Table 1.
Clinically used oral drug formulations involving CYP3A4 interaction and their pharmaceutical classification.
| Interaction with CYP3A4 a | Drug Examples | Drug Class | Indications | Formulations b | BDDCS Class c | BCS Class d | Log P e |
|---|---|---|---|---|---|---|---|
| Substrates | Alprazolam | Benzodiazepine | Anxiety disorders and panic disorder | Tablet, concentrated liquid | Class 1 | Class 2 | 2.12 |
| Atorvastatin | HMG-CoA reductase inhibitor | Hypercholesterolemia | Tablet | Class 2 | Class 2 | 6.36 | |
| Carbamazepine | Anticonvulsant | Seizures, bipolar disorder, trigeminal neuralgia, diabetic neuropathy | Tablet, capsule, suspension | Class 2 | Class 2 | 2.45 | |
| Cyclosporine | Immuno-suppressant | Prevention organ rejection severe psoriasis, severe rheumatoid arthritis | Capsule, solution | Class 2 | Class 2 | 1.4 | |
| Dexamethasone | Steroid derivative | Different inflammatory conditions: allergic disorders, psoriasis, rheumatoid arthritis, ulcerative colitis | Tablet, solution | Class 1 | Class 1/Class 3 | 1.83 | |
| Ethinyl estradiol | Hormone derivative | Contraceptive, menopausal symptoms | Tablet | Class 1 | Class 1 | 3.67 | |
| Felodipine | Calcium channel blocker | Hypertension | Tablet | Class 2 | Class 2 | 3.86 | |
| Indinavir | HIV protease inhibitor | Cocktails for HIV infections | Capsule | Class 2 | Class 4 | 3.49 | |
| Itraconazole | Azole antifungal | Infections caused by fungus, including the lungs, mouth or throat, fingernails. | Capsule, tablet, solution | Class 2 | Class 2 | 5.66 | |
| Lovastatin | HMG-CoA reductase inhibitor | Hypercholesterolemia | Tablet | Class 2 | Class 2 | 4.26 | |
| Ritonavir | HIV protease inhibitor | Cocktails for HIV infections | Capsule, tablet, solution | Class 2 | Class 4 | 6.27 | |
| Saquinavir | HIV protease inhibitor | Cocktails for HIV infections | Capsule, tablet | Class 2 | Class 4 | 4.7 | |
| Sildenafil | cGMP Phosphodiesterase-5 inhibitor | Erectile dysfunction, pulmonary arterial hypertension | Tablet, capsule, suspension | Class 1 | Class 2 | 2.75 | |
| Simvastatin | HMG-CoA reductase inhibitor | Hypercholesterolemia | Tablet, suspension | Class 2 | Class 2 | 4.68 | |
| Tadalafil | cGMP Phosphodiesterase-5 inhibitor | Erectile dysfunction, enlarged prostate | Tablet | Class 2 | Class 2 | 1.42 | |
| Triazolam | Benzodiazepine | Insomnia | Tablet | Class 1 | n/a | 2.42 | |
| Vardenafil | cGMP Phosphodiesterase-5 inhibitor | Erectile dysfunction, pulmonary arterial hypertension | Tablet | Class 1 | Class 2 | 2.79 | |
| Verapamil | Calcium channel blocker | Hypertension, angina, cardiac arrhythmias | Tablet | Class 1 | Class 1 | 3.79 at pH 9.0; 2.15 at pH 7.0 | |
| Inhibitors | Clarithromycin | Macrolide antibiotic | Bacterial infections: stomach ulcers caused by Helicobacter pylori | Tablet, suspension | Class 3 | Class 2 | 3.16 |
| Erythromycin | Macrolide antibiotic | Different types of bacterial infections | Capsule, tablet, liquid | Class 3 | Class 3 | 3.06 | |
| Fluconazole | Azole antifungal | Fungus infections, cryptococcal meningitis | Powder, tablet | Class 3 | Class 1 | 0.5 | |
| Ketoconazole | Azole antifungal | Fungus infections | Tablet | Class 2 | Class 2 | 4.34 | |
| Midazolam | Benzodiazepine | Anesthesia, anxiety, panic disorder, seizures | Syrup | Class 1 | Class 1 | 4.33 | |
| Nicardipine | Calcium channel blocker | Hypertension, angina, cardiac arrhythmias | Capsule | Class 1 | Class 2 | 3.82 | |
| Nifedipine | Calcium channel blocker | Hypertension, angina, cardiac arrhythmias | Tablet | Class 2 | Class 2 | 2.20 | |
| Tacrolimus | Immuno-suppressant | Prevention of graft rejection following solid organ or bone marrow transplantation | Capsule, granule, tablet | Class 2 | Class 2 | 3.03 | |
| Inducers | Phenobarbital f | Anticonvulsant | Seizures, sedation, insomnia | Elixir, tablet | Class 1 | Class 1 | 1.47 |
| Phenytoin | Anticonvulsant | Seizures, arrhythmia | Capsule, tablet, suspension | Class 2 | Class 2 | 2.47 |
a Effect of each drug on CYP3A4 is obtained from Philip et al., 2015 [60]; b the indication and formulation of each drug is found in MedlinePlus (https://medlineplus.gov/) and Drugs.com (https://www.drugs.com/); c BDDCS class for each drug is obtained from Benet et al., 2011 [61]; d BCS class for each drug is found from the following references [62,63,64,65,66,67,68,69,70,71]; e the Log P value of each drug is obtained from PubChem (https://pubchem.ncbi.nlm.nih.gov/), and the detailed references are listed in the Supplementary Materials; f Interactions between Phenobarbital and CYP3A4 was obtained from FDA [72].