Slow-release oral morphine

Background

• Morphine sulphate sustained release capsules (Kadian)
  • Beads contain both immediate release and slow release morphine
  • IR released by stomach acid and SR released in bowels at higher pH
  • Capsules themselves may pass in the stool
• Full opioid agonist
• Approved for chronic pain, but used off-label for opioid use disorder
• Appears likely to be equivalent to methadone, but higher patient satisfaction
• Peak plasma level 8.5 to 10 hours
• Elimination half life 11 13 hours

Dosing

• For daily dispensed, often opened and sprinkled on apple sauce or yoghurt, or water
• Capsule sizes include 10, 20, 50, and 100 mg
• Specify on the prescription if it is being used for OUD or chronic pain

BC OUD Guidelines

• Eligible in age >19 and switching from methadone or actively using opioids
• When transitioning from methadone, the eventual dose will usually be 8 times higher, but generally should start with a 4-times higher dose to be safe
  • Increase by 30 to 60 mg daily q48h
• For other opioids, start with dose of 30 to 60 mg
  • Increase doses q48h based on withdrawal symptoms
• Average stable doses are 60 to 1200 mg daily

Missed Doses

Number missed	Action
1	no change
2	40% reduction
3	60% reduction
4	80% reduction
5	re-initiate

St. Michael's Protocol

Day	Slow-release morphine	Instant-release morphine
1	200-300 mg	30-50 mg po q2h while awake + 30-50 mg po q3h prn
2	SR dose from Day 1 + 50% of IR dose from Day 3	30-50 mg po q2h while awake + 30-50 mg po q3h prn
3	SR dose from Day 2	30-50 mg po q3h prn
4	SR dose from Day 3 + 50% of IR dose from Day 3	30-50 mg po q3h prn
5	SR dose from Day 4	30-50 mg po q3h prn
6	SR dose from Day 5 + 50% of IR dose from Day 5	30-50 mg po q3h prn

Off-Guideline

• For induction from methadone or non-methadone opioids with high opioid tolerance
• Start at 200 to 300 mg, then increase by 100 to 150 q48h
• Missed days
  • 1: full
  • 2: 50% reduction
  • 3: 75% reduction or resume at initiation dose
  • 4: resume at initiation dose

Carries

• Per guidelines, doses should be indefinitely witness ingestion
• However, may be reasonable to do same for methadone
  • No carrier x 8 weeks, then one carry per week every month with weekly urine drug screens

Switch to Methadone

• Must stop SROM and start methadone titration from 30 mg

Switch to M-Eslon

• Split SROM dose for BID M-Eslon
• Dosages include 10, 15, 30, 60, 100, and 200 mg

Safety

• Adverse effects include GI cramping, abdominal pain, headache, hyperhidrosis, constipation, frequent urination, nausea/vomiting, and insomnia
• Risk of respiratory depression and other forms of opioid toxicity
• Safe in pregnancy
  • Small RCT suggests no difference from methadone in neonatal outcomes but possibly lower unprescribed drug use in SROM

Contraindications

• Hypersensitivity to morphine
• Respiratory
  • Significant respiratory depression
  • Acute or severe bronchial asthma
  • Severe respiratory compromise or obstructive disease
• Gastrointestinal
  • Known or suspected paralytic ileus
  • Short gut syndrome of transit time abnormalities
• Alcohol use, including intoxication and withdrawal
• MAOI use within 14 days