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: Joshua Nubla, PharmD, NCODA
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Description: This PQI will discuss management strategies for oncolytic medication induced diarrhea including combinations of fluid hydration therapies, antimotility agents such as loperamide, and dose modifications.

Background: A common side effect with many oncolytic therapies is medication induced diarrhea which can result from chemotherapy or targeted therapy regimens. Medication induced diarrhea will present with increasing frequency and consistency of bowel movements and drastic changes in hydration status and electrolyte levels. Oncolytic induced diarrhea can lead to life threatening dehydration and electrolyte imbalances.

PQI Process: Identify patients who are taking an oncolytic agent with a known diarrhea side effect.

Common oral oncolytic agents that cause diarrhea

  • Tyrosine Kinase Inhibitors (TKI)
  • Multi-kinase Inhibitors
  • Phosphatidylinositol-3-kinase (PI3K) Inhibitors
  • Capecitabine
  • Everolimus
  • Fluorouracil (5FU®)
  • Irinotecan

Upon receiving a prescription of any agents that commonly cause diarrhea:

  • Counsel patient on importance of diarrhea management and risks of dehydration
  • Provide loperamide and dosing instruction (see supplemental information)
  • Counsel patient on appropriate diet (see supplemental information)
  • Schedule follow up phone call within first few days or weeks of starting therapy to asses if patient is experiencing diarrhea
    • If not controlled with loperamide change in therapy may be needed
    • If severe, may need to provide IV fluid and electrolyte replacement

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) Supplemental Sheet
  • Adhere to suggested dosing and diet strategies
  • Start taking loperamide at the first onset of diarrhea
    • If taking antidiarrheal and without relief for 48 hours, then contact clinic
  • Drink plenty of fluids: 6-8 large glasses of water, clear liquids, soup per day
  • If on immunotherapy contact your clinic immediately at the first onset of diarrhea

References:

  1. Micromedex Drug Database
  2. Up To Date

Supplemental Information:

Diet

  • Avoid greasy, spicy, or fried food
  • Avoid milk, caffeine, alcohol
  • Avoid high fiber vegetables
  • Eat small meals
  • Follow B-R-A-T diet
    • Bananas, rice, apple sauce, toast/tea (decaffeinated)

Medication Therapy

  • Loperamide (OTC)
    • Mild-Moderate – Take two caplets (4 mg) by mouth at the onset of diarrhea, followed by one caplet (2 mg) every hour hours or after each loose stool
    • Persistent (12-24 hrs) – Take two caplets (4 mg) by mouth at the onset of diarrhea, followed by one caplet (2 mg) every two hours until no diarrhea for 12 hours
    • During the night, take 2 caplets (4 mg) by mouth at bed time and continue every four hours during the night until morning
    • Stop taking loperamide only after there is no sign of diarrhea for 12 hours
    • Max 16 mg per day (up to 24 mg per day for chemotherapy induced diarrhea under medical supervision)
  • Diphenoxalate/Atropine (Rx)
    • Take two tablets (5 mg) by mouth three to four times daily
    • Max 40 mg per day
    • Atropinism (dryness of the skin and mucous membranes, tachycardia, urinary retention, and hyperthemia) has been reported
    • Respiratory depression has been reported
  • Octreotide (Rx)
    • Inject 100-150 mcg subcutaneously three time daily
      • Rapidly escalate to 500 mcg subcutaneously three times daily if lower doses are not effective
    • Tincture of Opium (Rx)
      • Take 10-15 drops in water every three to four hours
    • Budesonide (Rx)
      • Take 9 mg by mouth once daily (off label)

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: Brady Quinn, PharmD and Britny Rogala, PharmD, BCOP – University of Rhode Island College of Pharmacy
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Description of PQI: Discuss prevention and management strategies for treatment related constipation.

 

Background: 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 Many chemotherapeutic medications, antiemetics, and pain regimens can commonly cause constipation (see supplemental information). Drug-induced constipation, often characterized by infrequent, hard, or difficult to pass bowel movements, can significantly impair quality of life or cause severe pain, rectal fissures, or bowel obstruction.1-3

PQI Process: Upon receipt of an oral chemotherapy agent with known constipation side effect

  • Counsel patient on constipation management
  • Provide information on foods to eat to prevent the onset of constipation
  • Provide stool softener and stimulant laxative to patient if patient reports signs of constipation (see supplemental information)
  • Keep stool softener and stimulant laxative well stocked if patient experiences intermittent constipation
  • Consider scheduling a follow up phone call with patient within one week after initiation of therapy to assess if patient is experiencing constipation
    • Assess the cause of constipation (chemotherapy/antiemetic/opioid)
    • If opioid therapy is the cause of the constipation and significant effort to alleviate constipation has been made with no relief, consider prescription therapy (ex. methylnaltrexone, naloxegol)
    • If antiemetic therapy is the cause of constipation provide a prescription for a different type of antiemetic for chemotherapy induced nausea/vomiting (ex. prochlorperazine, metoclopramide)

 Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) Supplemental Sheet
  • Educate patients on different forms of laxatives (bulk forming, polyethylene glycol), if bowl movements do not become regular continue on OTC agents and advise patient to:
    • Try to find a diet and regimen that helps to keep bowel movements regular
    • Attempt to treat to regular bowel movement schedule
    • Keep track of how many bowel movements are made in a week
    • Drink plenty of fluids while taking laxative and stool softening medications
    • Contact clinic if there have been no bowel movement in 2 or more days
    • Have patient notify provider OTC medications have been taken continuously for 7 days

References:

  1. McQuade RM, Stojnovska V, Abalo R, Bomstein JC, Nurgali K. Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments. Front Pharmacol. 2016;7:414.
  2. Andrews CN, Storr M. The pathophysiology of chronic constipation. Can J Gastroenterol. 2011;25:16B-21B.
  3. Kumar L, Barker C, Emmanuel A. Opioid-Induced Constipation: Pathophysiology, Clinical Consequences, and Management. Gastroenterology Research and Practice. 2014; https://doi.org/10.1155/2014/141737.

 

Supplemental Information:

Oral chemotherapy agents that commonly cause constipation (>30%): alectinib, crizotinib, ponatinib, ixazomib, lenalidomide, niraparib, pomalidomide, rucaparib temozolomide, and thalidomide

Anti-emetics that commonly cause constipation: 5-HT3 antagonists (ex. ondansetron)

Diet/Exercise:

  • Increase fiber intake; patients prone to small bowel obstruction (ex. abdominal surgery) should avoid additional fiber intake
    • Whole grains, brown rice, raw fruits and vegetables, etc.
  • Drink plenty of fluids
    • 8-10 glasses of water, fruit/vegetable juices, decaffeinated teas
  • Encourage physical activity

Drug Therapy

Osmotic Laxative

  • Polyethylene Glycol (OTC/Rx)
    • Take 1 capful/packet/heaping tablespoon (17 g) of powder dissolved in 4-8 ounces of any beverage daily
    • Onset of action:12-72 hours

Stool softener

  • Docusate Sodium (OTC)
    • Take 1 softgel (100 mg) up to 3 times per day in divided doses
    • Onset of action: 12-72 hours
    • Can take with in combination with a stimulant laxative for best results

Stimulant laxatives

  • Senna (OTC)
    • Take 2 tablets (17.2 mg) as one dose once daily to start. If needed can take up to 4 tablets (34.4 mg) twice daily
    • Onset of action: 6-12 hours
  • Bisacodyl (OTC)
    • Take 1 tablet (5 mg) once daily to start. If needed can take up to 3 tablets (15 mg) once daily
    • Onset of action: 6-12 hours


Prescription Options

  • Methylnaltrexone (Relistor®) (Rx)
    • Used to treat opioid-induced constipation
    • Rule out GI obstruction (contraindicated)
    • Inject 1 prefilled syringe (dose may vary) subcutaneously up to every other day as needed
    • Rotate injection site between abdomen, thighs, and upper arms
    • Discontinue methylnaltrexone immediately if severe/persistent diarrhea/abdominal pain occurs
  • Naloxegol (Movantik®) (Rx)
    • Used to treat opioid-induced constipation
    • Rule out GI obstruction (contraindicated)
    • Usual dose: take 1 tablet (25 mg) daily at least 1 hour before the first meal of the day (dose may differ due to tolerability)
    • Concomitant use with strong CYP3A4 inhibitors is not recommended
  • Lubiprostone (Amitiza®) (Rx)
    • Used to treat opioid-induced constipation
    • Rule out GI obstruction (contraindicated)
    • Usual dose: take 24 mcg by mouth twice daily

 

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: Neal Dave, PharmD and Julianne Orr, PharmD
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Description of PQI:  Discuss the prevention and management of opioid induced constipation.

Background: Constipation is a major side effect of opioid administration and should be assessed and managed by the healthcare team. In cancer patients receiving chronic opioid therapy, the prevalence of constipation can be as high as 60 to 90 %. Constipation is the most common manifestation of opioid induced bowel dysfunction (OBD) and typically occurs through activation of both peripheral and central opioid receptors. Opioid induced constipation (OIC) has the potential to effect patients’ quality of life or lead to complications such as bowel obstruction or anorexia. 

PQI Process: Once a prescription for an opioid is obtained:

  • Assess the medications patients are currently on
    • Look for causative medications in addition to opioids
    • If patient is already on an agent that is notorious for causing diarrhea, there may be no need for prevention of OIC
  • Educate patient on opioid induced constipation
    • Symptoms of constipation
      • Straining
      • Lumpy or hard stools
      • Sensation of incomplete evacuation
    • Consider adding preventative agents:
      • Docusate/Senna: Two tablets (17.2 mg sennosides plus 100 mg docusate) by mouth once daily
        • Max dose of senna: 68.8 mg by mouth twice daily
      • Polyethylene Glycol: 17 g orally 4-8 oz of water daily
      • Lactulose: 30 mL by mouth daily (avoid in patients who are lactose intolerant)
    • Pharmacologic options once preventative measures are ineffective, consider use with discretion as clinical efficacy varies:
      • Magnesium citrate: 195 – 300 mL by mouth given once or in divided doses
        • Consider milk of magnesia if citrate is unavailable
      • Methylnaltrexone (Relistor®): Dosing is according to body weight; Administer one dose subcutaneously once every other day as needed (Max: 1 dose/24 hours)
        • <38 kg: 0.15 mg/kg rounded to the nearest 0.1 mL
        • 38 to <62 kg: 8 mg
        • 62 to 114 kg: 12 mg
        • >114 kg: 0.15 mg/kg rounded to the nearest 0.1 mL
      • Naloxegol (Movantik®): 25 mg by mouth once daily
        • Can decrease to 12.5 mg if 25 mg not tolerated
      • Lubiprostone (Amitiza®): 24 mcg by mouth twice daily

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) Supplemental Sheet
  • Non-pharmacologic counseling
    • Increase fluids
      • Common recommendation for water consumption is eight 8-ounce glasses, which is about 2 liters (or a half gallon) per day
      • Caffeine can contribute to dehydration
    • Increase fiber
      • USDA fiber intake recommendation is between 25-38 g per day
    • Modifying diet
      • Eat several small meals throughout the day, rather than a few large ones
      • Avoid fatty, processed meats, and fast foods
      • Consuming natural laxatives:
        • Prunes, apple cider, bran cereals, watermelon, rhubarb, etc
      • Increase activity
        • Exercise can increase circulation, which can naturally accelerate movement of stool
      • Consider offering diet counseling books (ex. “Eating Well Through Cancer”)
      • Taking preventative agents daily
    • Patient Medication Education
      • Review maximum daily doses of any agent the patient starts
      • Relistor® – make sure the patient is aware that an instant bowel movement is possible after they receive their injection

References:

  1. Poulsen et al. Therap Adv Gastroenterol. 2015 Nov;8(6):360-72.
  2. Dhingra et al. Palliative Medicine. 2012 June;27(5):447-457.
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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