysis set)
| Comedications (by indication and ATC subclass) | Patients using comedication, n (%) | Examples of drug classes/individual agents with DDI potential relevant to androgen receptor inhibitorsc [4, 29, 30] | |
|---|---|---|---|
| Darolutamide + ADT (N = 955) | Placebo + ADT (N = 554) | ||
| Any comedication | 943 (98.7) | 543 (98.0) | |
| Cardiovascular disease | |||
| Agents acting on the renin–angiotensin system | 522 (54.7) | 276 (49.8) |
ACE inhibitors: atenolol (OATP1B1 substrate) ARBs: losartan (CYP3A4/CYP2C9 substrate), telmisartan (OATP1B1 substrate) |
| Antithrombotics | 409 (42.8) | 220 (39.7) |
Antiplatelet agents: clopidogrel (strong CYP2C8 inhibitor), ticagrelor (CYP3A4 substrate) Anticoagulants: rivaroxaban (CYP3A4 substrate), dabigatran etexilate (P-gp substrate) |
| Lipid-modifying agents | 329 (34.5) | 218 (39.4) |
Statins: atorvastatin (CYP3A4/OATP1B1/BCRP substrate), pravastatin (OATP1B1 substrate), rosuvastatin (BCRP/OATP1B1 substrate) Gemfibrozil (strong CYP2C8 inhibitor) |
| β-blocking agents | 283 (29.6) | 153 (27.6) | Propranolol (CYP2C19 substrate) |
| Calcium channel blockers | 217 (22.7) | 126 (22.7) | Amlodipine (CYP3A4 substrate), verapamil (moderate CYP3A4 inhibitor, P-gp inhibitor) |
| Cardiac therapies (e.g., glycosides, anti-arrhythmics, anti-anginals) | 212 (22.2) | 115 (20.8) |
Glycosides: digoxin (P-gp substrate) Anti-arrhythmics: amiodarone (CYP3A4 substrate, CYP2C8/CYP3A4 inhibitor); dronedarone, propafenone (CYP3A4 substrates) Anti-anginals: ranolazine (CYP3A4/P-gp substrate, weak CYP3A4/P-gp inhibitor) Spirolactones: eplerenone (CYP3A4 substrate) |
| Diuretics | 217 (22.7) | 102 (18.4) | Furosemide (BCRP/OATP1B1 substrate) |
| Vasoprotectives | 183 (19.2) | 113 (20.4) | – |
| Pain and inflammation | |||
| Analgesics | 514 (53.8) | 279 (50.4) | Opioids: fentanyl, oxycodone (CYP3A4/P-gp substrates) |
| Anti-inflammatories/DMARDs | 249 (26.1) | 124 (22.4) |
Sulfasalazine (BCRP substrate) Methotrexate (BCRP, OATP1B1, OAT1 and OAT3 substrate) NSAIDs: celecoxib (CYP2C9 substrate), diclofenac (CYP2C9/CYP3A4 substrate) |
| Corticosteroids (systemic)a | 122 (12.8) | 81 (14.6) | Dexamethasone (CYP3A4/P-gp inducer) |
| Urological disorders | |||
| Urologicals | 299 (31.3) | 176 (31.8) | ED agents: sildenafil, vardenafil (CYP3A4 substrates) |
| BPH treatments: dutasteride, tamsulosin (CYP3A4 substrates); silodosin (CYP3A4/P-gp substrate) | |||
| OAB treatments: darifenacin, oxybutynin (CYP3A4 substrates) | |||
| GI and metabolic disorders | |||
| Acid-related disorders | 281 (29.4) | 170 (30.7) | PPIs: lansoprazole (CYP2C19 substrate), omeprazole (CYP2C19 substrate), rabeprazole (CYP2C19 substrate) |
| Antidiabetics | 176 (18.4) | 119 (21.5) | Glitazones: pioglitazone (CYP2C9/CYP3A4 substrate) |
|
Meglitinides: repaglinide (OATP1B1/CY2C8 substrate) Sulfonylureas: glimepiride (CYP2C9 substrate) | |||
| Antidiarrhealsb | 145 (15.2) | 95 (17.1) | Loperamide: CYP3A4/P-gp substrate |
| Constipation medications | 156 (16.3) | 70 (12.6) | – |
| Infection | |||
| Antibiotics (systemic) | 257 (26.9) | 138 (24.9) | Macrolides: clarithromycin (strong CYP3A4 inhibitor), erythromycin (moderate CYP3A4 inhibitor) |
| Nervous system disorders | |||
| Psycholeptics | 188 (19.7) | 109 (19.7) | Antipsychotics: haloperidol, quetiapine, aripiprazole (CYP3A4 substrates) |
| Anxiolytics: buspirone (CYP3A4 substrate) | |||
| Carbamazepine (strong CYP3A4 inducer) | |||
| Benzodiazepines: alprazolam, midazolam (CYP3A4 substrates); diazepam (CYP2C19 substrate) | |||
| Psychoanaleptics | 108 (11.3) | 52 (9.4) | Bupropion (CYP2B6 substrate) |
| SARIs: trazodone (CYP3A4 substrate) | |||
|
SSRIs: citalopram, escitalopram (CYP3A4 substrates) Dementia treatments: donepezil, galantamine (CYP3A4 substrates) | |||
Data presented here are from the 17 January 2019 datacut
Includes medications ongoing at baseline or that were initiated after the study drug or after the end of the study drug but excludes any agents used locally/topically due to the lack of DDI risk (e.g., ophthalmologicals, nonsystemic respiratory products). As multiple ATC codes per drug are possible, some drugs may be counted in more than one category for the same patient
ACE angiotensin-converting enzyme, ADT androgen-deprivation therapy, ARB angiotensin II receptor blocker, ATC Anatomical Therapeutic Chemical, BCRP breast cancer resistance protein, BPH benign prostatic hyperplasia, CYP cytochrome P450 enzyme, DDI drug–drug interaction, DMARD disease-modifying antirheumatic drug, ED erectile dysfunction, GI gastrointestinal, NSAID nonsteroidal anti-inflammatory drug, OAB overactive bladder, OAT organic anion transporter, OATP organic anion-transporting peptide, P-gp P-glycoprotein, PPI proton pump inhibitor, SARI serotonin antagonist and reuptake inhibitor, SSRI selective serotonin reuptake inhibitor
aIncludes all uses of systemic corticosteroids
bIncludes intestinal anti-inflammatory/anti-infective agents
cOne or more agent in the drug class