PHRM 542 Oncology Supportive Care CRD, Hypersensitivity, Extravasation

Define chemotherapy related diarrhea (CRD)

An increase of 4 or more stools per day over baseline

Define grade 1 CRD

Change in stool consistency or frequency

Define grade 2 CRD

Increase of 4-6 stools per day over baseline

Moderate increase in ostomy output compared to baseline

Pediatrics:

- Limiting instrumental ADL or mild/moderate impact on age-appropriate normal daily activity

- Change in consistency or frequency AND limiting instrumental ADL or mild-moderate impact on age-appropriate normal daily activity

Define grade 3 CRD

Increase of ≥ 7 stools per day over baseline

Hospitalization indicated

Severe increase in ostomy output compared to baseline

Requires IV intervention

Pediatrics:

- Limiting self-care ADL or severe impact on age appropriate normal daily activity

Define grade 4 CRD

Life-threatening consequences

Urgent intervention indicated

What are treatment options for CRD?

Loperamide

Diphenoxylate/atropine

Octreotide

Describe loperamide treatment for CRD

4 mg PO at the first sign of diarrhea

2 mg PO q2h until diarrhea free for 12 hours

Do not take greater than 12 tablets/day

Describe diphenoxylate/atropine treatment for CRD

5 mg PO four times a day

May alternate with loperamide

Describe octreotide treatment for CRD

50-100 mcg SQ q8h up to 500 mcg SQ q8h

Define acute irinotecan induced CRD

Mean duration of symptoms = 30 minutes

Accompanied with cholinergic symptoms

What is the mechanism of acute irinotecan induced CRD?

Direct inhibition of acetylcholinesterase

What agent can be used for the treatment of acute irinotecan induced CRD?

Atropine

Describe delayed irinotecan induced CRD

Occurring more than 24 hours after administration (median onset = day 6)

Occurs at all doses

What is the treatment for delated irinotecan induced CRD?

Loperamide

What are common chemotherapy drug classes that cause hypersensitivity reactions?

Taxanes

Platinums

Monoclonal antibodies

Describe pre-medication for patients taking taxanes

Dexamethasone 20 mg and diphenhydramine 50 mg

H2 antagonist 30 minutes prior to paclitaxel

Describe pre-medication for patients taking platinums

None prophylactically, but can perform desensitization

Describe pre-medication for patients taking monoclonal antibodies

Methylprednisolone 80-125 mg + diphenhydramine 50 mg + acetaminophen 500-1000 mg PO (+/- H2 antagonist) 30-60 min prior

What symptoms are associated with anaphylaxis?

Urticaria, repetitive cough, wheeze, throat tightness/change in voice, and hypotension

What features can help you differentiate between an infusion reaction and anaphylaxis?

Fever and prominent muscular pain are NOT features of anaphylaxis, but indicate an infusion reaction

How should a mild hypersensitivity reaction be managed?

1. Stop infusion

2. Administer H1 blocker

3. Administer corticosteroid if concern for delayed reaction

How should a severe hypersensitivity reaction be managed?

1. Stop infusion

2. Administer oxygen

3. Nebulized bronchodilators if SOB

4. Administer H1 and H2 blockers

5. Administer corticosteroid (delayed reaction)

How should a life-threatening hypersensitivity reaction be managed?

1. Stop infusion

2. Place patient in recumbent position

3. Administer epinephrine IM

4. Administer oxygen

5. Give 1-2 L IV NS as rapid bolus

6. Administer H1 and H2 blockers

7. Administer corticosteroid (delayed reaction)

8. Acute ACLS for cardiac arrest

Define extravasation

The inadvertent administration of a vesicant solution from a vein to surrounding tissue

Define infiltration

The leakage of an irritant into the extravascular space

Define vesicant

Agents capable of causing soft tissue damage by causing blistering and necrosis

Joints and tendons may also be involved

Blood return is absent

Define irritant

Agents capable of causing inflammatory reaction but no necrosis

Short-term injury

Blood return remains intact

Describe extravasation from DNA binding vesicants

Bind to nucleic acids in DNA and healthy adjacent cell's DNA leading to prompt cell death

Larger, deeper and more painful

Describe extravasation from DNA non-binding vesicants

Indirect effect on the cells in the healthy tissue

Metabolized by the tissue and are more easily neutralized

Localized injury with mild-moderate pain

How can extravasation be prevented?

Central venous catheters (CVC)

Frequent checking of blood return throughout administration

IV sites as distant from hand, foot, joint space as possible

Bolus doses over 5-10 minutes

Flush after completion of infusion

How should patients be educated on extravasation?

Pain, tingling, burning, itchiness, etc.

How should extravasation be treated?

1. Stop infusion!

2. Aspirate any drug via IV cannula

3. Do not flush the line

4. Remove catheter/needle

5. Apply cold or warm packs as recommended

6. If antidote is available, instill through different IV site

7. Photograph extravasation area marked with marker

8. Monitor site for 24 hours, at 1 and 2 weeks, then prn

When should heat be used for extravasation treatment?

Vinca alkaloids and etoposide

15-20 minutes 4x/day

When should cold be used for extravasation treatment?

All other agents besides those that use heat

Cold pack for 15-20 minutes at least 4x/day

What is the antidote for extravasation caused by anthracyclines?

Dexrazoxane

What is the MOA of dexrazoxane?

EDTA potent intracellular chelating agent

Describe the treatment of antracycline extravasation with dexrazoxane

1000 mg/m^2 on days 1 and 2 (MDD = 2000 mg/day)

Followed by 500 mg/m^2 on day 3 (MDD = 1000 mg/day)

Begin treatment ASAP within 6 hours of extravasation

When should dexrazoxane be dose adjusted?

CrCl < 40 mL/min = reduce dose by 50%

What are common AEs of dexrazoxane?

Bone marrow suppression, N/V, edema, fatigue, AST/ALT elevations

What is the antidote for extravasation as a result of vinca alkaloids, paclitexel or docetaxel?

Hyaluronidase

How should hyaluronidase be dosed when being used for the treatment of extravasation?

Inject 1 mL of solution as five separate injections each containing 0.2 mL of hyaluronidase around the site

What is the MOA of hyaluronidase?

Modifies the permeability of connective tissue through hydrolysis of hyaluronic acid

Increases the dispersion and absorption of locally injected or extravasated IV medications