Module 4, CPOP

Question 1

What is CPOP?

Answer 1

• community program for opioid pharmacotherapy
• a program co-managed by the Medicines and Poisons Regulatory Branch and Next Step Drug & Alcohol Services to enable the provision of methadone and buprenorphine for the treatment of opioid dependence across WA through public and private providers
• Over 3500 patients receive opioid substitution treatment in WA with around 60% prescribed methadone and 40% receiving treatment with buprenorphine
• Half of the patients are treated by private prescribers, almost 40% by doctors from public services, and just under 10% by medical practitioners in Corrective Services. Altogether around 140 doctors are authorised to prescribe opioid substitution treatment
• Over 300 pharmacies are authorised to provide supervised dispensing of methadone and buprenorphine in WA and all WA prisons also participate in the program

Question 2

What is the agonist treatment rationale?

Answer 2

• Opioid Substitution Treatment (OST) with methadone or buprenorphine is appropriate for those with significant opioid dependence wishing to cease illicit opioid use
• OST replaces short-acting opioids, such as heroin or oxycodone, with a long-acting opioid that can be taken orally
• OST is designed to have a minimal intoxicating effect, blocking the euphoria associated with use of exogenous opioids and preventing withdrawal
• OST is highly effective in engaging opioid dependent people in treatment

Question 3

What is CPP?

Answer 3

• community pharmacotherapy program
• Provides expert advice, information, referral, training, resource and policy development on all aspects of opioid pharmacotherapy treatment in WA with a specific focus on clinical support
• Review all community applications for Community Program for Opioid Pharmacotherapy (CPOP) treatment and process to HDWA for authorisation
• Supports CPOP prescribers, pharmacists, and clients with access, prescribing and dispensing issues
• Supports prison release arrangements for continuing pharmacotherapy treatment in the community
• Arranges interstate and international transfers for opioid pharmacotherapy clients coming to and leaving from WA
• Coordinates the Clinical Advisory Service

Question 4

What is the CAS?

Answer 4

• clinical advisory service
• The Clinical Advisory Services operates a 24/7 phone service for health professionals to access clinical advice on patient management involving alcohol and drug use issues with access to experienced medical practitioners through Next Step Drug & Alcohol Services
• CAS doctors can also provide interim CPOP prescriptions on behalf of all CPOP prescribers to ensure continuity of treatment. CPP coordinates the CAS during business hours.

Question 5

What is the CRC?

Answer 5

• clinical review committee
• The CPOP Clinical Review Committee meets to review and endorse applications for OST that fall outside the WA Policies and Procedures, to review the management of clients with special dosing approval, and to respond to clinical management issues which may impact upon service providers and clients of the Program.
• The Committee comprises the Director of Clinical Services (Next Step), Addiction Medicine Consultants, the Manager of the Community Pharmacotherapy Program (CPP) and the Clinical Coordinator (CPP). The Committee provides specialist advice to service providers participating in the Program, the Community Program for Opioid Pharmacotherapy Management Committee, and the Department of Health.

Question 6

Who can be a CPOP prescriber?

Answer 6

• To become an authorised CPOP prescriber a medical practitioner must successfully complete an approved training program and assessment and agree to comply with the clinical policies and procedures of the WA CPOP. Authorisation lasts for a period of three years and may be renewed for further periods following a review process.
• Two training options exist:
  
  • CPOP Prescriber Training enables prescribing of methadone and buprenorphine for up to 50 patients (25 for solo rural practitioners)
  • Buprenorphine Prescriber Online Training enables prescribing of buprenorphine products for up to 5 patients
• Every three years prescribers are required to complete a Reaccreditation Assessment and provide feedback on their level of confidence in areas related to CPOP treatment to continue their authorisation. Prescribers can also re-attend training in order to revisit and revise the policies and procedures.

Question 7

CPOP Authorised Pharmacies…?

Answer 7

• Pharmacies dispensing and supervising methadone and buprenorphine treatment for opioid dependence must be authorised by the Department of Health
• A prescriber must identify the dosing pharmacy when applying for opioid pharmacotherapy treatment
• In 1997 there were 30 pharmacies participating in CPOP, by 2000 there were over 190, today we have over 330 pharmacies authorised to provide CPOP treatment
• The pharmacy proprietor is required to ensure that all pharmacists dispensing and supervising CPOP are trained in the WA policies and procedures

Question 8

How do you prescibe OST?

Answer 8

Prescribers submit an Application to Prescribe Opioid Substitution Treatment detailing:

1. The type of application
2. The patient (ID, demographics)
3. Transfer (from other CPOP prescriber)
4. Treatment (OST type, induction plan)
5. Other treatment details (interacting meds)
6. Pharmacy
7. Drug use
8. Patient acknowledgement (signed)
9. Prescriber
10. Prescriber declaration (signed)

Applications from community CPOP prescribers are reviewed by CPP for clinical issues prior to submissions to the Health Department. In 2017 a total of 1135 Applications were processed. Applications from Next Step Drug & Alcohol Services are directly submitted to HDWA.

Question 9

What are some CPOP treatment implications?

Answer 9

• Patients considering CPOP Treatment must be fully aware that commencing pharmacotherapy treatment of opioid dependence results in their name being placed on the WA Drugs of Addiction Record
• Patients acknowledge this on their Application for CPOP Treatment. The Record restricts access to other prescribed Schedule 8 medicines. Information from the Record is only provided to health professionals who are involved in the patient’s treatment and not available to employers, police or other agencies.
• Treatment also requires the patient to attend a pharmacy daily for supervised dispensing which can impact on travel and employment opportunities and will attract a dispensing fee set by the pharmacy

Question 10

What does a CPOP prescription look like?

Answer 10

Question 11

Which drugs are used as OST?

Answer 11

• methadone
• buprenorphine

Question 12

What is methadone?

Answer 12

• potent synthetic μ-opioid receptor agonist
• well absorbed orally and has a long plasma half-life
• Two preparations are registered for the treatment of opioid dependence in Australia:
  
  • Methadone Syrup – This formulation contains 5 mg/ml methadone hydrochloride, sorbitol, glycerol, ethanol (4.75%), caramel, flavouring, and sodium benzoate
  • Biodone Forte – This formulation contains 5mg/ml methadone hydrochloride and permicol-red colouring
• also used in the treatment of pain as physeptone tablets

Question 13

Describe methadone PK?

Answer 13

• highly lipophilic
• binds to a range of body tissues including the lungs, kidneys, liver and spleen such that the concentration of methadone in these organs is much higher than in blood
• Methadone is primarily broken down in the liver via the cytochrome P450 enzyme system with approximately 10% of orally administered methadone eliminated unchanged
• Onset of effects: 30 minutes
• Peak effects: 3-4 hours
• Half-life (in MMT): 13–47 hours (mean 24)
• Time to stabilisation: 5–10 days (Levels rise during the first week)
• Withdrawal onset: 36–48 hours (Symptoms peak within 5–7 days)

Question 14

What is buprenorphine?

Answer 14

• a derivative of the morphine alkaloid thebaine
• is a partial opioid agonist at the μ-opioid receptors in the nervous system
• Although buprenorphine is a potent pain reliever there is a ‘ceiling’ on its maximal opioid activity and many clients report less sedation on buprenorphine than on methadone
• Buprenorphine has a higher affinity for the μ-opioid receptors than most full opioid agonists, and can block the effects of other opioid agonists in a dose-dependent fashion
• By its dual effects of reducing cravings and decreasing the response to administered opioids, buprenorphine reduces the self-administration of other opioids

Question 15

How is Buprenorphine Different?

Answer 15

• Unlike methadone which is a full opioid agonist, the effect of buprenorphine on respiratory depression reaches a ceiling
• Higher doses do not increase respiratory depression to a significant degree
• Dose response studies show that, because of the ceiling effects of buprenorphine, high doses (16 mg daily or more) do not result in substantially greater peak opioid effects than lower doses (8 or 12mg).

Question 16

What does buprenorphine come in?

Answer 16

• Subutex sublingual tablets – The tablets come in 0.4mg, 2mg or 8mg strengths of buprenorphine hydrochloride
• Suboxone sublingual film – The films come in 2mg or 8mg strengths of buprenorphine hydrochloride with 0.5mg or 2mg naloxone respectively (a ratio of 4:1). Buprenorphine depot preparations delivered as weekly or monthly injections are an emerging treatment option in Australia.

Question 17

What is the PK of buprenorphine?

Answer 17

• a partial agonist at the µ (mu) receptor
• When the µ receptor is stimulated by buprenorphine it sets in motion a chain of nerve cell activities that bring about most of the familiar opioid effects, like pain reduction, feelings of well-being or pleasure, and respiratory suppression
• By stimulating the receptor only partially, buprenorphine creates those effects with less intensity than heroin, morphine, or methadone, all of which stimulate the receptor fully. Whereas those drugs can cause powerful euphoria and intoxication, buprenorphine provides a positive but moderate psychoactive effect that reduces craving and blocks the effects of other opioids
• Partial agonists cause less conformational change and receptor activation than full agonists. At low doses, both full and partial agonists may provide similar effects to their full agonist cousins. However, when the dose of partial agonists increases, the analgesic activity will plateau, and further increases in doses will not provide additional relief but may increase the adverse effects

Question 18

Buprenorphine has a high affinity for the µ receptor

Answer 18

• Buprenorphine binds tightly to µ receptors, more than other opioids. If a person takes another opioid in addition to buprenorphine the binding of the buprenorphine will block other opioids from reaching the receptors and producing the desired effects
• If buprenorphine is given to an individual who has already taken another opioid, it displaces the other opioid from the receptors. The phenomenon of precipitated withdrawal has particular clinical relevance during the induction of opioid dependent clients to buprenorphine due to its high receptor affinity and low intrinsic activity when competing with other agonists such as methadone, morphine or heroin. Buprenorphine displaces other agonists from opioid receptors, and may not produce sufficient agonist effects initially to compensate for the displaced methadone or heroin. The client may experience opioid withdrawal within 1-4 hours after first administration
• This effect necessitates care when a clinician initiates buprenorphine therapy; depending on the dosage of buprenorphine, the patient’s level of physical dependence, and when he or she last administered an opioid, the abrupt stripping of the other opioid from the µ receptor can precipitate withdrawal

Question 19

Buprenorphine disassociates from the µ receptor gradually

Answer 19

• Buprenorphine detaches from µ receptors slowly leading to a long duration of action
• Buprenorphine has a bi or tri-exponential, long terminal elimination phase with a halflife of between 20 to 73 hours
• The peak clinical effects occur 1 to 4 hours after sublingual administration. Typical effects will continue to be experienced for up to 12 hours at low sublingual doses (2mg), and as long as 48 to 72 hours at higher doses (16-32mg)
• the prolonged duration of effect at high doses enables alternate-day, and even thirddaily dispensing regimes with sublingual dosing
• Depot buprenorphine products contain modified release solutions for injection in single-dose prefilled syringes. The modified release properties of Buvidal Weekly and Buvidal Monthly are based on FluidCrystal® injection depot technology. Once injected, it transforms from a low viscous solution to a highly viscous liquid crystal gel that encapsulates the buprenorphine which is then slowly released as the depot biodegrades
• The syringe is assembled in a safety device to prevent post-injection needlestick injury

Question 20

Buprenorphine is an antagonist of the δ and κ opioid receptors

Answer 20

• In addition to its high-affinity partial agonist effect at μ opioid receptors buprenorphine is also a high-affinity antagonist at the δ (delta) and κ (kappa) opioid receptors, and a moderate-affinity partial agonist at the nociception opioid receptors
• While buprenorphine’s interaction with the µ receptor gives rise to its most important attributes and advantages as a treatment for opioid dependence the significant action of buprenorphine on the κ opioid receptor also assists reduction of withdrawal symptoms associated with opioid dependence. Activation of δ receptors produces analgesia, perhaps by potentiation of μ-opioid receptor agonists, and may produce respiratory depression. The antagonist effect of buprenorphine may moderate the effect of opioid intoxication and overdose. Stimulation of the κ opioid receptor produces some of the major symptoms associated with opioid withdrawal, such as agitation and anxiety and some of the postacute withdrawal symptoms like depression. Pharmacological modelling suggests that by attaching to the κ receptor and slowing its activity κ opioid receptor antagonists may
  
  • i. block stress-induced potentiation of drug consumption
  • ii. prevent stress-induced relapse during abstinence periods
  • iii. limit negative emotional states during both acute withdrawal and more prolonged abstinence periods

Question 21

What is the onset of effects for buprenorphine?

Answer 21

• Onset of effects: 30–60 minutes
• Peak effects: 1–4 hours
• Half life: 20–72 hours (mean 34)
• Time to reach stabilisation: 7–10 days
• Withdrawal onset: 2–5 days
• symptoms generally milder than withdrawal from other opioids

Question 22

What is a takeaway dose?

Answer 22

• one that is provided to the patient for unsupervised dosing on the following day
• managed closely within the CPOP and should not be considered until the patient is assessed as stable and there are no current contraindications
• Because stability assessment requires the development of a strong therapeutic relationship and examination of corroborative supporting evidence, takeaway doses should not be considered until the patient has been in six months of continuous treatment
  *

Question 23

What do you do when the patient has missed a dose?

Answer 23

• OST is provided as a daily dose (or option of second-daily for Suboxone) requiring attendance at the pharmacy for dose supervision
• When concerns are raised regarding regular non-attendances for dosing, early review of the patient should be undertaken
• CPOP pharmacists can dose the patient on their regular dose if a stabilised patient has missed no more than two consecutive days of dosing
• Where a patient misses 3 or more consecutive days the pharmacist must consult with the prescriber before providing the dose. CAS can be consulted the prescriber is not available
• Any missed doses during induction need to be reported to the prescriber before a dose can be supplied

Question 24

The schedule for missed doses…

Answer 24

Question 25

What are some pharmacy incidents related to CPOP?

Answer 25

• Missed doses (>2 days)
• Diversion of dose
• Intoxicated presentation
• Abusive behaviour or theft
• Other behaviour indicating instability
• Payment issues
• Dosing errors
• Expired prescriptions

Question 26

How do you deal with an OD?

Answer 26

• Naloxone is a medication that is given for the temporary reversal of the effects of opioids
• this should be given in any emergency situation where is it known or suspected that an overdose has occurred and that opioid drugs may be involved
• Repeat administration of naloxone may be required to overcome the effects of opioid sedation
• Prenoxad Injection (naloxone hydrochloride 1mg/ml solution for injection) or the nasal spray 1.8 mg (single use), 2, Nyxoid, PBS

Question 27

WHat if the patient is travelling?

Answer 27

• Community Pharmacotherapy Program provides support for CPOP clients to transfer treatment interstate on a temporary or permanent basis
• Taking methadone or buprenorphine overseas requires careful consideration of the stability of the patient and the rules and customs of the country being visited
• The Clinical Review Committee provides an avenue for CPOP prescribers to seek approval for additional takeaways to cover international travel