(A) Frequency of CRS event grades by the Penn, Lee, and ASTCT grading scales (N = 111). (B) Cross-classification of NT by 3 grading scales: CTCAE, ASTCT, and mCRES. Monitor Closely (2)elagolix will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information. fosphenytoin decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Limitations of this analysis include its retrospective nature and the consequent insufficient detail for full implementation of the CARTOX grading system (eg, the prospective part of the CARTOX-10 score questionnaire), thus requiring the grouping of grade 1/2 NT events together. European journal of haematology. $L5'ZZ-.GUK)3~ We conclude that CTCAE v4.03 was not designed for, and is suboptimal for, grading CAR-T cell therapy-associated NT. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. doi: 10.1007/s00280-002-0447-1. Events graded as NT by CTCAE, but not mCRES and ASTCT. After leukapheresis, manufacturing of tisagenlecleucel was carried out at centralized facilities in Morris Plains, New Jersey, and in Leipzig, Germany. darunavir increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. -, Uzel I., Ozguroglu M., Uzel B., et al. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. Use Caution/Monitor. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study. %PDF-1.4 fexinidazole will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Standard epinephrine and methylprednisolone were available at the bedside in the event of any anaphylactic reaction. Monitor Closely (1)ribociclib will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. -, Moskowitz C. H., Nademanee A., Masszi T., et al. commonly, these are "non-preferred" brand drugs. Use Caution/Monitor. Federal government websites often end in .gov or .mil. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. carbamazepine decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Modify Therapy/Monitor Closely. <>>>/Rotate 180/MediaBox[0 0 612 792]>> In the JULIET trial, NT was identified and graded per protocol according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.10 Because it was not designed specifically for CAR-T cell therapy trials, the CTCAE scale has shortcomings in accurately capturing the severity, timing, and spectrum of NT. NT by ASTCT criteria provided concordance for 34 patients, a lower grade for 31 patients, and a higher grade for 3 patients compared with the CTCAE scale (Figure 1B). Cancer Chemother Pharmacol. Ms. R's symptoms resolved within 40 minutes, and the brentuximab vedotin infusion was able to be continued over a prolonged period of more than 4 hours. All patients with fever in the setting of chemotherapy-induced neutropenia require immediate medical attention regardless of the toxicity grade. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. It works by slowing or stopping the growth of cancer cells. D.G.M. According to the NCI's. government site. %%EOF Use Caution/Monitor. Solved A patient receiving an initial brentuximab infusion - Chegg Poster presented at the 22nd Congress of the European Hematology Association. PDF Implementing Laboratory Toxicity Grading for CTCAE Version 5 posaconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Monitor patients for adverse reactions. 0000009670 00000 n Avoid or Use Alternate Drug. Journal of the National Comprehensive Cancer Network : JNCCN. . 2002 May;49 Suppl 1:S13-20. The sponsor is expected to provide the name of the scale and version used to map the terms, 0000001593 00000 n Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. Monitor Closely (1)encorafenib, brentuximab vedotin. z**5p`'_O%4TUX^\O. Monitor patients for adverse reactions. lasmiditan increases levels of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. 0000001503 00000 n (a) Computed tomography (CT) of the chest showing patchy, nodular ground glass opacities, MeSH Use Caution/Monitor. . After reconstitution (see section 6.6), each mL contains 5 mg of brentuximab vedotin. NCI CTCAE v5.0 hematologic toxicity Neutropenia, thrombocytopenia, anemia, and lymphocytopenia are determined from the complete blood count. Use Caution/Monitor. Typically, CTCAE grading is directly collected from the site on the adverse experience case report form. 2010;16(3):888897. The .gov means its official. Use Caution/Monitor. This information does not assure that this product is safe, effective, or appropriate for you. <> The site is secure. is employed by Novartis. An official website of the United States government. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. Brentuximab vedotin desensitization in a patient with refractory Hodgkin's lymphoma. According to the US Food and Drug Administration definition of NT using CTCAE, 62 of 106 patients infused with tisagenlecleucel had NT as of September 2017. Consider dose reduction of sensitive CYP3A4 substrates. 2018 Oct;5(10):e450-e461. Kymriah safety profile. Use Caution/Monitor. and transmitted securely. % ADL, activities of daily living; CSF, cerebrospinal fluid; EEG, electroencephalogram; ICP, intracranial pressure. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.This drug may make you dizzy. SIDE EFFECTS: See also Warning and How to Use sections.Nausea, vomiting, diarrhea, dizziness, headache, or unusual tiredness may occur. endstream Monitor Closely (1)isoniazid increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. The information may not cover all possible uses, actions, interactions, or side effects of this drug, or precautions to be taken while using it. 2015 Mar;16(3):284-92. doi: 10.1016/S1470-2045(15)70013-6. Either increases toxicity of the other by immunosuppressive effects; risk of infection. 2013 Dec;14(13):1348-56. doi: 10.1016/S1470-2045(13)70501-1. Monitor Closely (1)phenytoin decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. The https:// ensures that you are connecting to the CD30-directed antibody-drug conjugate (ADC) consisting of chimeric IgG1 antibody cAC10, specific for human CD30 and the microtubule disrupting agent, monomethyl auristatin E (MMAE, or vedotin), Conjugate binds to cell expressing the CD30 antigen and forms a complex that is internalized within the cell and MMAE is released; MMAE induces cell cycle (G2/M phase) arrest by binding to tubules and disrupting cellular microtubule network, Peak plasma time: 20-30 min (ADC); 1-3 days (MMAE), Steady-state: 21 days (1.8 mg/kg q3Weeks); 56 days (1.2 mg/kg q2Weeks), Data indicated MMAE metabolism occurs primarily via oxidation by CYP3A4/5, Excretion: Feces and urine (24% of the total MMAE [72% unchanged and recovered in feces]), Do not mix or administer with other medicinal products, Adhere to proper handling, dispensing, and administration of anticancer drugs, Unopened vials: Refrigerate at 2-8C (36-46F) in original carton to protect from light, Diluted solutions or reconstituted vials: Refrigerate at 2-8C (36-46F) for up to 24 hr. endstream endobj startxref lopinavir increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. tecovirimat will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Grading of neurological toxicity in patients treated with However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. 8600 Rockville Pike is a scientific advisor to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, and Wugen; and an allogene consultant with grant options for Cellular Biomedicine Group, Inc. %%EOF ADCETRIS until toxicity is Grade 2, then restart treatment at a reduced dose to 0.9 mg/kg up to a . However, these therapies are associated with unique, but common, adverse events that must be identified and managed appropriately: cytokine release syndrome (CRS) and neurological toxicity (NT).3,10,14-18 NT after CAR-T cell therapy generally occurs after the onset of CRS, and higher grades of NT tend to occur concurrently with higher grades of CRS.10,19 Clinical features of CAR-T cell therapy-associated NT are numerous, and patients can experience events such as headache, dizziness, delirium, seizures, dysphasia, hallucinations, and impaired motor and language skills.1,3-5,8,10 This may be distressing to the patient and the patients family, but fortunately, NT and CRS generally resolve within days with standard supportive therapy such as corticosteroids. Monitor patients for adverse reactions. Monitor Closely (1)oxcarbazepine decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor Closely (1)tecovirimat will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Brentuximab Approved for High-Risk Hodgkin Lymphoma in Children and Adolescents, Brentuximab May Mean Less Radiation for Children, Teens with Hodgkin Lymphoma. xb```f``5x2@qu5mVux"jKD. % Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. 0 Monitor Closely (1)ketoconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. - Febrile neutropenia - - ANC <1000/mm3 with a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour Life-threatening consequences; urgent intervention indicated Death Definition: Use Caution/Monitor. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, diabetes.Brentuximab can make you more likely to get infections or may make current infections worse. Chimeric antigen receptor-T (CAR-T) cell therapy uses reprogrammed T cells to target and kill cancer cells, and thus has become a promising treatment for patients with advanced hematologic malignancies.1-10 Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) or r/r transformed follicular lymphoma may receive CD19-directed CAR-T cell therapy after 2 systemic therapy options such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone).11,12 Two such CD19-directed CAR-T cell therapies are currently commercially available: tisagenlecleucel and axicabtagene ciloleucel. If unavoidable, reduce CYP3A substrate dose according to product labeling. };wN:iyUFYg,Wyi^dgvBMu9L> {Ij{>i JS8Lk6P&adAQWEPN_aKe7+S|O[u/_>v~?W I}yr>T%D$D5fqYsms xp `sv@K4([MhT3O Clipboard, Search History, and several other advanced features are temporarily unavailable. itraconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. The first dose of brentuximab vedotin was administered without difficulty, at full dose (1.8 mg/kg) at a standard infusion time of 30 minutes. Use Caution/Monitor. With these simplistic criteria, deriving the toxicity grades was a simple task. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates. Use Caution/Monitor. Use Caution/Monitor. Accessibility Monitor Closely (1)berotralstat will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. Brentuximab vedotin is given with cyclophosphamide, doxorubicin hydrochloride, and prednisone in adults. The most current release files are in order of appearance: CTCAE_5.0; CTCAE v5.0 in the NCI Thesaurus .xlsx format; CTCAE v5.0 in the NCI Thesaurus .xls format; CTCAE v5.0 in the original CTEP .xlsx format Presented at 15th International Conference on Malignant Lymphoma; 18-22 June 2019; Lugano, Switzerland. Steroid use by CTCAE, mCRES, and ASTCT grade, Steroid use in patients with NT per CTCAE, but no NT per mCRES and ASTCT criteria, The CTCAE grades by medical experts also varied from those reported by the FDA, using a broader definition based on the CTCAE system (Table 5). East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018, Cytokine release syndrome with the novel treatments of acute lymphoblastic leukemia: pathophysiology, prevention, and treatment, Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma, Efficacy and safety of bispecific T-cell engager (BiTE) antibody blinatumomab for the treatment of relapsed/refractory acute lymphoblastic leukemia and non-Hodgkins lymphoma: a systemic review and meta-analysis, Correlative analyses of cytokine release syndrome and neurological events in tisagenlecleucel-treated relapsed/refractory diffuse large B-cell lymphoma patients. Assessed using Balis scale; Grade 2. ]KAyQYi!8w;hb N4T'ea=AHU !YlmNv,94c4. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. Secondary endpoints of the JULIET trial were duration of response, overall survival, safety, and cellular kinetics.10. Patients were randomly assigned in a 1:1 ratio to receive A+AVD (1.2 mg of brentuximab vedotin per kilogram of body weight, 25 mg of doxorubicin per square meter of body-surface area . Peripheral T-cell lymphoma that has the CD30 protein. and R.T.M. Use Caution/Monitor. Contraindicated because of increased risk of pulmonary toxicity. Avoid or Use Alternate Drug. Avoid or Use Alternate Drug. It is anticipated that future studies will have prospective data collected using more specific ICANS grading and allowing more precise comparisons of clinical trial adverse events. Guidance for Industry - Food and Drug Administration Monitor Closely (1)siponimod and brentuximab vedotin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. PMC Brentuximab may harm an unborn baby. Tecovirimat is a weak CYP3A4 inducer. Given the clear benefits of brentuximab consolidation in improving progression-free survival post transplant (Moskowitz et al., 2015) in high-risk Hodgkin lymphoma, it was thought the benefit of brentuximab vedotin consolidation outweighed the possible risks of subsequent infusions. Monitor patients for adverse reactions. Monitor patients for adverse reactions. Lancet Oncol. palifermin increases toxicity of brentuximab vedotin by Other (see comment). Use Caution/Monitor. C- Modify Therapy/Monitor Closely. In conclusion, this is the first study to retrospectively apply the CTCAE, mCRES, and ASTCT systems to the same patient data set. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information. The recipient will receive more details and instructions to access this offer. Because of the possible risk to a nursing infant, breast-feeding while using this drug is not recommended. Cancers | Free Full-Text | Brentuximab-Induced Peripheral Neurotoxicity Consider increasing CYP3A substrate dose if needed. Use Caution/Monitor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Tell your doctor right away if you have any serious side effects, including: numbness/tingling/weakness/pain of the hands/feet/arms/legs, muscle weakness, shortness of breath, easy bruising/bleeding, signs of liver disease (such as nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine), severe diarrhea, severe constipation, black stools, vomit that looks like coffee grounds.This medication may lower your ability to fight infections. Monitor patients for adverse reactions. 113 19 Use Caution/Monitor. Avoid or Use Alternate Drug. Poster PF305, 2020 by The American Society of Hematology, Copyright 2023 by American Society of Hematology, https://doi.org/10.1182/bloodadvances.2019001305, https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf, https://www.hcp.novartis.com/products/kymriah/diffuse-large-b-cell-lymphoma-adults/safety-profile/, Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental ADL, Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL, Life-threatening consequences; urgent intervention indicated, Patient in critical condition, and/or obtunded and cannot perform assessment of tasks, Stage 1-2 papilledema, or CSF opening pressure <20 mm Hg, Stage 3-5 papilledema, or CSF opening pressure 20 mm Hg, or cerebral edema, Partial seizure, or nonconvulsive seizures on EEG with response to benzodiazepine, Generalized seizures, or convulsive or nonconvulsive status epilepticus, or new motor weakness, 0: patient is unarousable and unable to perform ICE, Patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse. Use Caution/Monitor. The CTCAE contain a grading scale for each adverse event term representing the severity of the event. %PDF-1.6 % Use Caution/Monitor. Components and Organization CATEGORY A CATEGORY is a broad classification of AEs based on anatomy and/or pathophysiology. 0 Use Caution/Monitor. The brentuximab vedotin infusion was again held, and 100 mg of IV methylprednisolone was administered. Elagolix is a weak-to-moderate CYP3A4 inducer. National Cancer Institute Monitor patients for adverse reactions. Would you like email updates of new search results? Adjust dose of drugs that are CYP3A4 substrates as necessary. at the National Institutes of Health, An official website of the United States government, Drugs Approved for Different Types of Cancer, Drugs Approved for Conditions Related to Cancer, Complementary & Alternative Medicine (CAM), Find Clinical Trials for Brentuximab Vedotin, U.S. Department of Health and Human Services, Adults whose cancer has not been treated. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. Version 1.2019. Contribution: R.T.M., S.J.S., D.G.M., and F.L.L. istradefylline will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates. In addition, the mCRES scale used here may have underestimated the actual CRES grade 1/2 because the CARTOX-10 score might pick up subtle mental status changes not recognized or reported by the investigators using CTCAE. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. . If you log out, you will be required to enter your username and password the next time you visit. Avoid or Use Alternate Drug. Use Caution/Monitor. Two patients received corticosteroids for persistent neurotoxicity after resolution of CRS.26, NT comparison among CTCAE, mCRES, ASTCT, and FDA label. . Bone marrow biopsy was negative. Vital signs were checked every 15 minutes during the infusion reaction and remained stable throughout. cyclophosphamide will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. what you should know about this drug before using it, other drugs that may interact with this drug, and. Avoid or Use Alternate Drug. You'll get a detailed solution from a subject matter expert that helps you learn core concepts. Lancet (London, England) 2015;385:18531862. Use Caution/Monitor. is employed by Novartis. endstream endobj 1187 0 obj <>/Metadata 39 0 R/OCProperties<>/Outlines 66 0 R/PageLabels 1182 0 R/PageLayout/OneColumn/Pages 1184 0 R/PieceInfo<>>>/StructTreeRoot 79 0 R/Type/Catalog>> endobj 1188 0 obj <>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/StructParents 0/Type/Page>> endobj 1189 0 obj <>stream Use Caution/Monitor. %PDF-1.4 (b) CT of the chest showing resolution of previously seen opacities after discontinuation. Minor (1)acetazolamide will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. Serious - Use Alternative (1)tepotinib will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada). affecting hepatic/intestinal enzyme CYP3A4 metabolism. Consult your doctor for more details. Bioorganic & medicinal chemistry letters. Among 106 patients receiving tisagenlecleucel included in the FDA label, 62 (58.5%) patients were reported as having NT, including 43 (40.6%) with grade 1/2 and 19 (17.9%) with grade 3 or higher NT. Use Caution/Monitor.elagolix will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical Cancer Research. brentuximab vedotin and bleomycin both increase Other (see comment). A simplified grading scale derived from the CTCAE was also created. Most patients receiving BV will experience some degree of BVIN, resulting in the primary reason for dose modification . Finally, based on the individual examples given here, evaluating NT using the CTCAE system is highly subjective when used by practitioners to capture CAR-T-associated encephalopathy. lenacapavir will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Per protocol, NT events in the JULIET trial were identified and graded using the CTCAE v4.03 criteria. Brentuximab vedotin consolidation therapy was prescribed in the post-transplant consolidation setting, beginning 45 days after stem cell reinfusion, given the patient's high risk for recurrence. 2017 Mar;77(4):435-445. doi: 10.1007/s40265-017-0705-5. elagolix will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. Patients treated with selinexor may experience neurological toxicities. . xref Monitor Closely (1)efgartigimod alfa will decrease the level or effect of brentuximab vedotin by receptor binding competition. PDF ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS - European Medicines Agency If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling. The investigators thank the patients, their families, and the clinical study teams who participated in the JULIET trial. 8 0 obj Men and women using this medication should ask about reliable forms of birth control during treatment and for 6 months after the last dose. 0000001178 00000 n Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. Use Caution/Monitor. fedratinib will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]>>/Rotate 180/MediaBox[0 0 612 792]>> Reevaluation according to the mCRES/ASTCT criteria downgraded 31 events deemed NT by CTCAE to grade 0. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.Serious - Use Alternative (1)tucatinib will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. TOXICAN: a guide for grading dermatological adverse events of - PubMed The study was sponsored by Novartis Pharmaceuticals Corporation. Epub 2016 Apr 17. Blood and lymphatic system disorders: Febrile neutropenia, Gastrointestinal disorders: Acute pancreatitis and gastrointestinal complications (including fatal outcomes), Infections: PML, serious infections and opportunistic infections, Metabolism and nutrition disorders: Hyperglycemia, Respiratory, thoracic and mediastinal disorders: Noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and ARDS (some with fatal outcomes), Skin and subcutaneous tissue disorders: Toxic epidermal necrolysis, including fatal outcomes, Concomitant use of brentuximab with bleomycin because of pulmonary toxicity, Peripheral neuropathy (predominately sensory neuropathy) and motor neuropathy reported; drug-induced peripheral neuropathy is cumulative; monitor for symptoms of neuropathy (eg, hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, weakness), Fatal and serious cases of febrile neutropenia reported; monitor complete blood counts (CBC) prior to each dose; start primary prophylaxis with G-CSF beginning with Cycle 1 for patients who receive drug with chemotherapy for previously untreated Stage III or IV cHL or previously untreated PTCL and pediatric patients who receive this medication in combination with chemotherapy for previously untreated high risk cHL, Grade 3 or 4 thrombocytopenia or anemia can occur, Frequency of Grade 3 adverse reactions and deaths reported to be greater in patients with severe renal or hepatic impairment compared to patients with normal renal/hepatic function, Serious cases of hepatotoxicity, including fatal outcomes reported after first dose or after rechallenge; serious cases of hepatotoxicity, including fatal outcomes; preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase risk; monitor liver enzymes and bilirubin; patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of therapy, JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death reported (see Black Box Warnings), Closely monitor for emergence of bacterial, fungal or viral infections, Events of noninfectious pulmonary toxicity (eg, pneumonitis, interstitial lung disease, acute respiratory distress syndrome [ARDS]), some with fatal outcomes, reported, Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) reported; if SJS or TEN occurs, discontinue treatment and administer appropriate medical therapy, Acute pancreatitis, including fatal outcomes, reported, Fatal and serious gastrointestinal (GI) complications (eg, perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus) reported; lymphoma with preexisting GI involvement may increase risk of perforation; promptly evaluate for any new or worsening GI symptoms, and treat appropriately, Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome; closely monitor and treat appropriately, Serious events of hyperglycemia (eg, new-onset hyperglycemia), exacerbation ofpreexisting diabetes mellitus, and ketoacidosis (including fatal outcomes) have beenreported; occurred more frequently in patients with high body mass index or diabetes;monitor serum glucose and if hyperglycemia develops, administer antihyperglycemicmedications as clinically indicated, Based on the findings from animal studies and mechanism of action, brentuximab may cause fetal harm, Available data from case reports in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes, There is no information related to the presence of brentuximab vedotin in human milk, the effects on the breastfed child, or the effects on milk production, Owing to the potential for serious adverse reactions in a breastfed child from brentuximab, including cytopenias and neurologic or gastrointestinal toxicities, breastfeeding is not recommended during treatment.