Methadone Flashcards
Indications for Methadone
- Pain in patients with tolerance, toxicity or allergy to morphine or other opioids
- Renal failure or on dialysis
- Evolving opioid-induced hyperalgesia
- Neuropathic component to pain
- Methadone maintenance therapy
Advantages of Methadone
- Effective for bone and neuropathic pain
- NMDA receptor antagonism may attenuate opioid tolerance (e.g. reduce activation of NMDA receptors, stimulation of which leads to CNS sensitization and hyperalgesia or allodynia)
- No known active metabolites
- titrated in small increments
Contraindications to Methadone
- Hypersensitivity
- Mild, intermittent, or short duration pain that can be managed with other pain medications
- Initiation in an acute, unstable pain scenario
- Patients taken monoamine oxidase inbitors (MAOIs)
- Patients with severe liver disease
Also consider:
- Acute respiratory depression, cor pulmonale, elevated pCO2
- Acute alcohol intoxication or withdrawal
- Severe CNS depression
- Paralytic ileus
Conditions that merit caution in prescribing methadone
- Severe COPD
- Severe sleep apnea
- Long QTc (>450msec)
- Drug interactions
- Drinking alcohol (may result in increased plasma levels of methadone)
Delivery of Methadone
- Liquids
- Tablets (preferred for PO delivery)
- Rectal
- SL/Buccal
Is methadone associated with osteoporosis?
No - though those on methadone may have osteoporosis due to other risk factors
Frequency of dosing methadone for pain
For treatment of addiction, methadone dosing is once per day. However, the in the treatment of pain, more constant plasma levels are required necessitating more frequent dosing
Can methadone impair sexual function
Chronic use of all opioids can suppress gonadotropin levels. - as can underlying illness - testosterone replacement may be helpful
Pharmacology of Methadone
High volume of distribution
High plasma protein binding
High lipophilicity (large reservoir of tissue binding sites)
Long, variable half life and slow elimination phase (half life usually 15-60 hours, but may be as high as 120 hours). Duration of half analgesia of approximately 8 hours, elimination half life averaging approximately one day.
Steady state may take five days or more - do not raise doses more frequently than every 3 days
Racemic mixture of R-methodone (opioid receptor agonist, NMDA antagonist) and S-methadone (norepi and serotonin re-uptake inhibitor, NMDA antagonist)
How Methadone is released
- Dose administered saturates tissue binding sites (creating reservoir) while a fraction is free in the plasma, providing analgesic effect
- Free fraction in plasma is maintained slowly, even after methadone is discontinued, until the tissue binding site reservoir is exhausted (could take days)
Absorption of methadone
- Oral dose - 80-90% absorbed
- Rectal is comprabale to oral
- SL is approximately 34% and most absorbed in the first 2.5 minutes, but note that much of the SL administered methadone may be subsequently absorbed in the proximal small bowel
Common drug interactions:
- Antidepressants
- Antibiotics
- Antifungals
- Antipsychotics
Most drugs will increase plasma methadone levels (risking toxicity).
Grapefruit juice, anticonvulsants, and Rifampin can DECREASE plasma methadone levels
Methadone in renal failure
20% eliminated by kidneys, but if in renal failure, liver will eliminate instead. No need for dose adjustment
Initiation strategy: Start Low and go Slow
- Start a dose approrpiate to dosing in an opioid naive person (usually 1-2.5 mg PO q8h)
- Slow titration, changing dose every 5 days
When to use methadone as a first line opioid
- History of severe intolerance to other opioids
- Likelihood of very long term opioid therapy (e.g. severe non-cancer pain)
- Renal failure
- Financial considerations precluding prescribing of SR med, and for whom q4h dosing is impractical