Written by: Andrea Clarke, PharmD and Becky Fahrenbruch, PharmD, BCOP
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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.
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Written by: Michelle Hoa and Natasha Heimbigner, PharmD – Summit Cancer Centers
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Description of PQI: Patients undergoing cancer treatment are more susceptible to infections due to their compromised immune system. Proactive steps can be taken before cancer therapy to avoid infections. It is important to know which vaccinations patients can or cannot use, when to use them, and to treat them accordingly so they have the proper protection against preventable infections.

Background: Cancer treatments weaken the immune system rendering it more susceptible to infections.1,2 In order to prevent these infections, cancer patients can either take antimicrobial prophylaxis, get vaccinated, or avoid contact with germs.2 Knowing which vaccinations and when to use them are key to avoid patient harm. Generally, it is best to get vaccinated prior to the start of cancer therapy. Live vaccines should be administered at least four weeks prior to the start of chemotherapy and/or at least 3 months after completion of treatment.1,3 Inactive vaccines should be administered 2 weeks prior to the start of therapy for maximal effect; however, they can be given during therapy. Patients vaccinated during chemotherapy treatment with an inactive vaccine should consider revaccination at least 3 months after therapy as they could be rendered ineffective.3

 

Type of ImmunizationPrinciple of ActionExamplesComments
Non-replicating vaccinesBased on toxoid, protein subunits, bacterial, antigens, or immunogenic proteins obtained with recombinant, technology.Tetanus, diphtheria, pertussis, poliomyelitis, hepatitis B, influenza, varicella zoster (shingles) (Shingrix®), Haemophilus influenza, pneumococcus, meningococcusUsually requires 3–5 doses; antibody titers diminishes with time
Replicating live vaccinesProduced by disabling the virulent properties of a disease-producing virus or bacteriumMeasles-mumps-rubella, varicella (chicken pox), varicella zoster (shingles) (Zostavax®) intranasal influenza, yellow fever, oral polio, oral typhoidSevere reactions are possible; transmission of live pathogen may occur; most provide immunity with 1 dose
Passive immunizationAntibodies are infused to provide short-term protectionVaricella Immunoglobulin, hepatitis B immunoglobulinProtection diminishes after weeks or months

PQI process:

  • Obtain patient vaccination history and reference with CDC recommendations to ensure they are current.
  • Determine type of vaccination chemotherapy patient needs.
    • Non-replicating (inactive) vaccines: should be given at least 2 weeks before the initiation of chemotherapy or other immunosuppressive therapy to maximize immune response.1
      • For a healthy immune system, it typically takes up to 2 weeks after vaccination for the immune system to respond to exposed pathogen. Immunocompromised patients may have reduced or no response to vaccine, which may hinder the effectiveness of immunity for patient. Vaccination, 2 weeks prior to chemotherapy, allows immune systems to build an immune response against the targeted pathogen.
      • Antibody response is suboptimal if given vaccination during immunosuppressive therapy but is better than not vaccinating.1
      • The immune response to vaccine antigens is not as good as that of an immunocompetent patient; repeat vaccination or boosters may be beneficial in prolonging immunity.4
    • Replicating live vaccines: should be given at least 4 weeks prior to and at least 3 months after immunosuppressive therapy.1
      • Live vaccinations contain a weak live version of the virus it is intended to vaccinate against; however, an immunocompromised system will not be able to fight against it. The live virus could cause vaccine-derived infections
      • An adequate immune response usually occurs 3 to 12 months after the completion of chemotherapy. Patients should wait at least 3 months after the completion of therapy to receive live vaccination.5
      • Vaccination should be delayed for at least 6 months after treatment if the patient is receiving anti-B-cell antibodies.2
    • Based on chemotherapy regimen
      • Guide patients to reference the package insert for all oncolytic specific vaccination suggestions

Patient Centered Activities:

  • If patient has not been vaccinated, counsel patient on the importance of vaccination.
  • Patients who are immunocompromised are at higher risk for certain diseases; additional vaccines are recommended.4
    • Immunocompromised patients recommended to receive TIV and polysaccharide-based vaccines (PCV, PPV, MCV4, MPSV, and Hib vaccines).8
    • Do get flu vaccination. Do NOT get nasal mist flu vaccine since it is a live vaccine. Live vaccinations are not recommended for immunocompromised patients.
      • Influenza-related hospitalization is 3 to 5 times higher in cancer patients.
    • Pneumococcal vaccine (PCV13 and PPV23)
      • Immunocompromised children and adults should receive PCV13 and are recommended to receive PPV23 vaccine about 8 weeks later.8 Patients then receive a second dose of PPV23 5 years after the first PPV23.8
      • Patients that received at least one dose of PPV23 should receive PCV13 no sooner than 1 year after last PPV23 dose.8
      • Help patients with weak immune systems fight off serious lung, blood, or brain bacterial infections.7
      • Beneficial for patients with multiple myeloma, lung cancer, chronic lymphocytic leukemia, and lymphoma.1
    • Zostavax® vs Shingrix®
      • Zostavax® is a live attenuated vaccine whereas Shingrix® is an inactivated recombinant zoster vaccine.
      • Zostavax® is contraindicated in immunocompromised patients due to it being a live attenuated vaccine.
      • While Shingrix® is not contraindicated in immunocompromised persons, it is not recommended by ACIP at this time due to its lack of research.9
  • Counsel patients who are on immunotherapy on vaccination recommendations and precautions.
    • Immunotherapy has variable immunomodulatory and immunosuppressive effects. Patients undergoing immunotherapy may or may not experience a suppressed immune response.
    • Vaccine may be triggering an exaggerated immune response in certain patients.11
        • Recent reports suggest that influenza vaccines given to patients on certain types of immunotherapy triggered an amplified immune-related adverse reaction.10,11
        • Some patients receiving immune checkpoint inhibitors experienced an intensified immune response.11
    • Consult with prescriber if vaccination is appropriate with current immunotherapy.
  • Follow up with patient 3 months after chemotherapy is complete.
    • If patient had inactive vaccine during chemotherapy, remind patient to get revaccinated 3 months after treatment.
    • If patient is over 65 or has an altered immune system, the CDC recommends a flu vaccine every year and pneumonia vaccine (PPSV23) every 5 years. PCV13 vaccine should only be given once.
    • Booster Tdap vaccination should be considered for patients who have completed chemotherapy.1 Tdap booster should also be given every 10 years since last Tdap/Td vaccination.
  • Counsel family on receiving live vaccines around patients undergoing chemotherapy.

 

Vaccination Flow Chart:

 

References:

  1. Ariza-Heredia, Ella J, and Roy F Chemaly. “Practical Review of Immunizations in Adult Patients with Cancer.” Human Vaccines & Immunotherapeutics 11.11 (2015): 2606–2614.
  2. nccn.org/patients/resources/life_with_cancer/managing_symptoms/infections.aspx
  3. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm
  4. Centers for Disease Control and Prevention. Recommendations of the advisory committee on immunization practices (ACIP): Use of vaccines and immune globulins in persons with altered immunocompetence. Morbidity and Mortality Weekly Report. 1993;42(RR-4). Available from: https://dosinghealth.com/wp-content/uploads/2017/09/rr4204.pdf
  5. https://www.medscape.com/viewarticle/413557
  6. http://chemocare.com/
  7. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/infections/vaccination-during-cancer-treatment.html
  8. https://www.pharmacytimes.com/news/cdc-committee-high-risk-adults-should-get-2-pneumococcal-vaccines
  9. https://www.cdc.gov/vaccines/vpd/shingles/hcp/shingrix/faqs.html
  10. https://www.cancernetwork.com/oncology-journal/immunizing-cancer-patients-which-patients-which-vaccines-when-give
  11. https://www.pharmaceutical-journal.com/news-and-analysis/news/influenza-vaccine-may-cause-exaggerated-immune-response-in-patients-on-cancer-immunotherapy/20202682.article?firstPass=false

 

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Written by: Brady Quinn and Britny Rogala, PharmD – University of Rhode Island College of Pharmacy
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The utilization of proper diet, over-the-counter medications, and alternative prescriptions can be helpful for patients suffering from multisource drug-induced constipation. Preventing this type of constipation requires less interventions than treating the symptoms once they occur.1

Continue reading Chemotherapy-, Antiemetic-, and Opioid-Induced Constipation

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Written by: Andrew Kowalski, PharmD and Osama Abdelghany, PharmD, MHA, BCOP
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Description of PQI:

There are a number of treatment options for patients with follicular lymphoma that has relapsed or is refractory to first-line options. In September 2017, the FDA approved copanlisib for the treatment of adults who have received at least two other previous therapies.

Background:

Non-Hodgkin’s lymphoma includes a variety of both aggressive and indolent malignancies. Follicular lymphoma is the most common subtype of indolent Non-Hodgkin’s Lymphoma.

Select treatment options include:

  • Cyclophosphamide, vincristine, prednisone (CVP) + obinutuzumab or rituxima
  • Rituximab
  • Lenalidomide +/- rituximab
  • Ibritumomab tiuxetan
  • Idelalisib (refractory to alkylator and rituximab)
  • Copanlisib (refractory to two prior therapies)
  • Duvelisib (refractory to two prior therapies)

Copanlisib is an intravenous phosphatidylinositol 3-kinase (PI3K) inhibitor. PI3K pathways are often hyperactive in B-Cell malignancies. The first FDA approved PI3K inhibitor for follicular lymphoma was idelalisib which is efficacious but is associated with potentially serious toxicities including hepatic dysfunction, colitis, autoimmune toxicity, and pneumonitis. A phase II study demonstrated an objective response rate of 43.8% with copanlisib. The most common treatment related adverse events were hyperglycemia (59.5%), hypertension (54.8%), fatigue (48.8%) and diarrhea (40.5%). Grade 3+ adverse events were observed in 31%, 4.8% and 11.9% of patients, respectively. The most common grade 3+ adverse events were lung infection (10.7%), diarrhea (3.6%) and febrile neutropenia (3.6%).

PQI Process:

Upon receipt of an order for copanlisib:

  • Ensure patient is an appropriate candidate for copanlisib and has received at least two prior therapies
  • Discuss potential risks of copanlisib therapy
    • Increased risk of infection
      • Monitor for signs and symptoms of infection, including pneumocystis jirovecii pneumonia (PJP)
      • For suspected PJP infection of any grade: Withhold copanlisib; if infection is confirmed, treat infection until resolution, then resume copanlisib at previous dose with concomitant PJP prophylaxis.
    • Hyperglycemia
      • Monitor blood glucose at least pre- and post-dose. It may be necessary to monitor more frequently as clinically indicated
      • Grade 3 or 4 hyperglycemia has occurred in >25% of patients. In clinical trials, copanlisib induced hyperglycemia peaked 5-8 hours post-infusion and returned to baseline within 24 hours
      • Pre-dose fasting blood glucose ≥160 mg/dL or random (non-fasting) blood glucose ≥200 mg/dL:
        • Withhold copanlisib until fasting glucose is ≤160 mg/dL or a random (non-fasting) blood glucose is ≤200 mg/dL.
    • Pre-dose or post-dose blood glucose ≥500 mg/dL:
      • First occurrence: Withhold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random (non-fasting) blood glucose is ≤200 mg/dL. Reduce dose from 60 mg to 45 mg.
      • Subsequent occurrences: Withhold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random (non-fasting) blood glucose is ≤200 mg/dL. Reduce dose from 45 mg to 30 mg. If hyperglycemia is persistent at the 30 mg dose, discontinue copanlisib.
  • Hypertension
    • Monitor blood pressure at least pre- and post-dose. It may be necessary to monitor more frequently as clinically indicated
    • Transient hypertension was observed in clinical trials in ~30% of patients but was not a significant cause of treatment delay
    • In clinical trials, blood pressure remained elevated 6-8 hours post infusion
    • Potential intervention:
      • For pre-dose elevation: withhold copanlisib until blood pressure is <150/90 (both systolic and diastolic) based on 2 consecutive measurements at least 15 minutes apart
      • For post-dose elevation: If elevation in blood pressure is life threatening, discontinue copanlisib. If antihypertensive therapy is not required, continue copanlisib at the previous dose. If antihypertensive treatment is necessary, consider copanlisib dose reduction from 60 mg to 45 mg (or from 45 mg to 30 mg). Discontinue copanlisib if blood pressure remains uncontrolled (>150/90) despite appropriate antihypertensive treatment.
    • Drug-Drug Interactions
      • Copanlisib is a major substrate of CYP3A4
      • Avoid concomitant use of strong CYP3A4 inhibitors
        • Potential intervention: If concurrent therapy cannot be avoided, reduce the copanlisib dose to 45 mg

Patient Centered Activities:

  • Educate patients on copanlisib therapy and recommend appropriate interventions:
    • Hyperglycemia
      • Monitor patients for signs of confusion, feeling sleepy, more thirst, more hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit
    • Hypertension
      • Monitor patients for signs/symptoms of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
    • Diarrhea
      • Monitor for how many bowel movements occur each day. Recommend to patients to drink 8–10 glasses of water or fluid each day unless care provider has instructed to limit your fluid intake. Antidiarrheal medications be used to help control symptoms
    • Allergic or cutaneous reactions
      • Monitor for signs of rash, hives, itching, red/swollen/blistered/peeling skin with/without fever, wheezing, tightness in the chest/throat, trouble breathing/swallowing/talking, unusual hoarseness, or swelling of the mouth/face/lips/tongue/throat
    • Infections and pneumonitis
      • Monitor for any signs of lung or breathing problems like shortness of breath or other trouble breathing, fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal

References:

  1. Dreyling M, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Annals of Oncology. 2017; 28: 2169-78. doi:10.1093/annonc/mdx289
  2. Aliqopa (copanlisib) [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc. 2017.
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Written by: Latha Radhakrishnan, PharmD, BCPS, BCOP
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Description of PQI:

The Granisetron Transdermal System is a 5-HT3 Receptor Antagonist (5-HT3 RA) that allows for an alternate medication delivery compared to oral or parenteral administration.  This can be particularly beneficial to those patients that do not have intravenous access, are unable to swallow, or have adherence issues. 

Background:

The Granisetron Transdermal System was approved in 2008 for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy (MEC and/or HEC) for up to 5 consecutive days1.  The National Comprehensive Cancer Network (NCCN) Antiemesis Practice Guideline includes granisetron transdermal system/patch as a 5-HT3 RA option for use in the prevention of acute and delayed intravenous MEC and HEC chemotherapy.  It is also a choice in high to moderate chemotherapy emesis prevention2. The pharmacokinetic profile of the formulation reveals continuous delivery of granisetron through the skin for over 6 days3Boccia et. al. conducted a double-blind, phase III, non-inferiority trial comparing the efficacy and tolerability of the granisetron transdermal system to daily oral granisetron for the control of CINV.  The results revealed non-inferiority to oral granisetron.  Both granisetron formulations were well tolerated with constipation being the most common side effect4.

Based on clinical practice experience, consider using the granisetron transdermal system in the following patient situations:

  1. Moderate to highly emetogenic multi-day chemotherapy
  2. Difficulty swallowing tablets due to oral mucositis, tumor location, vomiting, etc.
  3. Combination radiation + chemotherapy (head and neck regimens, etc.)
  4. Limited gut motility and absorption due to opioids or tumor location
  5. Difficulty remembering to take oral medications
  6. Refractory nausea and vomiting despite receiving appropriate preventative anti-emetics
    • Place patch on patients on the last day of multi-day intravenous chemotherapy

PQI Process:

Upon receipt of an order for granisetron transdermal system:

  • Ensure appropriateness of use in either MEC/HEC intravenous or high to moderate oral chemotherapy
  • Check start date of chemotherapy cycle
    • Apply 1 patch (3.1mg) 24-48 hours on clean, dry, intact skin on the upper outer arm prior to the start of c hemotherapy to the upper arm (do not cut)
    • Wear throughout chemotherapy treatment up to 7 days total
    • Remove at least 1 day (24 hours) after chemotherapy completed
  • Verify prescription coverage.  If issues, use Patient Rx Solutions to assist in coverage options
  • Discuss the use of surgical bandages or medical adhesive tape at the edges of the transdermal system to keep it in place
  • Provide a prescription for a rescue medication (i.e. prochlorperazine, metoclopramide, etc.) to assist with breakthrough nausea and vomiting.  Other 5-HT3 RA such as ondansetron should not be used as rescue medications to avoid QT prolongation, constipation, and headache.

Patient Centered Activities:

  • Application Instructions
    • Ensure that patients understand where to apply the patch
    • Educate on avoiding sunlight and heating sources (heating pads, tanning beds)
  • Patient Education
    • Review common side effects which include constipation and headache
      • Constipation – provide recommendations for a stimulant laxative (bisacodyl, sennosides, etc.) PLUS a stool softener
    • Explain when to apply and remove the patch – a calendar would assist
    • Remind to keep patch area covered under clothing and for another 10 days after the patch is removed to avoid potential skin reactions from natural or artificial sunlight
  • Financial Assistance
    • Patient Rx Solutions (https://www.patientrxsolutions.com or 1-800-676-5884)
      • Coverage option for uninsured patients
      • Co-pay Assistance Cards
      • Sancuso Patch Replacement Program– If chemotherapy is delayed or rescheduled

References:

  1. Sancuso [package insert, Bedminster, NJ: ProStrakan, Inc.; 2015.
  2. National Comprehensive Cancer Network. Antiemesis (Version 3.2018). https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf Accessed January 3, 2018.
  3. Howell J, Smeets J, Drenth H, et al. Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting. J Oncol Pharm Practice. 2009; 15: 223 – 231.
  4. Boccia RV, Gordan LN, Clark G et al. Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Support Care Cancer.2011; 19: 1609-1617.
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