Hospice & Palliative Care in Developing Countries

Compounding End of Life Medications

WHO Recommendations to Developing Countries

Russ Zakarian, Pharm.D. FASCP

What is Compounding?

Compounding is the method of preparing customized medications to help meet unique physician and patient needs.

Pharmacy

The art or profession of preparing and preserving drugs, and of compounding and dispensing medication according to the prescriptions of physicians.

– Early 20th Century Webster Dictionary

Also known as a problem solver, a compounding pharmacist’s ultimate goal in preparing customized

medications is to help the physician and patient achieve a more positive therapeutic outcome.

Hospice

Alternative routes of administration Individualized pain management Nausea & vomiting Inhalation therapy Emergency kits Mouth ulcers Saliva stimulants Adjunctive therapies

Meeting Unique Needs In:

Hospice Pain Management Bio-identical Hormone Replacement Therapy Veterinary applications

– Household pets– Equine– Zoos– Exotics

Dental Dermatology

Compounded Dosage Forms

Oral capsules and liquids Transdermals Lollipops and popsicles Troches, tablet triturates and sublingual

drops Rapid dissolve tablets Suppositories, enemas and rectal rockets

Compounded Dosage Forms

Nasal and otic preparations Topical creams, ointments, gels, powders

and sprays Oral adhesives, mouthwashes and rinses Sterile products

– Inhalation solutions, injections, ophthalmics, TPNs

Compounded Capsules

Medications formulated in capsules enable the patient to get the exact dosage needed, while avoiding unwanted dyes and fillers.

Compounding for Pain Management

Capsules– Morphine Sulfate SR caps up to

900mg/cap– Oxycodone SR caps

Compounded Oral Liquids

Preparing medications in a liquid form allowathe patient who can’t swallow pills to get the appropriate medicine in a vast range of flavors, such as tutti-frutti or vanilla butternut.

Compounded Oral Liquids

Difficulty swallowing

Avoid unwanted ingredients

Increased compliance

Anhydrous formulations

Compounding for Pain Management

Oral Liquids– Magic Mouthwash

Morphine oral solutions 50mg/ml(commercial dose is 20mg/ml)

Transdermal Gels

Transdermal Drug Delivery

Drug Classes Used in Transdermals NSAIDS Muscle relaxants Antinausea agents Antiviral agents Anti-inflammatory agents Anesthetics Anti-anxiety agents

Transdermal Drug Delivery

Drug Classes Used in Transdermals Anti-diabetic agents Antidepressant / anti-psychotic agents Anti-hypertensive agents Thyroid medication Antihistamines Anti-infective agents

Compounding for Pain Management

Transdermal Gels– ABHR– Alprazolam– Dexamethazone– Diazepam– Gabapentin– Haloperidol– Ketamine

Compounding for Pain Management, cont

Transdermal Gels– Hydroxyzine– Metochlopramide– Oxycodone– Promethazine– Temazepam– Diphenhydramine

Medicated Lollipops

Local effects– Anesthetic– Antifungal– Antiviral– Anti-inflammatory– Saliva stimulant– Healing agents

Medicated Lollipops

Systemic effects– Anti-anxiety– Antipyretic– Analgesic

Narcotic Non-narcotic

Troches

Soft gelatin-flavored troches, such as those prepared in the 24 and 30-count molds, provide medication in an easy-to-take and pleasant-tasting form.

Rapid Dissolve Tablets

Compounded Sterile Products

USP <797> standard compliant Infusion pain management with CADD infusion

pumps Routes of infusion: SQ, MediPort, PICC MS 50mg/cc Hydromorphone 10mg/cc Fentanyl 50mcg/cc Lorazepam 2mg/cc Midazolam 5mg/cc

Suppositories and Enemas

Rectal or vaginal use Helpful to patients who

have difficulty in swallowing, nausea/vomiting

Injections cause pain, anxiety

Rapid local affect

Compounding for Pain Management

Suppositories– ABHR– Chloral Hydrate– Diazepam– Morphine– Phenytoin– Gabapentin

The Rectal Rocket

Quality & Safety Steps in the Compounding Laboratory

IAHPC Meds for Palliative Care –Pharmacist Prospective

List includes 33 medications of which 17 already included in WHO list.

Medications were rated on effectiveness and safety profile.

Final list was approved by panel of 28 professional organizations.

Refer to handout for list of meds.

Anti-depressants

TCA local anesthetic type properties due to its “sodium channel blockade.”

Not shared by SSRI anti-depressants. Decreasing depression can de-amplify the

sensation of pain. Plasma steady state takes 2 weeks.

Adverse Drug Effects

Amitriptyline (TCA)– Dose related Anti-cholinergic effects– Co-morbidities such as CV disease and drug interactions

limits its use. Desipiramine (TCA)

– Lowest risk of anti-cholinergic effects Mirtazapine/Trazadone

– Dual action of NaSSA and Tetracyclic Cymbalta (not on the IAHPC list)

– FDA approved for nerve injury pain

OPIOID ANALGESICS

Opioids classifies as full morphine-like agonists.– Do not exhibit dose-ceiling expect when limited by

toxicities. Antagonize NMDA receptors mu, kappa, delta receptors are target

molecules for analgesia

MORPHINE

Gold standard IAHPC list both IR and SR forms WHO only list IR forms Highest dose list for SR is 30mg tabs MSIR sol dose listed is 10mg/5ml

SPECIAL CONSIDERATIONS

Neurotoxicity– Opioid Induced Hyperalgesia (OIH)

… more pain with more drug Tolerance

– Neuronal excitotoxicity via cell death– Changes in glutamate availability– NMDA receptor excitability– Ratio of M6G/M3G– NMDA blockers – ketamine, clonidine, methadone– Signal of disease progression

OXYCODONE

mu & kappa receptor agonist Metabolized CYP 2D6 pathway

– Dose adjustments necessary with drugs that inhibit CYP 2D6 (Haldol,Paxil,Prozac)

10-20% metabolized to oxymorphone. Oxycodone IR 5mg on IAHPC list

– Oxycodone SR not included

FENTANYL

Potent mu agonist PO conversion to patch

– Convert oral opioid to equivalent dose of oral morphine– Half this dose and convert to mcg for appropriate patch size– Reverse should not be used

Metabolized CYP 450 3A4 25mcg for Opioid Naïve patients

METHADONE

Elimination half-life (8-59 hours) is longer than its duration of action (4-5 hours)

High dose and prolonged QT intervals a marker for deadly cardiac problems

Dose conversion is challenging Not a first line drug DEA restricts distribution to 10mg tabs

LIST OF ESSENTIALMEDICATIONS, CONT

Bisacodyl/Senna/Mineral Oil Prednisone/Dexamethasone Acetaminophen Valium/Lorazepam Midazolam/Zolpidem Haldoperidol Gabapentin

List of Essential Medications ,cont

IBU Carbamazepine Codiene Loperamide Metoclopramide Tramadal

GETTING PAST THE STIGMA

Reasons Pharmacist stock inadequate supplies of opiods– Concerns with DEA monitor usage– Illicit use and fraud– Fear of theft

Questions???

For more information Russ Zakarian,Pharm.D. Model Drug Pharmacy 1-800-585-3785 russ@modeldrug.com