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Everything You Wanted to Know!

Everything You Wanted to Know!. Methadone 101. GOAL. To educate healthcare professionals about methadone pharmacotherapy the advantages and disadvantages and how to convert other opiods to methadone in order to provide safe effective and efficient pain management to patients at

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Everything You Wanted to Know!

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  1. Everything You Wanted to Know! Methadone 101

  2. GOAL To educate healthcare professionals about methadone pharmacotherapy the advantages and disadvantages and how to convert other opiods to methadone in order to provide safe effective and efficient pain management to patients at the end of life.

  3. Objectives • Discuss the basic principles of methadone pharmacotherapy • Identify the advantages of methadone • Demonstrate how to initiate and monitor methadone treatment • Explain the equianalgesic conversion of opioids to methadone • Discuss the disadvantages of methadone

  4. History of Methadone • Originally produced in Germany in 1942 during WW II • Major use in the U.S. has been for the treatment of heroin addiction • Now being used more for pain control • Brand name = Dolophine

  5. Indications for Methadone • Long acting opioid therapy • Intolerable side effects from another opioid • Inadequate pain control from another opioid • Need for treatment of neuropathic pain

  6. Understanding Pain Pathways Neuropathic pain caused by direct stimulation of peripheral or central neurons Nociceptive pain caused by a painful stimulus acting on pain receptors They may co-exist

  7. Why Methadone? • Synthetic opioid with properties similar to morphine • Strong analgesic efficacy • More “complete” analgesic • Dual mechanism of action • Lack of neuroactive metabolites • Relative lack of side effects • Favorable cost/benefit ratio

  8. The Mu Receptor • Two mu receptors: • mu1 – mediates analgesia, euphoria • mu2 – mediates sedation, respiratory depression • There is one clear marker for risk of breathing difficulties:sedation Caregivers should look for signs of toxicity (drowsiness)

  9. Comparisons MORPHINE OXYCODONEMETHADONE -Mµ receptor -ĸ agonist -Mµ, κ, δ agonist agonist -NMDA antagonist -affects serotonin& norepinephrine reuptake stimulates -more “complete” receptorto cancel out pain

  10. Methadone - Properties • Well absorbed by both oral and rectal route • Available: pill, a liquid, and in IV form • Can be made into a suppository • Dosage not affected by route of administration • GI absorption nearly complete • Oral bioavailability = 80% • Onset of analgesia 30-60 minutes • Less binding to mu receptors • Less constipation • Less nausea

  11. Methadone - Pharmacokinetics • Time to peak plasma concentration: • 2.5 to 4 hours for oral solution or tablets • Because of slower onset of action, may need other opioid early on • Morphine for breakthrough until Methadone dose is reached • Large inter-individual variation • Acts differently in different people

  12. Methadone - Elimination • Biphasic pattern of elimination • Alpha-elimination phase • Lasts 8-12 hours • Correlates with its analgesic period • Beta-elimination phase • Ranges from 30-60 hours • During this phase, methadone can accumulate and produce drug levels that can cause toxicity

  13. Methadone - metabolism • Metabolized predominantly by the liver • Methadone is broken down by the same pathway as other commonly used medications • Some medications raise methadone levels and some decrease

  14. Antifungals Antibiotics Ciprofloxacin (Cipro) Clarithromycin (Biaxin) Desipramine (Norpramin) Diclofenac (Voltaren) Doxycycline Erythromycin Fluoxetine (Prozac) Isoniazid Nafcillin Paroxetine (Paxil) Phenobarbital Phenytoin (Dilantin) Propofol Protease inhibitors Quinidine Rifampin Sertraline (Zoloft) St. John’s wort Verapamil Potential Interactions withMethadone and CYP3A4 metabolic pathways

  15. Methadone -metabolism • Metabolites inactive • Less confusion and hallucinations • Less myoclonus • No dosage adjustments needed in stable liver and renal failure • Less xerostomia

  16. Opioid Price Comparison

  17. In Review • Methadone has the same action as Morphine • Can be used to treat neuropathic pain • Effective without opiod side-effects • Associated with less neurotoxicity • Slower onset but more stable steady state • Long half life • Excellent cost/benefit ratio

  18. Conversions The higher the dose of morphine, the more potent methadone will be when you do the conversion

  19. IMPORTANT! as morphine dose increases – methadone becomes a Much Much Much stronger drug

  20. Conversion Protocols • Multiple conversion models • Which one do I use? • Use a variable dose conversion factor based on an escalating ratio: The higher the dose of morphine, the larger the conversion factor used ALL CONVERSIONS ARE BASED ON THE ORAL DOSE OF MORPHINE

  21. Morphine to Methadone Equianalgesia Less than 100 mg/day Morphine 4:1 101 – 300 mg/day Morphine 8:1 301 – 600 mg/day Morphine 12:1 15:1 601 – 799 mg/day Morphine 20:1 800 mg and greater/day Morphine

  22. Morphine to Methadone • Calculate total daily dose of Methadone • Stop current opioid • Divide total dose to q 8-hour schedule Start methadone • Breakthrough dose is 10% of total daily dose (minimum 5mg) given q 3-4 hours • Watch closely for signs of increasing drug level (sedation)

  23. Three Cases Studies

  24. CASE STUDY 1 Patient Mrs. Jones is a 48 year-old woman with metastatic breast cancer to the spine. She is being admitted to service from a regional hospital. She is currently on morphine sulfate by IV at a continuous rate of 6 mg/hr. She has not used any breakthrough medication in the past 24 hours. Place this patient on an appropriate dose of methadone

  25. Important Information for Conversion • 48 year-old woman with metastatic breast cancer to the spine. • Currently on morphine by IV at a continuous rate of 6 mg/hr. • No breakthrough medication in the past 24 hours. • How to convert this to Methadone?

  26. The Steps Step One:Add up the total daily amount of Morphine For Mrs. Jones this would be: 6mg/hr IV x 24 hrs = 144 mg/day Step Two: Convert IV to oral using conversion factor of 1:3 Using 144mg /day 144 x 3 = 432 mg po daily

  27. Step Three: Convert Morphine to Methadone Mrs. Jones is taking an equivilent to 432 po mg/day of Morphine Use conversion factor of 12:1 Divide 432 by 12 = 36 mg Methadone/day

  28. Final Step: Convert to an 8 hour dosing schedule We figured 36mg/day 24 hours divided by 3 = 8 hours 36 divide by 3 = 12mg methadone q 8 hours Rounded to 10mg q 8 hours Breakthrough dose is 10% of 24 hour total 36mg = 3.6mg (5mg minimum) AND THE DOSE IS…

  29. The dose for Mrs. Jones is: DAILY = 10mg q 8 hours Breakthrough= 5mg q 3 – 4 hours prn

  30. Case Study 2 Patient Joe Brown is a 73 year old male with metastatic lung cancer. He has had progression of his lung cancer and is status post radiation therapy. He was previously on Duragesic 50 ug patch every 72 hours, but was experiencing increased pain and therefore was switched to MS Contin 60mg every 12 hours. Dexamethasone was added due to a complaint of constant stabbing to his ribs but he continues to use MSIR 10mg ii (2) three times a day. Additionally, he is complaining of anorexia due to nausea and shaking of his arms.

  31. Important Information for Conversion • 73 year old male with metastatic lung cancer • On MS Contin 60mg every 12 hours • Breakthrough is MSIR 10mg ii used three times a day • How to convert this to Methadone?

  32. Step One:Add up the total daily amount of Morphine For Mr. Brown this would be: MS Contin 60 mg q 12 = 120mg 3 breakthrough doses of ii 10mg MSIR = 60mg Total daily Morphine:120 + 60 = 180 mg

  33. Step Two: Convert Morphine to Methadone If the Morphine is180 mg Then the conversion factor is 8:1 Therefore, 180 divided by 8 = 23mg

  34. Final Step: Convert to an 8 hour dosing schedule 23 mg divided by 3 = 8mg q 8 hours Rounded to 10mg q 8 hours Breakthrough dose is 10% of 24 hour total 23mg = 2.3 mg(5mg minimum) AND THE DOSE IS…

  35. The dose for Mr. Brown is: Daily = 10mg q 8 hours Breakthrough= 5mg q 3 – 4 hours prn

  36. CASE STUDY 3 Patient Michael Smith is a 69 year-old male with laryngeal carcinoma. He is unable to swallow pills and is moaning in discomfort. Currently he is on Dilaudid sub-q 2mg every three hours. His wife reports he has not slept in three days.

  37. Important Information for Conversion • 69 year-old male with laryngeal carcinoma • Unable to swallow pills • On Dilaudid sub-q 2mg every three hours • How to convert this to Methadone?

  38. Step One:Add up the total daily amount of Dilaudid For Mr. Smith this would be: Every 3 hours = 24 hours divided by 3 = 8 2mg every 3 hours (2 X 8) = 16mg/day Step Two: Convert IV to oral Dilaudid using the conversion factor of 1:5 Using 16mg /day 16 x 5 = 80 mg po Dilaudid daily

  39. Step Three: Convert oral Dilaudid to oral Morphine Conversion factor for Dilaudid to Morphine is 1:4 80 mg x 4 = 320 mg oral Morphine Step Four: Convert Morphine to Methadone If the Morphine is 320 mg Then the conversion factor is 12:1 320mg Morphine divided by 12 = 27 mg

  40. Final Step: Convert to an 8 hour dosing schedule We figured 27mg/day 24 hours divided by 3 = 8 hours 27mg divide by 3 = 9 mg Methadone q 8 hrs Rounded to 10mg q 8 hours Breakthrough dose is 10% of 24 hour total 27mg = 2.7mg (5mg minimum) 5 mg q 3-4 hours AND THE DOSE IS…

  41. The dose for Mr. Brown is: Daily = 10mg q 8 hours Breakthrough = 5mg q 3 – 4 hours prn

  42. Did you notice? • The methadone dose for all three cases was the same? • Case 1: Morphine IV at 6 mg/hr = 144 mg/day = 12 mg po Morphine = 10 mg Methadone q 8 hours • Case 2: Equivalent of 180 mg morphine = 10 mg Methadone q 8 hours • Case 3: Equivalent of 320 mg morphine = 10 mg Methadone q 8 hours • As the dose of morphine rises, methadone becomes more potent

  43. References • “Methadone 101” presentation by Joel S. Policzer, MD, Senior Medical Director, VITAS, Ft. Lauderdale, FL • UpToDate, vol.12 no.3 • VITAS pharmacy • “Case-Based Use of Methadone – Practical Applications” presented at 2005 AAHPM Annual Meeting, New Orleans, LA, January 21, 2005.

  44. Questions and Discussion

  45. Everything you wanted to Know! Methadone 101

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