Table 4.
Substrates with a clinically meaningful gastric pH-dependent mechanism of interaction (n = 38)
| Drug | Antacid | H2RA | PPI |
|---|---|---|---|
| Acalabrutinib | Separate by 2 h | Take 2 h before H2RA | × |
| Atazanavir | Take 2 h before or 1 h after antacid |
HIV treatment-naïve patients: take 2 h before or 10 h after H2RA in those unable to tolerate ritonavir; patients receiving ritonavir should take H2RA simultaneously with atazanavir and food or atazanavir 10 h after H2RA HIV treatment-experienced patients: take H2RA simultaneously with atazanavir and food or atazanavir 10 h after H2RA |
× Can be administered with boosted atazanavir 12 h after PPI in patients that are treatment-naïve to atazanavir |
| Bisacodyl DR | Separate by at least 1 h | – | – |
| Bismuth subcitrate potassium, metronidazole, tetracycline hydrochloride | × | × with cimetidine and other inhibitors of CYP | ✓ |
| Bosutinib | Separate by minimum of 2 h | Separate by minimum of 2 h | × |
| Cefditoren pivoxil | × | × | × |
| Cefpodoxime proxetil | Separate by 2 h | Separate by minimum of 2 h | Monitor |
| Cefuroxime axetil | Take 1 h before or 2 h after antacid | × | × |
| Dabigatran etexilate mesylate | Canada: take 2 h before antacid; monitor | USA: ✓ | USA: ✓ |
| Dasatinib | Separate by minimum of 2 h | × | × |
| Delaviradine | Separate by 1 h | × | × |
| Digoxin | Monitor | – | Monitor |
| Emtricitabine, rilpivirine hydrochloride, tenofovir disoproxil fumarate (Complera®) | Take 4 h before or 2 h after antacid | Take 4 h before or 12 h after H2RA | × |
| Erlotinib | Separate by a few hours | Take 2 h before or 10 h after H2RA | × |
| Ferrous sulfate | Separate as much as possible, monitor | – | – |
| Gefitinib | Separate by 6 h | Separate by 6 h |
× If necessary, separate by 12 h |
| Hyoscyamine | Administer before meals and antacid after meals | – | – |
| Indinavir | – | Monitor | Monitor |
| Itraconazole | Separate by 2 h; consider administering with non-diet cola | Separate by 2 h; monitor; administer with non-diet cola | Separate by 2 h; monitor; administer with non-diet cola |
| Ketoconazole | Take 2 h before or 1 h after antacid; monitor | Monitor; administer with non-diet cola | Monitor; administer with non-diet cola |
| Lapatinib | USA: ✓ UK: × | USA: ✓ UK: × | USA: ✓ UK: × |
| Ledipasvir, sofosbuvir (Harvoni®) | Separate by 4 h | Time simultaneously or 12 h apart | Simultaneously under fasting conditions |
| Mefenamic acid | × | – | – |
| Mesalamine | × | – | – |
| Nelfinavir | – | Monitor | × |
| Neratinib | Take 3 h after antacid | Take 2 h before or 10 h after H2RA | × |
| Nilotinib | Separate by 2 h | Take 2 h before or 10 h after H2RA | × |
| Pazopanib | × | × | × |
| Phenytoin | Do not take at same time of day | – | – |
| Posaconazole oral suspension (Noxafil®) | ✓ | ✓ for H2RA other than cimetidine; × for cimetidine | × |
| Raltegravir (Isentress®) | × for aluminum and/or magnesium antacids; × for calcium carbonate for high-dose raltegravir; ✓ for raltegravir | – | ✓ |
| Riociguat | Separate by 1 h | – | ✓ |
| Risedronate sodium (Atelvia DR) | × | × | × |
| Sofosbuvir, velpatasvir (Epclusa®) | Separate by 4 h | Time simultaneously or 12 h apart |
× If necessary, take with food and 4 h before PPI |
Medications were identified via searches and screens of the PDR3D: Reed Tech Navigator™, University of Washington Drug–Drug Interaction Database (DIDB), and DailyMed databases as detailed in Sect. 4.1
CYP cytochrome P450, DR delayed release, H2RA histamine H2 receptor antagonist, PPI proton pump inhibitor, ✓ coadministration shows no interaction, × coadministration not recommended, – no information available