CT is a 72-year-old woman with metastatic breast cancer experiencing aching pain in her chest with shooting pains down her arm that have become increasingly uncontrolled over the past 2 weeks. She also has oral thrush that developed a few days ago. She has a history of asthma, exacerbated by her breast cancer and recently completed a 6-day steroid taper. You note that she was treated with fluconazole 2 months ago for a prior case of oral thrush. You decide to recommend methadone to better manage her pain and an antifungal course. What is your starting dose of methadone? Which antifungal do you recommend?
Current pain medications:
- Morphine SR 160mg PO Q12H
- Morphine 20mg/mL; 1.5ml (30mg) PO Q4H PRN (~6 doses per day; pain decreases from 8 to 5 rating on VAS after each breakthrough dose)
Recommendation listed in steps:
- Assessment: Uncontrolled pain, somatic and neuropathic in nature; Oral thrush due to steroid use.
- Total Daily Usage of Current Opioids: Morphine PO 500mg/day that, until recently, controlled her pain well.
- New Opioid Requested: Methadone tablets
- New Dose and Interval: Using standard conversion table (provided below), 500mg/day of Morphine is equivalent to 33mg/day of Methadone, using a 15:1 conversion ratio. Place order for Methadone 10mg tablet; 1 tablet PO Q8H. Maintain current breakthrough regimen with Morphine concentrate with increased dose of 3ml (60mg) PO Q4H PRN
- Oral thrush therapy: Nystatin suspension; Swish and swallow 5ml PO Q.I.D. x 10 days
- Monitor for therapeutic effectiveness (pain severity rating, breakthrough doses used) and toxicity (increased sedation or confusion, difficulty arousing patient).
- Assess, and Titrate dose if needed, after 5-7 days. Note: more frequent dose increases may result in adverse effects/overdose.
Case-specific recommendation of Methadone therapy and Nystatin suspension
- Methadone is active at mu-opioid and NMDA receptors and inhibits reuptake of serotonin and norepinephrine. These actions make methadone ideal for patients experiencing different types of pain concomitantly. CT is experiencing somatic pain (muscle aches and pain) and neuropathic pain (shooting).
- Methadone is often not recommended as the breakthrough medication to complement a scheduled methadone regimen. Methadone may cause excess accumulation if a patient is taking many breakthrough doses in addition to a scheduled regimen. Short-acting opioids such as morphine, oxycodone or hydromorphone are beneficial when initiating methadone until a patient is on a stable dose.
- Specific enzymes are responsible for methadone metabolism and can be affected by a number of medications. Medications that induce (speed up or increase) or inhibit (slow down or decrease) metabolism of methadone do so by affecting one of these enzymes. A potential drug-drug interaction exists between azole antifungals, such as fluconazole (Diflucan®), which causes increased concentrations of methadone. Nystatin suspension is considered a safer alternative.
Considerations in Hospice/Palliative care:
- Hospice patients often present with mixed pain making methadone ideal in appropriate candidates. Candidates for methadone include those with a true opioid allergy, high pill burden, uncontrolled pain despite increasing opioid doses, renal impairment, neuropathic pain, and difficulty swallowing or presence of a PEG tube (with routine dosing methadone can take on long-acting properties even with the liquid formulation).
- Hospice patients are often prescribed a number of medications. It is important to review medication profiles for potential drug-drug and drug-disease interactions on admission and before initiating any new therapy.
For additional information on this topic, please review these references:
- Enclara Pharmacia’s On Demand Educational Webinar, “Methadone: A Review for Hospice Clinicians”. Click here, Enclara Client Portal, to log in.