מדריך לאינטראקציות בין תרופתיות עם Paxlovid

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

1. ניתן לבחור כמה רשומות יוצגו בכל עמוד באמצעות הרשימה הנפתחת מעל הטבלה בצד שמאל.
2. ניתן לדפדף בין הרשומות בטבלה באמצעות החיצים ‘הקודם’ ו-‘הבא’ מתחת לטבלה בצד ימין, אולם מומלץ להשתמש בתיבת החיפוש שנמצאת מעל הטבלה בצד ימין.
3. 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.
4. לחיצה על כותרת של עמודה תסדר את העמודה לפי ABC, לחיצה נוספת תסדר אותה בסדר הפוך.
5. 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
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
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
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
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
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
Sedative hypnotics/ Sleeping aids	Bondormin	Brotizolam	up	sedation	3 hours		· Use PAX · Reduce brotizolam dose to 50%
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
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
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