One would think that converting from one opioid to another would be a simple thing. In theory it is. Just find the right ratio, do the math, and voila! However, experts disagree on what the appropriate ratios are.30,47 Recent studies have challenged traditional conversion ratios, which historically were often based on single dose comparisons rather than chronic dosing. Proper conversion is dependent upon a variety of factors - drug dosage, cross-tolerance (or lack thereof) among opioids, and physiologic differences in drug metabolism. As if this were not enough, the skill of converting opioids requires more than the use of simple conversion rates. The conversion process must take into account such factors as the amount of residual drug in the patient's system and the time to achieve steady-state blood levels with the new drug as well as individual patient responses during the conversion process. Pereira and Anderson's articles, referenced above, offer excellent recent reviews of controversies in this area for those who wish to pursue further reading. Here, I offer some principles that should help guide conversion efforts:
|Example. Mr. Smith had been taking sustained-release oral morphine 60 mg q12. His family just managed to get him to take his last oral dose two hours ago. He is admitted to the hospital and can no longer take pills. His pain is well controlled. You wish to start him on a SC (or IV) infusion of morphine. How do you convert to parenteral morphine?|
|1. Old 24 hour oral morphine dose = 120 mg.|
|2. Conversion tables show that the oral to parenteral ratio for morphine is 3:1. Therefore, divide 120 mg by 3 to obtain the 24-hour equivalent of parenteral morphine = 40 mg parenteral morphine per 24h.|
|3. Basal infusions of morphine are written q1h. Therefore divide 40 mg by 24 = 1.66 mg/h.|
|4. As his pain is well controlled, round-down 1.66 to 1.5 mg/h IV or SC. This is the target basal dose.|
|5. As approximately 10 hours of sustained-release morphine is in the patient's system, this basal dose should be started in approximately 10 hours. Until then breakthrough doses (approximately 1 mg q30 minutes) may be used. This is the initial drug order.|
|6. If the patient begins to need frequent breakthrough doses before 10 hours pass, a low basal dose, 0.5-1.0 mg/h, may be initiated based on the reported pain score and breakthrough drug usage. This is the process of adjusting the initial order in the direction of the target order.|
The reviews cited above demonstrate that particular caution should be used in converting from one opioid to another at high doses.30,47 As opioids may differ significantly in terms of their mechanisms of action (for example, methadone's NMDA antagonism) and the degree of cross-tolerance and metabolism, conversion tables may be inaccurate for calculating true equivalent doses, which risks overdosage with the new drug (or occasionally underdosage). This has been found to be particularly true in converting from high doses of opioids such as morphine and hydromorphone to methadone; appropriate morphine-to-methadone ratios tend to be much higher than commonly published ratios.31,49 That is, a lower methadone dose than is suggested by most published tables is appropriate.
|Table 4.1. 24-Hour Drug Equivalencies of Selected Opioids|
|Drug, delivery route||Dosage by route|
|Morphine sulfate, parenteral||60 mg IM, SC, IV|
|Morphine sulfate, oral||180 mg PO (chronic use)|
|Methadone||10-40 mg PO|
|Hydromorphone, parenteral||9-12 mg IM, SC, IV|
|Hydromorphone, oral||45-60 mg PO|
|Oxycodone||120 mg PO|
|Fentanyl||50-100 mcg/h patch (change q72h)|
|Codeine||1200 mg PO|
|Hydrocodone||No consensus on equivalent dose|
|All equivalencies are approximations, not starting doses. There is no universal agreement on equivalent doses. Individual dose adjustment is essential!|
Recent articles have demonstrated the complexities of opioid conversion and argue against simplistic reliance on tables. Review of these articles is strongly recommended.30,47 These values are presented as crude guidelines for conversion. As discussed in the text, as important or more important than simply converting milligrams or micrograms is using a protocol that allows adjustment of conversion doses based on individual patient characteristics and responses over time.
|Using above values to convert between drugs|
|1. Calculate current drug 24-h dose (dose times number of times given per day).|
2. Multiply this current 24-h dose times the ratio of 24-h equivalent dose of new drug over 24-h equivalent of old drug. This gives 24-h dose of new drug (equivalent doses from table above).
|3. Divide new 24-h drug dose by number of times drug to be given per day. This gives new individual drug dose.|
|4. Order new individual drug dose to be divided per the dosing interval determined above. This is the target dose.|
|5. Accounting for residual drug in the system, if any, increase new drug toward this target, adjusting as necessary.|
Example. Convert sustained-release morphine to parenteral hydromorphone (using conservative conversion - may need to increase hydromorphone later).
Current order reads: Sustained-release morphine 60 mg BID.
1. Current 24-h dose is 60 X 2 = 120 mg.
2. 120 mg (old 24-h oral morphine dose) times 9 mg (hydromorphone, parenteral) divided by 180 mg (morphine, oral) = 6 mg/24 h (new dose hydromorphone, parenteral).
3. Divide this 24-h dose by dosing interval - 24 - for q1 hour basal dose = 0.25 mg/h (hydromorphone, parenteral). This is the target dose.
4. If residual drug is in the patient's system, initially use prn hydromorphone doses. Increase the basal dose based on patient response and prn usage.
Figure 4.4. Example conversion calculation. Writing in drug name, route, and time intervals in calculations helps avoid serious conversion errors.
Methadone. Considerable controversy has arisen regarding conversion ratios for methadone. Experts have noted a useful principle: The higher the dosage of the opioid being converted to methadone, the lower the conversion methadone dose that should be used. Thus, if a patient were on a high dose of morphine, in converting to methadone I would initially use a conservative 180 mg oral morphine: 10 mg of methadone conversion ratio from Table 4.1. As summarized by Ripamonti, "The results of our study confirm that methadone is a potent opioid, more potent than believed. Caution is recommended when switching from any opioid to methadone, especially in patients who are tolerant to high doses of opioids."31 I strongly advise using low equivalent doses of methadone initially, gradually increasing the dose while using more liberal doses of breakthrough opioid in the conversion process.
Hydromorphone, parenteral. Controversy exists as to the potency ratio of hydromorphone compared to morphine. Earlier studies suggested that parenteral hydromorphone was seven times as potent as parenteral morphine. More recent studies suggest a 5:1 relative potency.50 The oral:parenteral ratio for hydromorphone is 5:1 in most tables.
Oxycodone. While American conversion tables have listed oxycodone as being equianalgesic to oral morphine, there is some debate as to equivalency. Some have listed oxycodone as being two times as potent as morphine (Canada). A recent study suggested that oxycodone may be approximately 1.5 times as strong as morphine (Bruera, 1998). Thus, 120 mg of oxycodone is suggested here.
Fentanyl. Fentanyl comes in patches from 25 to 100 ug/h. Patches are changed every 72 hours. A 25 ug/h patch is approximately equal to 50 to 75 mg of oral morphine over 24 h. Levy suggests a simple rule of thumb: that the Fentanyl patch strength (in mcg/h e.g., 25, 50, 100, etc.) is equal to the SR morphine dose given BID.34 Thus, by this rule a 150 mcg/h patch is equivalent to 150 mg SR morphine q12h. Jannsen, the manufacturer of fentanyl patches, suggests a more conservative dosing schedule in converting to fentanyl patches. Jannsen's dosing table does not allow for a simple conversion value. They suggest a relatively higher patch strength at low oral morphine equivalents (25 mcg patch for 45-134 mg morphine/24h - consistent with Levy's rule) and a relatively lower patch strengths at higher morphine doses (200 mcg patch at 675-764 mg morphine/24h - not consistent with Levy's rule). (See manufacturer's product information for details). Their product information stresses that conservative conversion values used for converting to fentanyl patches may result in drug overdosage if used to convert from patches to other opioids, highlighting the danger of a simplistic use of conversion tables.
Codeine. Although this is the classic conversion value listed in tables, codeine is metabolized into morphine in the liver via the P450 system. About 10% of the population have trouble doing this, and many drugs - for example, Cimetidine and SSRIs - may inhibit this, resulting in even lower potency. Thus actual potency is highly variable.
Hydrocodone. Most conversion tables do not list an equivalent dose for hydrocodone. I have found hydrocodone:oral morphine ratios that range from 6:1 to .75:1 Thus, no recommendation can be given. My impression is that Vicodin (hydrocodone) and Percocet (oxycodone) are very similar in potency.
Please learn from my mistake! For years I lectured residents and students on principles of pain management along the lines above. Trainees were inspired to go forth and do good deeds. They applauded, I basked in a teacher's glory, and nothing changed. In my teaching I had stressed attitudes (treating pain is important) and knowledge but had underweighted skill training. I found, for example, that most trainees could not use even a basic opioid conversion table (let alone deal with such subtleties as are discussed above). Most residents carried an opioid conversion table in their "peripheral brain" - a small handbook or, recently, a PDA. However, when I asked them to demonstrate the skill of using the conversion table to switch from one opioid to another, they could not. They got confused converting from one drug dosed q12h to another drug dosed TID or q1h. Conversion tables listed an equivalent dose of fentanyl q1 hour, but they could not figure out how this related to the fact that the fentanyl patch is changed q72h. Being unskilled in using tables, they would not use them, fearful of making a mistake (and potentially killing a patient). Thus, it is critical that trainees demonstrate the skills outlined above. Ideally, the practice of such skills will occur in real life under appropriate supervision (as is the case for other medical skills). Barring this, it is strongly recommended that trainees practice skills such as opioid conversion using cases in groups or via self-directed learning. Teachers may wish to make up their own cases and ask trainees to perform certain skills (such as writing appropriate opioid orders using a conversion table), or trainees may wish to work independently.
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Palliative Care Perspectives
James L. Hallenbeck, M.D.
Copyright © 2003 by Oxford University Press, Inc.
The online version of this book is used with permission of the publisher and author on web sites affiliated with the Inter-Institutional Collaborating Network on End-of-life Care (IICN), sponsored by Growth House, Inc.