Chemotherapy Preparation and Dispensing

hazardous drug

Drug that meets at least 1 of the following:

• Carcinogenic

• Teratogenic

• Fertility impairment

• Organ toxicity at low doses (

carcinogenic

cancer causing

teratogenic

causes congenital disabilities

genotoxicity

damages DNA, which can cause cancer

yes

Can exposure to hazardous drugs cause acute and long term AEs?

contaminated surfaces

What is the most common route of exposure with hazardous drugs?

skin, ocular, flu-like symptoms, HA

What are the acute reactions with exposure to hazardous drugs?

fetal abnormalities, loss of fertility, secondary cancers

What are the chronic reactions with exposure to hazardous drugs?

- Inhalation

- Accidental injection

- Ingestion of contaminated food or mouth contact with contaminated hands

- Dermal contact with contaminated surface

What are the routes of exposure with hazardous drugs?

non-chemo hazardous drugs

• Warfarin

• Fluconazole

• Isotretinoin

• Dronedarone

• Finasteride

• Paroxetine

• Phenytoin

• Colchicine

• Spironolactone

• Estrogens

• Progesterone

• Temazepam

• Cyclosporine

• Liraglutide

USP

provides regulatory standards for sterile compounding

USP 797

outlines sterile product preparation

USP 800

describes handling strategies for HD

ASHP

provides information on implementing recommendations and requirements for handling and compounding hazardous drugs

low risk hazardous drugs

-Limited risk of causing harm

-Counting and packaging tablets

-Do not require following all USP 800 requirements

-Safety Measures:

• Dedicated tray for counting

• Use of gloves

-Examples: finasteride, misoprostol

PIC

Who makes the rules on how you treat low risk hazardous drugs?

high risk hazardous drugs

• High risk of causing harm

• IV compounding; splitting tablets

• Must follow USP 800 requirements

• Example: IV chemotherapy

USP

Who makes the rules when handling high risk hazardous drugs?

-neg pressure room

-room externally vented

-a vertical flow biological safety cabinet

-appropriate air changes per hr

What is required per USP 800 in a compounding area?

at least 30 per hr in a room where the hood is located

What is the appropriate air change amount per hour in a compounding area per USP 800?

personal protective equipment per USP 800

- Double gloves or chemo rated gloves

- Impermeable gowns

- Double shoe covers

- Respiratory protection for spills/cleaning

• Dress from "dirtiest to cleanest"

- Exact order may differ between settings (shoes, hair, mask, gown, gloves)

Closed System Drug Transfer Device (CSTD)

-"a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of the hazardous drug or vapor concentrations outside the system."

- Recommended to use throughout HD-handling chain from compounding to patient administration

negative

Hazardous drugs must be stored in a __________ pressure room.

segregate

You should __________ HD stock from other inventory.

must

Staff ______ wear gloves when handling HD inventory.

distinctive labels

Drug packages and storage areas must bear __________ for special handling precautions

PRONTO

Use of a standardized checklist can help reduce risk of error

patient

What does the P in PRONTO stand for?

regimen

What does the R in PRONTO stand for?

Organ system

What does the O in PRONTO stand for?

Numbers

What does the N in PRONTO stand for?

Toxicity

What does the T in PRONTO stand for?

Order verification

What does the O in PRONTO stand for?

Patient part in PRONTO

Review chart to gain an overview of the patient.

- What type of malignancy does the patient have?

- What is the goal of treatment? (curative vs palliative)

- What is the patient's performance status (ECOG score)?

- What type of line access does the patient have? (Central versus peripheral)

- What is the current treatment?

- What are current lab values?

ECOG 0

Fully active, able to carry on all pre-disease performance without restriction

ECOG 1

Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; e.g. light house work, office work

ECOG 2

Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours

ECOG 3

Capable of only limited self care, confined to bed or chair more than 50% of waking hours

ECOG 4

Completely disabled. Cannot carry on any self care. Totally confined to bed or chair

ECOG 5

dead

typically 0-2

What ECOG scores do we typically consider tx for?

typically 3-5

What ECOG scores do we typically consider comfort care for?

Regimen/dose part in PRONTO

Does the regimen match a published regimen and make sense for the patient?

- Do you have a reference that supports the regimen?

- Is the patient due for chemo based on cycle and day?

- Is the dosing of chemotherapy appropriate?

• Dose, route, dilution fluid, rate

- Is the sequencing of chemotherapy appropriate?

safety

What is the primary responsibility at the R-regimen/dose step in PRONTO?

drug information resources (Lexi, Micromedex)

these references are the least helpful with dosing regimens

cycle

how frequent the regimen is repeated

day

the day of each cycle the medication is given

1)vesicant -> irritant -> nonvesicant

2) efficacy/safety

3) stability

What is the sequencing of chemo?

less

The _____ stable agents of chemo should go first.

Organ function/labs part in PRONTO

Do the patient's organ function and labs warrant full dose treatment?

- CBC

- Electrolytes

- Renal Function (CrCl)

- Liver Function

- Urinalysis

- Echocardiogram/EKG

organ function/labs section to determine appropriate dosage adjustments and monitoring

When should you use drug info resources in PRONTO?

Numbers part in PRONTO

Dose Calculations

- CrCl

- BSA

- AUC

Admixture and Administration Numbers

- Concentrations

- Rate of Infusion

- Fluid type

BSA

estimate of cardiac output and distribution to the liver and kidneys and is commonly used for dosing in chemo

Carboplatin Dose (mg)= target AUC x (GFR + 25)

What is the Calvert Equation used for AUC dosing of Carboplatin?

Toxicities part in PRONTO

Does patient have appropriate medications to

prevent toxicities?

- Nausea/Vomiting?

- Infusion related reactions?

- Neutropenia?

- Tumor lysis syndrome?

Any risk of drug-drug interactions with other medications?

Order verification part in PRONTO

1. Independent Double Check of "PRONT" step

2. Compare chemotherapy order, label and product

Extravasation

The inadvertent instillation or leakage of a cytotoxic drug into the perivascular space during infusion

Irritant

• May induce a local inflammatory response

• Short-term injury; does not lead to tissue necrosis/injury

• Vein may be tender or have burning/erythema

• Blood return remains intact

Vesicant

• Severe necrosis; erythema and blistering of skin around extravasation

• May take up to 6-12 hrs for symptoms to appear

• Blood return is absent

• Anthracyclines, taxanes, vinca alkaloids

-use central catheter

-educate pt on s/s to report

-check for blood flow throughout admin

-bolus doses of irritant/vesicant chemo should be given over 5-10 mins through a free-flowing IV line

What are the ways to prevent extravasation?

pain, redness, swelling at injection site

What should the patient look out for to alert us that extravasation may be taking place?

extravasation tx

1. Stop infusion

2. Aspirate any drug via the intravenous cannula

3. Do NOT flush the line

4. Remove the catheter/needle

5. Elevate and immobilize the affected limb

6. Apply cold or warm packs as recommended (Warm: Vinca alkaloids; Cold- most everything else)

7. Administer antidote, if available

8. Photograph site and/or mark around area with permanent marker

9. Monitor site closely for 24 hrs and up to 2 weeks for redness, swelling, pain, ulceration, and/or necrosis

Dexrazoxane

-admin: IV infusion

-MOA: Prevent free-radical formation and reduce oxidative stress

-useful against Anthracyclines

Dimethyl sulfoxide (DMSO)

-admin: topical

-MOA: Neutralizes free radicals, promotes absorption of vesicant

-usedful against Anthracyclines, Cisplatin

Hyaluronidase

-admin: SC into infiltration site

-MOA: accelerates local connective tissue breakdown and absorption

-useful against Vinca or taxanes

Sodium thiosulfate

-admin: SC injection into infiltration site

-MOA: binds and neutralizes vesicant

-useful against Cisplatin

no

Are all tumors with (-omas) at the end malignant?

BSA

is believed to be a more accurate measure that eliminates"adipose" effects. Criticized for not taking into account inter-patient variation in pharmacokinetics and PGx.

-hormone therapy

-surgery

-bone marrow transplantation

-immunotherapy

-radiation therapy

-targeted therapy

-chemotherapy

What are the conventional tx options for cancer?

-surgery

-radiotherapy

-cytotoxic chemotherapy

-molecularly targeted therapy

-immunotherapy

What are the pillars of cancer care?

gene therapy

What will be the new and upcoming pillar of cancer care?

Neoadjuvant

Chemotherapy delivered BEFORE the main treatment, to help reduce the sizeof a tumor or kill cancer cells that have spread. In many cancers, its used to down stage select patients with malignant tumors, thereby rendering the primary tumors and metastases resectable in some cases

Adjuvant

Chemotherapy delivered AFTER primary treatment which attempts to eliminate micrometastasis; given to prevent a possible cancer recurrence

First line chemotherapy

Chemotherapy determined to have the best probability of treating a given cancer. This may also be called standard therapy.

Second line chemotherapy

Chemotherapy that is given if a disease has not responded or reoccurred after first line chemotherapy. In some cases, this may also be referred to as salvage therapy.

Palliative

Chemotherapy aimed at improving or managing symptoms

Curative

Elimination of all known tumor mass (Complete and Durable Response)

narrow

The therapeutic window for most cancer drugs is _________

wider

The ________ the therapeutic window the better.

therapeutic index

toxic dose/effective dose

safer

A therapeutic index of 3 or greater is a _______ drug.

adverse effects (off-target) of chemo

-alopecia

-mucositis

-pulmonary fibrosis

-N/V

-cardiotox

-Diarrhea

-Local reaction

-Cystitis

-Renal failure

-Sterility

-Myelosuppression

-Myalgia

-Neuropathy

-Phlebitis

• 5HT3 receptor antagonist (-setron class)

• Dexamethasone

• NK1 receptor antagonist (-pitant class)

Drug classes that treat CINV (nausea and vomiting)

no FDA approved therapies...yet (duloxetine)

Drug classes that treat CIPN (peripheral neuropathy)

bisphosphonates

Drug classes that treat bone loss (CIBL)

neutrophil enhancers

Drug classes that treat neutropenia (CIN) and febrile neutropenia (CIFN

platelet enhancers

Drug classes that treat thrombocytopenia (CIT)

erythropoietin stimulating agents (ESA)

Drug classes that treat anemia (CIA)

1) a therapy that targets

2) a population of cancer cells

3) a particular host environment

What is the 3 component system of cancer therapy?

intrinsic resistance

exists before drug tx

acquired resistance

is induced after therapy

50%

What % of cancer pts have drug resistance?

staging

describes the extent or spread of disease at the time of diagnosis

cancer extent and severity

What is staging in cancer used to gauge?

-summary

-TMN

What are the 2 staging systems generally used with cancer?

The Summary Staging System

more general of a system for staging

-in situ

-localized

-regional

-distant (metastatic)

What are the 4 main types of the summary staging system?

in situ

is early cancer that is present only in the layer of cells in which it began

localized

is cancer that is limited to the organ in which it began, without evidence of spread

regional

is cancer that has spread beyond the original (primary) site to nearby lymph nodes or organs and tissues