Methadone

Question 1

MOA?

Answer 1

long acting mu receptor agonist

Question 2

typical dosing regimen and doses?

Answer 2

Daily unless BD for pain reasons

60 - 100mg/day

Question 3

how long to reach steady state?

Answer 3

3 - 10 days

Question 4

starting doses and increments?

Answer 4

10 - 30mg depending on tolerance levels
A second dose of up to 10mg may be given 4 - 6 hours later if in significant withdrawal
Increase no more than 10mg per week

Question 5

what formulations are available?

Answer 5

syrup, tablet, IV

Question 6

what is the half life?

Answer 6

20 - 36 hours

Question 7

risks?

Answer 7

accumulation
respiratory depression
central sleep apnoea
prolonging QT interval (avoid if underlying structural cardiac disease or on medications that waste potassium)
severe constipation
dental problems

Question 8

Advantages over buprenoprhine?

Answer 8

Clients tend to cycle slower on/off methadone increasing the duration of MATOD and thus increasing the chances of stabilising the health and social situation

Question 9

What and when would be the main variation in dosing?

Answer 9

If a patient has pain issues or is a rapid metaboliser they may require BD dosing to cover their pain or prevent withdrawal

Question 10

Time to peak effect?

Answer 10

2.5 - 4 hours

Question 11

What is the inter-individual variability in metabolism?

Answer 11

Up to 17 times between individuals

Question 12

When to consider transfer to suboxone?

Answer 12

when dose increases or divided doses do not eliminate withdrawal symptoms prior to next dose (this may happen in about 1/3rd of clients on 60mg/day)

Question 13

Pharmacokinetics?

Answer 13

hepatic metabolism by CYP 3A4, 2D6, 2B6

Question 14

How long to reach maintenance dose?

Answer 14

2 - 6 weeks

*50mg - 65mg of methadone technically should cover the equivalent receptors to 1000mg per day of morphine

Question 15

How to manage missed doses?

Answer 15

If misses 4 doses in a row reduce dose by half to prevent overdose
If 6 missed doses they require re-stabilisation

Question 16

Maximum dose at end of first week?

Answer 16

50mg

Question 17

At what dose should QTc be assessed even if no risk factors for prolongation?

Answer 17

≥100mg (particularly > 120mg/day)

Question 18

how to transfer from Methadone to suboxone?

Answer 18

1) Methadone dose must be less than 40mg
2) the last dose must >24hrs ago
3) initiate suboxone when withdrawal symptoms are evident (COWS above 5) and start with 4mg suboxone and repeat dose if require 1 - 4 hrs later if ongoing symptoms
4) increase dose by 4 - 8mg per day as required (should stabilise between 2 -3 days)

Question 19

Transferring from suboxone to methadone?

Answer 19

• if suboxone <8mg then start with methadone 20 - 30mg
• if suboxone dose is 12mg or more start with methadone 40 - 60mg
• however these assumptions are not accurate and what should guide dosage is the clinical symptoms

Question 20

What rate is appropriate to wean off methadone?

Answer 20

5mg per fortnight

Question 21

What agents can increase toxicity of Methadone?

Answer 21

CYP3A inhibitors such as azole’s, ciprofloxacin, erythromycin and grapefruit juice