Epub 2017 Nov 13. Cyclophosphamide and metabolites are dialyzable; differences in amount dialyzed may occur due to dialysis system used. Consider therapy modification, Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Specifically, the risk of pulmonary toxicity may be enhanced. Hover over products below to view reaction partners. Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Pharmacogenomics J. tamoxifen pharmacologic class. Swallow capsules whole; do not open, crush, or chew. Monitor therapy, Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Dose and duration of therapy are factors in the risk for sterility related to cyclophosphamide. [, Zhang QH, Wu CF, Duan L, Yang JY: Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. 125. Unapproved uses include the treatment of granulomatosis with polyangiitis, severe rheumatoid arthritis, lupus erythematosus, advanced mycosis fungoides, and several of forms of vasculitis. Consider therapy modification, Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. The mechanism of action is thought to involve cross-linking of tumor cell DNA. If you believe you are experiencing an interaction, contact a healthcare provider immediately. Injection powder for reconstitution: Reconstitute with 25 mL for a 500 mg vial, 50 mL for a 1,000 mg vial, or 100 mL for a 2,000 mg vial to a concentration of 20 mg/mL using NS or SWFI. One regimen alternated the frequency based on week of therapy: Weeks 3, 9, 15, and 21: Doses administered once daily for 5 days (in combination with etoposide); Weeks 6, 12, 18, and 24 administered once daily for 3 days (in combination with doxorubicin and vincristine) (Green 2007). Chronic lymphocytic leukemia (CLL). Management: Vaccine efficacy may be reduced. A 10 mg/mL oral suspension may be prepared by reconstituting one 2 g vial for injection with 100 mL of NaCl 0.9%, providing an initial concentration of 20 mg/mL. Mesna should begin at the start of treatment, and continue at least 24 hours following the last dose of cyclophosphamide. Cyclophosphamide is associated with a moderate to high emetic potential (depending on dose, regimen, or administration route); antiemetics may be recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Paw Cho Sing 2019; Roila 2016). May also dilute for infusion in NS at concentrations of 0.24 to 20 mg/mL. Drug Metab Dispos. Monitor therapy, Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. The risk or severity of bleeding can be increased when Abciximab is combined with Cyclophosphamide. Monitor therapy, Amiodarone: Cyclophosphamide may enhance the adverse/toxic effect of Amiodarone. Cy120 (cyclophosphamide total dose of 120 mg/kg): Use IBW or ABW until >120% IBW; then use ABW25 for patients >120% IBW. Data from a limited number of patients in a small nonrandomized study suggest that cyclophosphamide (in combination with dacarbazine and vincristine) may be beneficial for the treatment of malignant pheochromocytoma Huang 2008. Chemotherapy, if indicated, may be administered to pregnant women with breast cancer as part of a combination chemotherapy regimen (common regimens administered during pregnancy include doxorubicin (or epirubicin), cyclophosphamide, and fluorouracil); chemotherapy should not be administered during the first trimester, after 35 weeks' gestation, or within 3 weeks of planned delivery (Amant 2010; Loibl 2006). Curr Drug Metab. Cyclophosphamide ( CP ), also known as cytophosphane among other names, [3] is a medication used as chemotherapy and to suppress the immune system. Malignancy: Manufacturers labeling: Dosing in the manufacturers labeling may not reflect current clinical practice. Cyclophosphamide is a nitrogen mustard used to treat lymphomas, myelomas, leukemia, mycosis fungoides, neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma. The trade name in New Zealand is Cycloblastin. Chronic myelogenous leukemia (CML). Cyclophosphamide Mechanism of Action and Pharmacokinetics. 60 mg/kg/day for 2 days (in combination with busulfan and total body irradiation) (Anderson 1996). Consider therapy modification, Sargramostim: Cyclophosphamide may enhance the adverse/toxic effect of Sargramostim. Pharmaceutical Utilization Management Program VA Inc. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Npoje s vysokm obsahom antioxidantov, ako s vitamny C a E, preukzatene zlepuj erektiln funkciu tm, e brnia pokodeniu buniek, produkujcich oxid dusnat," hovor Pearlmanov. Consider therapy modification, Lenograstim: May enhance the adverse/toxic effect of Cyclophosphamide. Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain. The mean (dose-corrected AUC) increased by 38% in patients with moderate renal impairment (CrCl 25 to 50 mL/minute), increased by 64% in patients with severe impairment (CrCl 10 to 24 mL/minute), and by 23% in patients undergoing hemodialysis (CrCl <10 mL/minute), when compared to a control group. Gestational trophoblastic tumors, high-risk (off-label use): IV: EMA/CO regimen: 600 mg/m2 on day 8 of 2-week treatment cycle (in combination with etoposide, methotrexate, dactinomycin, and vincristine), continue for at least 2 treatment cycles after a normal hCG level (Escobar 2003; Lurain 2006). Stable for 56 days refrigerated. Cyclophosphamide Prescribing Information, Baxter Healthcare Corporation, Deerfield, Il, May, 2013.20103616. Ocrelizumab. Monitor therapy, Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Urinary/renal toxicity: Cyclophosphamide is associated with the development of hemorrhagic cystitis, pyelitis, ureteritis, and hematuria. Cross-sensitivity with other alkylating agents may occur. Monitor therapy, Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. [, Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Store refrigerated (in glass container) for up to 14 days. Additional data may be necessary to further define the role of dacarbazine in this condition. The metabolism of Cyclophosphamide can be increased when combined with Abatacept. R-EPOCH (dose adjusted) regimen: 750 mg/m2 on day 5 every 3 weeks (in combination with rituximab, etoposide, prednisone, vincristine, and doxorubicin) for 6 to 8 cycles (Garcia-Suarez 2007). Cardiotoxicities reported have included arrhythmias (supraventricular and ventricular [some with QT prolongation]), congestive heart failure, heart block, hemopericardium (secondary to hemorrhagic myocarditis and myocardial necrosis), myocarditis (including hemorrhagic), pericarditis, pericardial effusion including cardiac tamponade, and tachyarrhythmias. Avoid combination, Dermatologic: Alopecia (reversible; onset: 3 to 6 weeks after start of treatment), Endocrine & metabolic: Altered hormone level (increased gonadotropin secretion), amenorrhea, Gastrointestinal: Abdominal pain, anorexia, diarrhea, mucositis, nausea and vomiting (dose-related), stomatitis, Genitourinary: Azoospermia, defective oogenesis, hemorrhagic cystitis, oligospermia, sterility, Hematologic & oncologic: Anemia, bone marrow depression, febrile neutropenia, leukopenia (dose-related; recovery: 7 to 10 days after cessation), neutropenia, thrombocytopenia, <1%, postmarketing, and/or case reports: Acute respiratory distress, anaphylaxis, auditory disturbance, blurred vision, cardiac arrhythmia (with high-dose [HSCT] therapy), cardiac failure (with high-dose [HSCT] therapy), cardiac tamponade (with high-dose [HSCT] therapy), cardiotoxicity, confusion, C-reactive protein increased, dizziness, dyschromia (skin/fingernails), dyspnea, erythema multiforme, gastrointestinal hemorrhage, heart block, hematuria, hemopericardium, hemorrhagic colitis, hemorrhagic myocarditis (with high-dose [HSCT] therapy), hemorrhagic ureteritis, hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease), hepatitis, hepatotoxicity, hypersensitivity reaction, hyperuricemia, hypokalemia, hyponatremia, increased lactate dehydrogenase, interstitial pneumonitis, jaundice, malaise, mesenteric ischemia (acute), metastases, methemoglobinemia (with high-dose [HSCT] therapy), multi-organ failure, myocardial necrosis (with high-dose [HSCT] therapy), neurotoxicity, neutrophilic eccrine hidradenitis, ovarian fibrosis, pancreatitis, pericarditis, pneumonia, pulmonary hypertension, pulmonary infiltrates, pulmonary interstitial fibrosis (with high doses), pulmonary veno-occlusive disease, pyelonephritis, radiation recall phenomenon, reactivation of disease, reduced ejection fraction, renal tubular necrosis, reversible posterior leukoencephalopathy syndrome, rhabdomyolysis, sepsis, septic shock, SIADH, skin rash, Stevens-Johnson syndrome, testicular atrophy, thrombocytopenia (immune-mediated), thrombosis (arterial and venous), toxic epidermal necrolysis, toxic megacolon, tumor lysis syndrome, urinary fibrosis, weakness, wound healing impairment, CBC with differential and platelets, BUN, UA, serum electrolytes, serum creatinine; monitor for signs/symptoms of hemorrhagic cystitis or other urinary/renal toxicity, pulmonary, cardiac, and/or hepatic toxicity. Ann N Y Acad Sci. Ectrodactylia was found in two of the three cases. High-dose cyclophosphamide: HD-CAV/IE regimen: P6 Protocol: Limited data available (Kushner 1996): Children 10 years and Adolescents: IV: 2,100 mg/m2 over 6 hours with mesna and hydration on Days 1 and 2 of a 21-day treatment cycle in combination with vincristine and doxorubicin for courses 1, 2, 4, and 6, alternate with ifosfamide and etoposide for courses 4, 5, and 7. Cyclophosphamide crosses the placenta and can be detected in amniotic fluid (D'Incalci 1982). In a scientific statement from the American Heart Association, cyclophosphamide has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate/major) (AHA [Page 2016]). Regularly drinking tea is thought to have many potential health benefits. Monitor therapy, Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Cardiotoxicity is related to endothelial capillary damage; symptoms may be managed with diuretics, ACE inhibitors, beta-blockers, or inotropics (Floyd 2005). Cyclophosphamide also possesses potent immunosuppressive activity. 2006 Dec;5(12):993-6. Behcet disease Cicatrical pemphigoid Pemphigus vulgaris Paraneoplastic pemphigus Mycosis fungoides. Bladder toxicity: To minimize bladder toxicity, increase normal fluid intake during and for 1 to 2 days after cyclophosphamide dose. Consider therapy modification, BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Morning administration may be preferred to ensure adequate hydration throughout the day; do not administer tablets/capsules at bedtime. Drug Type: Cyclophosphamide is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. 2007 Jun;1108:35-40. Aplastic anemia, severe; refractory: Limited data available: Children and Adolescents 2 years: High-dose therapy: IV: 45 to 50 mg/kg/day for 4 days has been used in several small trials; concurrent prophylactic antimicrobial therapy should be considered (Audino 2010; Brodsky 1996; Brodsky 2010; DeZern 2011; Jaime-Perez 2013). Here's an overview of the tests and procedures used. Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat. Cyclophosphamide may diminish the therapeutic effect of Lipegfilgrastim. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Cyclophosphamide (pronounced sigh-clo-fos-fah-mide) is a type of chemotherapy. alkylates and crosslinks to DNA, disrupting its replication. Secondary malignancies: Secondary malignancies (bladder cancer, myelodysplasia, acute leukemias, lymphomas, thyroid cancer, and sarcomas) have been reported with both single-agent and with combination chemotherapy regimens; onset may be delayed (up to several years after treatment). The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Cyclophosphamide. Label shake well and refrigerate. Breast cancer. Expert Opin Investig Drugs. American College of Rheumatology guidelines for screening, treatment and management of lupus nephritis, Eighth International Workshop on Waldenstrm Macroglobulinemia (IWWM), Bone marrow suppression: Leukopenia, neutropenia, thrombocytopenia, and anemia may commonly occur; may be dose related. It interferes with spermatogenesis and oogenesis. This idea was already realized in the drug "Honvan" (diethylstilbestrol diphosphate) used in the treatment of prostate cancer. Use ABW25 for patients >120% IBW. (i) Cancer of the breast Cyclophosphamide is used alone and also in combination therapy for the treatment of breast cancer. [1] [2] Desmoplastic small round cell tumor (DSRCT): Limited data available (Kushner 1996): High-dose cyclophosphamide: HD-CAV/IE regimen: P6 Protocol: Children <10 years: IV: 70 mg/kg over 6 hours with mesna and hydration on Days 1 and 2 of a 21-day treatment cycle in combination with vincristine and doxorubicin for courses 1, 2, 4, and 6, alternate with ifosfamide and etoposide for courses 4, 5, and 7. 20% of cyclophosphamide is protein bound with no dose dependent changes. older women (in about 10 percent vs. up to 50 percent). It is a cell cycle phase nonspecific agent. Specifically, the risk for serious infections may be increased. Cancer Res. In addition, late onset pneumonitis (>6 months after therapy initiation) may be associated with increased mortality. 1 Cyclophosphamide has several mechanisms of action, partly dependent upon the dose of the drug being utilized. Monitor therapy, Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Post-transplant lymphoproliferative disease (PTLD): Limited data available: Infants, Children, and Adolescents: IV: 600 mg/m2 on Day 1 every 21 days for 6 cycles in combination with prednisone (all 6 cycles) and rituximab (first 2 cycles only); the youngest patient included in the reported experience was 0.8 years of age (Gross 2012). Pure red cell aplasia (antibody-induced)c. Data from a retrospective review of erythropoietin-related pure red cell aplasia (PRCA) suggest cyclophosphamide (in combination with prednisone) may be utilized for management of antibody-induced PRCA Bennett 2005. Pulmonary toxicities: Pulmonary toxicities, including pneumonitis, pulmonary fibrosis, pulmonary veno-occlusive disease, and acute respiratory distress syndrome, have been reported. Waldenstrm macroglobulinemia (off-label use): DRC regimen: Oral: 100 mg/m2 twice daily on days 1 to 5 every 21 days (in combination with dexamethasone and rituximab) for 6 cycles (Dimopoulos 2007). Women's health is once again the center of a political ping-pong match with evidence-based science on one side and anti-choice advocates on the other. Hypersensitivity: Anaphylactic reactions have been reported. Br J Cancer. Cyclophosphamide also possesses potent immunosuppressive activity. Immune thrombocytopenia, refractory (off-label use; Provan 2010): Oral: 1 to 2 mg/kg/day for at least 16 weeks. When. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be needed. ( Furthermore, ANGPTL1 remained highly expressed throughout the treatment . . Smoothie. Consider therapy modification, Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Based on recommendations from the Eighth International Workshop on Waldenstrm Macroglobulinemia (IWWM), cyclophosphamide (in combination with dexamethasone and rituximab) may be used for the treatment of Waldenstrm macroglobulinemia. Children 3 years and Adolescents: 1,200 mg/m2. Monitor therapy, Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Batch CBD Full-Spectrum Gummies. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). Acute lymphoblastic leukemia, relapsed or refractory: Limited data available: Hijiya 2011: Children and Adolescents: IV: 440 mg/m2 over 30 to 60 minutes in combination with clofarabine and etoposide; number of doses dependent on phase of protocol: Induction: Days 1 to 5, and Consolidation: Days 1 to 4. Amenorrhea and decreases in estrogen . Following IV administration, elimination half-life (t ) ranges from 3 to 12 hours with total body clearance (CL) values of 4 to 5.6 L/h. Cyclophosphamide Mechanism : Cyclophosphamide is bio transformed principally in the liver to active alkylating metabolites by microsomal oxidase system. Granulomatosis with polyangiitis (Wegener granulomatosis) (off-label use; in combination with glucocorticoids): Low-dose: Oral: 1.5 to 2 mg/kg/day (Jayne 2003; Stone 2010) or 2 mg/kg/day until remission, followed by 1.5 mg/kg/day for 3 additional months (de Groot 2009; Harper 2012). Treatment beyond 90 days may increase the potential for sterility in males. Women who receive a diagnosis can take some comfort in the advances made in recent decades. Cyclophosphamide is used in combination therapy for the treatment of retinoblastoma. Use with caution in patients with preexisting cardiovascular disease or those at risk for cardiotoxicity. Bladder fibrosis may also occur, either with or without cystitis. Bladder cancer usually occurs in patients previously experiencing hemorrhagic cystitis; risk may be reduced by preventing hemorrhagic cystitis. 2023 Medicine.com All rights reserved. Avoid combination, Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Build, train, & validate predictive machine-learning models with structured datasets. IV: 300 to 1,000 mg/m2 for 1 to 3 doses every 2 to 4 weeks. Bone marrow failure has been reported. Oncology uses: Treatment of acute lymphoblastic leukemia (ALL), acute myelocytic leukemia (AML), breast cancer, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), Hodgkin lymphoma, mycosis fungoides, multiple myeloma, neuroblastoma, non-Hodgkin lymphomas (including Burkitt lymphoma), ovarian adenocarcinoma, and retinoblastoma, Limitations of use: Although potentially effective as a single-agent in susceptible malignancies, cyclophosphamide is more frequently used in combination with other chemotherapy drugs, Nononcology uses: Nephrotic syndrome: Treatment of minimal change nephrotic syndrome (biopsy proven) in children who are unresponsive or intolerant to corticosteroid therapy. Solution Reconstituted, Injection [preservative free]: Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. [, Khan O, Middleton MR: The therapeutic potential of O6-alkylguanine DNA alkyltransferase inhibitors. Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Monitor therapy, Thiotepa: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Monitor therapy, CycloSPORINE (Systemic): Cyclophosphamide may decrease the serum concentration of CycloSPORINE (Systemic). This information should not be interpreted without the help of a healthcare provider. Talk with the doctor. Low sodium like headache, difficulty focusing, trouble with memory, confusion, weakness, seizures, or change in balance. The chemistry of the metabolites of cyclophosphamide. CP-induced cardiotoxicity ranges from 7 to 28% and mortality ranges from 11 to 43% at the therapeutic dose of 170-180 mg/kg, i.v. Management: Consider alternatives to succinylcholine in patients who have received cyclophosphamide in the past 10 days, or reduced succinylcholine doses (a serum pseudocholinesterase assay may help inform this reduction) with close monitoring. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Although direct toxicity to immunocompetent cells is probably the major me-chanism of immunosuppression, cyclophosphamide is also immunomodulatory in T cells. Liquid solutions for oral administration may be prepared by dissolving cyclophosphamide injection in Aromatic Elixir, N.F. 1997 May 15;57(10):1946-54. The mechanism of action is thought to involve cross-linking of tumor cell DNA. Cyclophosphamide is associated with a moderate to high emetic potential (depending on dose, regimen, or administration route); antiemetics may be recommended to prevent nausea and vomiting (Hesketh 2017; Paw Cho Sing 2019; Roila 2016). VAC/IE regimen: Limited data available (Grier 2003): Children and Adolescents: IV: 1,200 mg/m2 with mesna on Day 1 of a 21-day treatment cycle in combination with vincristine and doxorubicin (then dactinomycin when maximum doxorubicin dose reached), alternate with IE (ifosfamide and etoposide) for a total of 17 cycles. Patient weight >12 kg: IV: 2,100 mg/m2 over 6 hours with mesna on Days 1 and 2 (in combination with doxorubicin and vincristine). Drink plenty of fluids. [, Yang L, Yan C, Zhang F, Jiang B, Gao S, Liang Y, Huang L, Chen W: Effects of ketoconazole on cyclophosphamide metabolism: evaluation of CYP3A4 inhibition effect using the in vitro and in vivo models. [Instructions and implementations for percutaneous renal biopsy. Data from a small study support the use of cyclophosphamide (in combination with dactinomycin and vincristine) in the management of malignant ovarian germ cell tumors following optimal surgical debulking Slayton 1985. The immune effects of cyclophosphamide differ depending on the dose, route of administration, and duration of cyclophosphamide therapy.1-4,54,56 As with other . Below, check out the tour dates, as well as a weird tour . Data from another study which also included patients <50 years of age support the use of cyclophosphamide (in combination with mesna, vincristine, and dactinomycin) for intermediate-risk rhabdomyosarcoma Arndt 2009. Data from a non-inferiority study support the use of cyclophosphamide (in combination with doxorubicin and vincristine) in the management of refractory small cell lung cancer von Pawel 1999. 1. Specifically, granulocytopenia may be enhanced. Hemorrhagic cystitis, severe: Discontinue treatment. Monitor for enhanced pulmonary toxicity when cyclophosphamide and lenograstim are given in combination. High-dose regimens should be accompanied by vigorous hydration with or without mesna therapy. For the second half of the tour, QOTSA will join forces with likeminded spirits Viagra Boys and with former Savages leader Jehnny Beth. May use IV dosing for more resistant cases (Diaz-Llopis 2009). What are side effects of Cytoxan? Monitor therapy, CYP2B6 Inducers (Moderate): May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). [, FDA Approved Drug Products: Cyclophosphamide Intravenous Injection [, Preiss R, Schmidt R, Baumann F, Hanschmann H, Hauss J, Geissler F, Pahlig H, Ratzewiss B: Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. InChI=1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12), 2-[bis(2-chloroethyl)amino]-1,3,2lambda5-oxazaphosphinan-2-one, Use our structured and evidence-based datasets to. Last updated February 6, 2020. Thalidomide. Lupus nephritis (off-label use): IV: 500 mg once every 2 weeks for 6 doses or 500 to 1,000 mg/m2 once every month for 6 doses (Hahn 2012) or 500 to 1,000 mg/m2 every month for 6 months, then every 3 months for a total of at least 2.5 years (Austin 1986; Gourley 1996). Avoid combination, Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. These CBD candies offer a simple and flexible . COPADM 2 regimen: Induction 2: Infants 6 months, Children, and Adolescents: IV: 500 mg/m2/dose over 15 minutes every 12 hours on Days 2 to 4 (6 doses) (in combination with doxorubicin, vincristine, prednisone, methotrexate, +/- Rituximab) (Cairo 2007; Goldman 2013; Goldman 2014). [, Wang H, Tompkins LM: CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme. 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