Table 2.
Drug–drug interaction (DDI) potential of commonly administered medications
| Class (use in pivotal trials)a | No expected DDI | Require possible dose adjustment | Contra-indicated |
|---|---|---|---|
| Analgesics/anti-inflammatory agents (30 and 11 % of patients received non-opioid and opioid analgesics, respectively) |
Acetaminophenb
Aspirin Buprenorphineb Celecoxib Codeine Diclofenac Etodolac Fenoprofen Flurbiprofen Ibuprofen Indomethacin Ketoprofen Ketorolac Methadoneb Morphine Naloxoneb Naproxen Piroxicam Sulindac Suprofen |
Fentanyl (↓) Hydrocodoneb (↓) Hydromorphone (↓) Meloxicam (↓) Meperidine (pethidine) (↓) Oxycodone (↓) Tramadol (↓) |
None |
| Diuretics (26 % of patients)c | Amiloride Chlorthalidone Hydrochloro-thiazide Torsemide Triamterene |
Furosemide (↓ ≤50 %)b,d
Xipamide (↓)c |
None |
| Antihypertensive agents (26 % of patients)c | Atenolol Azilsartan Betaxolol Bisoprolol Captopril Carteolol Fosinopril Lisinopril Metoprolol Nadolol Nebivolol Perindopril Propranolol Quinopril Ramipril Sotalol Spironolactone Timolol Zofenopril |
Amlodipine (↓50 %)b
Candesartan (↓) Enalapril (↓) Eprosartan (↓) Irbesartan (↓) Losartan (↓) Olmesartan (↓) Telmisartan (↓) Valsartan (↓) Start lowest dose: Diltiazem Nicardipine Nifedipine Nitrendipine Verapamil Avoid use: Nisoldipine Felodipine |
None |
| Antidiabetic agents (5 % of patients) | Acarbose Glimepiride Glipizide Metforminb Pioglitazone Rosiglitazone Sitagliptine Tolbutamide Vildagliptin |
Repaglinide (↓) Glibenclamide (glyburide) (↓) Saxagliptin (limit dose to 2.5 mg once daily) |
None |
| α1-Adrenergic blockers (26 % of patients)c | None | Use with caution: Doxazosin (↓) Avoid use: Tamsulosin |
Alfuzosin |
| Hypnotic/sedative agentsd (2 % of patients) | Oxazepam Temazepam Zolpidemb |
Alprazolam (↓)b
Clonazepam (↓) Diazepamb (↑)d Estazolam (↓) Eszopiclone (↓) Flunitrazepam (↓) Lorazepam (↓) Midazolam (parenteral)d Prazepam (↓) Quazepam (↓) Zaleplon (↓) Zopiclone (↓) |
Midazolam (oral) Triazolam |
| Antibiotics and antifungals (anti-infectives) (7 % of patients) | Amoxicillin Azithromycin Cephalexin Ciprofloxacin Clarithromycine Sulfamethoxazole/trimethoprimb Caspofungin Micafungin Anidulafungin |
Ketoconazole (limit dose to 200 mg)b
Itraconazole (limit dose to 200 mg) Use with caution: Posaconazole (↓) Voriconazolef |
Fusidic acid Rifampin (rifampicin) |
| Phosphodiesterase type 5 inhibitors (<1 % of patients) | None | Sildenafil (↓ for erectile dysfunction)d,g
Tadalafil (↓)d,h Vardenafil (↓)d,i Avoid use: Avanafil |
Sildenafil (for PAH) |
| Antidepressants (22 % of patients) | Bupropiond
Citalopram Duloxetineb Escitalopramb Fluoxetine Milnacipran Paroxetine |
Fluvoxamined
Mirtazapine (↓) Reboxetine (↓) Sertraline (↓) Trazodone (↓) Venlafaxine (↓) |
St. John’s Wort |
| Antacids/proton pump inhibitors (16 % of patients) | Almagate Aluminum hydroxide Calcium carbonate Cimetidine Famotidine Magaldrate Magnesium hydroxide Ranitidine |
Dexlansoprazole (↑)d
Esomeprazole (↑)d Lansoprazole (↑)d Omeprazole (↑)b,d Pantoprazole (↑)d Rabeprazole (↑)d |
None |
| Antiplatelet agents/anticoagulants (26 % of patients)c | Acenocoumarold
Aspirin Enoxaparin Fluindione Fondaparinux Phenprocoumand Prasugreld Warfarina,b |
Apixaban (restrict dose to 2.5 mg twice daily) Dabigatran (↓)d Avoid use: Clopidogrel Rivaroxaban |
None |
| Antiarrhythmic agents (26 % of patients)c | Digoxinb,d
Flecainided Mexiletined |
Use with caution: Amiodarone (↓)d Disopyramide (↓)d Dronedarone (↓)d Propafenone (↓)d Quinidine (↓)d |
None |
| Lipid-modifying agents (2 % of patients) | Choline fenofibrated
Colesevelemj Colestipolj Fenofibrated Mipomersen Niacin Omega-3 fatty acids |
Pravastatin (↓50 %)b
Rosuvastatin (limit maximum daily dose to 5–10 mg)b Start lowest dose: Cerivastatin Ezetimibe Fluvastatin Pitavastatin Avoid use: Atorvastatin |
Gemfibrozilb
Lovastatin Simvastatin |
| β-Adrenergic agonists (14 % of patients received β-adrenergic agonists/anti-allergics/respiratory agents) | Albuterol (salbutamol) | Use with caution: Formoterol (↓)d Not recommended: Salmeterol |
None |
| Antiepileptic agents (3 % of patients) | Felbamate Gabapentin Levetiracetam Sodium valproated Topiramate Vigabatrin |
Lamotrigine (↑)d
Use with caution: Tiagabine (↓) Zonisamide (↓) |
Carbama-zepine Phenytoin Phenobarbital |
| Steroidsc (8 % of patients) | Beclomethasone Ciclesonide |
Use with caution: Budesonide (↓)f Dexamethasone (↓) Fluticasone (↓)f Methyl-prednisolone (↓) Mometasone (↓) Prednisone (↓) Triamcinolone (↓) |
None |
| Contraceptives (<1 % of patients received hormonal contraceptives) | Progestin-only OCPsb
Non-hormonal contraceptives |
None | Ethinyl estradiol-containing OCPsb |
| Thyroid replacement therapy (7 % of patients) | None | Levothyroxined | None |
OCPs oral contraceptive pills, PAH pulmonary arterial hypertension, 3D direct-acting antiviral agent combination of ombitasvir, paritaprevir, ritonavir, and dasabuvir
↑ dose increase recommended, ↓ dose decrease recommended
aPercentage of patients who received the class of drugs concomitantly for at least 6 weeks during treatment with the 3D regimen in pivotal clinical trials [227]
bFor these drugs, formal DDI studies have been performed with the 3D regimen [25, 26]
cThe percentage represents patients who received antihypertensive agents, antiarrhythmic agents, antiplatelet agents/anticoagulants, diuretics or α1-adrenergic blockers for at least 6 weeks during treatment with 3D regimen in pivotal clinical trials [227]
dSuggest monitoring drug levels or clinical response or side effects during 3D treatment to determine dose adjustment requirements
eNo dose adjustment needed for individuals with normal renal function
fBudesonide, fluticasone, and voriconazole should only be used with the 3D regimen if the potential benefits outweigh the risks of treatment
gLimit dose to 25 mg every 48 h for the treatment of erectile dysfunction
hLimit dose to 10 mg every 72 h for erectile dysfunction; initiate 20 mg once daily for PAH after at least 1 week of 3D treatment. The dose may be increased to 40 mg once daily if tolerated and clinically indicated
iLimit dose to 2.5 mg every 72 h for erectile dysfunction; initiate 20 mg once daily for PAH after at least 1 week of 3D treatment. The dose may be increased to 40 mg once daily if tolerated and clinically indicated
jAdminister 4 h after 3D administration