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| Oral Monitoring & Counseling

Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Afinitor® () HR+, HER2- breast cancer BBW: None Administration: Swallow whole, don’t crush or chew (with exemestane); pNET; • Take consistently with regards to food 2.5, 5, 7.5, 10mg Blister pack: RCC: 10mg PO daily Baseline & periodically: CBC w/ differentials, SCr, fasting serum • Avoid grapefruit/juice 28 tablets glucose/lipids • Missed dose should be taken if <6 hrs (4 x 7 tabs each) Disperz 2, 3, 5mg SEGA: Initial 4.5mg/m2, • Liver dysfxn: dose adj. based on Child Pugh score • Hazardous agent, use precautions when handling Blister pack: tablets for titrate at week 2 to attain • Dose adj. based on ADE (see PI) oral suspension trough conc. of 5-15ng/mL • S/sx of infection or new or worsening respiratory symptoms ADE: Stomatitis, N/V/D, cough, dyspnea, peripheral edema, rash, (4 x 7 tabs each) fatigue, decreased appetite, HTN DDI: CYP3A4 substrate (major) MOA: mTOR inhibitor •  dose to 2.5mg daily with CYP3A4 inhibitor •  risk of angioedema with ACE-inhibitor Alecensa® () Anaplastic BBW: None Administration: kinase (ALK)-positive, • Take with food 150mg metastatic non-small cell Baseline & periodically: LFT, heart rate, BP, CPK • Do not open or dissolve the contents of the capsule Bottle: 240 capsules lung cancer (NSCLC) who * Embryo-fetal toxicity, use contraception during tx & 1 week after • If a dose is missed or occurs after taking a dose, take the final dose MOA: TKI of ALK & RET have progressed on or are next dose at the scheduled time intolerant to : DDI: No pharmacokinetic interactions with alectinib requiring • Store in the original container to protect from light & moisture 600mg PO BID dosage adjustment have been identified ADE: Fatigue, constipation, edema, myalgia, rash, cough, N/V/D, dyspnea, Alkeran® () Ovarian, MM: Various BBW: Antineoplastic experienced doctor Administration: regimens exist • Store refrigerated 2mg Baseline & periodically: CBC with differentials • Take on empty stomach, food  Bottle: 50 tablets Typical: 0.2mg/kg to 10mg • Bone marrow suppression: Infection, bleeding or anemia • Perform good oral hygiene PO daily for up to 7 days MOA: Alkylating agent • Hazardous agent, use precautions when handling ADE: Bone marrow suppression, , mouth sores, pulmonary toxicity Arimidex® (anastrozole)* Breast Ca: 1mg PO daily generic available

1mg tablet

MOA: nonsteroidal inhibitor** BBW: None Aromasin® (exemestane) Breast Ca: 25mg PO daily Administration (Exemestane): Take after a meal generic available Baseline & periodically: (Anastrozole): LFTs & Bili q3-6 months ADE: Hot flashes, peripheral edema, N/V/D, arthralgia & weakness  25mg tablet ( frequency with hepatic metastases) • Thrombosis & hot flashes less common than with Tamoxifen DDI: w/ Tamoxifen  effectiveness • Does not affect cortisol or aldosterone MOA: nonsteroidal inhibitor** • Not indicated for premenopausal women or women w/ ER- tumors • Long-term effects: Osteoporosis & hypercholesterolemia Femara® (letrozole) Breast Ca: 2.5mg PO daily generic available

2.5mg tablet

MOA: nonsteroidal inhibitor** * Anastrozole is a nonsteroidal inhibitor that interferes with estradiol production in peripheral tissues by inhibiting conversion of adrenally-generated androstenedione to estrone by aromatase. ** Arimidex, Aromasin & Femara are Aromatase Inhibitors (available as daily dose)

MARCH 2018 | 1 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Bosulif® (bositinib) Chronic, accelerated or BBW: None Administration: Swallow tablets whole, don’t crush or chew blast phase Ph+CML 100mg • Take with food resistant or intolerant to Baseline & periodically: CBC with differential & , SCr, LFT • Avoid grapefruit/juice Bottle: 120 tablets  prior therapy: 500mg PO • dose to 200mg daily (If LFTs rise >5x ULN, hold until <2.5x ULN & • Missed dose should be taken if <12 hrs resume at 400mg) 500mg once daily (if no CHR by • Hazardous agent, use precautions when handling week 8 or CCyR by week 12 • CrCl 30-50ml/min: 400mg, <30ml/min:300mg Bottle: 30 tablets  dose to 600mg daily) • Grade 3+ or myelosuppression, hold until ≤Grade 1 &  dose by ADE: Myelosuppression, N/V/D, abdominal pain, edema, fatigue, 100mg MOA: TKI of BCR-ABL headache, rash DDI: CYP3A4 substrate (major) Cabometyx™ Indicated for the BBW: Administration: 60mg orally once daily, do not eat for at least 2 hours () treatment of patients None before and at least 1 hour after taking Cabometyx. Do not ingest foods 60mg Bottle: 30 tablets with advanced renal or nutritional supplements known to inhibit during cell carcinoma (RCC): Baseline & periodically: Clinical and radiologic evidence of tumor response may Cabometyx therapy. Swallow whole with a full glass of water; do not 40mg Bottle: 30 tablets Recommended dose is 60mg indicate efficacy, blood pressure, before drug initiation and regularly during therapy, crush tablet. 20mg Bottle: 30 tablets Signs and symptoms of perforations or fistulas once daily, patients instructed ADE: Hypertension, hair color changes, hypocalcemia, not to eat for at least 2 hours Concomitant use of Cabometyx with a strong CYP3A4 inhibitor increased the MOA: Inhibits the tyrosine DDI: hypophosphatemia, weight decreased, abdominal pain, constipation, before and at least 1 hour kinase activity of MET, exposure of Cabometyx compared to the use of Cabometyx alone decreased appetite, dental pain, diarrhea, nausea, stomatitis, after taking VEGFR-1, -2 and -3, AXL, • Increased Cabometyx exposure may increase the risk of exposure-related toxicity. taste sense altered, vomiting, lymphocytopenia, , RET, ROS1, TYRO3, MER, Reduce the dosage of Cabometyx if concomitant use with strong CYP3A4 inhibitors , fatigue, elevated ALT/AST KIT, TRKB, FLT-3, and TIE-2. cannot be avoided (refer to PI for dosing recommendations) These receptor tyrosine Concomitant use of Cabometyx with a strong CYP3A4 inducer decreased the kinases are involved in both exposure of Cabometyx compared to the use of Cabometyx alone normal cellular function and • Decreased Cabometyx exposure may lead to reduced efficacy. Increase the pathologic processes such dosage of Cabometyx if concomitant use with strong CYP3A4 inducers cannot as oncogenesis, metastasis, be avoided (refer to PI for dosing recommendations) tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment. Calquence® () Adult patients with BBW: None Administration: 100mg orally approximately every 12 hrs; 100mg mantle cell lymphoma Baseline & periodically: CBC with differential & platelets, monitor for atrial swallow whole with water & with or without food Bottle: 60 capsules (MCL) who have received fibrillation & atrial flutter, S/S of infection ADE: Myelosuppression, headache, N/V/D, abdominal pain, at least one prior constipation, vomiting, fatigue, bruising, myalgia MOA: Inhibit Bruton DDI: therapy: Recommended tyrosine kinase (BTK) dose is 100mg orally • CYP3A inhibitor & inducer by covalently bonding approximately every twelve • Strong CYP3A inhibitor= avoid concomitant use. Interrupt Calquence therapy to a cysteine residue at hrs; swallow whole with if acute use, e.g. anti-infectives the active BTK site. This water & with or without • Moderate CYP3A inhibitor= 100mg once daily prevents activation of the food • Strong CYP3A INDUCER= avoid concomitant use. If inducers cannot be signaling proteins CD86 & avoided, increase Calquence dose to 200mg twice daily CD69, as well as inhibits • PPI’s= avoid concomitant use proliferation & survival of • H2-receptor antagonists= take Calquence 2 hrs before taking an malignant B cells H2- • Antacids= separate dosing by at least 2 hrs

MARCH 2018 | 2 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Caprelsa® () Medullary thyroid cancer, BBW: None Administration: Don’t crush tablets, can be dispersed in 2oz of metastatic or locally water & swallow immediately 100, 300mg Baseline & periodically: CBC, serum electrolytes, TSH, BP, ECG advanced: 300mg PO daily • May take with or without food Bottle: 30 tablets • Dose adj. based on Grade 3+ ADE (see PI) • Avoid grapefruit/juice MOA: DDI: CYP3A4 substrate (major) • Missed dose should be taken if <12 hrs TKI of EGFR • QT prolongation additive effect ADE: HTN, fatigue, rash, N/V/D *Casodex® (bicalutamide) Metastatic prostate BBW: None Administration: May take with or without food generic available in combo with LHRH • Usually in combination with LHRH agonist analogs Baseline & periodically: LFTs (d/c if ALT >2x ULN or patient develops jaundice) 50mg agonist: 50mg PO daily • Hazardous agent, use precautions when handling • PSA Bottle: 30 tablets ADE: Hot flashes, gynecomastia, breast tenderness,decreased DDI: CYP3A4 inhibitor MOA: Androgen receptor libido, edema, arthralgia & weakness • Monitor INR closely with warfarin inhibitor *CeeNu® () HL, malignant glioma: BBW: Antineoplastic experienced doctor Administration: Take on empty stomach as a single dose at generic available 100-130mg/m2 PO once bedtime, about 30 minutes after an antiemetic Baseline & periodically: CBC w/ differentials (dose adjust for platelets<75,000) q6wks • Hazardous agent, use precautions when handling 10, 40, 100mg • CrCl 10-50ml/min= by 25% dose Bottle: 20 capsules ADE: Myelosuppression (dose-limiting & delayed), pulmonary DDI: CYP2D6 substrate (minor), 3A4 inhibitor (weak) MOA: DNA/RNA synthesis toxicity, Mod emetogenic potential, use antiemetic inhibitor Cotellic™ () Unresectable or BBW: None Administration: Take with or without food metastatic melanoma • If a dose is missed or if vomiting occurs when the dose is 20mg Baseline & periodically: CBC, LFTs, LVEF, ECG, ophthalmological evaluation with a BRAF V600E taken, resume dosing with the next scheduled dose Bottle: 63 tablets if visual disturbance or V600K mutation, • S/sx of dermatologic toxicity, hemorrhage, noncutaneous malignancy, • Avoid grapefruit/juice MOA: MEK Inhibitor in combination with photosensitivity, & rhabdomyolysis ADE: Rash/photosensitivity/skin reactions, N/V/D, pyrexia, (downstream of BRAF) : 60mg PO DDI: CYP3A4 (major) alopecia, myelosuppression, lab abnormalities daily on days 1-21 of each • Avoid concurrent use with strong or moderate CYP3A4 inhibitors, 28-day cycle * if unavoidable (14 days or less)  dose to 20mg • Avoid concurrent use with strong or moderate CYP3A4 inducers Cometriq® (cabozanitinib) Medullary thyroid cancer, BBW: GI perforations & fistula, hemorrhage Administration: Swallow capsules whole metastatic: 140mg PO daily • Take on empty stomach 1 hr before or 2 hrs after food 20, 80mg Baseline & periodically: CBC & Chem 12, GI perforation, urine UA, BP at each visit • Avoid grapefruit/juice Blister packs: Combo of & at home • Missed dose should be taken if <12 hrs 20mg & 80mg to make 60mg, • Dose adj. based on ADE (see PI) 100mg, 140mg/day ADE: H-F syndrome, HTN, fatigue, N/V/D, stomatitis, dysphonia DDI: CYP3A4 substrate (major) MOA: TKI of RET, •  dose by 40mg with strong CYP3A4 inhibitor MET, VEGFR •  dose by 40mg with strong CYP3A4 inducer

Cytoxan® Several Indications with BBW: None Administration: Swallow capsules whole () other therapy: 1-5mg/kg • May take w/ food to decrease (but empty  bioavailability) Baseline & periodically: CBC w/ differential, SCr generic available PO daily • Take tabs in AM & hydrate (3L of fluid) to eliminate of toxic • CrCl <10ml/min or bili 3.1-5ULN:  dose by 25% 25, 50mg tablets/capsules metabolite (acrolein)  Bottle: various counts DDI: CYP3A4 inducer hepatic conversion to toxic metabolites • Hazardous agent, use precautions when handling •  digoxin levels MOA: ADE: Hair loss in 50% of patients (reversal d/c tx), N/V, Leukopenia Alkylating agent (dose-limiting toxicity)

* FDA approved in combination with vemurafenib

MARCH 2018 | 3 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Emcyt® (estramustine) Metastatic and/or BBW: None Administration: Progressive Prostate Cancer: • Advise patient to avoid vaccines during therapy due to drug-induced 140mg Palliative treatment 14mg/kg Baseline & periodically: immunosuppression Bottle: 100 capsules orally daily in 3-4 divided doses • Slowing the progression of metastatic and/or • Instruct both male & female patients to use reliable contraception, as drug (range of 10-16mg/kg/day) progressive disease may cause fetal harm if pregnancy occurs during treatment. This applies MOA: • Ultrasonic measurement A during treatment & up to 6 months post therapy. • Calcium levels • Patient should take at least 1 hr before or 2 hrs after meals derivative of estradiol • Testosterone levels • Instruct patient that drug should not be administered with milk, milk products, • Hepatic enzyme & bilirubin or calcium-rich foods & drugs • Blood pressure • Inform patient of proper procedures for handling & disposal of chemotherapy • Fluid retention ADE: DDI: Avoid live vaccines if possible due to increased risk • This drug may cause body fluid retention, gynecomastia, diarrhea, nausea, of infection vomiting, impotence, dyspnea, cardiovascular disease, or angioedema • Instruct patient to report signs/symptoms of myelosuppression or hepatic dysfunction Erivedge® () Basal cell carcinoma, BBW: Embryo fetal death, severe birth defects Administration: Swallow capsule whole metastatic or locally advanced: • May take with or without food 150mg Baseline & periodically: CBC & Chem-12 150mg PO daily • Don’t donate blood during & for 7 months after final dose Bottle: 28 capsules • Pregnancy test within 1 week prior to initiation • Females of reproductive potential: Use effective ADE: Muscle spasms, alopecia, fatigue, N/V/D, constipation, decreased appetite, MOA: Hedgehog contraception during & 7 months after last dose weight loss, arthralgia, dysgeusia pathway inhibitor • Males use condoms during & 3 months after

DDI: No significant interactions Erleada™ (apalutamide) Non-metastatic castration- BBW: None Administration: May take with or without food 60mg resistant prostate cancer. Baseline & periodically: PSA, fracture and fall risk ADE: Hypertension, peripheral edema, rash, flushing, weight decreased, decrease in Patients should also receive Bottle: 120 tablets DDI: Concomitant use with medications that are sensitive appetite, diarrhea, nausea, arthralgia, fatigue a gonadotropin-releasing MOA: An androgen receptor substrates of CYP3A4, CYP2C19, CYP2C9, UGT, P-gp, BCRP, or hormone (GnRH) analog inhibitor indicated for the OATP1B1 may result in loss of activity of these medications concurrently or should have had treatment of patients with bilateral orchiectomy: 240mg non-metastatic castration- (4 x60mg tablets) once daily with resistant prostate cancer or without food. Exjade® (deferasirox) Transfusional iron overload, BBW: Renal failure, hepatic failure, GI events Administration: Dissolve tablets completely in water, try to obtain mixer (If tablets 125, 250, 500mg ≥2 years old: 20mg/kg PO not fully dissolved, can cause diarrhea) Baseline & periodically: Serum ferritin, CBC with Bottle: 30 tablets daily.  5-10mg/kg daily to • Take on an empty stomach, same time each day, at least 30 minutes before differential, CrCl at baseline & monthly thereafter for suspension patient response food; maintain adequate hydration (unless instructed to restrict fluid intake) • Baseline & annual auditory/ophthalmic exam Non-Transfusion-Dependent MOA: Iron chelator • S/sx GI ulcer or hemorrhage ADE: Abdominal pain, N/V/D,  serum creatinine, rash Thalassemia: 10mg/kg PO See also: Jadenu daily, consider increasing up to DDI: CYP3A4 inducer (weak/moderate) 20mg/kg daily based on FIC • Avoid aluminum containing antacids Farydak® () with 2 prior BBW: Severe diarrhea, cardiac toxicities Administration: Swallow capsules whole with cup of water regimens: 20mg PO every other • May take with or without food 10, 15, 20mg day for 3 doses each week during Baseline & periodically: CBC with differential & • Avoid grapefruit/juice Blister pack: 6 capsules weeks 1 & 2 only of 21-day platelets, serum electrolytes, ECG, LFT,GI toxicity • Missed dose should be taken if <12 hrs, don’t repeat dose if vomiting occurs, • Dose adj. based on ADE (see PI) consider antiemetic MOA: HDAC inhibitor cycle (with & • Hazardous agent, use precautions when handling ) DDI: CYP3A substrate (major), CYP2D6 (mod.) • Take for 8 cycles, consider add. •  dose 10mg daily with strong 3A4 inhib. ADE: Myelosuppression, fatigue, edema, N/V/D, fever 8 cycles if benefit w/ out toxicity • QT prolongation additive effect

MARCH 2018 | 4 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Gilotrif® () Metastatic NSCLC, EGFR+: 40mg PO daily BBW: None Administration: Take on empty stomach at least 1 hr before or 2 hrs after food 20, 30, 40mg Baseline & periodically: CBC & Chem 12, LFT, SCr, skin • Missed dose should be taken if <12 hrs Bottle: Tablets toxicity, s/sx interstitial lung disease • Dose adj. based on ADE, renal fxn (see PI) ADE: Acneiform rash, diarrhea, stomatitis, nail changes MOA: TKI of EGFR DDI: Pgp substrate Gleevec® () Ph+CML (chronic phase); MDS/MPD, ASM, HES/ BBW: None Administration: Swallow tablets whole, may be dispersed in generic available CEL; unresectable GIST: 400mg PO daily water/apple juice, stir until dissolved & use immediately Baseline & periodically: CBC with differential; HOLD if ANC • Take with food & large glass of water to 100mg Ph+ALL, refractory; Ph+CML (accelerated or blast <1000 or plts <50,000  GI irritation Bottle: 90 tablets phase): 600mg PO daily • LFT, HOLD for bili >3X ULN (until <1.5 ULN) • Avoid grapefruit/juice 400mg • HOLD for severe fluid retention • Doses >400mg should be administered BID Bottle: 30 tablets DDI: CYP3A4 substrate (major) ADE: Fluid retention (periorbital or in lower limbs, can be MOA: TKI of BCR-ABL • May enhance anticoagulant effect of warfarin managed with diuretics), muscle cramps, fever, bleeding, diarrhea, fatigue, rash Hexalen® () Persistent or recurrent ovarian CA, second line: BBW: Antineoplastic experienced doctor Administration: Take 4 times daily (after meals & at bedtime) 260mg/m2/day PO divided QID for either 14 or 21 50mg Baseline & monthly: CBC & Chem12 ADE: N/V/D, , myelosuppresion days in 28-day cycle Bottle: 100 capsules • Neurologic exam Serious ADE: Neurologic changes • GI intolerance, ANC <1000, plt <75K or neurotoxicity: dose to MOA: Alkylating agent (tremor, seizures, vertigo), hepatotoxicity 200mg/m2/day

DDI: Cimetidine  t-half-life Hycamtin® () SCLC, relapsed (platinum sensitive): BBW: Myelosuppression use in patients with neutrophil Administration: 2.3mg/m2 PO counts (greater than/equal to) 1500 cells/mm3 & • Swallow capsules whole 0.25, 1mg daily x 5 days counts 100,000 cells/mm3 • Take with or without food Bottle: 10 capsules every 21 days • Hazardous agent, use precautions when handling Baseline & monthly: CBC w/ differentials • Store refrigerated MOA: Topoisomerase • SCr (30-39 mL/min dose to 1.5mg/m2); SCr ≤30mL/min  I-inhibitor Round to nearest 0.25mg capsule dose dose to 0.6mg/m2 (may titrate by 0.4mg/m2 after 1st course if ADE: N/V/D, fatigue, anorexia • Should not treat w/ subsequent course until neutrophils no GI or blood toxicities) (>1000 cells/m3), platelets (>100,000 cells/mm3) & • If neutropenia (<500 cells/mm3 or 500-1000 cells/mm3 beyond hemoglobin (>9.0 g/dL) recover day 21)  dose by 0.4mg/m2

DDI: Cytotoxic drugs  myelosuppression risk Hydrea® (hydroxyurea) CML, H&N or sickle cell: 15mg/kg PO daily, titrate BBW: May cause severe myelosuppression Administration: Swallow capsules whole with water generic available per PI • Hazardous agent, use precautions when handling Baseline & periodically: 500mg ADE: Severe myelosuppression, N/V/D (interrupt dose) • May cause macrocytosis & mask folic acid WBC & PLT (Hold for WBC <2500 or PLT <100,000) Bottle: 100 capsules deficiency; folic acid is recommended during • Pregnancy status in females of reproductive potential • Avoid pregnancy during & at least 6 months • S/sx of pancreatitis MOA: therapy after discontinuation • Skin erythema hypothesized to inhibit • Hair loss DNA synthesis by acting as DDI: Antiretrovirals can  peripheral neuropathy • Sun exposure, wear sunscreen a ribonucleotide reductase • Live vaccines inhibitor, without interfering with the synthesis of RNA or protein

MARCH 2018 | 5 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Ibrance® () Ibrance + fulvestrant for postmenopausal BBW: None Administration: Swallow capsule whole women with HR+/HER2- advanced or • Take with food at same time every day 75, 100, 125mg CBC with differential metastatic breast cancer for disease Baseline & periodically: • S/sx of infection & pulmonary embolism • Avoid grapefruit/juice Bottle: 21 capsules progression following endocrine therapy • Grade 3+ ADE: Withhold until symptoms resolve to • If missed dose or vomiting occurs, don’t take add. dose MOA: CDK 4 & 6 inhibitor Ibrance + letrozole for first-line treatment Grade 1/2 & resume at 100mg daily (see PI) ADE: Myelosuppression, fatigue, N/V/D, stomatitis, alopecia, of postmenopausal women with HR+/HER2- DDI: CYP3A4 substrate peripheral neuropathy metastatic breast cancer 125mg PO daily for 21 days on & 7 days off

Iclusig® () Ph+CML, T315I+ (chronic, accelerated or BBW: Vascular occlusion; heart failure; hepatotoxicity Administration: Swallow tablets whole 15mg blast phase); Ph+ALL + (chronic, accelerated • May be taken with or without food Bottle: 30, 60, 180 tablets or blast phase): 45mg PO daily Baseline & periodically: CBC w/ differential & • Avoid grapefruit/juice 45mg Consider reducing dose for chronic or accelerated platelets, LFTs, electrolytes & lipase Bottle: 30, 90 tablets phase if MCR is achieved • Dose interrupt &/or modify on ADE (see PI) ADE: Myelosuppression, HTN, rash, abdominal pain, fatigue, • Cardiac function: CHF, HTN, QT prolongation headache, dry skin, constipation, arthralgia, nausea, pyrexia MOA: TKI of BCR-ABL with mutant T315I DDI: Avoid strong CYP3A4 inducer •  to 30mg with strong CYP3A4 inhibitor

Imbruvica® () CLL; CLL 17p ; WM; small lymphocytic BBW: None Administration: Swallow capsules whole 140mg lymphoma, small lymphocytic lymphoma Baseline & periodically: CBC, renal/hepatic fxn, uric acid • Take with or without food with full glass of water in patients with 17p chromosome deletion: • Take missed dose as soon as remembered if on same day Bottle: 90, 120 capsule • Interrupt for Grade 3+ non-heme/neutropenia or 420mg PO daily • Avoid grapefruit/juice MOA: BTK inhibitor Grade 4+ hematologic until Grade ≤1 MCL, 1 previous therapy; marginal zone • If reoccurs,  dose by 140mg each time ADE: Diarrhea, myelosuppression, fatigue, edema, bruising, lymphoma in patients previously treated with dyspnea, N/V, rash at least one anti-CD20-based therapy: DDI: CYP3A4 substrate (major) 560mg PO daily •  dose by 140mg with moderate CYP3A4 inhib. cGVHD; 420mg orally once daily until progression of chronic graft-versus-host disease, recurrence of underlying malignancy, unacceptable toxicity, or medical assessment supporting discontinuation of therapy Inlyta® () Advanced RCC, 1 prior therapy: 5mg PO BID BBW: None Administration: Take with or without food & full glass of water 1mg • Dose is titrated to tolerability & if Baseline & periodically: Hepatic function (LFT & bili), • If missed dose/vomit, an additional dose shouldn’t be taken Bottle: 180 tablets normotensive, up to 10mg BID if tolerated thyroid function, urinalysis, BP, heart function • Avoid grapefruit/juice 5mg (see PI) • S/sx of RPLS, GI bleed • Encourage BP monitoring at home Bottle: 60 tablets ADE: N/VD, fatigue,  appetite, dysphonia, H-F syndrome MOA: TKI including VEGF DDI: CYP3A4 substrate (major) • Avoid use with strong CYP3A4 inhibitors; if needed, Serious ADE: HTN (crisis), hemorrhage, RPLS, thromboembolic  dose by 50% & then adjust events, cardiac failure

MARCH 2018 | 6 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Intron® A (interferon alfa-2b) Malignant melanoma, adjuvant to BBW: Cause/aggravate life-threatening disorders Administration: Not recommended for IV admin 10,18, 50MIU/ml, surgery at high risk for systemic • Powder for inj. doesn’t have a preservative recurrence: • Use 25-30 gauge needle for SQ shot, sterile technique Solution/Powder vial Baseline & periodically: CBC with differential & platelets, LFT MOA: Protein responsible for Induction: 20MIU/m2 IV over 20 minutes x weekly at induction, then monthly ADE: Flu-like symptoms (headache, fever, chills, myalgia & fatigue) induction of certain enzymes, 5 day/week • Hold for severe ADE & reinitiate at 50% dose suppression of cell proliferation, Maintenance: 10MlU/m2 SQ 3 day/week enhancement of the phagocytic DDI: CYP3A4 inhibitor (weak) activity of macrophages, augmentation of specific cytotoxicity of lymphocytes for target cells Iressa® () Metastatic NSCLC, EGFR+: 250mg PO daily BBW: None Administration: Swallow whole or immerse tablet in 4-8oz of water, stir for ~15 minutes & immediately drink 250mg Withhold for up to 14 days for s/sx Baseline & periodically: • May take with or without food pulmonary/ ocular disorder, Grade2+ diarrhea, Grade 3+ skin rxn. Bottle: 30 tablets • Missed dose should be taken if <12 hrs Resume if ≤Grade 1 • Monitor INR if on warfarin MOA: TKI of EGFR • D/C if ILD, severe hepatic impairment, GI perforation, persistent ulcerative keratitis ADE: Skin reactions, diarrhea, vomiting, stomatitis,  appetite DDI: CYP3A4 substrate (major) • CYP3A4 strong inducer:  to 500mg daily • Take 12 hrs before/after PPI, 6 hrs before/after H2RA or antacid Jadenu® (deferasirox) Transfusional iron overload, ≥2 years old: BBW: Renal/hepatic failure, GI hemorrhage Administration: Swallow tablets whole with water 14mg/kg PO daily, max: 28mg/kg daily • Take on an empty stomach or with light meal 90, 180, 360mg Baseline & periodically: Serum ferritin, CBC with differential, SCr, (>7% fat content & approximately 250 calories) Bottle: 30 tablets Non-Transfusion- Dependent Thalassemia: CrCl at baseline & monthly thereafter. Adjust dose at same time each day 7mg/kg PO daily, max: 14mg/kg daily q3-6 months. MOA: Iron chelator, • From Exjade to Jadenu should be  ~ 30% • Baseline & annual auditory & ophthalmic exam ADE: (based on Exjade studies): see also: Exjade (nearest whole tab) • Abdominal pain, nausea, vomiting, diarrhea,  serum DDI: CYP3A4 inducer (weak/moderate) creatinine, skin rash (typically resolves within 1 week) • Avoid aluminum containing antacids Jakafi® () Int-high risk myelofibrosis: 5-20mg PO BBW: None Administration: Take with or without food BID, may  dose by 5mg BID to a max dose • If patient has feeding tube: mix each tablet with 40mL of water, 5, 10, 15, 20, 25mg Baseline & periodically: CBC, renal & hepatic function, of 25mg BID stir for 10 minutes (give within 6 hrs of mixing), flush feeding Bottle: 60 tablets s/sx of infection tube with water before & after medication is given Polycythemia vera, after hydroxyurea • Modify dose for thrombocytopenia, titrate dose based on MOA: JAK1 & JAK2 inhibitor • Avoid grapefruit/juice therapy: 10mg PO BID, dose titrated based efficacy & safety (see PI) • When d/c therapy, taper by 5mg PO BID each week on Hg & platelet count (see PI) • Skin lesions ADE: Myelosuppression, bruising, dizziness, headache, DDI: CYP3A4 substrate (major) weight gain • Modify dose with CYP3A4 strong inhibitor

MARCH 2018 | 7 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Kisqali () Breast cancer, Metastatic or advanced, BBW: None Administration: Take at about the same time each day HER-2 negative, hormone receptor- for 21 days on & 7 days off, preferably in the morning with 200mg tablets Baseline & periodically: Tumor response may indicate efficacy. positive, postmenopausal women, CBC, including differential: Prior to therapy initiation, every 2 aromatase inhibitor (taken for 28 days). Take with or without Blister pack (21 tablets) – each in combination with an aromatase weeks for the first 2 cycles, at the start of each subsequent food. Avoid eating & drinking pomegranate & grapefruit juice blister pack contains 21 tablets inhibitor for initial endocrine-based 4 cycles, & as clinically indicated. Liver function tests: Prior to during treatment as they may increase the levels of Kisqali in (200mg per tablet) (600mg daily treatment: 600mg orally (three 200mg therapy initiation, every 2 weeks for the first 2 cycles, at the start the blood dose) tablets) taken once daily with or without of each subsequent 4 cycles, & as clinically indicated Blister pack (14 tablets) – each food for 21 consecutive days followed ADE: Alopecia, constipation, diarrhea, nausea, vomiting, • Pregnancy test: Prior to initiation of treatment in females with leukopenia, neutropenia, headache, fatigue, prolonged QT blister pack contains 14 tablets by 7 days off treatment. Co-administer reproductive potential (200mg per tablet) (400mg daily with letrozole 2.5mg orally once daily (or interval, anemia • Serum electrolytes, including potassium, calcium, phosphorus, dose) another aromatase inhibitor) throughout & magnesium: Prior to therapy initiation, the start of the first 6 the 28-day cycle; give both medications at Blister pack (21 tablets) – each cycles & as clinically indicated blister pack contains 21 tablets the same time each day, preferably in the • ECG: Prior to therapy initiation, at day 14 of the first cycle, at the (200mg per tablet) morning start of the second cycle, & as clinically indicated MOA: Ribociclib is an inhibitor DDI: CYP3A4 (major) of cyclin-dependent kinase • Avoid concurrent use with strong or moderate CYP3A4 (CDK) 4 & 6. These kinases inhibitors, if unavoidable,  dose to 400mg once daily are activated upon binding to • Avoid concurrent use with strong CYP3A4 inducers & consider D-cyclins & play a crucial role an alternative to concomitant medication with no or minimal in signaling pathways that potential to induce CYP3A lead to progression & cellular proliferation. The • Co-administration of midazolam (a sensitive CYP3A4 substrate) with multiple doses of KISQALI (400mg) increased the cyclin D-CDK4/6 complex midazolam exposure by 3.8-fold in healthy subjects, compared regulates cell cycle progression with administration of midazolam alone through phosphorylation of the retinoblastoma protein (pRb) • Avoid co-administration of Kisqali with medicinal products with a known potential to prolong QT such as antiarrhythmic medicines • Avoid eating & drinking pomegranate & grapefruit juice during treatment as they may increase the levels of Kisqali in the blood

Lenvima® () Locally recurrent or metastatic, BBW: None Administration: Take at same time each day with or without food progressive, radioactive iodine-refractory • Missed dose should be taken if <12 hrs 4, 10mg Baseline & periodically: Electrolytes, TSH, proteinuria, BP, LVEF, differentiated thyroid cancer (DTC): 24mg • Cytotoxic agent, use precautions when handling 5-day blister card x 6 cards LFTs, RPLS PO daily • Dose adj. based on ADE (see PI) ADE: HTN, fatigue, N/V/D (Mod emetogenic potential, use MOA: TKI including VEGF antiemetic),  appetite, arthralgia, HF syndrome, dysphonia DDI: CYP3A4 (minor), BCRP • QT prolongation additive effect

Leukaran® () CLL, HL, NHL, BBW: Suppress bone marrow, teratogenic Administration: Store refrigerated mycosis fungoides: • Take on empty stomach 1 hr prior or 2 hrs after food 2mg 0.03-0.2mg/kg PO daily Baseline & periodically: CBCs & platelets weekly, WBC 3-4 days • Dose ≤0.1mg/kg/day when lymphocytic infiltration of bone Bottle: 50 tablets after each weekly CBC marrow is present (bone marrow is hypoplastic) • CrCl1:0-50ml/min=75% dose, <10ml/min=50% MOA: Alkylating agent ADE: Bone marrow suppression Rare ADE: urticaria, tremors & nausea

MARCH 2018 | 8 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Lonsurf® (Trifluridine Metastatic colorectal cancer previously BBW: None Administration: Take within 1 hr after completion of and tipiracil) treated with fluoropyrimidine, morning & evening meals CBC prior to each cycle & on day 15 - & -based Baseline & periodically: • Do not take additional doses to make up for missed 15mg/6.14mg chemotherapy, an anti-VEGF biological of each cycle (or more frequently if clinically necessary); signs/ or held doses Bottle: 20, 40, 60 tablets therapy, & if RAS wild-type, an anti-EGFR symptoms of GI toxicity • Cytotoxic agent, use precautions when handling 20mg/8.19mg therapy: 35mg/m2 up to a maximum of Do not initiate the cycle of LONSURF until: Bottle: 20, 40, 60 tablets 80mg per dose (trifluridine component) PO • Absolute neutrophil count (ANC) ≥1,500/mm3 or febrile ADE: Myelosuppresion, fatigue/asthenia, N/V/D,  BID on days 1-5 & days 8-12 of each 28-day netropenia is resolved appetite, pyrexia MOA: Thymidine cycle. Round dose to nearest 5mg • Platelets ≥75,000/mm3 phosphorylase inhibitor • Grade 3 or 4 non-hematological adverse reactions are resolved to Grade 0 or 1

DDI: No pharmacokinetic drug-drug interaction studies have been conducted Matulane® ( HCl) Stage III & IV HL: 2-6mg/kg/ day BBW: Antineoplastic experienced doctor Administration: Take with or after meals once daily or in 2-3 divided doses 50mg 100mg/m2 CBC w/ differentials, platelet & (MOPP regimen): Baseline & periodically: • High emetic potential, antiemetics are recommended Bottle: 100 capsules reticulocyte count, urinalysis, LFTs, SCr • Hazardous agent, use precautions when handling

MOA: RNA, DNA, protein DDI: ADE: N/V, myelosuppression, CNS depression, hypotension, synthesis inhibitor • Anticoagulant effect may be musculoskeletal pain, rash, generalized allergic rxn, jaundice • CNS depressant effect may be Mekinist® () Unresectable or metastatic melanoma BBW: None Administration: Take on empty stomach 1 hr before or 2 hrs with BRAF V600E or BRAF V600K after meal 0.5, 1, 2mg Baseline & periodically: CBC, LFTs, LVEF, ophthalmological mutation: 2mg PO daily • Store refrigerated in original container Bottle: 30 tablets evaluation if visual disturbance • Missed dose should be taken if <12 hrs • S/sx of bleed, pulmonary or derm toxicity, secondary • Hazardous agent, use precautions when handling MOA: MEK inhibitor FDA-approved monotherapy or in combo with infections, BP, diarrhea (downstream of BRAF) • Dose adj. based on ADE (see PI) ADE: Rash, myelosuppression, diarrhea, stomatitis, lymphedema, HTN,  AST/ALT DDI: CYP2C8 inhibitor (weak), CYP3A4 inducer (weak/moderate) Nexavar® () Unresectable HCC; Advanced RCC; BBW: None Administration: Take on empty stomach 1 hr before or 2 hrs Differentiated thyroid cancer: 400mg PO after food 200mg Baseline & periodically: CBC with differential, electrolytes, LFTs, BID • Avoid grapefruit/juice Bottle: 120 tablets BP, thyroid function • Hazardous agent, use precautions when handling • ECG if at risk for QTc prolongation MOA: multi-TKI •  dose for ADE, renal, hepatic dysfxn (see PI) ADE: H-F syndrome, rash, N/V/D, HTN, fatigue, alopecia, myelosuppression, bleeding DDI: CYP3A4 substrate (minor), CYP2C9 inhibitor (moderate) • May enhance anticoagulant effect of warfarin

MARCH 2018 | 9 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Ninlaro® () Multiple myeloma with BBW: None Administration: Take once a week on the same day & at approximately at least one prior the same time for the first three weeks of a four week cycle 2.3, 3, 4mg gelatin capsule CBC with differential & platelet, SCr, LFTs therapy, in combination Baseline & periodically: • Take on empty stomach 1 hr before or 2 hrs after food • S/sx: GI & dermatologic toxicity, peripheral neuropathy, • Single blister pack with & • Swallow capsule whole, don’t crush or chew peripheral edema • Three single packs in a carton dexamethasone: • If dose is delayed or missed, take only if the next scheduled Embryo-fetal toxicity, use contraception during tx & 90 days after final dose MOA: Reversible Recommended dose is ≥72 hrs away; missed dose should not be taken starting dose: Ninlaro: within 72 hrs of the next scheduled dose inhibitor Prior to initiating a new cycle of therapy: 4mg PO once a week on • Absolute neutrophil count (ANC) ≥1000/mm3 • If vomiting occurs after dose, do not repeat the dose, resume Days 1, 8, & 15 of a 28-day • Platelet count ≥75,000/mm3 dosing at the time of the next scheduled dose treatment cycle • Non-hematologic toxicities generally recovered to baseline condition • Store capsules in original packaging, don’t remove the capsule Lenalidomide: 25mg PO or ≤Grade 1 from the packaging until just prior to taking daily on Days 1-21 of a 28- • Hazardous agent, use precautions when handling day treatment cycle DDI: CYP3A4 substrate (major) Dexamethasone: 40mg PO • Avoid concomitant administration with strong CYP3A inducers ADE: URI, N/V/D, constipation, peripheral edema & on Days 1, 8, 15, & 22 of a neuropathy, thrombocytopenia, neutropenia, eye disorders 28-day treatment cycle Nolvadex® (tamoxifen) Breast cancer prophylaxis BBW: Uterine malignancies, stroke, PE in ductal carcinoma in situ/high Administration: Swallow tablet whole generic available & treatment: 20 - 40mg risk breast ca setting • Take with or without food PO daily • Dose >20mg/day should be divided BID 10, 20mg tablets Baseline & periodically: CBC & platelets, LFTs Bottle: various • gynecological exam: breast, mammogram ADE: Flush, altered menses, fluid retention, hot flashes, nausea • Risk of endometrial & uterine cancer MOA: Anti-estrogen DDI:  INR in patients on warfarin • QT prolongation additive effect Odomzo® Locally advanced basal BBW: Embryo-fetal toxicity Administration: Take on empty stomach 1 hr before or 1 hr after food ( phosphate) cell carcinoma (BCC), • Hazardous agent, use precautions when handling Serum CK, SCr, LFTs not candidate for or Baseline & periodically: ADE: Muscle spasms, alopecia, dysgeusia, fatigue, N/V/D, 200mg capsule recurrence following • S/sx of musculoskeletal toxicity  Blister pack or bottle: 30 surgery or radiation • Interrupt dose for CK 2.5-10 ULN appetite, abdominal pain, headache, pruritus MOA: Hedgehog therapy: 200mg PO daily DDI: CYP3A4 (major), BCRP inhibitor pathway inhibitor • Avoid concomitant administration with strong CYP3A inducers&inhibitors Pomalyst® MM (with BBW: Embryo-fetal toxicity, thromboembolism Administration: Swallow capsule whole with water (pomalidomide) dexamethasone), after • Take on empty stomach 1 hr before or 1 hr after food CBC with differential & platelet, SCr, LFTs, TSH 2 prior therapies: 4mg Baseline & periodically: • Pregnancy test before & during treatment • S/sx of thromboembolism & neuropathy 1, 2, 3mg PO daily on days 1-21 of 28 • Contraception or abstain from heterosexual sex during & 4 weeks • Dose modify for hematologic toxicity (see PI) Bottle: 21, 100 capsules day cycle after therapy *POMALYST REMS: Patient, MOA: Immunomodulator with DDI: CYP1A2, 3A4 substrate (major) ADE: Myelosuppression, fatigue, dyspnea, edema, fever, N/V/D, prescriber & pharmacy antineoplastic activity •  dose by 50% with strong CYP3A4+1A2 inhibitor musculoskeletal pain, UTI, dizziness, rash must be enrolled

MARCH 2018 | 10 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Promacta® (eltrombopag) Aplastic anemia, severe; BBW: Hepatic decompensation (if HCV+) Administration: Take on an empty stomach at least 1 hr before or chronic hepatitis C 2 hrs after food 12.5, 25, 50, 75mg Baseline & periodically: CBC with differential & platelet, monthly LFTs infection-associated • Separate from antacids, foods high in calcium, or minerals Bottle: 30 tablets •  by 25mg to maintain platelet >50k, if ineffective after thrombocytopenia; chronic ITP such as iron, calcium, aluminum, magnesium, & zinc by at 4 weeks, d/c MOA: TPO-receptor agonist >6 year old: 50mg PO daily least four hrs • Bone marrow biopsy with staining for fibrosis initially; max dose 75mg daily • Food, esp. dairy may  absorption • Ophthalmic exam at baseline & during treatment • 25mg daily for patients of ADE: N/V/D, fatigue, headache, cataracts, hepatotoxicity East-Asian ethnicity DDI: Cations  serum concentration (jaundice) Purinethol® ALL (as part of a combo BBW: None Administration: Take on empty stomach, for suspension (/ 6-MP) regimen): Various regimens exist shake well for 30 seconds Baseline & periodically: CBC w/ differentials, LFTs & bili, serum uric acid generic available Typical: 1.5-2.5mg/kg PO daily • Hazardous agent, use precautions when handling • CrCl <50 mL/min interval adjustment: q 48h 50mg ADE: Myelosuppression, stomatitis, mucositis, rash, DDI: allopurinol (need to  dose of 6-MP by 75%), warfarin, & other Bottle: 25 or 250 tablets photosensitivity, nausea (low emetogenic potential) hepatotoxic medications MOA: Nucleoside metabolic Serious ADE: Hepatotoxicity: jaundice & hyperbilirubinemia occur inhibitor that results in cell-cyle after 1-2 months & can be dose limiting arrest & death Revlimid® (lenalidomide) MCL, after 2 therapies; MM BBW: Embryo-fetal risk toxicity, hematologic toxicity, thromboembolism Administration: Swallow capsule whole with water (with dexa): 25mg PO daily on • Take on empty stomach 1 hr before or 1 hr after food 2.5, 5, 10mg Baseline & periodically: CBC with differential, SCr, LFT days 1-21 of 28 day cycle • Pregnancy test before & during treatment Bottle: 28, 100 capsules • S/sx of thromboembolism, infection • Contraception or abstain from heterosexual sex during & 4 15, 20, 25mg MDS w/ 5q deletion: 10mg PO • Dose modify for hematologic toxicity (see PI) weeks after therapy Bottle: 21, 100 capsules daily DDI: Pgp substrate ADE: Myelosuppression, N/V/D, fatigue, rash, dyspnea, fever, MOA: Immunomodulator with *REVLIMID REMS: Patient, • Additive immunosuppressive musculoskeletal pain, dizziness, UTI antineoplastic activity prescriber & pharmacy must be enrolled

MARCH 2018 | 11 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Rydapt® () Acute myeloid , newly diagnosed, FLT3 mutation-positive, in BBW: None Administration: combination with standard & induction & cytarabine • Give with food 25mg, liquid filled capsules Baseline: consolidation chemotherapy Unit dose packs of 56 & 112 • FLT3 mutation: Prior to initiation, with an FDA- • Swallow capsule whole; do Systemic mast cell disease, aggressive systemic mastocytosis, systemic approved companion diagnostic test available at not open or crush MOA: Midostaurin is an mastocytosis with associated hematological neoplasm, or mast cell leukemia: www.fda/gov/companiondiagnostics • Missed dose or vomiting: inhibitor of multiple receptor AML: 50mg orally twice daily (12-hr intervals) with food Do not make up the dose; tyrosine kinases & has the • Pregnancy status (women of reproductive potential): ASM, SM-AHN, MCL: 100mg orally twice daily (12-hr intervals) with food until disease Within 7 days prior to initiation of therapy give at the next usual ability to inhibit FLT3 receptor scheduled time signaling & cell proliferation. progression or unacceptable toxicity • CBC: At least weekly for the first 4 weeks, every Midostaurin induces Dose adjustment: other week for the next 8 weeks, & monthly in leukemic cells that express thereafter during therapy including a differential ADE: may include edema, Criteria Rydapt Dosing petechiae, hyperglycemia, FLT3 mutant kinases (ITD & DDI: TKD) or overexpress wild type • ANC less than 1 x 109/L attributed to Rydapt • Interrupt Rydapt until ANC greater than or abdominal pain, constipation, FLT3 & PDGF receptors. Mast in patients without MCL, or ANC less than 0.5 equal to 1 x 109/L, then resume Rydapt at • Co-administration of Rydapt with strong CYP3A diarrhea, headache, dysnea cell apoptosis & inhibition of x 109/L attributed to Rydapt in patients with 50mg twice daily, & if tolerated, increase to inhibitors may increase midostaurin concentrations. baseline ANC value of 0.5-1.5 x 109/L 100mg twice daily KIT signaling, cell proliferation, The increase in midostaurin concentrations may & histamine release were also • Platelet count less than 50 x 109/L attributed • Discontinue Rydapt if low ANC persists for be pronounced if strong CYP3A inhibitors are demonstrated to Rydapt in patients without MCL, or platelet >21 days & is suspected to be related to administered during the first week of Rydapt count less than 25 x 109/L attributed to Rydapt administration Rydapt in patients with baseline platelet • Interrupt Rydapt until platelet count greater • Increased midostaurin concentrations may increase count of 25-75 x 109/L than or equal to 50 x 109/L, then resume the risk of toxicity. [CONSIDER ALTERNATIVE • Hemoglobin less than 8 g/L attributed to Rydapt at 50mg twice daily, & if tolerated, THERAPIES THAT DO NOT STRONGLY INHIBIT Rydapt in patients without MCL, or life- increase to 100mg twice daily CYP3A] threatening anemia attributed to Rydapt in • Discontinue if low platelet count persists patients with baseline hemoglobin value of for >21 days & is suspected to be related • Co-administration of Rydapt with strong CYP3A 8 -10 g/L to Rydapt inducers may decrease midostaurin concentrations • Grade 3/4 nausea and/or vomiting despite • Interrupt Rydapt until hemoglobin greater • Decreased midostaurin concentrations may reduce optimal antiemetic therapy than or equal to 8 g/L, then resume Rydapt efficacy[AVOID CO-ADMINISTRATION OF RYDAPT • Other Grade 3/4 non-hematological toxicities at 50mg twice daily, & if tolerated, increase WITH STRONG CYP3A INDUCERS] to 100mg twice daily • Discontinue if low hemoglobin persists for >21 days & is suspected to be related to Rydapt • Interrupt Rydapt for 3 days (6 doses), then resume Rydapt at 50mg twice daily, & if tolerated, increase to 100mg twice daily • Interrupt Rydapt until event has resolved to ≤Grade 2, then resume Rydapt at 50mg twice daily, & if tolerated, increase to 100mg twice daily

ANC: Absolute Neutrophil Count CTCAE severity: Grade 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms; 4 = life-threatening symptoms.

MARCH 2018 | 12 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Rubraca® () , Monotherapy, in advanced disease BBW: None Administration: with deleterious BRCA mutations (germline or somatic), • Instruct patients to take Rubraca orally twice 200, 300mg tablets with 2 or more previous : 600mg orally Baseline: daily with or without food. Doses should be Bottle: 60 tablets twice daily, continue until disease toxicity or disease • Presence of deleterious tumor BRCA mutation taken approximately 12 hrs apart. Advise progression. (germline and/or somatic): Prior to initiation with an patients that if a dose of Rubraca is missed MOA: poly (ADP-ribose) FDA-approved companion diagnostic test available at polymerase (PARP-1, PARP-2, or if the patient vomits after taking a dose Dose adjustment: http://www.fda/gov/CompanionDiagnostics. & PARP-3) inhibitor that causes of Rubraca, patients should not take an • Renal, mild to moderate impairment (CrCl 30 to 89 mL/ • CBC; evaluate prior to initiation of therapy & monthly extra dose, but take the next dose at the regular DNA damage, apoptosis, & cell min estimated with Cockcroft-Gault equation): No initial thereafter; if prolonged hematological toxicities occur, death, especially in tumor cell time. adjustment needed monitor CBC weekly until recovery • Recommend female patients avoid pregnancy lines with deficiencies in BRCA1/2 • Hepatic, mild impairment (total bilirubin ULN or lower Periodically: during therapy & for at least 6 months & AST greater than ULN, or total bilirubin 1 to 1. 5 times after discontinuation ULN & any AST): No initial adjustment needed • Tumor response in patients with advanced ovarian cancer is indicative of efficacy • Advise patient to report symptoms • Adverse events: Interrupt therapy or reduce dose; first of myelodysplastic syndrome or acute myeloid reduction, 500mg twice daily; second reduction, 400mg DDI: In vitro, rucaparib had a low metabolic turnover rate in leukemia twice daily; third reduction, 300mg twice daily human liver microsomes, & was metabolized primarily by • Tell patient to use sunscreen, wear protective • Hematologic: Interrupt therapy until recovery to grade 1 CYP2D6 & to a lesser extent by CYP1A2 & CYP3A4. In vitro, clothing, & avoid tanning beds due to potential or lower. If recovery does not occur after 4 weeks, refer rucaparib was shown to be a substrate of P-gp & BCRP, but for photosensitivity to a hematologist for investigation. If myelodysplastic not a substrate of renal uptake transporters OAT1, OAT3, syndrome or is confirmed, & OCT2, or hepatic transporters OATP1B1 & OATP1B3. ADE: May include vomiting, abdominal pain, discontinue rucaparib Concomitant treatment with proton pump inhibitors has no dysgeusia, constipation, decreased appetite, clinically meaningful change in steady-state exposures diarrhea, or dyspnea Sprycel® () Ph+CML (chronic phase): 100mg PO daily (140mg daily*) BBW: None Administration: Swallow tablet whole, don’t crush or chew 20, 50, 70mg Pediatric Ph+CML (Chronic phase: newly diagnosed or Baseline & periodically: CBC with differential • Take with or without food Bottle: 60 tablets resistant/intolerant to prior therapy): Weight-based • Bone marrow biopsy q 3 months • Take with a full glass of water 80, 100, 140mg dosing, refer to package insert • LFT, electrolytes (Ca, Phos, Mag) • Avoid grapefruit/juice Bottle: 30 tablets • ECG monitoring if at risk for QTc prolongation Ph+ALL, refractory; Ph+CML (accelerated or blast phase): • S/sx fluid retention, cardiac function ADE:  MOA: TKI including BCR-ABL 140mg PO daily ( 180mg daily*) • Myelosuppression, CNS or GI hemorrhage, fluid * if not achieving hematologic or cytogenic response) DDI: CYP3A4 substrate (major) retention (including pleural effusion), skin rash, • Avoid PPIs & H2RA (if needed may consider antacid 2 N/V/D, fatigue hrs before or 2 hrs after dose) • QT prolongation additive effect •  anticoagulant effect of antiplatelet drugs Stivarga® () Metastatic colorectal cancer after failure BBW: Hepatotoxicity Administration: Swallow tablet whole with water of Folfox/Folfiri, & ; GIST, • Take with meal <30% fat & <600 calories 40mg CBC with differential & platelets, advanced or metastatic: 160mg PO daily on days 1-21 of Baseline & periodically: 3 Bottles of 28: 84 tablets 28 day cycle LFTs, BP ADE: Fatigue, anorexia, N/V/D, fever, GI & abdominal • Dose modify for ADE (see PI) pain, dysphonia, H-F syndrome, mucositis, HTN MOA: Multi-TKI DDI: CYP3A4 substrate (major) Serious ADE: GI perforation, hemorrhage, • warfarin may  toxicity of Stivarga & bleeding hepatotoxicity Sutent® () GIST, after imatinib tx; RCC, advanced: 50mg PO daily x 4 BBW: Hepatotoxicity Administration: Take with or without food weeks on then 2 weeks off • Avoid grapefruit/juice 12.5, 25, 37.5, 50mg Baseline & periodically: Electrolytes, LVEF, ECG, LFTs, BP, UA Metastatic or advanced pNET: 37mg PO daily continuously Bottle: 28 capsules • S/sx thyroid, hypoglycemia ADE: Myelosuppression, peripheral edema, N/V/D, • Dose modify by 12.5mg based on tolerability electrolyte changes, fatigue, HTN, dizziness, H-F Multi-TKI MOA: syndrome, alopecia, cough,  AST/ALT, arthralgia, UTI DDI: CYP3A4 substrate (major), Pgp inhibitor • Avoid strong 3A4 inhibitors, if can’t  12.5mg/day • Avoid strong 3A4 inducers, if can’t  12.5mg/day • QT prolongation additive effect

MARCH 2018 | 13 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Sylatron® Melanoma with nodal involvement, adjuvant tx: 6mcg/ BBW: Depression & suicidal ideation Administration: Dissolve lyophilized powder (peginterferon alfa2-b) kg/week SQ for 8 doses, followed by 3 mcg/kg SQ for up to • Visually inspect the solution & discard if Baseline & periodically: CBC with differential & platelets, 5 years particulates 296mcg x 1 or 4 vials electrolytes, LFT, serum glucose • Withdraw no more than 0.5ml reconstituted 444mcg x 1 or 4 vials • S/sx of depression solution 888mcg x 1 or 4 vials • CrCl 30-50ml/min= initial 4.5mg/kg & 2.25mg/kg • Premedicate w/APAP 500 - 1000mg PO 30 •  dose for toxicity (see PI) MOA: Protein responsible for minutes prior to first dose & prn for subsequent induction of certain enzymes, DDI: CYP1A2 & 2D6 inhibitor doses suppression of cell proliferation, ADE: Fatigue, pyrexia, headache, anorexia, myalgia, enhancement of the phagocytic N/V,  AST/ALT activity of macrophages, augmentation of specific cytotoxicity of lymphocytes for target cells Tabloid® (thioguanine/6TG) AML, induction or consolidation: 2mg/kg PO daily, after 4 BBW: None Administration: Take on empty stomach for generic available weeks  to 3mg/kg daily if tolerated absorption Baseline: CBC, Chem12 & LFTs, then weekly for first month, • Compounded oral solution formula available 40mg then monthly once stable Bottle: 25 tablets • May require TLS prevention w/allopurinol • Hazardous agent, use precautions when handling

MOA: DDI: Cross resistance between mercaptopurine ADE: Nausea, Mucositis, myelosuppression Serious ADE: GI perforation, hepatotoxicity Tafinlar® (dabrafenib) Unresectable or metastatic melanoma with BRAF V600E or BBW: None Administration: Swallow tablet whole, don’t crush BRAF V600K mutation: 150mg PO BID or chew 50, 75mg Electrolytes, glucose, SCr Baseline & periodically: • Take on empty stomach 1 hr before or 2 hrs Bottle: 120 capsules FDA-approved monotherapy or in combo with trametinib • S/sx derm, infection, uveitis, hemolytic anemia after food • Dose modify for ADE (see PI) MOA: BRAF inhibitor • Missed dose should be taken if <6 hrs DDI: CYP3A4 & 2C8 substrate (major) • Hazardous agent, use precautions when handling • GI acid reducers may  effect, monitor therapy • QT prolongation additive effect ADE: Fatigue, hyperkeratosis, alopecia, H-F syndrome, rash, musculoskeletal pain, fever, headache

Serious ADE: Secondary malignancy Tagrisso® () Metastatic epidermal growth factor receptor (EGFR) T790M BBW: None Administration: Take with or without food mutation-positive non-small cell lung cancer (NSCLC), • If a dose is missed, do not make up the missed 40, 80mg Baseline & periodically: Confirm T790M epidermal refractory after prior EGFR TKI therapy: 80mg PO daily dose & take the next dose as scheduled Bottle: 30 tablets growth receptormutation by an FDA-approved test prior to treatment. ECG, electrolytes, QTc, LVEF Difficulty swallowing: TKI of EGFR MOA: • S/sx: ILD or pneumonitis • Disperse tablet in 4 tsp (~50ml) of non- carbonated water only, stir until completely * Embryo-fetal toxicity, use contraception during tx & 6 weeks dispersed & swallow (or through NG tube) (4 months for males) after final dose immediately. Do not crush or heat DDI: Strong CYP3A Inducers • Add 4-8 oz of water into the container & drink • Avoid concomitant administration with strong CYP3A to make sure full dose is taken inducers (e.g. phenytoin, rifampin, carbamazepine, ADE: Diarrhea, rash, dry skin, nail toxicity, St. John’s wort). Refer to PI for Tagrisso dosing when myelosuppression, dermatologic, & GI toxicity Tagrisso & concomitant Strong CYP3A Inducer is unavoidable.

MARCH 2018 | 14 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Tarceva® () NSCLC (refractory; maintenance; EGFR+ first line): BBW: None Administration: Swallow tablets whole, may be dissolved in 100ml 150mg PO daily water 25, 100, 150mg Baseline & periodically: LFTs, SCr, electrolytes • Take on empty stomach 1 hr before or 2 hrs after food Bottle: 30 tablets Pancreatic Ca (with ): 100mg PO daily • If both AST/ALT & TBili >1.5 x UNL, or ADE consider • Avoid grapefruit/juice  dose (see PI) MOA: TKI of EGFR • Hazardous agent, use precautions when handling • S/sx pulmonary toxicity

DDI: CYP3A4 substrate (major) ADE: Rash, diarrhea, asthenia, cough, dyspnea,  appetite • May need to  or  dose with strong CYP3A4 inducer/inhibitor • Avoid PPI; separate H2RA 10 hrs after & 2 hrs before; separate antacids by several hrs • Consider max dose 300mg if smoker & tolerating Targretin® () CTCL, refractory: (oral): 300mg/m2/day to nearest whole BBW: Birth defects assoc. with Administration: Take with food tablet (can  to 400mg/m2 if no tumor response after • Do not take if pregnant 75mg Baseline & periodically: CBC with differential, LFTs, 8 weeks) (topical): Apply gel sufficiently to lesions once • Hazardous agent, use precautions when handling Bottle: 100 capsules lipid panel, thyroid function every other day x 1 per week,  frequency 1% •  dose for toxicity (see PI) ADE (oral): Lipid abnormalities, hypothyroidism, headache, up to 4x day asthenia, rash, myelosuppression, nausea, edema, abdominal Gel: 60mg/60g tube DDI: CYP3A4 substrate (minor), inducer pain, dry skin MOA: Activates X • Multivitamin (ADEK, folate, iron) may  toxicity receptor ADE (topical): rash, pruritus, pain Tasigna® () Ph+CML, newly diagnosed: 300mg PO BID BBW: QT prolongation, sudden deaths Administration: Swallow capsules whole or disperse contents in 1 tsp of applesauce 150, 200mg Ph+CML, resistant or intolerant: 400mg PO BID Baseline & periodically: CBC with differential, LFTs, • Take on empty stomach 1 hr before or 2 hrs after food with a Blister Pack: 28 ECG, electrolytes, serum lipase full glass of water 112 capsules • Bone marrow biopsy q 3 months • Avoid grapefruit juice (4X28 blister packs) • Dose modify for ADE (see PI) ADE: Myelosuppression, rash, pruritus, headache, N/V/D, MOA: TKI including BCR-ABL DDI: CYP3A4 substrate (major) fatigue, alopecia, abdominal pain, myalgia, edema, dry skin • Avoid PPIs; H2RA: 10 hrs before & 2 hrs after; antacids: 2 hrs after dose • QT prolongation additive effect Temodar® Anapestic astrocytoma Initial dose: 150mg/m(2) BBW: None Administration: Swallow capsule whole with water () ORALLY once daily for 5 days; cycle every 28 days; • Take consistently with or without food Baseline & periodically: CBC with differentials & generic available increase dose to 200mg/m(2)/day for 5 days per 28-day • N/V is decreased on an empty stomach or at bedtime, don’t platelets, LFTs cycle; continue therapy until disease progression, up repeat if vomiting occurs 5, 20, 100, 140, 180, 250mg • Dose  200mg/mg2 Cycle 2-6 based on • Missed dose: skip dose to a maximum of 2 years; optimal therapy duration is Bottle: capsules ANC & platelets unknown ADE: Myelosuppression, N/V, constipation, anorexia, headache MOA: Alkylating agent DDI: Valproic acid  by 5% Glioblastoma Multiforme initial dose, concomitant with focal radiotherapy: 75mg/m(2) orally once daily for 42 days, up to 49 days • Maintenance dose, cycle 1 (4 weeks after completion of initial therapy): 150mg/m(2) orally once daily for 5 days followed by 23 days without treatment • Maintenance dose, cycles 2 to 6 (each 28 days): 200mg/m(2) orally once daily for 5 days followed by 23 days without treatment

MARCH 2018 | 15 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Thalomid® (thalidomide) MM (with dexamethasone): 200mg PO daily BBW: Embryo-fetal risk toxicity, thromboembolism Administration: Swallow capsule whole with water • Take preferably at bedtime 1 hr after evening meal 50, 100, 150, 200mg THALOMID REMS: Patient, prescriber & pharmacy must be enrolled CBC with differential, Baseline & periodically: • Pregnancy test before & during treatment Blister pack: 28 capsules platelets • Contraception or abstain from heterosexual sex MOA: Immunomodulator • S/Sx neuropathy, thromboembolism during & 4 weeks after therapy with antineoplastic activity DDI: Additive immunosuppressive ADE: Confusion, constipation, dyspnea, edema, neuropathy, rash Trexall® Several indications: 15-30mg/m2 PO weekly BBW: High dose regimens require close monitor Administration: Leucovorin rescue () • Important to keep hydrated to reduce risk of renal CBC with differentials, LFTs generic available Baseline & periodically: damage in patients receiving prolonged tx, uric acid Generic: 2.5mg only • SCr (dose adj for CrCl <80 ml/min) ADE: Myelosuppresion, mucositis, pulmonary Bottle: 10, 36, 100 tablets pneumonitis, alopecia, stomatitis, N/V, D (report to MD, DDI: Avoid drugs that increase MTX levels (i.e. may be signs of toxicities) MOA: Dihydrofolic acid salicylates, sulfas, probenecid, PCNs, vitamin C) reductase inhibitor Tykerb® Metastatic HER2+ breast cancer in combination with Xeloda: BBW: Hepatotoxicity Administration: () 1250mg po daily days 1-21 • Take on empty stomach 1 hr before or 1 hr after CBC with differential, Baseline & periodically: food with a full glass of water 250mg electrolytes, ECG, LFTs Metastatic HER2+ breast cancer in combination with letrozole: • Avoid grapefruit/juice Bottle: 150 tablets •  dose w/ Child-Pugh Class C or ADE ≥Grade 2 1500mg po daily • D/C if LVEF >Grade 2 ADE: N/V/D, dyspepsia, myelosuppression, stomatitis, MOA: TKI of EGFR & HER2 • S/sx of ILD, fluid retention, diarrhea, derm toxicity rash, H-F syndrome, fatigue, xerosis, LVEF reduction (60%)  AST/ALT DDI: CYP3A4 substrate (major) • Avoid CYP3A4 strong inhibitor/inducer • QT prolongation additive effect Valchlor® CTCL, received prior skin-directed therapy: Apply thin film once daily BBW: None Administration: Apply area within 30 minutes of (mechlorethamine) to affected areas of intact skin removal from refrigerator & return to refrigerator Dermatologic toxicity- skin Baseline & periodically: promptly after each use 0.016% ulcers, blistering, dermatitis (mod-severe) • Allow contents to dry 4 hrs before or 30 minutes Tube: 60g gel DDI: No known interaction after washing & 5-10 minutes before covering with clothes MOA: Alkylating agent • May apply emollient 2 hrs before or after application • Avoid fire, flame, smoking until dried

ADE: Dermatitis, pruritus, bacterial skin infection

MARCH 2018 | 16 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Venclexta® () CLL, in patients with 17p chromosome deletion, BBW: None Administration: Give with a meal & water at who have received at least 1 prior therapy: Ramp-up about the same time each day. Swallow tablets 10, 50, 100mg Baseline & periodically: CBC throughout treatment, S/Sx of dosage, 20mg orally once daily during week 1; 50mg whole. If a dose is missed within 8 hrs of usual Starting Pack Wallet infection & toxicity, pregnancy test prior to initiation, blood once daily during week 2; 100mg once daily during week time; take dose as soon as possible & resume Unit dose Wallets 3; 200mg once daily during week 4, then usual dosage. chemistry at each ramp-dose or S/Sx’s of daily schedule Bottle: 120x100mg Usual dosage, begin 400mg orally once daily during week DDI: CYP3A4 metabolized. Reduce Vencelxta dose by at least • Recommend females of reproductive 5 & continue thereafter MOA: Selective 75% when used concomitantly with strong CYP3A4 inhibitors. • Premedication, begin allopurinol or xanthine oxidase potential avoid pregnancy during therapy & at small-molecule Resume the Venclaxta dose that was used prior to initiating the inhibitor 2 to 3 days prior to venetoclax in all patients; least 30 days after discontinuation inhibitor of beta cell CYP3A4 inhibitor 2-3 days after discontinuation of the inhibitor. If in high tumor burden, give allopurinol & consider ADE: Diarrhea, nausea, anemia, upper lymphoma-2, an anti- moderate inhibitor or P-gp is used, consider alternative treatment, rasburicase if baseline uric acid is elevated OR, reduce Venclexta dose by at least 50%. Resume the Venclaxta respiratory infection, fatigue, pneumonia, apoptotic protein • Prehydration (low-tumor burden, all lymph nodes less dose that was used prior to initiating the CYP3A4 inhibitor 2-3 autoimmune hemolytic anemia, tumor lysis than 5 cm & absolute lymphocyte count less than 25 x days after discontinuation of the inhibitor. Avoid grapefruit syndrome 10(9)/L), 1.5 to 2 L orally or IV products. • Prehydration (medium-tumor burden, any lymph node 5 to less than 10 cm or absolute lymphocyte count 25 x Avoid concomitant use of Venclexta with strong CYP3A4 inducers, 10(9)/L or greater), 1.5 to 2 L orally or IV, plus consider or consider alternative treatments. additional IV hydration • Prehydration (high-tumor burden, any lymph node 10 cm or greater or absolute lymphocyte count 25 x 10(9)/L or greater & any lymph node 5 cm or greater), 1.5 to 2 L orally or IV, plus IV hydration 150 to 200 mL/ hrs as tolerated VePesid® SCLC or testicular cancer: 50-100mg/m2 PO daily BBW: Antineoplastic experienced doctor Administration: Store refrigerated (/VP-1) (Usually 2x IV dose) • May take with or without food Baseline & periodically: CBCs w/ differentials, generic available • Hazardous agent, use precautions when • Bili (dose adj. for TBili >1.5) handling 50mg • CrCl 15-50%  by 25%, <10ml/min=  by 50% Package: 2x10 caps ADE: Myelosuppression & mucositis (dose- DDI: Monitor INR if on warfarin (hypoprothrombic) MOA: Topoisomerase II limiting toxicities) low-moderate nausea, inhibitor inhibiting DNA alopecia, rash synthesis Verzenio™ Breast Cancer, Advanced or metastatic, HER2- BBW: None Administration: () negative, HR+ • 150mg po BID in combination with fulvestrant Baseline & periodically: CBC: At baseline, every 2 weeks for 500mg IM on days 1, 15, & 29 & once monthly 50, 100, 150, 200mg 150mg po BID in combination with fulvestrant 500mg IM the first 2 months, monthly for 2 months, & then as clinically thereafter Blister packs in 7-day (14 on days 1, 15, & 29 & once monthly thereafter indicated, including differential. • 200mg po BID as monotherapy tablets) 200mg po BID as monotherapy LFT’s: At baseline, every 2 weeks for the first 2 months, monthly • Avoid grapefruit/juice MOA: Inhibits cyclin- for 2 months, & then as clinically indicated ADE: Abdominal pain, decreased appetite, dependent kinases 4 Pregnancy status: In females of reproductive potential diarrhea, N/V, Anemia, Leukopenia, Neutropenia, & 6 (CDK4 & CDK6). prior to initiating therapy headache, fatigue, increased ALT/AST When these kinases are activated by cyclin D1 Signs & symptoms of thrombosis & pulmonary embolism in estrogen receptor- positive breast cancer DDI: CYP3A4 substrate (major) cells, they promote Avoid strong CYP3A4 inducer/inhibitor (if needed,  dose to retinoblastoma protein 100mg BID. For patients on 100mg BID due to adverse events, (Rb) phosphorylation, reduce dose to 50mg BID. Patients should avoid grapefruit juice). cell cycle progression, & cell proliferation

MARCH 2018 | 17 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Vesanoid® () APL (FAB M3) after failure or toxicity: BBW: Retinoic acid-APL syndrome Administration: Swallow capsules whole generic available 45mg/m2/day PO divided BID • Take total dose divided evenly twice daily Baseline & periodically: CBC, lipids, LFTs • d/c therapy 30 days after CR or after 90 days 10mg • Ensure negative pregnancy test prior to initiation ADE: Edema,  LFTs, bone pain, neuropathy, Bottle: 100 capsules • Monitor for retinoic acid syndrome visual changes, pain

MOA:  proliferation of DDI: CYP 3A4, 2C8, 2E implications RA-APL Syndrome: Severe fluid retention, APL cells swelling, chest discomfort, difficulty breathing, respiratory compromise

Votrient® () Advance RCC; Advanced STS, refractory: 800mg PO BBW: Hepatotoxicity Administration: Swallow tablet whole daily with water 200mg Baseline & periodically: LFTs, UA, thyroid function, electrolytes, • Take on empty stomach 1 hr before or 2 hrs Bottle: 120 tablets ECG, LVEF after food • Mod hepatic impair: 200mg daily MOA: mulit-TKI • Avoid grapefruit/juice • S/sx GI perforation • Maintain adequate hydration & nutrition DDI: CYP3A4 substrate (major) • Missed dose should be taken if <12 hrs • Avoid strong CYP3A4 inducer/inhibitor (if needed,  dose to ADE: HTN, fatigue, N/V/D, headache, electrolyte 400mg daily with monitoring) changes, anorexia, hair discoloration, H-F • QT prolongation additive effect syndrome,  AST/ALT

Xalkori® (crizotinib) Metastatic NSCLC, ALK+: 250mg PO BID BBW: None Administration: Swallow capsules whole • Take with or without food 200, 250mg Baseline & periodically: CBC with differential, LFT, SCr,heart • Missed dose should be taken if <6 hrs Bottle: 60 capsules rate, BP • Avoid grapefruit/juice • S/sx pulmonary MOA: TKI of ALK •  dose with ADE Grade 3/4 ADE: N/V/D, edema, rash, fatigue, myelosuppression, neuropathy,  ALT/AST, DDI: CYP3A4 substrate (major) visual disturbance • QT prolongation additive effect Xeloda® () Metastatic breast cancer, refractory; metastatic BBW: Warfarin interaction: frequently monitor INR Administration: Swallow tablet whole with water generic available colorectal cancer: 1250mg/m2 PO BID x 2 weeks, • Take within 30 minutes of food Baseline & periodically: CBC with differential, hepatic function, 150mg then 1 week off SCr, INR if concomitant warfarin ADE: Diarrhea, mild N/V, stomatitis, fatigue, Bottle: 60 tablets • Dose modify for ADE (see PI) hand-foot syndrome 500mg • CrCl 30-50 ml/min  dose by 25%; for CrCl <30 ml/min: Dose held Bottle: 120 tablets DDI: CYP2C inhibitor (strong) MOA: DNA & RNA • Monitor phenytoin carefully protein synthesis • Avoid >100% RDA folate   toxicity inhibitor

MARCH 2018 | 18 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Xtandi® (enzalutamide) Metastatic castration-resistant prostate cancer: BBW: None Administration: Swallow capsules whole 160mg PO daily Baseline & periodically: CBC with differential, LFTs, BP • Take with or without food 40mg • ADE ≥Grade 3, hold dose x1 wk or ≤Grade 2 • Avoid grapefruit/juice Bottle: 120 capsules • S/sx of seizure ADE: Fatigue, back pain, constipation, MOA: Androgen DDI: CYP2C8, CYPA3A4 substrate (major) arthralgia, diarrhea, hot flashes, UTI, edema, receptor inhibitor • Avoid CYP2C8 strong inducer/inhibitor (if needed  dose to HTN, musculoskeletal pain, dizziness 80mg daily) Zejula® () Maintenance treatment of adult patients with BBW: None Administration: recurrent epithelial ovarian, fallopian tube, or Baseline & periodically: Bone Marrow Suppression: Test • Instruct patients to take their dose of Zejula at 100mg primary peritoneal cancer who are in complete or complete blood counts weekly for the first month, monthly for the approximately the same time each day. Each Bottle: 90 capsules partial response to platinum-based chemotherapy next 11 months & periodically thereafter for clinically significant capsule should be swallowed whole. Zejula changes. Monitor blood pressure & heart rate monthly for the may be taken with or without food. Bedtime MOA: Niraparib is an Dose is 300mg taken once daily with or without food inhibitor of poly (ADP- first year & periodically administration may be a potential method ribose) polymerase ***Refer to package insert for dose reductions based on * Apprise pregnant women of the potential risk to a fetus. Advise for managing nausea. Patients should start (PARP) enzymes, PARP-1 adverse reaction*** females of reproductive potential to use effective contraception treatment with Zejula no later than 8 weeks after their most recent platinum-containing & PARP-2, which play during treatment & for 6 months after the last dose of Zejula a role in DNA repair. regiment In vitro studies have DDI: No formal drug interaction studies have been performed ADE: Thrombocytopenia, anemia, neutropenia, shown that niraparib- with Zejula. Refer to package insert for in vitro studies leukopenia, palpitations, nausea, constipation, induced cytotoxicity vomiting, fatigue, headache, dizziness, rash, may involve inhibition hypertension of PARP enzymatic activity & increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis & cell death Zelboraf® (vemurafenib) Unresectable or metastatic melanoma with BRAF BBW: None Administration: V600E: (not for wild type BRAF melanoma) 960mg PO • Take with or without food 240mg Baseline & periodically: ECG, electrolytes, LFTs, bilirubin, derm Q12 hrs • If vomiting occurs do not repeat a dose Bottle: 112, 120 tablets evaluation • Avoid grapefruit/juice FDA approved in combination with cobimetinib MOA: BRAF kinase DDI: CYP3A4 substrate (major), Pgp inhibitor, CYP1A2 inhibitor (mod) • Missed dose should be taken if <6 hrs inhibitor • QT prolongation additive effect ADE: Arthralgia, rash, alopecia, fatigue, • May  concentration of warfarin, monitor therapy photosensitivity reaction, nausea, pruritus, cSCC, uveitis Zolinza® () CTCL, progressive, persistent, or recurrent after 2 BBW: None Administration: Swallow capsules whole systemic therapies: 400mg daily • Take with food 100mg Baseline & periodically: CBC, electrolytes, SCr Bottle: 120 capsules •  dose to 300mg if intolerant or bili 1-3×ULN or AST >ULN ADE: Fatigue, N/V/D, dysgeusia, alopecia, dry mouth, myelopsuppression, chills, anorexia MOA: HDAC inhibitor DDI: Monitor INR more frequently concurrent with coumarin derivatives

MARCH 2018 | 19 Medication Dose/FDA Indication Monitoring Parameters Key Counseling Points Zydelig® () CLL, relapsed; follicular BBW: Hepatotoxicity, diarrhea/colitis, pneumonitis, intestinal perforation Administration: Swallow tablets whole, don’t crush or chew B-cell NHL, relapsed; • May take with or without food 100, 150mg Baseline & periodically: CBC & LFT q2wk x3mo, q4wk next 3mo, q 1-3 mo malignant lymphoma-small • Missed dose should be taken if <6 hrs Bottle: 60 tablets thereafter lymphocytic, relapsed: 50mg • Avoid grapefruit/juice • Dose modify for ADE (see PI) MOA: PI3Kδ kinase inhibitor PO BID • S/sx diarrhea/colitis, intestinal perforation, derm ADE: Myelosuppression, pyrexia, N/V/D, headache,  ALT/AST, rash, arthralgia DDI: CYP3A4 substrate (major), inhibitor (strong) Zykadia® () Metastatic NSCLC, ALK+, BBW: None Administration: Swallow capsules whole intolerant to crizotinib: • Take on empty stomach 2 hrs before or 2 hrs after food 150mg Baseline & periodically: CBC, Scr, LFT, cardiac 750mg PO daily • If vomiting occurs do not repeat a dose Bottle: 70 capsules • S/sx GI & pulmonary toxicity • Dose modify for ADE (see PI) ADE: Fatigue, N/V/D, constipation,  appetite, neuropathy, MOA: TKI of ALK  ALT/AST, visual disturbance DDI: CYP3A4 substrate (major), inhibitor (mod) • Avoid strong CYP3A4 inducer/inhibitor (if needed,  dose by 1/3) • QT prolongation additive effect Zytiga® (abiraterone) Metastatic castration-resis- BBW: None Administration: tant prostate cancer (with • Take on empty stomach 250mg Baseline & periodically: ALT/AST, bili q2wks x 3mo, then monthly prednisone 5mg PO BID): Bottle:120 tablets thereafter; BP, edema monthly ADE: Fatigue, edema, mineralocorticoid excess, HTN, joint 1000mg PO daily • S/sx of mineralocorticoid insufficiency swelling, myalgia MOA: CYP17 inhibitor DDI: CYP3A4 substrate (major), CYP2C9 (mod) inhibitor

The risk of live vaccine-induced adverse reactions may be increased by co-administration of medications on this list

DEFINITIONS • CBC w/ differentials: WBC, ANC, H/H, Plts • Myelosuppression: including but not limited to neutropenia, thrombocytopenia, anemia • CYP450 metabolism: A key pathway for & from the body

ABBREVIATION GLOSSARY ACE = Angiotensin-Converting Enzyme CML = Chronic Myelogenous Leukemia ITP = Idiopathic Thrombocytopenic Purpura PIT = Plasma Iron Turnover ADE = Adverse Drug Event CTCL = Cutaneous T-Cell Lymphoma LVEF = Left Ventricular Ejection Fraction pNET = Pancreatic Neuroendocrine Tumor ALL = Acute Lymphocytic Leukemia CYP = Children & Young People MCL = Mantle Cell Lymphoma RCC = Renal Cell Carcinoma (Ph+ALL=-Positive ALL) DDI = Drug-Drug Interaction MDS = Myelodysplastic Syndrome SEGA = Subependymal Giant Cell Astrocytoma AML = Acute Myelogenous Leukemia DVT = Deep Vein Thrombosis MM = Multiple Myeloma SCLC = Small Cell Lung Cancer ANC = Absolute Neutrophil Count GIST = Gastrointestinal Stromal Tumors MOA = Mechanism of Action SCr = Serum Creatinine APL = Acute Promyelocytic Leukemia HCC = Hepatocellular Carcinoma NHL = Non-Hodgkin’s Lymphoma SLL = Small Lymphocytic Lymphoma BBW = Black Box Warning HER = Human Epidermal Growth Factor Receptor NSCLC = Non-Small Cell Lung Cancer STS = Soft Tissue Sarcoma CBC = Complete Blood Count H/H = Hemoglobin & Hematocrit mCRPC = Metastatic Castrate Resistant Prostate Cancer XRT = Radiation Therapy CEL = Chronic Eosinophilic Leukemia HL = Hodgkin’s Lymphoma mTOR = Mammalian Target of Rapamycin WBC = White Blood Cell CLL = Chronic Lymphocytic Leukemia HR = Hormone Receptor N/V/D = Nausea/Vomiting/Diarrhea WM = Waldenstrom Macroglobulenmia CMF = Cytoxan, Methotrexate, HTN = Hypertension PE = Pulmonary Embolism

REFERENCE: Package insert of individual medications & NCCN guidelines DISCLAIMER: This is a tool to assist with summarizing important information on the listed oral therapies for cancer treatments including some supportive care medications. This is meant to be a supplement to other drug information tools & not to replace medical advice. This is a summary only & is not a comprehensive list of ADRs, drug interactions or dosing. Indications in italics represent FDA-approved indication & dosing only, many other dosing strategies exist in clinical trials.

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