Written by: Kirollos S. Hanna, PharmD, BCPS, BCOP – University of Minnesota Medical Center & Mayo Clinic
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Description: This PQI will discuss optimal prevention and control of chemotherapy induced nausea and vomiting (CINV) which has been associated with improved adherence to oncolytic therapy.

Background: CINV remains one of the most debilitating toxicities associated with cancer therapy leading to poor compliance with further treatment, dehydration, metabolic imbalances, degeneration of self-care and functional inability, anorexia and decline in performance status.1,6 The emetogenic potential of the regimen should be coupled with other risk factors such as age, sex, history of alcohol consumption, combined chemoradiation, previous tolerability of chemotherapy and anatomical location of tumor (ex. head and neck) to select an optimal antiemetic regimen. As much as 80% of CINV can be prevented with appropriate administration of antiemetics.6

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

  • Assess the antiemetic potential of therapy, patient risk factors, and disease state
    • High emetogenicity: NK1R antagonists + 5-HT3 receptor antagonists + dexamethasone ± olanzapine
    • Moderate emetogenicity: 5-HT3 receptor antagonists + dexamethasone ± NK1R antagonists
    • Low emetogenicity: 5-HT3-receptor antagonist or dexamethasone or phenothiazine or metoclopramide
  • Evaluate drug-drug and drug-patient interactions to minimize adverse drug reactions (ex. benzodiazepine and phenothiazine dosing in elderly, olanzapine interactions (see Olanzapine (Zyprexa®) In Chemotherapy Induced Nausea and Vomiting PQI) dexamethasone dosing with fosaprepitant, etc.
  • Ensure take home antiemetics have been prescribed and will be in possession of the patient once home (may require coordination with caretakers and dispensing pharmacy)
  • Follow up with patients (who have moderate to high emetogenicity on day 2/3 of cycle 1) upon return for cycle 2 of chemotherapy and determine future plans as clinically appropriate:
    • Assess for adequate management and prophylaxis
    • Consider benzodiazepines for anticipatory nausea/vomiting
    • Determine the need to modify antiemetic regimen based on incidence of acute, delayed and breakthrough events

Patient Centered Activities:

  • Consider use of NCODA’s CINV Assessment Tool to assist in patient discussion
  • Provide Oral Chemotherapy Education (OCE) Supplemental Sheet
  • Provide antiemetic counseling to patients and caretakers with written or graphic visual aids to easily guide drug selection at home. This should include:
    • When to initiate take home 5-HT3 receptor antagonists if a long acting agent has been administered with chemotherapy
    • Prioritizing/sequencing different agents of home antiemetic regimen for adequate control of CINV
    • Ensure a clear understanding of scheduled antiemetics such as dexamethasone or olanzapine
    • Have patient verbalize how they plan to utilize their antiemetics at home
    • Review common side effects with the patient (sedation, headaches, constipations, extrapyramidal symptoms, etc.)
    • Inform patients to drink plenty of fluids and avoid/minimize alcoholic beverages
    • Ensure patients have contact information for the clinic and know when to contact the clinic

Drug therapy*: See Supplemental Information for dosing

  • 5-HT3 receptor antagonists: ondansetron, granisetron, dolasetron, palonosetron
  • NK1R antagonists**: aprepitant, fosaprepitant, rolapitant
  • Glucocorticoids: dexamethasone
  • Benzodiazepines: lorazepam
  • Dopaminergic agents: prochlorperazine, olanzapine, chlorpromazine
  • Combinations: netupitant/palonosetron, fosnetupitant/palonosetron
  • Other: metoclopramide, scopolamine, promethazine, meclizine, dronabinol, olanzapine

*Most commonly utilized agents, not inclusive of all agents

**Additional agents available as combination product

References:

  1. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. https://nccn.org/professionals/physician_gls/pdf/antiemesis.pdf (Accessed on August 11, 2018).
  2. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2017; 35:3240.
  3. Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy- induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 2016; 27:v119.
  4. Fujii H, Iihara H, Ishihara M, et al. Improvement of adherence to guidelines for antiemetic medication enhances emetic control in patients with colorectal cancer receiving chemotherapy of moderate emetic risk. Anticancer Res 2013;33:5549–56.
  5. Affronti ML, Schneider SM, Herndon JE 2nd., et al. Adherence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice. Support Care Cancer 2014;22:1897–905.
  6. Tageja N, Groninger H. Chemotherapy-induced nausea and vomiting: an overview and comparison of three consensus guidelines. Postgrad Med J. 2016;92(1083):34-40.

Supplemental Information:

Select Therapies for Chemotherapy-Induced Nausea and Vomiting Prevention

Risk CategoryAgentDosing on Day 1Dosing on subsequent days
High Emetic Risk (>90%)NK1R antagonist
(one of the following)
Aprepitant125 mg PO80 mg PO Days 2 & 3
Fosaprepitant150 mg IV
Rolapitant*180 mg PO or 166.5 mg IV
PLUS
5-HT3 antagonist
(one of the following)
Palonosetron0.5 mg PO or 0.25 mg IV
Granisetron2 mg PO or 1 mg IV
Ondansetron8 mg PO or IV
PLUS
Dexamethasone12 – 20 mg PO or IV8 mg PO or IV daily Days 2 to 4

(chemotherapy dependent)

PLUS
Olanzapine5 – 10 mg PO5 – 10 mg PO daily Days 2 to 4
OR
Netupitant + palonosetron or Fosnetupitant +

palonosetron

Once
PLUS
Dexamethasone12 – 20 mg PO or IV8 mg PO or IV daily Days 2 to 4

(chemotherapy dependent)

PLUS
Olanzapine5 – 10 mg PO5 – 10 mg PO daily Days 2 to 4

*Post marketing data show anaphylaxis, anaphylactic shock and other serious hypersensitivity reactions

Moderate Emetic Risk (10 to 30%)5-HT3 antagonist (one from high risk chart)
PLUS
Dexamethasone8 – 20 mg PO or IV8 mg PO or IV daily Days 2 to 4

(chemotherapy dependent)

MAY CONSIDER IF CARBOPLATIN-BASED OR HIGH-RISK POTENTIAL
NK1R antagonist (one from high risk chart)
Olanzapine5 – 10 mg PO5 – 10 mg PO daily Days 2 to 4
Low Emetic Risk (10%)Dexamethasone  4-8 mg PO or IV
OR
5-HT3 antagonist (one from high risk chart)
OR
Phenothiazine-type drug

All patients should have supportive antiemetic therapy at home
Select patients with minimal risk for CINV may not require any treatment

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: Natasha Khrystolubova, RPh, BCOP, Florida Cancer Specialists and Jody Agena, PharmD, Virginia Cancer Specialists
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This PQI is intended to address effective practices for the management of alpelisib induced hyperglycemia by focusing on a multidisciplinary approach.

Background: Alpelisib (in combination with fulvestrant) is indicated for the treatment of HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer in males and postmenopausal females following progression on or after an endocrine-based regimen. PIK3CA mutations are present in up to 40% of HR-positive, HER2-negative, primary and metastatic breast cancers.   Hyperglycemia is an expected on-target effect of PI3K inhibition. The phase 3 SOLAR-1 trial evaluated the combination of alpelisib and fulvestrant versus fulvestrant alone in patients with HR-positive, PIK3CA-mutated, advanced breast cancer who  had received prior endocrine therapy. Hyperglycemia was reported in 63.7% of patients treated with alpelisib including 33% with Grade 3 (FPG>250- 500 mg/dL) and 3.9% with Grade 4 (Fasting Blood Glucose (FBG) >500 mg/dL) events. Increases in fasting blood glucose and hemoglobin A1C were more pronounced in patients who were diabetic or prediabetic at baseline, with 83% and 74%of these patients experiencing hyperglycemia when treated with alpelisib, respectively.

PQI Process:

Upon receipt of alpelisib prescription:

  • Verify recommended starting dose for alpelisib in combination with fulvestrant: 300 mg (2×150 mg tabs) by mouth once daily with food
  • Evaluate patient medical history of diabetes and other risk factors that may contribute to treatment induced hyperglycemia (high BMI, age, concurrent medications)
  • Ensure baseline labs including HbA1C and FBG 6
    • Repeat weekly for two weeks, then monthly, and as needed
    • If blood glucose is elevated it is recommended to optimize blood glucose prior to initiation
    • If hyperglycemia develops, discuss initiation of metformin dosing with the provider as well as dose interruption and reductions (see supplemental information)

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) sheet
  • Provide and discuss with the patient a Patient Pocket-size Card from the manufacturer for educational purposes for other healthcare providers caring for patient
  • Consider developing a dietitian-based recommendations/handout for patients with hyperglycemia3,4
  • Recommend a use of glucometer for patients who cannot travel to weekly lab appointments

Supplemental Information:

Metformin Dosing Guidance from SOLAR 1 Trial

  1. Initiate metformin at 500 mg once a day with food
  2. Increase to 500 mg twice a day if tolerated
  3. Increase to 500 mg in am and 1000 mg in pm if tolerated
  4. Increase to 1000 mg twice a day if needed and tolerated. Do not exceed 2000 mg per day
    *Evaluate a patient for renal and hepatic impairment prior to the start of metformin
    **In SOLAR-1, 87% of patients who developed hyperglycemia were initially started on metformin followed by insulin sensitizers and DPP-4 inhibitors, in accordance with ADA recommendation

Dose Modifications: Based on Monitoring of Fasting Plasma Glucose (FPG)

  • Grade 1 (FPG > ULN – 160 mg/dL): No dose adjustment; Initiate metformin
  • Grade 2 (FPG > 160 – 250 mg/dL): Intensify antidiabetic therapy. Reduce by 1 level if no resolution of FPG ≤ 160 within 21 Days
  • Grade 3 (FPG > 250 – 500 mg/dL): Suspend alpelisib therapy. Intensify antidiabetic therapy and consider IV hydration and/or electrolyte replacement. Reduce by 1 level if no resolution of FPG ≤ 160 within 5 Days. Discontinue treatment if no resolution of FPG ≤ 160 within 21 Days
  • Grade 4 (FPG > 500 mg/dL): Suspend alpelisib therapy. Intensify antidiabetic therapy and consider IV hydration and/or electrolyte replacement. If FPG decreases to ≤ 500 mg/dL after 24 hours, follow Grade 3 guidelines. If no resolution after 24 hours, discontinue therapy 

Alpelisib Dose Adjustment Levels:

  • Recommended starting dose: 300 mg (2×150) by mouth once daily with food
  • If 300 mg reduce to 250 mg once daily with food
  • If 250 mg reduce to 200 mg once daily with food

Proposed Enhancements in EMR Protocol for Alpelisib – Collaborate with your providers

  1. When possible, add a baseline 7-day window in EMR regimen to alert the prescriber to schedule Fasting Blood Glucose and HbA1C tests
  2. Consider providing the patient with the prescription for a home glucometer to be purchased through retail drug store. The clinic can arrange teaching of a patient and/or caregiver on the use of glucometer and strips. May utilize Telehealth services. The new ICD-10 Code R09.65 was adopted in October of 2019 to cover Drug and Chemical induced diabetes mellitus with hyperglycemia (Ref. ICD10Data.com) (To note: Recommend prescribing generic glucometer and strips to ensure better insurance coverage)
  3. Add a dietitian consult at the start of the treatment if service is available or supply the patient with Internally developed patient handout discussing “Diet for Hyperglycemia”
  4. Add endocrinology referral note to alpelisib regimen which can be initiated at the point of need

Reference:

  1. PIQRAY® Package Insert. (n.d.). Retrieved April 07, 2021, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212526s000lbl.pdf.
  2. Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-Kinase, Growth Disorders, and cancer. N. ENgl J Med. 2018;379(21):2052-2062).
  3. Academy of Nutrition and Dietetics. Carbohydrate Counting for People with Diabetes.
  4. Link -https://www.eatright.org/health/diseases-and-conditions/diabetes/carbohydrates-part-of-a-healthful-diabetes-diet.
  5. Nature. 2018 Aug;560(7719):499-503. doi: 10.1038/s41586-018-0343-4. Epub 2018 Jul 4. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.
  6. Alpelisib Patient Management Guide for Clinicians. Novartis.
  7. Fabrice A, et.al. Alpelisib for PIK3CA-Mutated, Hormone Receptor -positive Advance Breast Cancer. N. ENg. J Med. 2019; 380:1929-1940.
  8. Schwartzberg L, Vidal G. Targeting PIK3CA Alterations in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-negative Advanced Breast Cancer.
  9. Early intervention for and management of alpelisib (ALP)-induced hyperglycemia: case studies from the Phase III SOLAR trial. Mayer,I et al. Poster presentation.

 

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: Derek Gyori, PharmD and Julianne Orr, PharmD
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Description: Abemaciclib is FDA-approved in combination with an aromatase inhibitor, fulvestrant, and as a single agent in metastatic breast cancer. This PQI will address effective practices for the management of abemaciclib associated diarrhea, a common toxicity with this therapy.

Background: Abemaciclib is an FDA approved Cyclin Dependent Kinase (CDK) 4 and 6 Inhibitor approved for use in hormone receptor (HR) positive and human epidermal growth factor 2 (HER2) negative metastatic breast cancer.1-3 Although the mechanism of abemaciclib-induced diarrhea is not fully understood, management of diet along with drug therapy remains the standard of care in patients with abemaciclib-associated diarrhea. In clinical trials, abemaciclib associated diarrhea most frequently occurred in the first cycle of treatment, with a median onset between 6 and 8 days. Diarrhea was often managed in the clinical trials using anti-diarrheal agents sparing the need for dosage reductions or interruptions in the majority of the population.1,2,3

PQI process: Upon receipt of abemaciclib prescription:

  • Screen for appropriate antidiarrheal medication:4,5,6
    • Loperamide (OTC)
      • Take two caplets (4 mg) followed by one caplet (2 mg) every four hours until diarrhea-free for 12 hours
      • Do not exceed 8 caplets (16 mg) per day
        • If diarrhea does not improve during the first 24 hours of taking loperamide, the patient should contact their health care provider
      • May take up to 12 caplets per day for chemotherapy-induced diarrhea under medical supervision
        • May schedule loperamide around the clock before adding another agent
    • Diphenoxylate/atropine (Rx)
      • Take 2 tablets (5 mg) three to four times daily (max of 8 tablets per day)
      • May alternate with loperamide to achieve around the clock coverage
      • Common side effects: dry skin and mucous membranes, tachycardia, urinary retention, hyperthermia
        • Although uncommon, respiratory depression can occur due to the diphenoxylate
    • Tincture of opium (Rx)
      • Deodorized tincture of opium 10 mg/mL of morphine – Take 0.6 mL (6 mg) in water every 3- 4 hours
      • Common side effects: CNS depression, drowsiness, urinary retention, constipation, nausea, headache
        • Although uncommon, respiratory depression can occur
  • Follow-up with patient by phone after the first week of therapy
    • If severe diarrhea (≥ 7 stools per day), may require inpatient admission for fluid and electrolyte administration

Abemaciclib Dose Modifications

CTCAE Grade of diarrheaAbemaciclib dose modification
Grade 1No dose modification required
Grade 2If toxicity dose not resolve within 24 hours to

≤Grade 1, suspend dose until resolution. No dose

reduction required

Grade 2 that persists or recurs after resuming the

same dose

Suspend dose until toxicity resolves to ≤Grade 1.

Resume at next lower dose

Grade 3 or 4 or requires hospitalizationSuspend dose until toxicity resolves to ≤Grade 1.

Resume at next lower dose

 

Patient Centered Activities:

  • Patient Education
    • Provide Oncology Chemotherapy Education (OCE) sheet for abemaciclib and Oncology Chemotherapy Education Supplemental Sheet for diarrhea
    • Explain abemaciclib associated diarrhea’s median time to onset in the trials was 6-8 days
    • Instruct patient to call their provider at the first sign of diarrhea
    • Encourage patients to take loperamide at the onset of a loose, watery stool and every two hours until resolution of diarrhea
      • If diarrhea hasn’t improved within 24 hours with treatment, consider reducing dose
    • Diet Recommendations:4,5,6
      • Avoid greasy, spicy, or fried food
      • Avoid milk, caffeine, alcohol, and high fiber vegetables
      • Eat small frequent meals
      • B.R.A.T Diet – Bananas, Rice, Apple Sauce, Toast
      • Drink three or more liters of clear fluid per day
        • Water, clear liquids, soup, sports drinks

References:

  1. Dickler MN, Tolaney SM, Rugo HS et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer. Clin Cancer Res 2017; 23(17): 5218-5224.
  2. Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine J Clin Oncol 2017; 35:2875-2884.
  3. Goetz, MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017; 35:3638-3646.
  4. National Comprehensive Cancer Network. Palliative Care (Version 1.2018). https://nccn.org/professionals/physician_gls/pdf/palliative.pdf. Accessed May 16, 2018.
  5. Rangwala F, Zafar SY, Abernathy AP. Gastrointestinal symptoms in cancer patients with advanced disease: new methodologies, insights, and a proposed approach. Curr Opin Support Palliat Care 2012; 6:69-76.
  6. Richardson G, Dobish R. Chemotherapy induced diarrhea. J Oncol Pharm Practice 2007; 13:181-198.
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: Andrea Clarke, PharmD and Becky Fahrenbruch, PharmD, BCOP
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Description: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that can occur with chemotherapeutics, including certain oral chemotherapy agents. Appropriate patient education and monitoring may assist with identifying early signs of peripheral neuropathy, but no agents have demonstrated efficacy in preventing CIPN. When patients experience chronic peripheral neuropathy not relieved by dose reductions or interruptions, further treatment may be warranted. Currently, the strongest evidence supports the use of duloxetine as treatment for CIPN. Other agents have demonstrated mixed results but may be useful for individual patients.

Background: CIPN can greatly affect a patient’s quality of life and influence their cancer treatment regimen. Definitive algorithms for the management of CIPN are currently lacking as most trials on prevention and/or treatment have failed to produce clinically significant results. The presentation of CIPN varies depending on the mechanism of the chemotherapy agent, which could have implications on treatment choice.1  The American Society of Clinical Oncology 2020 CIPN guidelines recommend only duloxetine for treatment; the European Society for Medical Oncology and the National Comprehensive Cancer Network extrapolate treatments for non-cancer peripheral neuropathy to CIPN in their cancer pain guidelines.2-4 Due to the paucity of evidence specific to CIPN and no evidence specific to oral CIPN, drug therapy is frequently based on trial and error with individual patients.

 

Oral chemotherapy agents that commonly cause peripheral neuropathy (incidence >10%)5

Brigatinib, capecitabine, crizotinib, encorafenib, imatinib, ivosidenib, ixazomib, lenalidomide, lorlatinib, pomalidomide, ponatinib, sorafenib, thalidomide, tretinoin, vemurafenib

Intravenous agents that commonly cause peripheral neuropathy (incidence >10%)5

Cisplatin, carboplatin, oxaliplatin, paclitaxel, docetaxel, cabazitaxel, vincristine, vinblastine, etoposide, carfilzomib

PQI Process: Upon receipt of an order for an oral chemotherapeutic with a known peripheral neuropathy side effect:

  • Assess for baseline peripheral neuropathy prior to initiation of oral chemotherapy agent
  • Patient education (refer to Patient Centered Activities)
  • Regularly assess patient for development of peripheral neuropathy throughout therapy
  • If peripheral neuropathy develops, ensure provider visit to address CIPN occurs
  • Recommend appropriate dose interruptions or modifications as indicated
  • If further intervention is necessary, recommend drug therapy options for the treatment of CIPN based on patient-specific factors such as comorbidities and drug interactions
  • Assess patient for change in symptoms within first 2 weeks of starting CIPN treatment

Patient Centered Activities:

  • Counsel patient on peripheral neuropathy
    • Signs and symptoms (discomfort or pain, numbness, tingling, burning, weakness, impaired hot/cold sensory perception in hands or feet)
    • Potential timeline for onset if known
    • Management options if neuropathy develops
  • For initiation of CIPN treatment, counsel patient on new therapy (see supplemental information)
    • Titration schedule
    • Side effects of new treatment: drowsiness, fatigue, nausea, sexual dysfunction
    • Risks of abrupt discontinuation
  • Ensure patients have contact information for the clinic and know when to call in

Patient-specific considerations:

  • Other causes of peripheral neuropathy
    • Diabetes6,7
      • If potential diabetic component to neuropathy, exploration of treatment options shown to be efficacious for diabetic neuropathy should be tried
      • glycemic control, pregabalin, tricyclic antidepressants, etc
    • Vitamin B12 deficiency
    • Vasculitis
  • Comorbidities: Renal function, cardiac function
  • Drug interactions

Non-pharmacologic interventions8

  • Consider integration of non-pharmacologic interventions into treatment plan such as using assistive devices, wearing hand/foot protection (oven mitts, gloves, socks/shoes), checking temperature of shower/bath before use with thermometer, and inspecting skin for cuts, abrasions, and burns that may not be felt daily

References:

  1. Majithia N, Loprinzi CL, and TJ Smith. New practical approaches to chemotherapy-induced neuropathic pain: prevention, assessment, and treatment. Oncology Williston Park. 2016;30(11): 1020-9.
  2. Hershman DL, Lacchetti C, Dworkin RH, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2020 Jun 214;38(28):3325-48.
  3. Fallon M, Giusti R, Aieli F, et al. Management of cancer pain in adult patients: ESMO clinical practice guidelines. Ann of Oncol. 2018;29(S4):iv166-iv191.
  4. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology: adult cancer pain v2.2021. https://www.nccn.org/professionals/physician_gls/pdf/pain.pdf.
  5. Lexicomp Online: Lexi-Drugs. Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2019.
  6. Bril V, England J, Franklin GM, Backonja M, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758.
  7. Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28(4):956.
  8. Hickey M and Newton S. Telephone triage for oncology nurses (2nd ed). Pittsburgh, PA: Oncology Nursing Society. 2012;203-205.
  9. Ogle NR and SR Akkerman. Guidance for the discontinuation or switching of antidepressant therapies in adults. J Pharm Pract. 2013;26:389–96.
  10. Smith EM, Pang H, Cirrincione C, et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA. 2013;309:1359-67.

Supplemental Information

Drug Therapy Options for CIPN Treatment-4, 9

  • Duloxetine10
    • Initiate at 30 mg by mouth daily x 1 week, then increase to 60 mg daily
    • Taper over 1-2 weeks if discontinuing therapy
    • Avoid use in severe renal insufficiency (CrCl < 30mL/min) and hepatic impairment
  • Alternatives – Previously used in practice, but no longer recommended by ASCO/NCCN
    • Gabapentin
      • Initiate at 100 to 300 mg by mouth nightly, then divided 2-3 times per day as dose increases to maximum dose of 3600 mg/day
      • Titrate every 3 days to effect with slower titration for the elderly or frail
      • Adjust for renal insufficiency (CrCl < 60 mL/minute)
      • Taper over at least 1 week if discontinuing therapy
    • Pregabalin
      • Initiate at 25 mg by mouth nightly, then divided 2-3 times per day as dose increases to maximum dose of 600 mg/day
      • Titrate every 3 days to effect with slower titration for the elderly or frail
      • Adjust for renal insufficiency (CrCl < 60 mL/minute)
      • Taper over at least 1 week if discontinuing therapy
    • Venlafaxine
      • Initiate at 37.5 mg by mouth daily
      • Titrate every week to effect up to maximum 225 mg daily
      • Adjust for renal insufficiency (CrCl < 90 mL/minute for extended release and ≤ 70 mL/minute for immediate release)
      • Adjust for hepatic insufficiency (Child-Pugh class A-C)
      • Taper by approximately 75 mg every 4 days when discontinuing therapy
    • Tricyclic antidepressants
      • Initiate at low dose and increase every 5 to 7 days if tolerated
      • Use with caution in patients with conduction abnormalities
      • Taper over approximately 4 weeks if discontinuing therapy
    • Opioids in combination with adjuvant therapy
    • Topical agents
      • Baclofen, amitriptyline, and ketamine
      • Gabapentin®
      • Low-concentration menthol
      • Lidocaine
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: Julianna Darling, PharmD, Indiana University Health Simon Cancer Center

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Positive Quality Intervention: Fostamatinib (Tavalisse) use in Chronic Immune Thrombocytopenia

Description: Fostamatinib is an oral spleen tyrosine kinase (Syk) inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. ITP is mediated by platelet antibodies that accelerate platelet destruction and inhibit their production. Common treatments for ITP include corticosteroids, rituximab, IVIG, splenectomy and/or thrombopoietin receptor agonists (TPO-RA).  This PQI will review appropriate use of fostamatinib in this setting.

Background: SyK signaling is central to phagocytosis based, antibody mediated platelet destruction in adults with ITP. Fostamatinib is a tyrosine kinase inhibitor with demonstrated activity against SyK. The major metabolite of fostamatinib, R406, inhibits signal transduction of Fc-activating receptors and B cell receptors, leading to decreased destruction of platelets.1 In two parallel, phase 3, multicenter, randomized, double blind, placebo-controlled trials (FIT1 and FIT2), adult patients with chronic ITP were randomized 2:1 to fostamatinib or placebo. Fostamatinib was dosed at 100mg BID for 24 weeks with a dose increase to 150mg BID in non-responders after 4 weeks. Primary endpoint was stable response, which was defined as platelet ≥50,000 x109/L at ≥4 of 6 biweekly visits, weeks 14 through 24, without rescue therapy. Stable responses occurred in 18% of patients in the fostamatinib group compared to 0% in the placebo group. Post hoc endpoints also showed an overall response rate of 43% and long term extension show 54% response by line of therapy. The most common adverse events were diarrhea, hypertension, nausea, dizziness, and ALT increase.

PQI process:

Upon receipt of fostamatinib:

  • Confirm appropriate dosing: Typical starting dose is 100 mg twice daily2
  • May increase to 150mg twice daily if 100 mg twice daily does not increase platelet count to >50,000 x109/L after 1 month
  • Use the lowest possible dose to achieve and maintain a platelet count of at least 50,000 x109/L
  • Fostamatinib may be taken with or without food. In the case of a missed dose, instruct patients to take their next dose at its regularly scheduled time
  • Obtain baseline LFTs and repeat monthly throughout therapy
  • Obtain baseline CBC and repeat monthly while on therapy. If ANC drops below 1.0 x 109/L for more than 72 hours temporarily interrupt until resolved
  • Monitor blood pressure (BP) every 2 weeks after starting therapy until patient is established on a stable dose, then obtain BP monthly
  • Screen for drug interactions with CYP3A4 inhibitors and inducers
    • Fostamatinib is a prodrug that is metabolized into its active metabolite, R406. Co-administration of ketoconazole caused a 2-fold increase in R406 exposure, verapamil increased R406 exposure by 39% and rifampicin co-administration decreased exposure by 75%3
  • Discontinue fostamatinib after 12 weeks of therapy if the platelet count does not increase to a level sufficient to avoid clinically important bleeding

Patient Centered Activities:

  • Provide thorough verbal and written medication education; including, but not limited to, the Oral Chemotherapy Education (OCE) sheet
  • Ensure the patient understands the lab schedule for follow up CBC, LFTs, and BP monitoring
  • Avoid eating or drinking grapefruit and grapefruit juice while taking this medication
  • If patient is of child-bearing age, review pregnancy and contraception information with them

Supplemental Information:

Dose adjustments for toxicity2

Usual maximum dose150 mg twice daily
First dose reduction100 mg twice daily
Second dose reduction150 mg once in the morning
Third dose reduction100 mg once in the morning

References:

  1. Clemons Bankston P, Al-Horani RA. New small molecule drugs for thrombocytopenia: Chemical, Pharmacological, and Therapeutic Use Considerations. Int J Mol Sci. 2019;20(12):3013.
  2. Tavalisse® (fostamatinib) [prescribing information]. South San Francisco, CA: Rigel Pharmaceuticals, Inc; April 2018.
  3. Martin P, Gillen M, Millson D, et al. Effects of CYP3A4 Inhibitors Ketoconazole and Verapamil and the CYP3A4 Inducer Rifampicin on the Pharmacokinetic Parameters of Fostamatinib: Results from In Vitro and Phase I Clinical Studies. Drugs R D. 2016;16(1):81-92. doi:10.1007/s40268-015-0118-4.
Important notice: National Community Oncology Dispensing Association, Inc. (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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