Oral Systemic Therapy- Adverse Drug Reaction Management Guide

CAPECITABINE
Most patients treated with Capecitabine will experience adverse effects, but the effects will differ
from one patient to the next.
Hand-foot skin reactions are very common in patients taking Capecitabine.
ADVERSE DRUG REACTION MANAGEMENT GUIDE
1. Myelosuppression 9. Dermatitis
2. Hand-foot skin reaction (HFSR) 10. Hair Loss (Alopecia)
3. Stomatitis 11. Fatigue and Weakness
4. Diarrhea 12. Myalgia (Muscle pain)
5. Nausea and Vomiting 13. Arthralgia (Joint pain)
6. Loss of appetite (Anorexia) 14. Pain problems
7. Taste disorder (Dysgeusia) 15. Fever
8. Bleeding problems

1. Myelosuppression
Capecitabine may cause suppression of the blood cell production in the myeloid tissues of the bone
marrow. This can result in lowering of white blood cells and platelets. It is important to have a
Complete Blood Count (CBC) blood test prior to the start of each cycle of this agent. If any blood cell
component is reduced below an acceptable level, the drug may need to be held until the blood cells
recover. Capecitabine must NOT be dispensed until the CBC test is completed and verified prior to
each cycle of the treatment. Verification will be done by an oncology health professional.

Prevention: General infection preventative measures should be followed while on this drug,
especially if the blood counts are low. Advise patient to:
• Limit contact with people who are sick, have colds, or have been recently vaccinated
• Rest often
• Do not eat uncooked vegetables
• Wash hands often
If the platelet count is low, tell the patient to take. Advise patient to:
• Take care when shaving or performing any activity of daily living where the skin could be cut
• Use a soft toothbrush.
• Tell your doctor before dental work is done.
Management: If the patient has a fever or other signs of an infection when the blood counts are low,
advise him/her to go directly to the Emergency Department and contact the oncologist when there.
The ER staff needs to be told that the patient is taking this drug, and that it is a form of
chemotherapy. Empiric antibiotics will be required.
If the patient has unusual bleeding when the platelet counts are low, advise him/her to go to the
Emergency Department, tell the ER staff about this drug, and contact the oncologist when there.
Revision Date: 04/14
 CAPECITABINE- Adverse Drug Reaction Management Guide

2. Hand-foot skin reaction (HFSR)

Hand-foot skin reaction (HFSR), also known as hand-foot syndrome and palmar-plantar
erythrodysesthesia, is a common side effect of Capecitabine. It may occur as soon as 11 days or as
late as a year after beginning treatment. HFSR is a potentially dose-limiting, skin-related side effect
of Capecitabine. In the early stages, skin on the hands and feet may become red and lightly swollen
and may cause the patient to experience a prickly feeling or numbness. If Capecitabine is not
stopped, the syndrome may escalate to painful swelling and redness that interferes with the use of
hands and/or feet. HSFR can increase to moist desquamation, ulceration, blistering or severe pain of
the hands and/or feet and/or severe discomfort that causes the patient to be unable to work or
perform activities of daily living. At this point, Capecitabine dosing must be interrupted until HSFR
resolves, and restarted at a lower dose.
If the patient tells you on the call back phone call that their hands or feet are bothering them, you
might want to have the patient drop by the pharmacy for you to have a look and determine if any
prevention or management is required.
Prevention: During the first 2–4 weeks of therapy, prevention of Counseling tips:
traumatic activity and rest are crucial. Tell your patient about prevention
Urge your patients to: of HFSR early in the treatment. If
• Have a manicure or pedicure to remove thickened skin or calluses; the patient is not prepared for
follow with moisturizing cream detailed counselling on the day the
• Use a moisturizing cream (e.g. Udderly Smooth®, Bag Balm®) prescription is picked up, plan a
• Take vitamin B6 150-200 mg daily (e.g. 100 mg BID with follow up call in a couple of days.
Capecitabine tablets)
• Wear loose-fitting, soft shoes or slippers, foam absorbing soles, gel
inserts to cushion pressure points, cotton socks
• Cushion callused areas with soft or padded shoes
• Reduce exposure of hands and feet to hot water (showers, dishwashing, etc.)
• Avoid excessive friction to hands or feet when performing tasks
• Avoid vigorous exercise or activities that place undue stress on the hands and feet
• Wear thick cotton gloves or socks to protect hands and feet and keep them dry
• Report any signs or symptoms immediately to ensure early-stage treatment
Management: For Mild HFSR, there are several management strategies you may consider:
• Avoid hot water; cool water or cold compresses may ease symptoms
• Diligently apply moisturizers to keep palms and soles soft and pliable to prevent cracks or breaks
in skin integrity- Use moisturizing creams twice daily; also use aloe vera lotion as needed and use
20% to 40% urea cream or 6% salicylic acid on callused areas
o Skin products in use for HFSR
 Cetaphil® skin cleansers  Udderly Smooth®, Gold Bond®,
 Aveeno® shower gel Aveeno® lotions
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 Norwegian Formula moisturizer and  Aquaphor® Healing Ointment

foot cream (Neutrogena®)  Kerasal®
 Bag Balm®  Sunblock
 Eucerin® cream and Dry Skin Therapy  Lipikar, Lipikar balm, and Xerand
• Soak feet in magnesium sulfate (Epsom salts) to soften calluses and reduce pressure pain
• Use low to moderate dose pain killers
• Advise patients to consult their doctor about reducing their dosage of Capecitabine, if symptoms of
HFSR worsen after being treated for 2 weeks
For Moderate to Severe HFSR, the patient will likely need prescribed therapy, such as:
• Topical corticosteroid (e.g., clobetasol 0.05% ointment)
• 2% lidocaine topical ointment
• Oral NSAIDS, codeine, pregabalin, for pain
• For thick, tender sores after acute rash with/without blisters resolves: 40% urea cream; or
Tazarotene 0.1% cream; or Fluorouracil 5% cream
• Dose modification of the Capecitabine
• If symptoms worsen after 2 weeks, interruption of Capecitabine treatment interruption may be
required

3. Stomatitis
Stomatitis (mouth sores) is a common side effect of Capecitabine. Integrity of mucous membranes
may be affected by Capecitabine treatment, leading to the swelling and reddening of membranes
lining the mouth. Mouth sores or cankers may develop. Patients may complain of changes on the inner
cheeks or mouth surfaces, even when mouth sores are not present or only a mild redness is evident.
Patients may experience:
• Mouth pain
• Difficulty chewing
• Painful swallowing (dysphagia)
This side effect may lead to Capecitabine dosage reductions. It is important to maintain good oral
health during treatment. Aggressive prevention may reduce incidence and severity of stomatitis.
Treatment during stomatitis event(s) can relieve symptoms (including oral pain, oral bleeding, dental
complications, soft tissue infection and dietary restrictions) and restore oral health, often within 7 to
14 days.
Prevention and Management: Good oral care is the key to prevention of stomatitis. If possible, the
patient should work with their dentist (and oncologist) to correct any pre-existing dental problems
before starting Capecitabine treatment. Careful and thorough oral hygiene is important, and
particularly irritating foods (e.g. very spicy foods, rough textures, alcohol-containing foods or liquids)
should be avoided.

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Management may be achieved in many patients without prescribed therapies. Most important is
meticulous oral hygiene:
• Toothbrushing, 3-4 times daily with soft-bristle toothbrush. Soak toothbrush in warm water to
soften bristles
• If brushing is painful, Toothettes (sponge-tipped stick with toothpaste), sponges, or gentle use of
Waterpik®
• Biotene toothpaste is non-irritating contains natural salivary enzymes to control bacteria
• Floss gently once daily to avoid gum injury
• Salt and baking-soda rinses (1/2 teaspoon of each ingredient in 1 cup of warm water at least 4 times
daily, especially after meals)
• Bland rinses, antimicrobial mouthwash (non-alcohoic)
• OTC analgesics, such as ibuprofen (e.g., Advil®, Motrin®) and acetaminophen (e.g., Tylenol®).
If the patient has difficulty eating or drinking sufficient fluids or if redness is associated with lesions
on the inner cheeks, tongue or lips, contact the cancer care team at once and tell the patient to
contact the oncology nurse or oncologist for immediate advice or a visit.
Topical preparations in widespread use for chemotherapy-induced stomatitis contain ingredients such
as lidocaine, benzocaine, milk of magnesia, kaolin, pectin, and diphenhydramine. Although there is no
significant evidence of the effectiveness or tolerability of these combinations, there may be a degree
of symptom management (e.g. oral pain, improved ability to maintain a proper diet). Clinical trials in
chemotherapy patients with stomatitis have shown no difference in the effectiveness of stomatitis
resolution from chlorhexidine mouthwash, “magic” mouthwashes that contain lidocaine, and salt-and-
baking soda rinses. Hydrogen peroxide may worsen mouth ulcers. In addition, mouthwash
preparations containing antifungals (i.e. nystatin), broad-spectrum antibiotics, or corticosteroids have
shown no benefit and possibly further worsening of stomatitis- these combinations are not
recommended!

4. Diarrhea
Diarrhea is very common in patients treated with Capecitabine. Dietary modifications are not
recommended in anticipation of diarrhea, but must be considered if diarrhea occurs.
Management:
For mild diarrhea (less than 4 loose stools per day)
• Follow instructions on loperamide (e.g., Imodium®) package insert: 2 tablets immediately, then 1
tablet after each liquid bowel movement (maximum: 8 tablets/24 hours)
For moderate diarrhea (more than 4 to 6 loose stools per day or night-time diarrhea), tell the patient
to be more aggressive with loperamide (e.g., Imodium®) for early-onset diarrhea
• Take 2 tablets immediately, then 1 tablet every 2 hours during the day and 2 tablets every 4 hours
during the night until bowel movements are normal for at least 12 hours
• This dosage is higher than packaging recommendations.

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Replace lost fluids: Fluid intake is more important than eating in patients with diarrhea. To replace lost
fluid, advise patients to increase fluids by up to 3 to 4 litres per day (unless there is a known
contraindication to increased fluid intake). The patient may drink several types of fluid, including plain
water and electrolyte-containing drinks, such as clear broth, gelatin desserts, sports drinks, flat soft
drinks, or decaffeinated tea
Anal care: Recommend to your patient to:
• Clean the anal area with mild soap and warm water after each bowel movement to prevent
irritation
• Apply a barrier cream or ointment, such as petroleum jelly or Isle’s paste
• Soak in a warm bathtub or sitz bath to relieve discomfort
Dietary changes during diarrhea: Advise your patients to change their diet while diarrhea is a problem:
• Eat and drink small quantities of food often
• Avoid spicy, greasy, or fried foods
• Follow the BRAT (banana, rice, applesauce, toast) diet, along with clear liquids, until diarrhea begins
to resolve
• Follow a lactose-free diet
• Avoid cabbage, brussel spouts, and broccoli, which may produce stomach gas, bloating and cramps

5. Nausea and Vomiting

Nausea and vomiting may occur in up to 45% of patients on Capecitabine. Unlike the nausea and
vomiting often experienced by patients on cytotoxic chemotherapy (acute onset, more emesis than
nausea), patients on Capecitabine tend to have nausea of lesser severity and longer duration, with or
without emesis. This can be more distressing to patients’ quality of life than acute nausea and
vomiting. Often patients will have nausea without the relief that comes from emesis.
Management: The following may provide relief from nausea and vomiting:
• Prophylactic antiemetic agents (e.g. dopaminergic agents such as prochlorperazine, or promotility
agents such as metoclopramide) given with each dose of Capecitabine and repeated as needed for
nausea control. While there is no evidence to support the use of dimenhydrinate, there is evidence
that ginger products (e.g. Gravol® Ginger) may be effective, with fewer adverse effects
• Avoid spicy or greasy foods that may contribute to the feeling of nausea. Bland foods, fresh air, and
plenty of clear water may reduce the feelings of nausea

6. Loss of appetite (Anorexia)

Between 1 and 10% of patients will experience a decreased appetite while taking Etoposide.
Prevention: Advise patient to:
• Have several small meals a day
• Eat slowly

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Management:
• Light exercise and fresh air may help
• Drink plenty of fluids
• Eat a high calorie meal plan
• Consider Cyproheptadine to stimulate appetite

7. Taste disorder (Dysgeusia)

Dysgeusia is an altered or distorted taste sensation, sometimes associated with cancer treatments and
other drugs. It is hard to determine exact etiology, since taste is related to sense of smell and other
stimuli. Change of taste sensation, or loss of taste, can impact quality of life for some patients, making
certain foods taste unpleasant or metallic. Often patients lose their taste for meats, if these foodstuffs
become excessively bitter or unpleasant. Patients may lose their appetite and lose weight over time.
Unpleasant sensations may become conditioned responses, leading to lifelong avoidance of certain
foods after dysgeusia is resolved.
Prevention: Advise patients to:
• Avoid eating ‘favorite’ foods when the dysgeusia is expected
• Choose bland, less flavorful, less odorful foods when dysgeusia is troublesome.
• Eat smaller meals more frequently
Management:
There are several OTC and prescription treatments to address dysgeusia:
• Consider zinc supplementation (25-100 mg PO daily)- zinc deficiency may cause dysgeusia, and may
be resultant from cancer treatments.
• If saliva production is lessened during dysgeusia, consider artificial saliva products, or systemic
pilocarpine (prescription)
• Consider alpha lipoic acid (ALA) as a natural health product. ALA is available in meats and yeast
products, as well as a supplement forms, and has been shown to improve taste sensation for several
patients in one study.

8. Bleeding problems
Patients may experience excessive or unusual bleeding or bruising. This may be accompanied by red
pinpoints on the skin or black, tar-like bowel movements or blood in stools. If bleeding or bruising is
unusual and will not stop, refer the patient to the Emergency Department.
Prevention: Advise the patient to:
• Use sharp objects with care
• Use a soft toothbrush
• Be careful when shaving
• Consult physician before any dental work is done

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9. Dermatitis
Dermatitis is a non-specific term for a variety of skin reactions that exhibit erythema, scaling, vesicles
and crusts (sometimes also called eczema). Skin changes always include an inflammatory response,
with initial erythema (redness) from vasodilation and usually edema from leakage of the engorged
vasculature. Swelling may lead to fluid-filled vesicles in the skin which may ooze or weap when broken
and then crust over as they dry. Dermatitis may be worsened by topical allergens or harsh soaps and
detergents, humid weather, excessive sweating, dietary allergens, and the itch-scratch cycle.
Prevention:
• Avoid use of any topical products that are irritating (e.g. soaps, deodorants).
• Wear breathable, loose-fitting clothing. Natural fabrics are usually less irritating than synthetic
fabrics. Always wash new clothes before the first use. Do not use fabric softeners or bleach in
washing or drying cycles.
Management:
• Use a systemic antihistamine, either an H1 blocker (e.g. diphenhydramine) or a non-sedating
antihistamine (e.g. loratidine, cetirizine, desloratidine). Consider adding an H2 blocker
antihistamine (e.g. ranitidine, famotidine) for chronic urticaria
• Bathing with colloidal oatmeal preparations (e.g. Aveeno®) and use of unscented moisturizing
creams after bathing may help with itchiness and dry skin
• Cooling salves, such as menthol or camphor-containing products (e.g. Gold Bond®) may provide
relief. Keep products in the refrigerator for additional cooling effect.
• Topical corticosteroids, beginning with OTC Hydrocortisone 0.5% cream and progressing as needed
to more potent prescription corticosteroid creams, are often used
• Acetaminophen may be added to the treatment of urticarial for more painful lesions.

10. Hair Loss (Alopecia)

Between 5 and 40% of patients will have hair loss while taking Capecitabine. Most patients will lose a
minimal amount of hair on the oral form of this agent.
Prevention:
• Although there is no way to prevent hair loss, you may advise the patient that hair will usually
regrow, once the treatments are over. The replacement hair may have a different colour or
consistency.
Management:
• If hair loss bothers the patient, a wig, hat, cap, scarf or hair piece may be worn

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11. Fatigue and Weakness

Some patients on Capecitabine will experience fatigue and/or asthenia (or general weakness). These
symptoms are not life-threatening but will significantly reduce quality of life.
Management: The following may provide relief from fatigue:
• There are no medications that have demonstrated an effect to relieve fatigue
• Mild exercise is very helpful to reduce fatigue, but must be manageable if there is also muscle
weakness

12. Myalgia (Muscle pain)

Aching muscles and muscle cramps can be very disruptive, lowering patient quality of life. Muscle
cramps may occur in the hands, feet, calves, or thighs. Cramps have been described as sustained
muscular contractions that follow a consistent pattern, frequency, and severity. Muscle cramps may
be related to exertion or could happen at night. Patients should avoid using quinine or drinking tonic
water (contains quinine).
Management: The following may provide relief from muscle aches or cramps:
• Mild pain medications- Acetaminophen preferred; do NOT use non-steroidal anti-inflammatory
agents, prescription or OTC due to risk of bleeding (e.g. ibuprofen, ASA, naproxen)
• Use of a muscle relaxant may be considered (e.g. cyclobenzaprine- prescription, or
acetaminophen/methocarbamol combinations-OTC)

13. Arthralgia (Joint pain)

Aching joints or arthritic pain is a common co-morbidity in cancer patients and can be initiated or
exacerbated by some medications.
Prevention:
• Some light exercise (e.g. walking, jogging) and regular physical activity will help reduce pain and
discomfort, even if it is painful to start some activities.
Management:
• Acetaminophen on a regular basis may help to manage pain. Try the controlled-release product, 1
or 2 tablets every 8 hours. Be careful not to take too much Acetaminophen (i.e. limit
Acetaminophem from other sources, such as PRN dosing or Acetaminophen-containing narcotic
analgesics
• Do NOT use systemic non-steroidal anti-inflammatory agents, prescription or OTC due to risk of
bleeding (e.g. ibuprofen, ASA, naproxen)
• For joint pain, consider the use of heating pads, ice packs, or topical arthritis creams and liniments
• Mild exercise and/or massage therapy may help reduce joint pain
• If the arthralgia persists, see a physician, and tell them about all medications, including the cancer
treatment drugs

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14. Pain problems

Patients on Capecitabine may experience other types of pain. About 5-10% of patients have
headaches while on this treatment. Generalized pain maybe a drug side effect or may be related to
the cancer.
Management: The following may provide relief from headaches and other general pain problems:
• Mild pain may respond to non-pharmacologic approaches, such as rest, distraction, cool cloth on
the forehead
• Mild pain medications- Acetaminophen preferred; do NOT use non-steroidal anti-inflammatory
agents, prescription or OTC due to risk of bleeding (e.g. ibuprofen, ASA, naproxen)
• Acetaminophen with codeine, either OTC (low dose) or on prescription (higher dose) may be
considered for more severe pain.
• If acetaminophen is not sufficient to control pain, consider prescription opioid analgesics for
management of more severe pain (possibly due to tumor)
• If there is a neuropathic component to the pain, consider a trial with a tricyclic antidepressant (e.g.
low dose amitriptyline or imipramine) or gabapentin

15. Fever
Fever, or increased body temperature, may occur with this drug. While fever is uncomfortable, be
careful if the patient is at risk of febrile neutropenia from the drug. Reducing fever can mask the
symptoms of emergent infection and cause a delay in management of this potentially life-threatening
problem.
Management: The following may provide relief from headaches and other general pain problems:
• Non-pharmacologic approaches, such as a sponge bath with tepid water, or a cool cloth on the
forehead, may provide some relief from fever
• Antipyretics- Acetaminophen preferred; do NOT use non-steroidal anti-inflammatory agents,
prescription or OTC due to risk of bleeding (e.g. ibuprofen, ASA, naproxen)

REFERENCES:
ONTarget Resource Guide, Common Side Effects from Targeted Therapy. The Groupe d’étude en
oncologie and The Canadian Association of Pharmacy in Oncology, 2012.
Xeloda Product Monograph, Hoffman LaRoche Ltd., 7 November 2008
Systemic Therapy Manual for Cancer Treatment, Cancer Care Nova Scotia, 2013
Patient Self-Care. Helping Your Patients Make Therapeutic Choices. Canadian Pharmaceutical
Association , 2010
Therapeutic Choices, Sixth Edition, Canadian Pharmaceutical Association , 2011

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