{"id":7053,"date":"2024-08-26T10:47:42","date_gmt":"2024-08-26T09:47:42","guid":{"rendered":"https:\/\/beigen.vipdev.lndo.site\/beigeneius\/?page_id=7053"},"modified":"2025-09-19T15:34:59","modified_gmt":"2025-09-19T13:34:59","slug":"btki-pharmacotherapy-expert-overview","status":"publish","type":"page","link":"https:\/\/beonemedaffairs.com\/begenius\/btki-pharmacotherapy-expert-overview\/","title":{"rendered":"BTKi pharmacotherapy: Expert overview"},"content":{"rendered":"

Introduction<\/h4>\n
\n
\n

Bruton’s tyrosine kinase (BTK) inhibitors have proved to be a valuable treatment option for several B-cell malignancies, transforming outcomes for many patients.<\/p>\n

In this short overview, hematologist Alessandra Tedeschi and pharmacologist Federico Pea outline the key pharmacotherapy considerations in the use of the BTK inhibitors ibrutinib, zanubrutinib, and acalabrutinib. Potential drug\u2013drug interactions (DDIs) with BTK inhibitors and commonly prescribed medication are described, along with some background on mechanisms of DDIs.<\/p>\n<\/div>\n

\n
\n
\n

\"Alessandra<\/p>\n

Alessandra Tedeschi<\/h5>\n<\/div>\n
\n

\"Federico<\/p>\n

Federico Pea<\/h5>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

BTK inhibition<\/h4>\n

Ibrutinib was the first-in-class BTK inhibitor, initially receiving approval for MCL in 2013.1<\/sup> It offers deep and durable responses with an acceptable toxicity profile, but patients may experience side effects attributed to significant off-target activity.2<\/sup> Cardiovascular adverse drug reactions are a notable challenge, with substantial real-world incidence of atrial fibrillation and hypertension among patients treated with ibrutinib.2-4<\/sup><\/p>\n

The next-generation BTK inhibitors zanubrutinib and acalabrutinib have greater selectivity for BTK compared with ibrutinib and have consistently demonstrated some notable advantages in terms of safety in head-to-head trials versus ibrutinib.5-7<\/sup> Notably, zanubrutinib and acalabrutinib have favorable cardiac safety profiles compared with ibrutinib.5-7<\/sup><\/p>\n

Efficacy outcomes have usually been similar between BTK inhibitors in head-to-head trials. However, in the ALPINE study in relapsed\/refractory (R\/R) CLL, zanubrutinib demonstrated a better overall response rate (83.5% vs. 74.2%) and 24-month progression-free survival (78.4% vs. 65.9%; hazard ratio: 0.65; P<\/em>=0.002) versus ibrutinib.7<\/sup><\/p>\n

These three covalent BTK inhibitors are currently approved as monotherapies by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of four B-cell malignancies (see Table 1).8<\/sup>\u2013<\/sup>13<\/sup><\/p>\n

Table 1. BTK inhibitor approvals in B-cell malignancies and pharmacology8<\/sup>\u2013<\/sup>14<\/sup><\/h6>\n\n\n\n\n\n<\/colgroup>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
<\/td>\nIbrutinib<\/strong><\/td>\nZanubrutinib<\/strong><\/td>\nAcalabrutinib<\/strong><\/td>\n<\/tr>\n
Approved indications in Europe (EMA)<\/strong><\/td>\nCLL*, MCL, WM\u2020<\/sup><\/td>\nCLL, MZL, WM<\/td>\nCLL\u2021<\/sup><\/td>\n<\/tr>\n
Approved indications in the USA (FDA)<\/strong><\/td>\nCLL*, WM\u2020<\/sup><\/td>\nCLL, MCL, MZL, WM<\/td>\nCLL\u2021<\/sup>, MCL<\/td>\n<\/tr>\n
Pharmaceutical forms in Europe (EMA)<\/strong><\/td>\nHard capsule: 140 mg
\nTablets: 140 mg, 280 mg, 420 mg, and 560 mg<\/td>\n		Hard capsule: 80 mg<\/td>\nHard capsule: 100 mg
\nTablet: 100 mg<\/td>\n<\/tr>\n
Pharmaceutical forms in the USA (FDA)<\/strong><\/td>\nCapsules: 70 mg and 140 mg
\nTablets: 140 mg, 280 mg, and 420 mg
\nOral suspension: 70 mg\/mL<\/td>\n		Hard capsule: 80 mg<\/td>\nHard capsule: 100 mg
\nTablet: 100 mg<\/td>\n<\/tr>\n
Approved dose<\/strong><\/td>\n420 mg QD for CLL and WM
\n560 mg QD for MCL<\/td>\n		160 mg BID or 320 mg QD<\/td>\n100 mg BID<\/td>\n<\/tr>\n
IC50<\/sub> against BTK, nM<\/strong><\/td>\n1.5<\/td>\n0.5<\/td>\n5.1<\/td>\n<\/tr>\n
Potency of major active metabolite against BTK<\/strong><\/td>\n~15-fold less potent compared with the parent molecule<\/td>\nN\/A<\/td>\n~2-fold less potent compared with the parent molecule<\/td>\n<\/tr>\n
Half-life, hours<\/strong><\/td>\n~4 to 6<\/td>\n~2 to 4<\/td>\n~0.6 to 2.8<\/td>\n<\/tr>\n
Plasma protein binding, %<\/strong><\/td>\n97.3\u201397.7<\/td>\n~94<\/td>\n97.4\u201397.5<\/td>\n<\/tr>\n
AUC0<\/sub>\u2013<\/sub>24h<\/sub> (CV%), ng\u00b7h\/mL<\/strong><\/td>\n420 mg QD: 707\u20131,159 (50%\u201372%)
\n560 mg QD: 865\u2013978 (69%\u201382%)<\/td>\n		160 mg BID: 2,295 (37%)
\n320 mg QD: 2,180 (41%)<\/td>\n		100 mg BID: 1,843\u20131,850 (38%\u201372%)<\/td>\n<\/tr>\n
fu. AUC0<\/sub>\u2013<\/sub>24h<\/sub>, nM\u00b7h<\/strong><\/td>\n420 mg QD: 37\u201360
\n560 mg QD: 46\u201351<\/td>\n		160 mg BID: 278
\n320 mg QD: 267<\/td>\n		100 mg BID: 103<\/td>\n<\/tr>\n
Plasma exposure of major active metabolite<\/strong><\/td>\n1- to 2.8-fold higher than parent AUC<\/td>\nN\/A<\/td>\n2- to 3-fold higher than parent AUC<\/td>\n<\/tr>\n
Median BTK occupancy in PBMC at trough<\/strong><\/td>\n420 mg to 820 mg QD: >90%<\/td>\n160 mg BID: 100%
\n320 mg QD:100%<\/td>\n		100 mg BID: \u226595%<\/td>\n<\/tr>\n
Median BTK occupancy in lymph node at trough<\/strong><\/td>\n420 mg QD: >90%<\/td>\n160 mg BID: 100%
\n320 mg QD: 94%<\/td>\n		100 mg BID: 95.8%
\n200 mg QD: 90%<\/td>\n<\/tr>\n
P-gp and brain penetration<\/strong><\/td>\nNot a P-gp substrate.<\/p>\n

Brain penetration data in patients available.<\/td>\n

Weak P-gp substrate.<\/p>\n

Brain penetration data in patients available.<\/td>\n

P-gp substrate.<\/p>\n

Likely limited brain penetration.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*Approved as monotherapy or with obinutuzumab, rituximab, or venetoclax for previously untreated CLL and as monotherapy or with bendamustine and rituximab for previously treated CLL. \u2020<\/sup>Approved as monotherapy or with rituximab for previously treated patients and untreated patients unsuitable for chemoimmunotherapy. \u2021<\/sup>Approved as monotherapy or with obinutuzumab. AUC, area under the curve; BID, twice a day; fu., fraction of unbound drug in plasma; IC50, half maximal inhibitory concentration; N\/A, not applicable; PBMC, peripheral blood mononuclear cell; QD, once a day.<\/p>\n

Tolerability with BTK inhibitors<\/h4>\n

Side effects associated with BTK inhibitors are usually manageable, but withdrawal or discontinuation of the agents may be required in some circumstances (see Table 2).2,5<\/sup>\u2013<\/sup>7<\/sup><\/p>\n

Table 2. BTK inhibitor side effect management9,11,12<\/sup><\/h6>\n\n\n\n<\/colgroup>\n\n\n\n\n\n
<\/td>\nDose adjustments or discontinuation<\/strong><\/td>\n<\/tr>\n
Ibrutinib<\/strong><\/td>\n\n
    \n
  • Ibrutinib should be withheld on the first, second, and third occurrence and discontinued after the fourth occurrence of Grade 3 or 4 non-hematological toxicities; Grade 3 or 4 neutropenia with infection or fever; and Grade 4 hematological toxicities<\/li>\n
  • Ibrutinib should be withheld on the first and second occurrence, and discontinued after the third occurrence of Grade 2 cardiac failure<\/li>\n
  • Ibrutinib should be withheld on the first occurrence and discontinued after the second occurrence of Grade 3 cardiac arrhythmias<\/li>\n
  • Ibrutinib should be discontinued after the first occurrence of Grade 3 or 4 cardiac failure or Grade 4 cardiac arrhythmias<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
Zanubrutinib<\/strong><\/td>\n\n
    \n
  • Zanubrutinib should be withheld on the first, second, and third occurrence and discontinued after the fourth occurrence of Grade \u22653 non-hematological toxicities; Grade 3 febrile neutropenia; Grade 3 thrombocytopenia with significant bleeding; Grade 4 neutropenia (lasting >10 consecutive days); or Grade 4 thrombocytopenia (lasting >10 consecutive days)<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
Acalabrutinib<\/strong><\/td>\n\n
    \n
  • Acalabrutinib should be withheld on the first, second, and third occurrence and discontinued after the fourth occurrence of Grade 3 thrombocytopenia with bleeding; or Grade 4 thrombocytopenia or Grade 4 neutropenia lasting longer than 7 days; or Grade 3 or greater non-hematological toxicities<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

    DDI overview<\/h4>\n

    Monitoring and managing the risk of potential DDIs is an important component of treatment with any drug, including BTK inhibitor therapy. Most patients with CLL, WM, MCL, or MZL are \u226560 years old at diagnosis and likely to have comorbidities that require medication.15<\/sup>\u2013<\/sup>18<\/sup> Acute conditions (such as infections) that require treatment will also arise over time in this patient population.<\/p>\n

    DDIs occur when one drug alters the activity of another drug and result from pharmacokinetic and\/or pharmacodynamic mechanisms, both of which are relevant to BTK inhibitors (see Figure 1).19<\/sup><\/p>\n

    Figure 1. DDIs with BTK inhibitors9,11,12,19,20<\/sup><\/h6>\n
    \n

    \"DDI<\/p>\n<\/div>\n

    Table 3. Potential DDIs with ibrutinib, zanubrutinib, and acalabrutinib in patients with B-cell malignancies<\/h6>\n

    Interaction strength: X<\/strong> major<\/span> (highly clinically significant), \u26a0<\/strong> moderate<\/span> (moderately clinically significant), and no known interaction<\/span>.<\/small><\/p>\n

    Interactions may increase (\u2191) or decrease (\u2193) a patient’s exposure to a BTK inhibitor.<\/small><\/p>\n

    \n
    \n\n\n\n\n\n\n\n\n
    <\/td>\nAlpha blockers<\/td>\nAnalgesics<\/td>\nAngiotensin-II receptor blockers<\/td>\nAntibiotics<\/td>\nAnticholinergics<\/td>\nAnticonvulsants<\/td>\nAntidepressants<\/td>\nAntidiabetics<\/td>\nAntihistamines<\/td>\nAnti-emetics<\/td>\nAntifungals<\/td>\nAntiplatelet therapies<\/td>\nAntipsychotics<\/td>\nAntithrombotics<\/td>\nBeta blockers<\/td>\nCalcium channel blockers<\/td>\nCardiac glycosides<\/td>\nDiuretics<\/td>\nGlucocorticoids<\/td>\nHypnotics<\/td>\nMuscle relaxants<\/td>\nNon-steroidal anti-inflammatory drugs (NSAIDs)<\/td>\nPotassium channel blockers<\/td>\nProton pump inhibitors (PPIs)<\/td>\nSedatives<\/td>\nStatins<\/td>\nUrology<\/td>\n<\/tr>\n
    <\/td>\nTamsulosin, Terazosin<\/td>\nAcetaminophen, Buprenorphine, Celecoxib, Codeine, Fentanyl, Hydrocodone, Hydromorphone, Meperidine, Methadone, Oxycodone, Piroxicam, Tramadol<\/td>\nIrbesartan, Losartan, Valsartan<\/td>\nClarithromycin<\/td>\nClindamycin<\/td>\nRifampin<\/td>\nSulfamethoxazole<\/td>\nBenztropine<\/td>\nCarbamazepine<\/td>\nEthosuximide<\/td>\nPhenytoin<\/td>\nValproic acid<\/td>\nAmitriptyline<\/td>\nBupropion<\/td>\nCitalopram<\/td>\nDuloxetine<\/td>\nEscitalopram<\/td>\nFluoxetine<\/td>\nMirtazapine<\/td>\nParoxetine<\/td>\nSertraline<\/td>\nTrazodone<\/td>\nVenlafaxine<\/td>\nGlipizide, Metformin, Pioglitazone, Rosiglitazone<\/td>\nChlorpheniramine, Diphenhydramine, Hydroxyzine, Loratadine<\/td>\nMetoclopramide<\/td>\nFluconazole<\/td>\nIsavuconazonium<\/td>\nItraconazole<\/td>\nVoriconazole<\/td>\nClopidogrel, Prasugrel, Ticagrelor<\/td>\nAripiprazole, Haloperidol, Olanzapine, Risperidone, Quetiapine, Ziprasidone<\/td>\nApixaban, Clopidogrel, Dabigatran, Rivaroxaban, Warfarin<\/td>\nCarvedilol, Metoprolol, Propranolol, Sotalol<\/td>\nDiltiazem<\/td>\nFelodipine<\/td>\nVerapamil<\/td>\nDigoxin<\/td>\nTriamterene<\/td>\nFluticasone<\/td>\nDiazepam, Midazolam<\/td>\nCarisoprodol, Cyclobenzaprine, Tizanidine<\/td>\nAspirin, Diclofenac, Etodolac, Ibuprofen, Indomethacin, Meloxicam, Naproxen, Piroxicam<\/td>\nAmiodarone<\/td>\nEsomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole<\/td>\nAlprazolam, Diazepam, Eszopiclone, Zolpidem<\/td>\nAtorvastatin, Lovastatin, Rosuvastatin, Simvastatin<\/td>\nSildenafil, Tadalafil<\/td>\n<\/tr>\n<\/thead>\n
    Ibrutinib<\/td>\n<\/td>\n<\/td>\n<\/td>\nClarithromycin is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\n<\/td>\nRifampin is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\n<\/td>\nCarbamazepine is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\nPhenytoin is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\nCitalopram may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nDuloxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nEscitalopram may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nFluoxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nParoxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nSertraline may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nVenlafaxine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\nFluconazole is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\nIsavuconazonium is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\nItraconazole is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\nVoriconazole is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\nClopidogrel, prasugrel, and ticagrelor may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nAntithrombotics may increase the risk of bleeding Warfarin or other vitamin K antagonists should not be administered concomitantly with ibrutinib. Monitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nDiltiazem is a moderate CYP3A4 inhibitorModify ibrutinib dose to 280 mg once daily<\/span><\/td>\n<\/td>\nVerapamil is a moderate CYP3A4 inhibitorModify ibrutinib dose to 280 mg once daily<\/span><\/td>\nDigoxin is a P-gp substrateDigoxin should be taken at least 6 hours before or after ibrutinib.<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\nNSAIDs may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nAmiodarone is a moderate CYP3A4 inhibitorModify ibrutinib dose to 280 mg once daily<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
    Zanubrutinib<\/td>\n<\/td>\n<\/td>\n<\/td>\nClarithromycin is a strong CYP3A4 inhibitorModify zanubrutinib dose to 80 mg once daily<\/span><\/td>\n<\/td>\nRifampin is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\n<\/td>\nCarbamazepine is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\nPhenytoin is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\nCitalopram may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\nDuloxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\nEscitalopram may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\nFluoxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\n<\/td>\nParoxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\nSertraline may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\n<\/td>\nVenlafaxine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\nFluconazole is a strong CYP3A4 inhibitorModify zanubrutinib dose to 80 mg once daily<\/span><\/td>\nItraconazole is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\nItraconazole is a strong CYP3A4 inhibitorModify zanubrutinib dose to 80 mg once daily<\/span><\/td>\nVoriconazole is a strong CYP3A4 inhibitorModify zanubrutinib dose to 80 mg once daily<\/span><\/td>\nClopidogrel, prasugrel, and ticagrelor may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\n<\/td>\nAntithrombotics may increase the risk of bleedingWarfarin or other vitamin K antagonists should not be administered concomitantly with zanubrutinib. Monitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\n<\/td>\nDiltiazem is a moderate CYP3A4 inhibitorModify zanubrutinib dose to 80 mg once daily<\/span><\/td>\n<\/td>\nVerapamil is a moderate CYP3A4 inhibitorModify zanubrutinib dose to 80 mg once daily<\/span><\/td>\nDigoxin is a P-gp substrateZanubrutinib may increase the concentration of digoxin.<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\nNSAIDs may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding and monitor complete blood counts.<\/span><\/td>\nAmiodarone is a moderate CYP3A4 inhibitorModify zanubrutinib dose to 80 mg once daily<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
    Acalabrutinib<\/td>\n<\/td>\n<\/td>\n<\/td>\nClarithromycin is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\n<\/td>\nRifampin is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\n<\/td>\nCarbamazepine is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\nPhenytoin is a strong CYP3A4 inducerAvoid concomitant use<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\nCitalopram may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nDuloxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nEscitalopram may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nFluoxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nParoxetine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nSertraline may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nVenlafaxine may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\nFluconazole is a strong CYP3A4 inhibitorAvoid concomitant use.<\/span><\/td>\nItraconazole is a strong CYP3A4 inhibitorAvoid concomitant use<\/span><\/td>\nItraconazole is a strong CYP3A4 inhibitorAvoid concomitant use.<\/span><\/td>\nVoriconazole is a strong CYP3A4 inhibitorAvoid concomitant use.<\/span><\/td>\nClopidogrel, prasugrel, and ticagrelor may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nAntithrombotics may increase the risk of bleedingWarfarin or other vitamin K antagonists should not be administered concomitantly with acalabrutinib. Monitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\n<\/td>\nDiltiazem is a moderate CYP3A4 inhibitorNo dose adjustment. Monitor patients closely for adverse reactions.<\/span><\/td>\n<\/td>\nVerapamil is a moderate CYP3A4 inhibitorNo dose adjustment. Monitor patients closely for adverse reactions.<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\nNSAIDs may increase the risk of bleedingMonitor patients receiving concomitant medications associated with a bleeding risk for signs and symptoms of bleeding.<\/span><\/td>\nAmiodarone is a moderate CYP3A4 inhibitorNo dose adjustment. Monitor patients closely for adverse reactions.<\/span><\/td>\nPPIs may interfere with acalabrutinib when administered as capsulesAvoid concomitant use with acalabrutinib 100 mg hard capsules; PPIs may be taken without dose adjustments with acalabrutinib 100 mg tablets.<\/span><\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n

    This table is for educational purposes only, not professional advice, and is not intended for a comparison of the three agents. The interaction strength of potential DDIs is based on the evaluation of information within the prescribing information or summary of product characteristics of each BTK inhibitor and other published studies.8\u201313,21,22<\/sup> No known interaction was assumed with a particular drug if no interaction data could be found, but this does not mean no interaction can occur in patients.<\/em><\/small><\/p>\n<\/div>\n

    \n

    Key takeaway messages<\/h4>\n
      \n
    • BTK inhibition has transformed outcomes for many patients with B-cell malignancies, but there are specific pharmacotherapy challenges associated with agents that are usually administered as continuous daily therapy, often over many years<\/li>\n
    • Covalent BTK inhibitors have the same mode of action, but next-generation agents have favorable safety profiles versus ibrutinib, with acalabrutinib (ELEVATE-RR) and zanubrutinib (ALPINE and ASPEN) leading to fewer treatment discontinuations and cardiovascular adverse events compared to ibrutinib<\/li>\n
    • Zanubrutinib has demonstrated superior efficacy versus ibrutinib in R\/R CLL, while acalabrutinib showed non-inferior efficacy compared to ibrutinib<\/li>\n
    • Side effects associated with BTK inhibitors are usually manageable, but dose reductions or discontinuations are necessary in some circumstances<\/li>\n
    • At initial treatment selection and in the long-term management of patients, physicians must be aware of the potential for DDIs with BTK inhibitors<\/li>\n
    • Most of the clinically relevant DDIs with BTK inhibitors relate to concomitant usage with inhibitors or inducers of CYP3A4 and\/or agents associated with a bleeding risk<\/li>\n<\/ul>\n

      Please refer to the current health authority-approved product information for definitive guidance on each medicine\u2019s drug interactions and recommended management.8\u201313<\/sup><\/p>\n<\/div>\n

      References<\/h6>\n
        \n
      1. Drugs.com. Imbruvica FDA approval history. Available at: https:\/\/www.drugs.com\/history\/imbruvica.html. Accessed June 2023.<\/li>\n
      2. Buske C, Jurczak W, Salem J-E et al.<\/em> Managing Waldenstr\u00f6m’s macroglobulinemia with BTK inhibitors. Leukemia<\/em> 2023; 37 (1): 35\u201346.<\/li>\n
      3. Baptiste F, Cautela J, Ancedy Y et al.<\/em> High incidence of atrial fibrillation in patients treated with ibrutinib. Open Heart<\/em> 2019; 6 (1): e001049.<\/li>\n
      4. Dickerson T, Wiczer T, Waller A et al.<\/em> Hypertension and incident cardiovascular events following ibrutinib initiation. Blood<\/em> 2019; 134 (22): 1919\u20131928.<\/li>\n
      5. Byrd JC, Hillmen P, Ghia P et al.<\/em> Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: Results of the first randomized phase III trial. J Clin Oncol<\/em> 2021; 39 (31): 3441\u20133452.<\/li>\n
      6. Tam CS, Opat S, D’Sa S et al.<\/em> A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstr\u00f6m macroglobulinemia: The ASPEN study. Blood<\/em> 2020; 136 (18): 2038\u20132050.<\/li>\n
      7. Brown JR, Eichhorst B, Hillmen P et al.<\/em> Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med<\/em> 2023; 388 (4): 319\u2013332.<\/li>\n
      8. Pharmacyclics LLC. IMBRUVICA \u2013 US prescribing information. Pharmacyclics LLC; South San Francisco, CA, USA, May 2023.<\/li>\n
      9. AstraZeneca AB. Calquence 100 mg hard capsules \u2013 summary of product characteristics. AstraZeneca AB; S\u00f6dert\u00e4lje, Sweden, May 2023.<\/li>\n
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        Introduction Bruton’s tyrosine kinase (BTK) inhibitors have proved to be a valuable treatment option for several B-cell malignancies, transforming outcomes for many patients. In this short overview, hematologist Alessandra Tedeschi and pharmacologist Federico Pea outline the key pharmacotherapy considerations in the use of the BTK inhibitors ibrutinib, zanubrutinib, and acalabrutinib. Potential drug\u2013drug interactions (DDIs) with […]<\/p>\n","protected":false},"author":3758,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"template-DDI-page.php","meta":{"_acf_changed":false,"editor_notices":[],"footnotes":""},"post-tag":[],"specialisation":[],"class_list":["post-7053","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/pages\/7053","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/users\/3758"}],"replies":[{"embeddable":true,"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/comments?post=7053"}],"version-history":[{"count":9,"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/pages\/7053\/revisions"}],"predecessor-version":[{"id":7666,"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/pages\/7053\/revisions\/7666"}],"wp:attachment":[{"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/media?parent=7053"}],"wp:term":[{"taxonomy":"post-tag","embeddable":true,"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/post-tag?post=7053"},{"taxonomy":"specialisation","embeddable":true,"href":"https:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/specialisation?post=7053"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}