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Methadone Dosing Methods and Examples:

Focus on Oxycodone Conversion to Methadone

1. Oxycodone converted to a morphine-equivalent dose.

Morphine: Oxycodone equianalgesic ratio 30:20-30^{1, 2, 3}

2. Morphine-equivalent dose converted to a methadone dose.

Multiple studies have been conducted on this issue due to patient variability, tolerance associated with opioid use, etc. Study results listed below:

A retrospective study examined the dose ratio of morphine to methadone. Dose ratios of 1:1, 4:1, 10:1 have been published, but these conversions had little supporting data. The results found that patients receiving greater than 1165 mg/day morphine equivalent experienced pain relief with methadone at a median dose ratio of 5.42:1. Patients receiving greater than 1165 mg/day experienced a dose ratio of 16.84:1. A unified median ratio of 11.36:1 was determined.⁴

Another study examined the dose ratio of morphine to methadone, stating that the dose ratios commonly published (1:1, 3:1, and 4:1) were conducted on opioid naïve subjects treated with single dose drugs. The results found a median dosage ratio of 7.75:1 following a three day period to achieve equianalgesia.⁵

Because there is an incomplete cross tolerance, the use of lower equianalgesic dosing is recommended.⁵

Due to differences in kinetic factors and analgesic duration, analgesic effects have taken a median of 5 days to stabilize. In addition, patients need to be monitored every few days when therapy is initiated or a dosage is adjusted.⁷

Titrate slowly.

3. Examples of Specific Dosing Methods

Morley – Makin Method:

The previous opioid is stopped and replaced by a fixed dose of methadone that is one tenth of the opioid’s calculated morphine-equivalent dose when the morphine equivalent dose is less than 300 mg/day. If the morphine-equivalent dose of opioid is greater than 300 mg/day, 30 mg of methadone is used. The fixed methadone dose is administered as needed for pain, but not more frequently than every three hours. This is continued for 6 days. On day 6, the total daily doses of the previous two days are averaged and divided into two doses for a 12 hour dosing regimen.⁵

Sample Calculation:

Step One: Calculate morphine equivalent dose.

Morphine:oxycodone is 30:20-30

80 mg/day oxycodone = 80-120 mg/day morphine equivalents

Step Two: Since morphine equivalent dose is less than 300 mg/day, calculate 10% of the morphine equivalent dose as the fixed dose. The patient should receive an 8-12 mg fixed dose given every 3 hours prn pain.

Step Three: On day six, total the daily doses of methadone used on the previous two days and average. Divide this average into two equal doses to be given every 12 hours. This is the new daily dose.

Note: PRN analgesic for breakthrough pain may be required with this dosing method.

Stop and Go Method

The Department of Veteran’s Affairs doses methadone using a variety of methods. A "stop and go" method involves discontinuing the morphine-equivalent dose and starting methadone on day one. Initial daily methadone doses are determined based on the morphine-equivalent dose (MOR-E). If MOR-E is less than 200 mg/d, administer 10-30% of the MOR-E as the methadone daily dose. If the MOR-E is 200-500 mg/d, administer 10-20% of the MOR-E as the methadone daily dose. If the MOR-E is 501-1000 mg/d, administer 5-10% of the MOR-E as the methadone daily dose. If the MOR-E is greater than 1000 mg/d, administer 5% or less of the MOR-E as the methadone daily dose. The calculated methadone starting daily dose should be divided and administered every 8 hours. This dosing strategy is recommended for patients with previous opioid use and chronic cancer pain where frequent monitoring is possible.⁷

Sample Calculation:

Step One: Calculate morphine equivalent dose.

Morphine:oxycodone is 30:20-30

80 mg/day oxycodone = 80-120 mg/day morphine equivalents

Step Two: Determine methadone dose.

Since daily morphine equivalent is less than 200 mg, give 10-30% of morphine equivalent as total daily methadone dose. For example, assume average of 100 mg/day morphine equivalents for oxycodone: 10-30% of 100 mg/day as morphine equivalents equals 10-30 mg of methadone.

Dose should be divided and administered every 8 hours. An conservative example would be 5 mg every 8 hours.

Note: May need to increase dose and titrate slowly. Remember the analgesic effect may take days to be appreciated.

Ripamonti Method:

The Ripamonti Method is based on tapering the current opioid dose while adding methadone over a three day period.

On Day 1, patient receives 2/3 (or 33% reduction) of previous opioid morphine equivalent dose. For example, if a patient were previously on 1000 mg morphine equivalents of an analgesic, that patient would receive 660 mg of the morphine-equivalent of that analgesic on Day 1. In addition, methadone would be added to replace the dose reduction of the previous opioid. This methadone daily dose is based on an equianalgesic ratio of 10:1 of the reduced opioid dose (in morphine equivalents). In the above example, the daily dose was reduced by 340 mg morphine equivalents. Therefore, a 10:1 ratio would result in a 34 mg daily dose of methadone. The calculated daily methadone dose is to be divided and administered every 8 hours.

On Day 2 of conversion, the morphine equivalent of the original opioid agent will be decreased another third, a 2/3 total reduction from the original dose. From the example, the patient would receive 330 mg of the original opioid agent. The patient will continue on the "Day 1" methadone dose with an increase in dose only if the patient experiences moderate to severe pain.

On Day 3, the previous opioid is discontinued. The patient continues on the "Day 1" methadone dose every 8 hours. The patient may receive an additional 10% of the total daily methadone dose for breakthrough pain.⁶

Step One: Calculate morphine equivalent dose, Morphine:oxycodone is 30:20-30

80 mg/day oxycodone = 80-120 mg/day morphine equivalents

Step Two: On Day 1, decrease the morphine equivalent dose by 33% and add the calculated methadone dose.

80-120 mg morphine equivalents of oxycodone reduced by 33% would be approximately 50-80 mg of morphine equivalents of oxycodone, resulting in an oxycodone dose of 50-55 mg/day (converted back to oxycode based on the respective morphine:oxycodone conversion ratios).

The 30-40 mg morphine equivalent reduction (33%) is replaced with a methadone in a 10:1 ratio. The methadone dose would be 3-4 mg/day divided and given every 8-12 hours. On Day 2, decrease the morphine equivalent dose by another third, 2/3 total reducion and continue the methadone dose.

An additional third reduction in the morphine equivalents of oxycodone would be approximately 25-40 mg morphine equivalents of oxycodone, resulting in an oxycodone dose of 25 mg/day based on respective morphine:oxycodone conversion ratios.

The patient will continue on the "Day 1" methadone dose. An increase may be warranted only if the patient is experiencing moderate to severe pain.

On Day 3, decrease the original morphine equivalent dose by the final third and continue methadone dose.

At this point, oxycodone is discontinued. And again, the patient will continue on the "Day 1" methadone dose. An increase may be warranted only if the patient is experiencing moderate to severe pain. A breakthrough dose of 10% the daily dose may be given prn breakthrough pain.

1. Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiological Approach. 5th ed. New York: McGraw-Hill; 2002.

2. Paronish, R. UPMC Health Systems Pain Management: Opioid Therapy Guidelines. http://www.upmc.edu/palliativecare/pdf%20files/painCard.pdf. Obtained July 26, 2002.

3. McEvoy, G. AHFS Drug Information. Bethesda: American Society of Health System Pharmacists, Inc; 2002.

4. Lawlor PG, Turner KS, Hanson J, Bruera ED. Dose ratio between morphine and methadone in patients with cancer pain: a retrospective study. Cancer 1998; 82: 1167-73.

5. Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, Conno F. Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio. J Clin Oncol 1998; 16:3216-21.

6. Ripamonti C, Zecca E, Bruera E. An update on the clinical use of methadone for cancer pain. Pain 1997; 70: 109-15.

7. Goodman F, Jones W, Glassman P. Methadone Dosing Recommendations for Treatment of Chronic Pain. Pharmacy Benefits Management Strategic Healthcare Group Department of Veterans Affairs. December 2001. http://www.vapbm.org/monitoring/ methadonedosing.pdf. Obtained July 26, 2002.