בשיתוף עם:

הקדמה
- הטיפול ב-PAXLOVID (Nirmatrelvir + Ritonavir) מסייע במניעת מחלה קשה בחולי קורונה סימפטומטיים, כאשר ניתן תוך 3-5 ימים מתחילת הסימפטומים.
- טיפול זה מורכב עקב אינטראקציות בינו לבין תרופות רבות.
- טבלה זו נוצרה על מנת לסייע לרופא המטפל להחליט האם המטופל מתאים לטיפול ב-PAXLOVID (מבחינת אינטראקציות), ובאילו תנאים.
- ההמלצות נכתבו על בסיס עיון במקורות מידע זמינים כגון העלון לרופא, מיקרומדקס, UpToDate ומעיון בספרות אם נמצאה כזו רלוונטית (ניתן לראות את רשימת המקורות העיקריים כאן), וממשיכות להתעדכן מעת לעת בעקבות עדכוני העלונים ושאלות והערות של קלינאים בשטח. המלצה יכולה להיות אחת מהבאות:
- לא לתת טיפול ב-PAXLOVID עקב אינטראקציה משמעותית ומסוכנת. פה המקום לשקול טיפול חלופי כגון Remdesivir או Molnupiravir.
- לתת PAXLOVID ולהמשיך טיפול תרופתי כרוני ללא שינוי – אולי תוך מעקב אחר תופעות לוואי ספציפיות.
- לתת PAXLOVID ולהפחית מינון טיפול כרוני במהלך הטיפול ב-PAXLOVID.
- לתת PAXLOVID ולהפסיק טיפול תרופתי כרוני בזמן הטיפול ב-PAXLOVID בהתבסס על זמן מחצית החיים של התרופה המופסקת, התועלת שבטיפול והסיכון בהפסקה זמנית של הטיפול. כל הנ”ל תלויים בשיקול דעתו של הרופא לגבי הסיכון בהפסקת הטיפול:
- דוגמא 1 – אם לחץ הדם גבוה מאד וקשה לאיזון (תחת הטיפול התרופתי), המלצה להפסיק טיפול ב-Lercanidipine למשל אולי לא מתאימה לחולה, ואילו בחולה מאוזן סביב 120/80 שמעולם לא היו לו לחצי דם מאד גבוהים, ניתן לשקול הפסקה זמנית של הטיפול.
- דוגמא 2 – בחולה שמטופל באנטיקואגולציה עקב פרפור פרוזדורים עם ציון CHADSVASC 2 נוכל להפסיק אנטיקואגולציה במהלך טיפול ב-PAXLOVID ואילו בחולה עם פרפור פרוזדורים, וציון CHADSVASC 6 עם אירועים מוחיים חוזרים, אולי עדיף לעבור ל-Enoxaparin במהלך הטיפול ב-PAXLOVID.
- דוגמא 3 – בחולה שעשה בעבר אצירת שתן על רקע הגדלת פרוסטטה לא נוכל להפסיק טיפול תרופתי, אך בחולה שסבל מתלונות קלות של פרוסטטיזם ומאוזן תחת טיפול, נוכל לשקול להפסיק טיפול זה זמנית על מנת לאפשר טיפול ב-PAXLOVID.
- טבלה זו מכילה תרופות שזמינות בישראל ואינה מכילה את כלל האינטראקציות עם PAXLOVID. במידה וחולה נוטל תרופה שאינה רשומה בטבלה זו, יש לברר באופן פרטני אינטראקציות עם PAXLOVID.
- ניתן להוריד את הגרסאות האחרונות של הטבלאות המקוריות כאן:
במידה ויש הערות או הצעות נוספות ניתן ליצור קשר עם:
ד”ר לי גולדשטיין | יו”ר האיגוד הישראלי לפרמקולוגיה קלינית | Goldstein_le@clalit.org.il | 050-6787786 |
נכתב ע”י ד”ר לי גולדשטיין בסיוע היחידות לפרמקולוגיה קלינית וטוקסיקולוגיה במרכז רפואי שמיר ובמרכז רפואי שיבא, ובסיוע מגר’ דותן שניו מהמרכז הרפואי קפלן.
הנחיות שימוש בטבלה
- ניתן לבחור כמה רשומות יוצגו בכל עמוד באמצעות הרשימה הנפתחת מעל הטבלה בצד שמאל.
- ניתן לדפדף בין הרשומות בטבלה באמצעות החיצים ‘הקודם’ ו-‘הבא’ מתחת לטבלה בצד ימין, אולם מומלץ להשתמש בתיבת החיפוש שנמצאת מעל הטבלה בצד ימין.
- ניתן לחפש לפי כל פרמטר שמופיע בטבלה, אולם הכי פשוט ומדוייק לחפש לפי שם מסחרי או החומר הפעיל של התרופה.
ניתן לחפש לפי קבוצה פרמקולוגית על מנת לראות את כל התרופות מקבוצה זו שמופיעות בטבלה. - לחיצה על כותרת של עמודה תסדר את העמודה לפי ABC, לחיצה נוספת תסדר אותה בסדר הפוך.
- ניתן לכתוב הערות או דיווחים על שגיאות בתגובות בתחתית העמוד והן תטופלנה בהקדם האפשרי.
טבלת האינטראקציות
תאריך עדכון אחרון: 13/7/2022
Drug Class | Commercial Name | Active Substance | Effect on Interacting Drug Concentration | Clinical effect | Half-life | Comments | Recommendations |
---|---|---|---|---|---|---|---|
Anti-arrhythmic | Tambocor | Flecainide | up | Arrhythmias as of 2nd-3rd day | 12-27 hours | Do not use PAX | |
Anti-arrhythmic | Profex, Rythmex | Propafenone | up | Arrhythmias as of 2nd day | 5-8 hours | Do not use PAX | |
Anti-arrhythmic | Rythmical | Disopyramide | up | 10 hours | Do not use PAX | ||
Anti-cancer | Erleada | Apalutamide | - | Decreased PAX | 3 days | Do not use PAX | |
Anti-cancer | Tibsovo | Ivosidenib | up | QTc prolongation, nephrotoxicity | 58-129 hours | Do not use PAX | |
Anti-cancer | Vincristine Teva | Vincristine | up | Neuromuscular, GI toxicity, Myelosuppression | 85 hours | Do not use PAX | |
Anti-epileptics | Tegretol | Carbamazepine | - | Decreased PAX | 15 hours | CYP3A4 inducer | Do not use PAX |
Anti-epileptics | Luminal, Phenobarbitone | Phenobarbital | - | Increased anti-epileptic agents | 80 hours | CYP3A4 inducer | Do not use PAX |
Anti-epileptics | Dilantin | Phenytoin | - | 22 hours | CYP3A4 inducer | Do not use PAX | |
Anti-epileptics | Prysoline | Primidone | - | 5-16 hours | CYP3A4 inducer | Do not use PAX | |
Anti-fungal | Ketoconazole | Ketoconazole | up | Prolonged QT | 8 hours | AUC X 3.4 If impossible to stop ketoconazole, do not use PAX | · Stop ketoconazole · Start PAX 24 hours later · Restart ketoconazole 24 hours after last dose of PAX |
Anti-fungal | Cresemba | Isavuconazole | up | Ritonavir down | 130 hours | Do not use PAX | |
Anti-infective | Rifadin | Rifampicin | - | Decreased PAX | 2-3 hours | Do not use PAX | |
Antipsychotics | Leponex, Lozapine | Clozapine | up | QT prolongation | 12 hours | Withdrawal effects if stopped abruptly | Do not use PAX |
Antipsychotics | Seroquel | Quetiapine | up | QT prolongation | 6 hours | Withdrawal effects if stopped abruptly | Do not use PAX |
Antipsychotics | Orap Forte | Pimozide | up | QT prolongation | 55 hours | Do not use PAX | |
Antipsychotics | Latuda | Lurasidone | up | 18-40 hours | Do not use PAX | ||
Cardiovascular agents | Coralan | Ivabradine | up | Bradycardia or conduction disturbances | 11 hours | Do not use PAX | |
Cystic fibrosis transmembrane conductance regulator potentiators | Orkambi | Lumacaftor / ivacaftor | - | Decreased PAX | 26 hours / 9 hours | · Lumacaftor is a strong inducer of CYP3A · Ivacaftor is a substrate of CYP3A4 | Do not use PAX |
HCV antivirals | Maviret | Glecaprevir/Pibrentasvir | up | Antiviral elevation | 7 / 25 hours | Do not use PAX | |
Immunosuppressants | Sandimmun, Deximune | Cyclosporine / ciclosporine | up | 19 hours | Elevated level of immuno-suppressant is expected. Dose reduction and close follow up of blood levels is recommended | · Use PAX under close medical supervision only (transplant expert etc.) · Consider non-interacting alternatives such as remdesivir or molnupiravir |
|
Immunosuppressants | Evetor | Everolimus | up | Elevated level of immuno-suppressant is expected. Dose reduction and close follow up of blood levels is recommended | · Use PAX under close medical supervision only (transplant expert etc.) · Consider non-interacting alternatives such as remdesivir or molnupiravir |
||
Immunosuppressants | Prograf, Advagraf, Tacrocel | Tacrolimus | up | 23-46 hours | Elevated level of immuno-suppressant is expected. Dose reduction and close follow up of blood levels is recommended | · Use PAX under close medical supervision only (transplant expert etc.) · Consider non-interacting alternatives such as remdesivir or molnupiravir |
|
Immunosuppressants | Rapamune | Sirolimus | up | 62 hours | Elevated level of immuno-suppressant is expected. Dose reduction and close follow up of blood levels is recommended | · Use PAX under close medical supervision only (transplant expert etc.) · Consider non-interacting alternatives such as remdesivir or molnupiravir |
|
Narcotics | Abstral, Actiq, Fenta | Fentanyl | up | Fatal respiratory depression | Depending on dosage form | Do not use PAX unless careful monitoring is possible | |
Narcotics | Methadone | Methadone | down | Withdrawal | 8-59 hours | Do not use PAX unless careful monitoring is possible | |
PDE5 inhibitor | Revatio | Sildenafil | up | Hypotension, syncope, erection | 4 hours | Do not use PAX | |
PDE5 inhibitor | Levitra, B-On | Vardenafil | up | Hypotension, syncope, erection | 4-6 hours | AUC increase 49-fold, Cmax increase 13-fold | · For pulmonary hypertension - Do not use PAX · For erectile dysfunction – stop vardenafil 24 hours before PAX, resume use 48 hours after the last dose of PAX |
Sedative hypnotics | Midazolam PO | up | Respiratory Failure | 2.5 hours | Specific instructions for patients on SOS midazolam | Do not use Midazolam PO, if patient is on PAX | |
Alpha Blockers | Xatral, Alfucal | Alfuzosin | up | Hypotension | 10 hours | Low chance of urinary retention Cmax+AUC x 2 | · Stop Alfuzosin · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
Alpha Blockers | Tamsulin, Omnic | Tamsulosin | up | Hypotension | 14 hours | Possible to continue treatment and monitor orthostatic hypotension and blood pressure | · Consider stopping Tamsulosin · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
Amphetamines | Attent | Amphetamine salts | up (via CYP2D6) | Serotonin syndrome | Possible to continue treatment but monitor blood pressure and signs of serotonin syndrome | · Consider stopping amphetamines · Start PAX · Restart amphetamines 24 hours after last dose of PAX |
|
Amphetamines | Ritalin, Concerta | Methylphenidate | Not metabolized via CYP | Use PAX, no interaction expected | |||
Analgesics and Narcotics | Optalgin | Dipyrone | CYP3A4 weak inducer | Use PAX regardless of OPTALGIN | |||
Analgesics and Narcotics | Dolestine, Demerol | Pethidin, meperidine | up | Respiratory depression | 2.5-8 hours | · Use PAX at least 12 hours after pethidine · Do not use Pethidine if patient on PAX |
|
Analgesics and Narcotics | Buvidal, Butrans | Buprenorphine | up | Not clinically significant | Use PAX | ||
Analgesics and Narcotics | Oxycod, Oxycontin | Oxycodone | up | Sedation, respiratory depression | 4 hours | Monitor sedation and consider reducing doses | Use PAX |
Analgesics and Narcotics | Hysingla | Hydrocodone | up | Sedation, respiratory depression | · Use PAX · Reduce hydrocodone dose by 50% during PAX · Resume normal dose 24 hours after stopping PAX |
||
Analgesics and Narcotics | Tramal, Tramadex | Tramadol | up | Sedation | 6-8 hours | Potentially reduced efficacy due to reduced active metabolites | Use PAX |
Anti-arrhythmic | Procor, Amiocard | Amiodarone | up | Arrhythmias | 50 days | No clinical effect expected | · Stop amiodarone · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
Anti-arrhythmic | Droncor, Multaq | Dronedarone | up | 20 hours | No clinical effect expected | · Stop dronedarone · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
|
Anti-cancer | Verzenio | Abemaciclib | up | Myelosuppression, GI toxicity | 18 hours | · Stop Abemaciclib · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
|
Anti-cancer | Kadcyla | Ado-trastuzumab-emtansine | up | 4 days | Toxicity of attached chemo | · Use PAX regularly between Kadcyla treatments · If Kadcyla is scheduled to be given during the 5-day PAX treatment, consult with the treating oncologist whether Kadcyla can be delayed until 48 hours after the last dose of PAX. If not, patients should be closely monitored for adverse reactions. |
|
Anti-cancer | Zykadia | Ceritinib | up | QTc prolongation, GI toxicity | 41 hours | If impossible to stop, reduce dose by 30% | · Stop Ceritinib · Start PAX 48 hours later · Restart 24 hours after last dose of PAX |
Anti-cancer | Sprycel | Dasatinib | up | Myelosuppression, QTc prolongation | 3-5 hours | · Stop Dasatinib · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
|
Anti-cancer | Braftovi | Encorafenib | up | QTc prolongation | 3.5 hours | · Stop Encorafenib · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
|
Anti-cancer | Tavalisse | Fostamatinib | up | Hepatic adverse effects | 15 hours | Monitor adverse reactions | Use PAX |
Anti-cancer | Imbruvica | Ibrutinib | up | · Arrhythmias · GI toxicity · Nephrotoxicity · Hemorrhage | 4-6 hours | Possible to reduce ibrutinib dose to 140 mg and monitor toxicity | · Stop Ibrutinib · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
Anti-cancer | Lorbrena | Lorlatinib | up | Adverse effects such as bradycardia | 24 hours | · Reduce from 100 mg to 75 mg daily · Reduce from 50 mg to 25 mg daily | · Use PAX · Reduce lorlatinib dose (see comments) |
Anti-cancer | Nerlynx | Neratinib | up | GI toxicity | 7-17 hours | · Stop Neratinib · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
|
Anti-cancer | Tasigna | Nilotinib | up | · QTc prolongation · Myelosuppression · Cardiotoxicity · Hemorrhage | 17 hours | · Stop Nilotinib · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
|
Anti-cancer | Venclexta | Venetoclax | up | Myelosuppression, GI toxicity | 26 hours | If patient on steady daily dosage, possible to reduce venetoclax dose by 75% | · Stop venetoclax · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
Anti-cancer | Blastovin | Vinblastine | up | · Myelosuppression · GI, pulmonary toxicity · Neurotoxicity | 25 hours | · Stop Vinblastine · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
|
Anticoagulants / antiplatelets | Coumadin | Warfarin | Variable | - | 40 hours | Variable effects | Continue warfarin, monitor INR |
Anticoagulants / antiplatelets | Xarelto | Rivaroxaban | up | Bleeding | 5-9 hours | · Consider risk of stopping anticoagulation for specific patient. · Possible to use alternative anticoagulant. · If risky to stop, don’t use PAX | · Stop rivaroxaban · Consider replacing with enoxaparin / apixaban · Start PAX 24 hours later. · Restart 24 hours after last dose of PAX |
Anticoagulants / antiplatelets | Eliquis | Apixaban | up | Bleeding | 12 hours | · Reduce Apixaban dose to 2.5 mg x 2/day · If that is usual dosage then replace with enoxaparin · If risky to stop, don’t use PAX | · Consider stopping/reducing apixaban (see comments) · Consider replacing with enoxaparin · Start PAX 12 hours later. · Restart 24 hours after last dose of PAX |
Anticoagulants / antiplatelets | Lixiana | Edoxaban | up | Bleeding | 10-14 hours | · No info on ritonavir interaction although potentially strong P-gp inhibitor, so dose reduction may be required. · Until further info, do not use with PAX | · Stop edoxaban · Consider replacing with enoxaparin / apixaban · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
Anticoagulants / antiplatelets | Pradaxa, Dabigatran Teva | Dabigatran | up | Bleeding | 12-17 hours | Dabigatran levels my rise due to P-gp inhibition. | · Stop dabigatran · Consider Enoxaparin or Apixaban · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
Anticoagulants / antiplatelets | Brilinta | Ticagrelor | up | Bleeding | 9 hours | Ticagrelor is converted to active drug via CYP3A4 | · Consider stopping ticagrelor (if possible). · If impossible, do not use PAX |
Anticoagulants / antiplatelets | Effient | Prasugrel | No effect | No clinically relevant effect on platelet activity | Use PAX | ||
Anticoagulants / antiplatelets | Plavix, Clood, Clopidexcel | Clopidogrel | Less conversion to active metabolite | Converted to active metabolite mostly by CYP2C19, so little effect is expected on platelet activity | · Use PAX · Consider not using PAX if close proximity (4 weeks) to PCI or acute ischemia (e.g. CVA, ACE) |
||
Antidepressants | Wellbutrin | Bupropion | down | Depression | 20 hours | Continue bupropion, monitor depression | |
Antidepressants | Trazodil | Trazodone | up | Nausea, hypotension, dizziness | 7-10 hours | Continue Trazodone, monitor patient | |
Antidepressants | Elatrol, Elatrolet | Amitriptyline | up | Adverse effects - dry mouth, blurred vision etc. | Monitor adverse effects | · Continue antidepressant · Use PAX |
|
Antidepressants | Tofranil | Imipramine | up | Adverse effects - dry mouth, blurred vision etc. | Monitor adverse effects | · Continue antidepressant · Use PAX |
|
Antidepressants | Deprexan, Norpramin | Desipramine | up | Adverse effects - dry mouth, blurred vision etc. | Monitor adverse effects | · Continue antidepressant · Use PAX |
|
Antidepressants | Nortylin | Nortriptyline | up | Adverse effects - dry mouth, blurred vision etc. | Monitor adverse effects | · Continue antidepressant · Use PAX |
|
Antidepressants | Prozac, Flutine, Prizma | Fluoxetine | up | Serotonin syndrome | Monitor adverse effects | · Continue antidepressant · Use PAX |
|
Antidepressants | Seroxat, Paxxet, Parotin | Paroxetine | up | Serotonin syndrome | Monitor adverse effects | · Continue antidepressant · Use PAX |
|
Antidepressants | Lustral, Serenada | Sertraline | up | Serotonin syndrome | Monitor adverse effects | · Continue antidepressant · Use PAX |
|
Antidepressants | Miro | Mirtazapine | up | Serotonin Syndrome, prolonged QT | 30-50 hours | Monitor serotonin syndrome | · Use PAX · Reduce mirtazapine dose to minimum |
Antidepressants | Remotiv | Hypericum perforatum | PAX down | Mild reduction of PAX | Use PAX | ||
Anti-diabetic | Novonorm | Repaglinide | up | hypoglycemia | 12 hours | Monitor hypoglycemia signs | Use PAX |
Anti-diabetic | Onglyza | Saxagliptin | 2.5 hours | · Use PAX · Max dose saxagliptin: 2.5 mg/day |
|||
Anti-epileptics | Depalept | Valproic acid | down | Possible reduced efficacy | 9-19 hours | Consider using PAX | |
Anti-epileptics | Lamictal, Lamogine | Lamotrigine | down | Possible reduced efficacy | 33 hours | Consider using PAX | |
Anti-epileptics | Midolam | Midazolam | up | Respiratory depression | Do not use if patient on PAX | ||
Anti-epileptics | Assival | Diazepam | up | Respiratory depression | Do not use if patient on PAX | ||
Anti-epileptics | Frisium | Clobazam | up | 36-42 hours | Monitor adverse effects | Use PAX | |
Anti-epileptics | Xcopry, Ontozry | Cenobamate | Mild decrease PAX | 50 hours | Use PAX | ||
Anti-fungal | Itranol, Sporanox | Itraconazole | up | Itraconazole up | 34-42 hours | Consider dose reduction if necessary | Use PAX, monitor adverse effects |
Anti-fungal | Vfend, Vori Teva, Vortimal | Voriconazole | down | 6-8 hours | · Low dose causes reduced AUC 39%, and reduced CMAX 24%. · Consider risk of lower voriconazole levels | · Continue voriconazole · Use PAX |
|
Anti-gout | Colchicine | Colchicine | up | Colchicine toxicity | 27-34 hours | Monitor signs of colchicine toxicity. Usually GI first | · Renal/ Hepatic failure - Do not use PAX · Normal renal/hepatic function – max. colchicine dose is 0.5 mg/day. · Resume normal dose 14 days after stopping PAX |
Anti-histamine | Telfast | Fexofenadine | up | Adverse effects | Monitor adverse effects | Use PAX | |
Anti-histamine | Allergyx, Loratadim, Lorastine | Loratadine | up | Adverse effects | Monitor adverse effects | Use PAX | |
Anti-infective | Karin, Klacid, Klaridex | Clarithromycin | up | QT prolongatio, Decreased active metabolite | 7-9 hours | Consider switching to roxithromycin or azithromycin | · Use PAX · Max clarithromycin dose: 1 gram/day · eGFR 30-60 ml/min - reduce dose by 50% · eGFR < 30 ml/min - reduce dose by 75% |
Anti-infective | Erythrocin | Erythromycin | up | QT prolongation | 2-3 hours | Consider switching to roxithromycin or azithromycin | · Stop erythromycin · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
Anti-infective | Mycobutin | Rifabutin | up | Side effects | 45 hours | With chronic ritonavir, dose of rifabutin is reduced to: 150 mg x 3/week | · Stop rifabutin · Start PAX · Restart 24 hours after last dose of PAX |
Anti-infective | Sirturo | Bedaquiline | up | 5.5 months | Very long half-life, not affected by a 5-day treatment | Use PAX, monitor patient for side effects | |
Anti-infective | Fucidin | Fusidic acid | up | Hepatotoxicity | Do not use PAX unless possible to stop fusidic acid | ||
Anti-infective | Rifadin | Rifampin, Rifampicin | PAX ineffective | Reduced PAX concentrations | Do not use PAX | ||
Anti-infective | Malarone | Atovaquone, Proguanil | down | Atovaquone effectivity reduced | Consider effect of reduced atovaquone efficacy or do not use PAX | Use PAX | |
Anti-infective | Deltyba | Delamanid | Up metabolite that causes QT prolongation | 38 hours | Use PAX if possible to monitor QT | ||
Anti-migraine agents | Relert | Eletriptan | up | 4 hours | · Do not use concomitantly with PAX. · Wait at least 72 hours after PAX before resuming treatment with eletriptan |
||
Anti-migraine agents | Ubrelvy | Ubrogepant | up | 5-7 hours | · Do not use concomitantly with PAX. · Wait at least 24 hours between PAX and ubrogepant, and vice versa. |
||
Anti-migraine agents | Nurtec | Rimegepant | up | 11 hours | AUC may increase 4-fold | · Do not use concomitantly with PAX. · Wait at least 24 hours between PAX and rimegepant, and vice versa. |
|
Antipsychotics | Haldol, Haloper | Haloperidol | up | Adverse effects of anti-psychotic | Due to CYP2D6 inhibition | Use PAX, monitor adverse effects of antipsychotic agent | |
Antipsychotics | Rispond, Risperdal | Risperidone | up | Adverse effects of anti-psychotic | Due to CYP2D6 inhibition | Use PAX, monitor adverse effects of antipsychotic agent | |
Antipsychotics | Ridazin | Thioridazone | up | Adverse effects of anti-psychotic | Due to CYP2D6 inhibition | Use PAX, monitor adverse effects of antipsychotic agent | |
Antipsychotics | Geodon | Ziprasidone | - | Use PAX | |||
Calcium Channel Blockers | Norvasc, Amlow | Amlodipine | up | hypotension | 30-50 hours | · Consider risk of stopping amlodipine · Hypotensive effect continues 72 hours | · Stop amlodipine (or reduce dose by 50%) · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
Calcium Channel Blockers | Vasodip, Lercapress | Lercanidipine | up | hypotension | 10 hours | · Consider risk of stopping lercanidipine · Hypotensive effect continues 24 hours | · Stop lercanidipine · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
Calcium Channel Blockers | Adizem, Dilatam | Diltiazem | up | Hypotension, bradycardia | IR: 3-4.5 hours ER: 5 hours | AUC up by 25% only, monitor patient for adverse effects | Continue diltiazem (consider dose reduction) |
Calcium Channel Blockers | Verapress, Cordamil | Verapamil | up | Hypotension, bradycardia | 3-7 hours | Monitor patient for adverse effects | Continue verapamil (consider dose reduction) |
Calcium Channel Blockers | Nifedilong | Nifedipine | up | hypotension | 2-5 hours | ER so starts decreasing after 24 hours (24 hours+ 5 X t1/2) | · Stop Nifedipine · Start PAX 24 hours later · Restart 24 hours after last dose of PAX |
Cardiac Glycosides | Digoxin | up | bradycardia | 36-48 hours | Mostly renal excretion. AUC elevated 22%. | · Continue digoxin if renal function is unchanged · Monitor Patient · Use PAX as usual |
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Cardiovascular agents | Inspra | Eplerenone | up | Hyperkalemia | 3-6 hours | · Stop eplerenone · Start PAX 24 hours later · If impossible to stop eplerenone, do not give PAX · Restart 24 hours after last dose of PAX |
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Cystic fibrosis transmembrane conductance regulator potentiators | Kalydeco | Ivacaftor | up | 12 hours | Reduce dose: · Stop evening dose of ivacaftor. · Take morning dose of one ivacaftor tablet on day 1 of PAX, and another morning dose on day 5. · Resume standard daily dosing (morning and evening) on day 9. | Reduce dosage when given with PAX - see comments | |
Cystic fibrosis transmembrane conductance regulator potentiators | Trikafta | Elexacaftor / Tezacaftor / Ivacaftor | up | 27 hours / 25 hours / 15 hours | Reduce dose: · Stop evening dose of ivacaftor. · Take morning dose of two elexacaftor / tezacaftor / ivacaftor tablets on day 1 of PAX, and another morning dose on day 5. · Resume standard daily dosing (morning and evening) on day 9. | Reduce dosage when given with PAX - see comments | |
Cystic fibrosis transmembrane conductance regulator potentiators | Symdeko | Tezacaftor / Ivacaftor | up | 15 hours / 13.7 hours | Reduce dose: · Stop evening dose of ivacaftor. · Take morning dose of one tezacaftor / ivacaftor tablet on day 1 of PAX, and another morning dose on day 5. · Resume standard daily dosing (morning and evening) on day 9. | Reduce dosage when given with PAX - see comments | |
Endothelin Receptor antagonists | Tracleer, Trasentan | Bosentan | up | 5 hours | Discontinue Bosentan at least 36 hours prior to PAX | ||
Endothelin Receptor antagonists | Adempas | Riociguat | up | 12 hours | Consider dose reduction if hypotension occurs | Use PAX, monitor for hypotension | |
HCV antivirals | Zepatier | Elbesavir / grazoprevir | up | ALT elevations | 24 / 31 hours | Monitor ALT, use PAX as usual | |
HCV antivirals | Vosevi | Sofosbuvir / velpatasvir / voxilaprevir | 0.5/17/36hours | Continue Vosevi, use PAX as usual | |||
Statins/Lipid modifying agents | Mevacor | Lovastatin | up | rhabdomyolysis | 2 hours | If risk of stopping lovastatin is high, change to rosuvastatin 10 mg/day | · Stop lovastatin · Start PAX 12 hours later · Restart 48 hours after last dose of PAX |
Statins/Lipid modifying agents | Simvacor, Simvaxon, Simovil | Simvastatin | up | unknown | If risk of stopping simvastatin is high, change to rosuvastatin 10 mg/day | · Stop simvastatin · Start PAX 12 hours later · Restart 48 hours after last dose of PAX |
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Statins/Lipid modifying agents | Lipitor, Litorva, Atorva | Atorvastatin | up | 14 hours | CYP3A4 + other metabolism pathways. Possible to continue and monitor signs of rhabdomyolysis | · Consider temporary stop · Start PAX · Restart 24 hours after last dose of PAX |
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Statins/Lipid modifying agents | Stator, Crestor | Rosuvastatin | up | 20 hours | CYP3A4 inhibitor so PAX increases (minor metabolism by CYP3A4) | Decrease dose to 10 mg daily during PAX treatment | |
Statins/Lipid modifying agents | Lojuxta | Lomitapide | up | Hepatic enzyme elevation | 40 hours | · AUC increase 27-fold · Monitor signs of rhabdomyolysis | · Stop Lomitapide · Start PAX 12 hours later · Restart 48 hours after last dose of PAX |
Statins/Lipid modifying agents | Pravalip | Pravastatin | No effect | 3 hours | Use PAX | ||
Contraceptive and hormonal therapy | Various combination preparations | Ethinylestradiol | down | Pregnancy | 13-17 hours | PAX induces CYP3A4 so contraceptive levels drop | · Continue contraceptive plus additional measures · Use PAX as usual |
Contraceptive and hormonal therapy | Orilissa | Elagolix | up | 4-6 hours | Non clinically relevant interaction due to short duration of PAX | Use PAX | |
Long-Acting Beta Agonists (LABA) | Serevent, Seretide Diskus (with fluticasone) | Salmeterol | up | QT prolongation, tachycardia | 5.5 hours | Systemic exposure possible via inhalation | · Consider safety of stopping · Stop salmeterol · Start PAX 12 hours later · Restart 24 hours after last dose of PAX |
Sedative hypnotics/ Sleeping aids | Alpralid, Xanagis | Alprazolam | up | sedation | 10 hours | Decrease dose to 50% Use PAX |
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Sedative hypnotics/ Sleeping aids | Clonex | Clonazepam | up | sedation | 30 hours | · Monitor for withdrawal effects. · Possible to replace with lorazepam or oxazepam in usual doses as needed | · Stop Clonazepam · Start PAX 12 hours later · Restart 48 hours after last dose of PAX |
Sedative hypnotics/ Sleeping aids | Ambien, Zodorm | Zolpidem | - | - | 3 hours | Clinically insignificant interaction | Use PAX |
Sedative hypnotics/ Sleeping aids | Imovane, Nocturno | Zopiclone | up | sedation | 5 hours | · Use PAX · Max dose of zopiclone: 5 mg |
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Sedative hypnotics/ Sleeping aids | Bondormin | Brotizolam | up | sedation | 3 hours | · Use PAX · Reduce brotizolam dose to 50% |
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Sedative hypnotics/ Sleeping aids | Midolam | Midazolam IV | up | Respiratory failure | Use with caution if patient is on PAX | ||
Sedative hypnotics/ Sleeping aids | Assival | Diazepam | up | extreme sedation and respiratory depression | ˜50 hours | · Monitor for withdrawal effects. · Possible to replace with lorazepam or oxazepam in usual doses as needed | · Stop Diazepam · Start PAX 12 hours later · Restart 48 hours after last dose of PAX |
Sedative hypnotics/ Sleeping aids | Tranxal | Clorazepate | up | extreme sedation and respiratory depression | ˜2.5 hours | · Stop Clorazepate · Start PAX 12 hours later · Restart 48 hours after last dose of PAX |
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Sedative hypnotics/ Sleeping aids | Vaben | Oxazepam | - | 6-20 hours | Use PAX | ||
Sedative hypnotics/ Sleeping aids | Lorivan | Lorazepam | - | 10-20 hours | Use PAX | ||
Systemic corticosteroids | up | Side effects | Use PAX as usual | ||||
PDE5 inhibitor | Viagra | Sildenafil | up | Hypotension, syncope, erection | 4 hours | Reduce dose to 25 mg max in 48 hours | · Stop sildenafil (or reduce dose - see comments) · Return to original dose 24 hours after last dose of PAX |
PDE5 inhibitor | Cialis, Tadam, Tadalamed | Tadalafil | up | Hypotension, syncope, erection | 15-35 hours | AUC increase 124% Cmax: no change | · Use PAX · Max dose of tadalafil: 10 mg every 72 hours with increased monitoring for adverse reactions. |
Thyroid hormone replacement therapy | Euthyrox, Eltroxin, Synthroid | Levothyroxine | down | Hypothyroidism | 6-8 days | No clinically significant effect is anticipated for short term treatment | Use PAX as usual |
Overactive bladder | Toviaz | Fesoterodine | up | Anticholinergic effects | 7 hours | · Reduce fesoterodine dose to 4mg/d · If EGFR < 50 ml/min stop fesoterodine while using PAX | · Use PAX · Start PAX 24 hours after last dose of fesoterodine · Reduce fesoterodine dose (see comments) · Return to original dose 24 hours after last dose of PAX |
Overactive bladder | Betmiga | Mirabegron | up | 50 hours | · If EGFR 30-90 ml/min reduce mirabegron to 25 mg/day · If EGFR < 30 ml/min stop mirabegron while using PAX | · Use PAX · Start PAX 24 hours after last dose of mirabegron · Reduce mirabegron dose (see comments) · Return to original dose 24 hours after last dose of PAX |
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Overactive bladder | Vesicare | Solifenacin | up | Anticholinergic effects, QT prolongation | 45-60 hours | · If EGFR > 30 ml/min reduce solifenacin dose to 5mg/day · If EGFR < 30 ml/min stop solifenacin while using PAX | · Use PAX · Start PAX 24 hours after last dose of solifenacin · Reduce solifenacin dose (see comments) · Return to original dose 24 hours after last dose of PAX |
Overactive bladder | Detrusitol | Tolterodine | up | Anticholinergic effects | 9 hours | · Max tolterodine dose: 2 mg/day · If EGFR < 30 ml/min stop tolterodine while using PAX | · Use PAX · Start PAX 24 hours after last dose of tolterodine · Reduce tolterodine dose (see comments) · Return to original dose 24 hours after last dose of PAX |
Overactive bladder | Trosmolyt, Spasmex, Trospas | Trospium | no | No effect expected | Use PAX |