Chapter 1. Pharmacokinetics, Pharmacodynamics, and Principles of Drug-Drug Interactions
Publication: Clinical Manual of Psychopharmacology in the Medically Ill
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Appendix A Psychotropic Drugs With Clinically Significant Pharmacokinetic Interactions
| Cytochrome P450 isozyme | |||||||
|---|---|---|---|---|---|---|---|
| Drug | 1A2 | 2Ca | 2D6 | 3A4 | MAO-A | UGT | P-gp |
| Anticonvulsants and mood stabilizers | |||||||
| Carbamazepine | I | I | S, I | S, I | S | ||
| Lamotrigine | S | S | |||||
| Oxcarbazepine | X | I | |||||
| Phenytoin | I | S, I | I | I | S | ||
| Valproate | I | S, X | |||||
| Antidepressants | |||||||
| Amitriptyline | S | S | S | S | S, X | ||
| Brexanolone | X | S | |||||
| Bupropion | X | S | |||||
| Citalopram | S | ||||||
| Clomipramine | S | S | S, X | S | |||
| Desipramine | S, X | X | |||||
| Desvenlafaxine | S | ||||||
| Doxepin | S | ||||||
| Duloxetine | S | S, X | |||||
| Escitalopram | S | S | |||||
| Esketamineb | S | S | |||||
| Fluoxetine | X | X | S, X | Metabolite S, X | |||
| Fluvoxamine | S, X | X | X | S | |||
| Gepirone | S | ||||||
| Imipramine | S | S | S | S | S, X | ||
| Levomilnacipran | S | ||||||
| Maprotiline | S | X | |||||
| Milnacipran | |||||||
| Mirtazapine | S | S | |||||
| Moclobemide | S | X | X | ||||
| Nefazodone | S, X | ||||||
| Nortriptyline | S | S | |||||
| Paroxetine | S, X | S, X | |||||
| Phenelzine | X | ||||||
| Sertraline | X | ||||||
| Tranylcypromine | X | X | |||||
| Trazodone | S | S | I | ||||
| Trimipramine | S | ||||||
| Venlafaxine | S | S | S | ||||
| Vilazodone | S | ||||||
| Vortioxetine | S | S | |||||
| Antiparkinsonian agents | |||||||
| Rasagiline | S | ||||||
| Selegiline | X | ||||||
| Antipsychotics | |||||||
| Aripiprazole | S | S | S | ||||
| Asenapine | S | S | |||||
| Brexpiprazole | S | S | |||||
| Cariprazine | S | S | |||||
| Chlorpromazine | S | S | X | ||||
| Clozapine | S | S | S | ||||
| Fluphenazine | S | X | |||||
| Haloperidol | S | S, X | X | ||||
| Iloperidone | S | S | |||||
| Lumateperone | S | S | S | S | |||
| Lurasidone | S | ||||||
| Molindone | S | ||||||
| Olanzapine | S | S | S | S | |||
| Perphenazine | S | ||||||
| Pimavanserin | S | ||||||
| Pimozide | S | X | |||||
| Quetiapine | S | S | |||||
| Risperidone | S | S, X | |||||
| Thioridazine | S | S | S | ||||
| Trifluoperazine | X | ||||||
| Ziprasidone | S | ||||||
| Anxiolytics and sedative-hypnotics | |||||||
| Alprazolam | S | ||||||
| Bromazepam | S | ||||||
| Buspirone | S | ||||||
| Clonazepam | S | ||||||
| Diazepam | S | S | |||||
| Lemborexant | S | ||||||
| Lorazepam | S | ||||||
| Midazolam | S | X | |||||
| Oxazepam | S | ||||||
| Phenobarbital | I | I | I | ||||
| Ramelteon | S | ||||||
| Suvorexant | S | ||||||
| Tasimelteon | S | ||||||
| Temazepam | S | ||||||
| Triazolam | S | ||||||
| β-Blockers | |||||||
| Metoprolol | S | ||||||
| Propranolol | S | S | S, X | X | |||
| Opioids | |||||||
| Alfentanil | S | ||||||
| Buprenorphine | S | ||||||
| Codeine | S | S | S | ||||
| Fentanyl | S | X | |||||
| Hydrocodone | S | ||||||
| Meperidine | S | ||||||
| Methadone | S | S | X | ||||
| Morphine | S | S | |||||
| Oxycodone | S | ||||||
| Tramadol | S | ||||||
| Opioid antagonists | |||||||
| Samidorphan | S | S | |||||
| Psychostimulants | |||||||
| Armodafinil | I | X | S, I | ||||
| Atomoxetine | S, X | ||||||
| Modafinil | I | X | S, I | ||||
| Viloxazine | X | S | S | ||||
| VMAT-2 inhibitors | |||||||
| Deutetrabenazine | S | ||||||
| Tetrabenazine | S | ||||||
| Valbenazine | S | S | S | ||||
Note. Pharmacokinetic drug interactions: I = inducer; S = substrate; X = inhibitor. Only significant interactions are listed. MAO-A = monoamine oxidase A; P-gp = P-glycoprotein efflux transporter; UGT = uridine 5′-diphosphate glucuronosyltransferase; VMAT-2 = vesicular monoamine transporter 2.
aCombined properties on 2C8/9/10 and 2C19 cytochrome P450 isozymes.
bEsketamine is also a CYP2B6 substrate.
Source. Compiled in part from Armstrong and Cozza 2002; Balayssac et al. 2005; Cozza et al. 2003; Eli Lilly 2015; English et al. 2012; Fiedorowicz and Swartz 2004; Flanagan et al. 2013; Gillman 2005; Guédon-Moreau et al. 2003; Hiemke et al. 2018; Kiang et al. 2005; Lexicomp Inc 2015; McEvoy 2015; Michalets 1998; Molenaar-Kuijsten et al. 2021; National Library of Medicine 2021; Pal and Mitra 2006; Procyshyn et al. 2015; Thummel et al. 2018; U.S. Food and Drug Administration 2019.
Appendix B Select List of Medications, Foods, and Herbals With Clinically Significant Pharmacokinetic Interactions
| Cytochrome P450 isozyme | |||||||
|---|---|---|---|---|---|---|---|
| Drug | 1A2 | 2Ca | 2D6 | 3A4 | MAO-A | UGT | P-gp |
| Antiarrhythmics | |||||||
| Amiodarone | X | S, X | X | S, X | X | ||
| Antifungals | |||||||
| Fluconazole | X | X | |||||
| Itraconazole | X | X | |||||
| Ketoconazole | X | S, X | X | ||||
| Posaconazole | X | S | S | ||||
| Antineoplastics | |||||||
| Cobimetinib | S | ||||||
| Everolimus | S | S | |||||
| Procarbazine | X | ||||||
| Antibiotics | |||||||
| Ciprofloxacin | X | X | S | ||||
| Clarithromycin | X | X | |||||
| Erythromycin | X | X | |||||
| Linezolid | X | ||||||
| Rifabutin | I | ||||||
| Rifampin (rifampicin) | I | I | S, I | I | S, I | ||
| Sulfamethoxazole-trimethoprim | X | ||||||
| Tedizolid | X | ||||||
| Antimigraine drugs | |||||||
| Almotriptan | S | S | |||||
| Rizatriptan | S | ||||||
| Sumatriptan | S | ||||||
| Zolmitriptan | S | S | |||||
| Antiretrovirals | |||||||
| Atazanavir | X | S, X | X | X | |||
| Cobicistat | S, X | ||||||
| Delavirdine | X | S, X | |||||
| Etravirine | S, X | S, I | X | ||||
| Indinavir | S, X | S | |||||
| Nelfinavir | S, X | S, X | |||||
| Ritonavir | I | X | X | S, X | S, X | ||
| Saquinavir | S, X | S, X | |||||
| Histamine H2-receptor antagonists | |||||||
| Cimetidine | X | X | X | X | S | ||
| Foods, substances, and herbal medicines | |||||||
| Caffeine | S | S | |||||
| Cannabinoids | S | S, X | |||||
| Cruciferous vegetablesb | I | ||||||
| Grapefruit juice | X | X | |||||
| Smoking (e.g., tobacco) | I | S | |||||
| St. John’s wort | I | I | |||||
| Tyramine-containing foodsc | S | ||||||
Note. Pharmacokinetic drug interactions: I = inducer; S = substrate; X = inhibitor. Only significant interactions are listed. MAO-A = monoamine oxidase A; P-gp = P-glycoprotein efflux transporter; UGT = uridine 5′-diphosphate glucuronosyltransferase. aCombined properties on 2C8/9/10 and 2C19 cytochrome P450 isozymes.
bCruciferous vegetables include cabbage, cauliflower, broccoli, brussels sprouts, and kale.
cTyramine-containing foods include banana peel, beer (all tap, “self-brew,” and nonalcoholic), broad bean pods (not beans), fava beans, aged cheese (tyramine content increases with age), red wines, sauerkraut, sausage (fermented or dry), soy sauce and soy condiments, pickled herring, and concentrated yeast extract (Marmite); 6 mg of tyramine is considered to be the cutoff for safe consumption (Shulman and Walker 1999).
Appendix C Some Websites With Drug-Drug Interaction Checking Software
| Epocrates | www.epocrates.com |
| Micromedex | www.micromedexsolutions.com |
| Lexicomp | www.uptodate.com (Wolters Kluwer) |
| Indiana University School of Medicine, Department of Medicine: Drug Interactions | https://drug-interactions.medicine.iu.edu |
| University of Liverpool HIV drug interactions | www.hiv-druginteractions.org/checker |
Note. Many of these require a username or subscription to use.
Information & Authors
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Published In
Clinical Manual of Psychopharmacology in the Medically Ill
Pages: 1 - 49
Editors: Ericka L. Crouse, Pharm.D., and Jonathan G. Leung, Pharm.D.
History
Published in print: 18 October 2023
Published online: 5 December 2024
© American Psychiatric Association Publishing
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