Take the 21st Century

Pharmacy Challenge!Tackling Issues Affecting Palliative Patients Across the Country!

Serena RixBSc Hons(Pharm) Pharm D

October 21, 2019Edmonton, Alberta

Conflict of InterestI am a pharmacist:

Covenant Health pays

me as such.

No conflicts of interest

to declare

No grants/research

support/honoraria/

consulting fees

/patents/or funding of

any kind.

The information

presented is unbiased.

Photo credit: jamanetwork.com

With a little help from my friends

Ron Marcinkoski will provide perspective as community

pharmacist from a sterile/compounding pharmacy.

Who are you?

Photo credit: Winnipeg Regional Health

Objectives

By the end of the presentation the participants should

be able to:

Explain the rationale behind the NAPRA Model Standards

and consequent effects on palliative patients.

Describe the opioid crisis and how this impacts palliative

patients and their caregivers.

Identify how pharmacists can offer alternative therapeutic

options when prescribed medications are unavailable.

Discuss how improving funding models to allow patients to

stay at home longer, may be economically viable.

Meet the “Perkins” Family

Petra is 30 yrs old, married to

James, a freelance

photographer.

3 children: Emma (9), Olivia

(7) & Tyler (5 ).

They live in Edmonton. Petra’s

parents & 3 sisters all live

nearby & help with care.

The Perkins family have a cat

and a dog,(Smudge & Curly).

Photo credits: today.com & warrenphotography.co.uk

“Petra Perkins”

Diagnosis: Ovarian cancer (June 2017).

Recent imaging shows extensive intra-abdominal disease,

malignant bowel obstruction, mild hydronephrosis, and ascites.

Symptoms: Pain, nausea, constipation, dyspnea, anxiety. PE

diagnosed one month ago.

Formerly a primary school teacher but has not worked since the

children were born. Home schools. Part-time fitness instructor.

There are financial concerns.

Petra wishes to die at home: family willing to support her there.

Transferred to TPCU to stabilize symptoms and return home.

BPMH on Discharge for TPCU.

Methadone 5 mg subcut q8h atc, & 1.5 mg subcut q1h prn pain/dyspnea.

Haloperidol 1mg subcut q8h & q1h prn nausea/anxiety.

Provide pre-loaded syringes for Haldol & methadone.

Tinzaparin 12 000 units subcut daily (Wt: 68 kg).

Morphine 0.1% gel to coccyx ulcer with dressing change.

Bisacodyl 10 mg PR daily prn constipation (&/or Fleet enema).

Home TPN (central line in place).

Venting PEG tube, PleurX catheter in place to drain ascites.

Allergies: none. GCD: M1.

CrCl 50 mL minute (need to monitor for hydronephrosis).

PPS 50 % . Prognosis: weeks to short months.

Fax Discharge Med Rec to Community Pharmacy…

Photo credit: 123rf.comPlease don’t do this on Friday night!

Why is she pulling her hair out?

Unable to provide subcut methadone or haloperidol syringes:

Need certified clean room.

Unable to provide morphine gel:

Need compounding environment with appropriate equipment.

Drug shortages:

Recent examples: scopolamine injection, hyoscine tablets.

Stock issues:

Tinzaparin preloaded syringes not currently in stock: must order.

Third party payers:

Will not pay fees to preload syringes, patient must pay out of pocket.

Time constraints:

This will take a lot of time to organize.

Sometimes a walk down memory lane is all takes to appreciate where you are today. Susan Gale

Photo credit: oursideofsuicide.com

Evolution of Pharmacy 1939-2019

Photo credits:amazon.com Photo credit: magazine.wsu.edu

These days have gone…

Daley’s Drugstore, Edmonton,

1882

Sun Drug Store, Edmonton 1922-

1956

Fort Edmonton Park

Pharmacy 2019

Clean Room (Sterile) Compounding Area

Photo credits: cleanroomtechnology.com & thecompoundingcentre.com

Struggles of the 21st Century Pharmacist. Expectations: (not just “lick & stick”)

Dispense prescriptions.

Prescribe/adapt

Immunize.

Conduct health histories,

Review medications.

Provide patient counselling.

Identify & resolve DRPs.

Comply with:

NAPRA standards.

Legislation.

Standards of practice & ethics

Answer the phone, tackle 3rd party payers, run the till, find wart remover…

Photo credit: pharmaceutical-journal.com & clipartlibrary.com

ACP Standards of Practice &

NAPRA Standards Following USP 797, 800, 795.

NAPRA: Model Standards for Compounding Non-Hazardous Sterile Preparations (eg: methadone injection)(Approved by ACP, Nov 2016).

NAPRA Model Standards for Compounding Hazardous Sterile Preparations (eg: chemotherapy) (Approved by ACP, Nov 2016).

Standards for Pharmacy Compounding of Non-sterile Preparations (eg: morphine gel) (revised July 2018).

Why? A little history lesson…

1990, Nebraska: 4 patients die in hospital from bacterial

infections from contaminated cardioplegia solution.

1990:, Pennsylvania: 2 patients use eye drops

contaminated with P. aeruginosa, losing vision. Drops were

compounded in community pharmacy: commercial

product had been available.

1998, California: 10 children contracted blood infection

from pre-filled syringed contaminated with Enterobacter.

Poor aseptic technique identified as root cause.

Ref: #1

Still more examples…

2001, Missouri: 4 pediatric patients in hospital

receive contaminated IV ranitidine, mixed in

automated compounding device. Lack of

appropriate garbing & hygiene cited as cause.

2002, South Carolina: 5 patients receive injectable

steroids contaminated with Exophiala spp, resulting

in 1 death. Untrained compounding personnel

cited as cause.Ref: #1

It continued…

2004, Maryland: 16 patients contracted Hepatitis

C from contaminated radio-isotope used in stress-

testing. Pharmacy non-compliant with aseptic

technique.

2007: Study reveals only 13% pharmacy graduates

are adequately trained in aseptic technique.

Ref: #1

Introduction of USP 797

Nov 2007: USP proposed Chapter 797, placing emphasis on individual training and evaluation of sterile products.

Launched in 2008.

Yet the errors continue…

2011: Pediatric patient dies due to compounding error.

2012: Widespread fungal meningitis linked to contaminated steroid injections prepared at non-compliant pharmacy. 751 affected.

2013 Connecticut: Magnesium sulphate contaminated with mold: pharmacy shut down.

2013 Texas: Contaminated IV Calcium gluconate. 15 infected & 2 die.

Ref # 1

Drug Quality & Security Act

Becomes law in 2013.

2015: Voluntary recalls across the US.

US Compounding Inc: all sterile products.

Downing Labs Inc: compounded materials.

Hospira: mold contamination.

46 clinical trials suspended: defects in manufacturing.

Ref: #1

Photo credit: thefader.com

What about the Great

White North?

NAPRA introduced Model

Standards of Practice

based on USP and adopted

by ACP (Nov 2016).

Compliance expected by

2018. Are we there yet?

Unable to find examples of

contaminated sterile

products in Canada.Photo credit: Etsy

So what’s in these Model Standards of Practice?

Core requirements for a sterile compounding

service:

Personnel & their conduct in sterile areas, policies &

procedures, facilities, equipment and maintenance.

Products & their preparation requirements:

BUD and dating methods, preparation protocols, logs,

packaging, storage, transport, delivery, incident &

accident management, waste management.

Quality assurance requirements.

Ref #;2

What does all this mean? (Briefly, please)

IV rooms and their personnel must meet these

strict criteria.

Beyond use dates (BUD) are related to both

chemical and microbial stability of the product.

To establish longer BUDs sterility testing must

performed on each batch, which remains

quarantined until designated safe.

Otherwise BUD determined according to risk of

microbial contamination.

Ref: #2

Contamination risk levels

Low Medium High

•Final product compounded using up to 3

“sterile units”

•No more than 2 septum punctures at the

injection site for each sterile unit

•Simple aseptic transfer technique

•Drug prepared for one patient (patient-

specific dose)

•Final product compounded using 4 or

more “sterile units”

•Complex manipulations

•Prolonged preparation time

•Batch preparations (preparing more than

one unit of the same composition during

one compounding session)

•Non-sterile ingredients or equipment

used before terminal sterilization

•Non-sterile preparations, containing

water, stored for more than 6 hours

before terminal sterilization

•Improper garbing or gloving by

compounding personnel

Beyond-use dates (BUDs) for compounded sterile preparations,

according to risk of microbial contamination

BUD without sterility testing

Risk of contamination At controlled room

temperature With storage in refrigerator With storage in freezer

Low 48 hours 14 days 45 days

Medium 30 hours 9 days 45 days

High 24 hours 3 days Ref #:2

At the GNH (Station 43)

Edmonton injectors no longer in use since July 2019

Except methadone

Until vials can be provided in Pyxis/fridge).

Methadone injection is a high-risk sterile product.

Compounded externally and sterility tested. BUD = 7 days fridge & 48 hrs at

room temp.

Wastage is a huge issue

Oxycodone similar issues but cost is prohibitive at present.

Hydromorphone & morphine provided in commercially available

vials up to 50mg/mL (with ROPE).

Some fentanyl infusions are only stable for 30h at room

temperature. Pharmacy provides only those stable for 48h.

Consequently at GNH…

The EI’s are changed every 2 days.

“Dose banded”

Increased pharmacy and nursing time.

Increased risk of error.

Increased wastage.

Contributing to shortages.

Before NAPRA initiated After NAPRA Initiated

~27 EI’s per month (10 months data) ~80 EI’s per month (6 months data)Data from April 2019

Begging the question…

Does this increased level of safety justify the cost?

No perceived issues previously:

Microbially.

Chemically.

Evidence of better outcomes now?

Can we find an equitable alternative?

Facilities and staff certified regularly?

Random product testing, technician

technique, & facility inspections.

Photo credit: prezi.com

In the community the same rules apply…

Need a pharmacy which can provide sterile

products and compounding services.

Time and equipment required are expensive.

Subsequent increased costs are frequently

incurred by patient/family.

Turn around time may be slow for

new/changed Rx.

Provision of after hours and delivery services

complex and costly.

Back to Petra…

Her discharge Rx requires:

A compounding pharmacy with a clean room which can provide

methadone & haloperidol in syringes.

Pharmacy authorized to compound morphine in Intrasite® gel.

Community pharmacy needs to order tinzaparin syringes.

Need to start organize home TPN & other homecare services.

Hospital pharmacist needs to be proactive prior to discharge

Give pharmacies adequate notice. Rx can be prepared in

advance, so patients/families do not have to wait for meds.

Provide sufficient patient history and our contact information.

Photo credits: brushlovers.com

Petra has been at home for 10 days…

She has run out of methadone syringes early.

Petra insists she has been taking her medications as directed.

Concerns regarding storage as there are small children and pets in the house.

Medications are stored in the cupboard above the fridge which is believed to be too high for the children to reach.

Fortunately, there have been no signs of opioid ingestion by the children/pets.

Further investigation reveals her sister’s boyfriend has been taking them.

The Opioid Crisis…

Refers to rise in deaths from opioid overdose:

Prominent media coverage.

Considered a major health concern in Canada.

May have impacted perceptions of patients, families and HCPs regarding the utility of opioids in palliative care patients.

Photo credit: yourfirststep.orgRef #: 3

Current Issues

Primarily resulting from use of illegally obtained

fentanyl or carfentanil (10 000 times more potent

than morphine and too toxic for human use).

Users believe they are taking heroin or oxycodone, but

dealers may have incorporated these cheap but

potent agents, in varying quantities, to increase

potency & thus profits.

These unknown potencies can lead to overdose and

potentially death.

Ref #: 3

Government acknowledgement: 2016 (1)

Health Canada’s Action on Opioid Misuse.

Better informing Canadians about the risks of opioids.

Supporting better prescribing practices.

Reducing easy access to unnecessary opioids.

Supporting better treatment options for patients.

Improving evidence base.

Joint Statement of Action to Address the Opioid Crisis

Commitment of health ministers & organizations to take

action.Ref #: 3

Government acknowledgement: 2016 (2)

Canadian drugs and substances strategy: A comprehensive, collaborative, compassionate, and evidence-based approach to drug policy.

Prevention: Preventing problematic drug and substance use.

Treatment: Supporting innovative approaches to treatment and rehabilitation.

Harm reduction: Supporting measures that reduce the negative consequences of drug and substance use.

Enforcement: Addressing illicit drug production, supply and distribution.

Ref #: 3

Spectrum of aberrant opioid-related behavior

Ref: #4

Addressing Concerns of Palliative Patients & Families.

May have concerns using fentanyl & other opioids to control pain in palliative patients.

Advise overdose uncommon if:

Prescribed/taken appropriately.

Used for legitimate pain/dyspnea control.

Closely monitored for efficacy & toxicity.

Ref #: 3 Photo credit: binsonsrx.com

Education for Patients & Families

Opioid tolerance: Body becomes tolerant to the medication & may necessitate dose increases.

Opioid dependence: withdrawal symptoms likely to occur if the drug is suddenly stopped. Therefore doses should be weaned when there is no further need for the medication.

Opioid addiction: when there is an overwhelming preoccupation with obtaining more medication without a medical need for it.

Craving, loss of control of amount used, compulsion to use, & continued use despite consequences.

Ref #: 3

Strategies for Palliative Patients (1)

Frequent assessment of pain & other symptoms.

Frequent reassessment of medical conditions,

prescriptions, including medication reviews.

Limit prescribers & pharmacies used & quantities

dispensed. Increased accountability.

When discharged from acute care setting stop any

existing refills.

Consider use of opioid-risk assessment tools.

Consider random pill counts &/or drug testing.

Ref #: 3

Strategies for Palliative Patients (2)

If substance abuse disorder is suspected consult addictions counselling.

If mental health diagnosis is present, consider consultation with psychiatry or mental health organizations.

Consult palliative care when necessary.

Educate patients about safe storage of opioids (preferably locked).

Unused medications must be returned to the pharmacy for safe disposal.

Ref #: 3

Information for Patients and FamiliesOpioid Medicines

SIGNS OF OVERDOSE

Call 911 or your local emergency response provider right away

if you suspect an opioid overdose or think you may have taken too

much. *

• Hallucinations

• Confusion

• Difficulty walking

• Extreme drowsiness/dizziness

• Slow or unusual breathing

• Unable to be woken up

• Cold and clammy skin

This handout is a summary and will not tell you everything about opioid medicines.

More information about the opioid you have been prescribed (or naloxone) can be found online in the Product Monograph: https://health-products .canada.ca/dpd-bdpp/index-eng.jsp

SERIOUS WARNINGS

• Opioid overdose can lead to death. Overdose is more likely to happen athigher doses, or if you take opioids with alcohol or with other sedating drugs(such as sleeping pills, anxiety medication, anti-depressants, muscle relaxants).

• Addiction may occur, even when opioids are used as prescribed.

• Physical dependence can occur when opioids are used every day. This canmake it hard to stop using them.

• Life-threatening breathing problems or reduced blood pressuremay occur with opioid use. Talk to the health professional who prescribed youropioid about whether any health conditions you have may increase your risk.

• Your pain may worsen with long-term opioid use or at higher doses.You may not feel pain relief with further increases in your dose. Talk to thehealth professional who prescribed your opioid if this happens to you, as alower dose or a change in treatment may be required.

• Withdrawal symptoms, such as widespread pain, irritability, agitation,flu-like symptoms and trouble sleeping, are common when you stop or reducethe use of opioids.

• Babies born to mothers taking opioids may develop life-threateningwithdrawal symptoms.

• Use only as directed. Crushing, cutting, breaking, chewing or dissolvingopioids before consuming them can cause serious harm, including death.

You have been prescribed an opioid medicine for the treatment of pain or for another condition.

Talk to the health professional who prescribed your opioid, or your pharmacist if you:

YOUR OPIOIDS MAY BE FATAL TO OTHERS

• Never give your opioid medicine to anyone.

• Store opioids (including used patches) in a secure place to prevent theft, problematic use or accidental exposure.

• Keep opioids out of sight and reach of children and pets. Taking even one dose by accident can be fatal.

• Never throw opioids (including used patches) into household trash where children and pets may find them.

• Return expired, unused or used opioids (including patches) to a pharmacy for proper disposal.

• Reduced physical and/or mental abilities, depression

• Drowsiness, dizziness, risks of falls/fractures

• Heart palpitations, irregular heartbeat

POSSIBLE SIDE EFFECTS

• Vision problems, headache

• Low sex drive, erectile dysfunction, infertility

• Severe constipation, nausea, vomiting

• Problems sleeping, may cause or worsen sleep apnea

• Have questions about your opioid medicine.• Do not understand the instructions for using the opioid medicine given to you.• Develop side effects or your condition worsens.

* Naloxone has been approved byHealth Canada to temporarily reverse known or suspected

opioid overdoses.

Date: 2019/03/15

Health Canada

mandated dispensed

opioids must have the

yellow sticker attached

and the information sheet

enclosed (Oct 2018)

Applies to pass meds

(April 2019)

Provide naloxone kits?

Naloxone KitsProvided free of charge in

Alberta pharmacies.

Injectable/nasal spray.

Saves lives in overdose situationsFamily/friends of patient

Deliberate or accidental

Palliative patients

Caution: may precipitate a pain crisis

Administer if RR less than 8 or other signs of opioid toxicity

CALL AMBULANCE

Photo credits: cbc.ca

Example of wastage…

Hydromorphone 1 mg

X 19

Hydromorphone 2 mg

X 21

Hydromorphone 4 mg

X 90

Hydromorphone 8mg

X 189

Hydromorph Contin®

3mg

X 46

Hydromorph Contin®

6mg

X 59

Hydromorph Contin®

18mg

X 32

Hydromorph Contin® 24

mg

X 37

Tylenol #3®

X 30

Nabilone 1 mg

X 29

Tramacet®

302

1 patient, opioids only, approximate wholesale price (no upcharge/fees)

~$613.80

What did the Perkin’s Family do?

Medications now stored in a safe.

Limited quantities dispensed.

Returned unwanted meds to pharmacy for safe disposal.

More cognizant of safer opioid practices.

Called police and pressed charges.

Sister is looking for a new boyfriend.

Photo credit: ntacare.com

As Petra’s Condition declines…

Need to

administer

clodronate

subcutaneously.

Can we do this

at home?

Photo credit: ottawacancer.ca

Drug shortages and discontinuations

Drugs which have been/are

in short supply recently

Scopolamine injection.

O&B supps (come and go).

Ranitidine/famotidine tablets.

Metoclopramide 10 mg.

Oxycodone powder.

Methylnaltrexone.

Naloxone.Photo credit: serviceskillssa.com.au

Why are there so many shortages?

Explanations include:

NAPRA/USP have forced factories to renovate.

NAPRA/USP have increased wastage of drugs due to shorter expiry dates.

Manufacturers unaware how changes may affect production.

Shortage of raw materials.

Contamination

Economic (decreased use of product leads to discontinuation).

Blame the government.

Manufacturers should accept some responsibility http://martincwiner.com/

Drugs discontinued & work-arounds

Methotrimeprazine was discontinued in the 2000’s

Pressure from palliative care physicians led to its re-introduction by importing product from the UK.

Clodronate injection has been discontinued.

Only bisphosphonate which can be given subcutaneously (home).

Is IV pamidronate or zoledronic acid an option for home use?

Oral bisphosphonate? Depends on the indication.

Compounding pharmacies may be able to supply clodronate in future.

Metoclopramide 10 mg tabs (short then discontinued)

Use 5mg tabs (still available)

Methylnaltrexone

Naloxegol now available (oral only: not useful if nausea/obstructed)

Prescribing pharmacists may provide alternative agents during a shortage.Eliminates need to contact original prescriber & ensures

seamless care in a timely manner.

Must be familiar with palliative care off-label uses/doses.

Collaboration between hospital & community pharmacist prior to discharge is essential to ensure patient care needs are met.

Photo credit: CPhA

What can the community pharmacist provide?

Monitoring

Efficacy

Adverse effects

DRPs

Adherence

Education

Support (most

accessible HCP)

Pharmacists: Caring for the Caregivers

Family members

The community pharmacist may be their pharmacist too

Ensure caregiver stays healthy

Provide support as needed

Refer if necessary

Other HCPs

Provide optimum service/communication to make their job easier

Seamless care

Photo credit: drugstorenews.com

Pharmacist

Education in PC

Palliative care has not been taught well in the schools of pharmacy. Focus on conditions with outcomes

perceived to be more amenable to pharmacy care. Diabetes, HTN etc.

All pharmacists will encounter palliative patients either hospital or community.

Urging modern programs to incorporate more instruction.

Pharmacists who graduated a while ago recognize the knowledge gap and wish for more education and resources to be available to them.

Work underway to resolve some of these issues.

Photo credit: ascp.com

Can Petra remain at home?

Home care involved.

Compounding pharmacies are supplying syringes

including methadone & haloperidol.

Local pharmacy provides other medications

including her tinzaparin.

Palliative Blue Cross covers some costs. However

prescriptions are still very expensive and becoming

an increasing burden to the family.

As Petra’s condition declines further…

Family experiencing Caregiver burnout.

Symptoms more difficult to manage.

Increased financial stresses.

Forced to take her to ERThey feel they have let her down.

Disposition alternativesAcute care/TPCU.

Hospice.

Home

Photo credit: healthline.com

The cost of dying is high

Up to $40 000 for cancer patients (2009 data).

~75% of costs for acute care services.

Costs to family may be up to $25 000 per month.

Including lost wages and other out-of-pocket expenses.

High-cost traditional care, may not be optimal care.

Ongoing curative treatments which may not provide

benefit.

Ref #: 5

Disposition Options

Acute care: most costly alternative.

Hospice: more cost-effective when Petra meets criteria (PPS 40% and GCD C1 or C2).

Returning home is, not an option for financial reasons, (drug costs are high), yet this is Petra’s preference.

https://videoconferencingdaily.com

Could we make home a viable option for Petra?

Considering:

Cost of acute care/hospice.

Shortage of beds.

Aging population will require more services in the future.

Could we make an economic argument to provide

more support at home including subsidizing the high

costs of medications (including sterile services)?

Would government provide funding for these

services if it were to their economic advantage?

In the ideal world…

Increased government funding could provide:

Better access to medications including subsidies allowing sterile

products to become more affordable.

Enhanced pharmacy services including after-hours services.

Dispensing of smaller quantities of medications with no increased

cost to patient, thus decreasing wastage & potential diversion.

Fund pharmacists to conduct pill counts to ensure compliance.

Home visits with physicians, home care and EMS: pharmacists

would be part of the team providing services in the home (care

plans, teaching, monitoring, review of safe storage requirements).

Improved communications between HCPs using technology.

The final chapter…

Petra remained on the TPCU

She was able to use the inter-

disciplinary team to help her

& her family prepare.

She died peacefully with her

husband, parents and sisters

at bedside

Would she have gone home

if more resources available?

Photo credit:kidsworldfun.com

Conclusions

NAPRA standards are making provision of sterile products both difficult to provide and costly.

Despite the opioid crisis palliative patients should have continued access to adequate opioid therapy but within strict criteria and monitoring.

Drug shortages continue to be an issue for many reasons, and we need to adapt accordingly.

Subsidy of costly medications may allow patients to remain at home longer, freeing up hospital beds.

Pharmacists provide essential services to palliative patients and their caregivers.

“How people die

remains in the

memory of those

who live on.” Dame Cicely Saunders

Parting Thoughts…

Photo credit: nairaland.com

serena.rix@covenanthealth.ca

References 1: A timeline of sterile compounding events and actions taken.

Blog.pharmacyonesource.com posted 11/12/15 accessed online Jan 2019

2: Model standards for pharmacy compounding of non-hazardous sterile

preparations. NAPRA (2015) accessed on-line Jan 2019

3: What is happening with the opioid crisis in Canada? What should I know t

use opioids safely in palliative care patients? Virtualhospice.ca (accessed

inline March 2019)

4:Opioid prescribing in an opioid crisis: what basic skills should an oncologist

have regarding opioid therapy? Arthur J, Reddy A: Curr. Treat Options in

Oncol (2019) 20:39

5:Canadian Hospice Palliative Care Association: Cost-effectiveness of palliative care (http://hpcintegration.ca/media/24434/TWF-Economics-

report-Final.pdf: accessed on-line April 2019)