Written by Julianne Orr, PharmD, Indiana University Health Simon Cancer Center
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Description: Olanzapine is an FDA approved atypical antipsychotic that blocks multiple neuronal receptors involved in nausea/vomiting pathways.1 Olanzapine has been studied for breakthrough2 chemotherapy induced nausea and vomiting (CINV) as well as prophylaxis of highly and moderately emetogenic regimens.3,4,5 Additionally, olanzapine has been studied in replacement of NK1 receptor antagonists (ex. aprepitant) as well as in addition to standard triplet prophylaxis regimens which include NK1 receptor antagonists.4,5,6,7 The results of these trials suggest olanzapine is at least as effective as aprepitant and combination olanzapine with aprepitant has led to promising reports of CINV control. Based on the results from these various studies, national guidelines (National Comprehensive Cancer Network (NCCN) guideline on Antiemesis) recommend olanzapine 5-10 mg PO daily as an option within prophylaxis regimens for HEC and MEC chemotherapy regimens. Clinically, lower doses of 5 mg and 2.5 mg have been used in patients where sedation may be a concern.

Background: Nausea and vomiting remains a common and difficult to manage side effect of chemotherapy despite prophylaxis. These symptoms can often lead to a decreased quality of life, dehydration, and malnutrition. Historically, patients have been prescribed dexamethasone along with a 5HT3 antagonist (ex. ondansetron) to prevent nausea and vomiting. For patients receiving highly emetogenic chemotherapy (HEC) and often moderately emetogenic chemotherapy (MEC), a NK1 receptor antagonist, such as fosaprepitant, is added to the antiemesis regimen. Despite the use of these dual and triple agent preventative strategies as recommended by national guidelines, nausea and vomiting remains a significant complication of chemotherapy.

PQI Process: Upon receipt of an order for a HEC or MEC chemotherapy regimen:

  • Screen for appropriate antiemesis medications:
    • Dexamethasone
    • 5HT3 Antagonist
    • NK1 Receptor Antagonist
    • +/- Olanzapine
  • If olanzapine if not initially included in the orders, consider recommending the addition of olanzapine 5-10 mg by mouth daily days 1 through 4 of chemotherapy
  • If the patient is elderly or over-sedated, consider using a lower dose upon initiation8
  • Use caution when prescribing olanzapine with metoclopramide or haloperidol, as this combination may lead to a higher risk of extrapyramidal symptoms

Patient Centered Activities:

  • Patient Compliance
    • Encourage patients to take this medication each day, as prescribed
    • This is particularly important for any patients receiving HEC or MEC regimens in the outpatient setting
  • Patient Education
    • Explain CINV and the different medications that are being prescribed to help prevent nausea and vomiting
    • Outline the reason patients take olanzapine on days 1 through 4 only*
    • Olanzapine may be administered without regard to meals
    • Review common side effects with the patient
      • Drowsiness
      • Headache
      • Disturbed sleep
      • Increased appetite
      • Constipation
      • Extrapyramidal reaction
      • Orthostatic hypotension
  • Drowsiness will potentially diminish over time

*Some multiple day HEC regimens may call for more than 4 days of olanzapine

 References:

  1. Tan L, Liu J, Liu X, et al. Clinical research of olanzapine for prevention of chemotherapy induced nausea and vomiting. J Exp Clin Cancer Res 2009; 28: 1-7.
  2. Navari RM, Nagy CK, Gray SE. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Support Care Cancer 2013; 21: 1655-63.
  3. Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy induced nausea and vomiting: a randomized phase 3 trial. J Support Oncol 2011; 9: 188-95.
  4. Mizukami N, Yamauchi, Koike K, et al. Olanzapine for the prevention of chemotherapy induced nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy: a randomized, double blinded, placebo controlled study. J Pain Symptom Manage 2014; 47: 542-50.
  5. Abe M, Hirashima Y, Kasamatsu Y, et al. Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin based chemotherapy in gynecological cancer. Support Care Cancer. E-pub ahead of print: 01 July 2015. DOI: 10.1007/s00520-015-2829-z
  6. Passik SD, Navari RM, Jung S, et al. Phase I trial of olanzapine for the prevention of delayed emesis in cancer patients: A Hoosier Oncology Group study. Cancer Investigations 2004; 22(3): 383-388.
  7. Navari A phase II trial of olanzapine, dexamethasone,and palonosetron for the prevention of chemotherapy induced nausea and vomiting: a Hoosier oncology group study. Support Care Cancer 2007; 15:1285–1291
  8. Hashimoto H, Yanai T, Nagashima K, et al. A double blind randomized phase II study of 10 versus 5mg olanzapine for emesis induced by highly emetogenic chemotherapy with cisplatin [abstract]. J Clin Oncol 2016; 34: Abstr 10111.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional.  This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented.  NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
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Written by: Kirollos Hanna, PharmD, BCPS, BCOP, University of Minnesota Medical Center & Mayo Clinic
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Description: Ixazomib is an oral proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma after at least one prior therapy. This PQI highlights the management, safety, and efficacy of ixazomib.

Background: Multiple Myeloma (MM) is an incurable disease resulting from malignant plasma cells. MM is rare in younger patients (median age at diagnosis: 72 year). Patients with MM often experience “CRAB” symptoms defined as: hypercalcemia, renal dysfunction, anemia, and bone lesions. Patients generally relapse multiple times and are treated with multi-drug regimens, preferably triplets; common drugs include proteasome inhibitors (PI), immunomodulatory drugs (IMiD), monoclonal antibodies, and steroids. Select patients may be eligible for an autologous stem cell transplant depending on risk factors associated with disease.

Ixazomib is an oral PI that may be used in the relapsed/refractory (r/r) setting in combination with lenalidomide/dexamethasone. Off-label considerations include utilizing ixazomib in the front-line setting regardless of transplant eligibility in combination with lenalidomide and dexamethasone or in the r/r setting with pomalidomide/dexamethasone or with dexamethasone alone. Ixazomib provides an all oral treatment option in patients with MM. In a clinical phase 1/2 trial, front-line ixazomib/lenalidomide/dexamethasone was associated with a very good partial response in 58% of patients. In the r/r setting, ixazomib-containing regimens demonstrated an improvement in response rates and/or progression free survival. The most common side effects associated with ixazomib in ≥20% of patients include:  diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, and back pain.

PQI Process:

Upon receipt of prescription for ixazomib:

  • Prior to therapy initiation, obtain baseline labs CBC/diff, CMP, and relevant MM labs to assess treatment response
    • Select MM labs: lactate dehydrogenase (LDH), beta-2 microglobulin, protein analyses, bone marrow aspirate, and cytogenetic studies
    • Platelet and neutrophils nadir occurs on days 14-21 of each cycle. Labs should be monitored monthly but may be more frequent with the first three cycles
  • Ixazomib should be dose reduced for severe renal impairment (or ESRD requiring dialysis), or moderate and severe hepatic impairment at baseline. If toxicity occurs during treatment, ixazomib should be withheld and dose reduced to the next lower dose if attributed to therapy
    • Baseline CrCl <30 ml/min or ESRD requiring dialysis: 3 mg PO daily on days 1, 8, 15 every 28 days
    • Baseline total bilirubin >1.5x ULN: 3 mg PO daily on days 1, 8, 15 every 28 days
  • Ixazomib is metabolized by multiple CYP enzymes and non-CYP proteins. Avoid concomitant administration of ixazomib with strong CYP3A inducers
  • Ixazomib is available as 4 mg, 3 mg, and 2.3 mg allowing for 25% incremental dose adjustments
Alternating Dose Reductions with Lenalidomide
ReactionPlateletsNeutrophilsRash
Parameter< 30,000/mm3< 500/mm3Grade 2 or 3
First Occurrence·       Withhold ixazomib and lenalidomide

·       Upon recovery, resume both but reduce lenalidomide at next lower dose and continue ixazomib at most recent dose

Subsequent Occurrence·       Withhold ixazomib and lenalidomide

·       Upon recovery, resume both but reduce ixazomib at next lower dose and continue lenalidomide at most recent dose

      *Continue alternating dose reductions for additional occurrences and review resources for additional information on managing other adverse events

  • Monitor for peripheral neuropathy
  • Ensure patients receiving PI therapies are also receiving antiviral therapy to prevent against herpes zoster reactivation. Patients on IMiDs (lenalidomide or pomalidomide) should be on aspirin for DVT/PE prophylaxis or therapeutic anticoagulation based on clotting history and risk factors
  • Patients receiving ixazomib are likely to receive IMiD therapy. Ensure REMS requirements are met with IMiD therapy for a timely initiation of treatment and to keep cycles on track
  • It is highly recommended that a therapy calendar be utilized for all patients with MM due to complexity of therapies, older age of patients, and the potential lack of a medically-integrated pharmacy (ex. triplet-drug regimens may arrive from different sources). See supplemental index for example

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) sheet and therapy calendar to all patients
  • Ensure patients understand the dosing schedule. Ixazomib is administered on days 1, 8 and 15 every 28 days. IMiDs and steroids will have a different schedule
  • Advise patients that a missed dose should not be taken with 3 days of the next scheduled dose. If vomiting occurs, do not repeat dose
    • Steroid component of regimen may be taken prior to ixazomib to help with nausea control but steroids should be taken with food. Ixazomib should be taken on an empty stomach (at least 1 hour before or 2 hours after a meal or snack
  • Financial resources are available through Takeda Oncology

Supplemental Information

Example 28-Day Dosing Calendar (ixazomib, lenalidomide, dexamethasone)
 Week 1Week 2Week 3Week 4
 Day 1Days 2-7Day 8Days 9-14Day 15Days 16-21Day 22Days 23-28
Ixazomib     
LenalidomideTake every day on days 1-21  
Dexamethasone    

References:

  1. Ninlaro® (ixazomib) [prescribing information]. Cambridge, MA: Takeda Pharmaceutical Company Limited; February 2020.
  2. SEER Stat Fact Sheets: Myeloma. Available at http://seer.cancer.gov/statfacts/html/mulmy.html.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional. This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented. NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
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Written by: Jeremiah Moore, PharmD, University of Rochester Medical Center

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This PQI will provide background on the novel medication selinexor for patients with multiple myeloma (MM) who have received at least one prior therapy, relapsed, refractory multiple myeloma (RR-MM), and relapsed, refractory diffuse large b-cell lymphoma (RR-DLBCL) and discuss effective practices to maximize the use of selinexor therapy.
Continue reading Selinexor (Xpovio®) Patient Management

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