Pain Management
5. G.G., a 40-year-old woman, is admitted to hospice with stage IV ovarian cancer, metastatic to pelvis, liver, and lungs. She was diagnosed after many months of nonspecific complaints of gastric distress and bloating. On laparotomy, she was staged as stage III and underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy and tumor debulking at that time. She has undergone subsequent chemotherapy and repeated tumor debulkings. In the past 6 months, her weight has decreased from 175 lb to 153 lb (she is 52 in. tall). Her primary complaints are constant nausea, constipation, and gripping abdominal pain, which she characterizes as burning and twisting. She quantifies the pain as 8/10 (on a 0- to 10-point scale) and describes the pain as one that moves into her groin and leg. Her family is unhappy about the drowsiness she experiences from her medications; they believe she is overmedicated. She has no known allergies. Current medications are Duragesic transdermal system 75 mcg/hour Q 72 hr, Kadian 50 mg PO once daily (sustained-release morphine intended for once daily administration), DSS 250 mg daily, Prevacid 30 mg PO daily, and lorazepam 0.5 mg Q 4 hr PRN nausea and anxiety. What is your assessment of her pain management regimen?
G.G. is currently using two long-acting opioids (i.e., Duragesic, Kadian), but is still unable to achieve relief of her pain, which is probably neuropathic pain (burning and twisting). The use of two long-acting agents is duplicative and should be replaced with one opioid. Methadone would be a better a long-acting agent because it has activity against neuropathic pain (see Chapter 8). When converting the fentanyl (i.e., Duragesic transdermal) and Kadian to methadone, the following should be considered: (a) patient compliance and ability to follow prescription directions, (b) use of an appropriate conversion formula, (c) converting a transdermal formulation of fentanyl to an oral opioid formulation, and (d) a supplemental opioid for breakthrough pain.
P.6p8
Due to its long and variable elimination half-life, the dose of methadone should generally be adjusted only once every 4 to 6 days, and patients must be able and willing to precisely follow directions for its use. Although formulas and tables are available to assist practitioners in the conversion of a short-acting morphine formulation to long-acting methadone, these have caused problems.57,58 A better, safer conversion plan is to use the methadone prescribing information59 and to follow a general rule of thumb not to exceed 30 mg of morphine as an initial oral dose.60
| Total Daily Baseline Oral Morphine Dose (i.e., Dose of Morphine Equivalents) | Estimated Daily Oral Methadone Requirement (as % of Total Daily Morphine Dose) |
|---|---|
| <100 mg | 20%-30% |
| 100-300 mg | 10%-20% |
| 300-600 mg | 8%-12% |
| 600-1,000 mg | 5%-10% |
| >1,000 mg | <5% |
Once the conversion is made, the calculated dose is adjusted and the dosing interval is set at every 12, 8, or 6 hours, based on patient age, previous use of opioids, and current clinical status. Clinical judgment is vital in individualizing a regimen for each patient based on his or her needs.
Before calculating the conversion to methadone for G.G., an important consideration in patients using transdermal fentanyl is an assessment of its absorption.61 The fentanyl from the transdermal system is absorbed through several layers of the skin and deposited in the subcutaneous fat, from which it is absorbed into the systemic circulation. It is generally observed that transdermal fentanyl is not effective in very thin, cachectic patients. In those cases, the conversion would be made without including the fentanyl. The patch would be removed at initiation of the first methadone dose and supplemented with medication for breakthrough pain if needed. In patients using multiple patches, one patch can be removed every 3 days. Despite weight loss, G.G. (52 in. and 153 lb) is not cachectic, and the fentanyl should be included when calculating the conversion of her current opioid dose to a comparable methadone dose. In this patient, her sustained morphine formulation (i.e., Kadian 50 mg PO TID) is equivalent to 150 mg/day of oral morphine. Her fentanyl transdermal system 75 mcg/hour is equivalent to about 150 mg of oral morphine equivalent/day. Her total morphine equivalents (MEs) per day = 150 mg + 150 mg = 300 mg. Using a 1:5 ratio for conversion of MEs to methadone, the calculated dose of oral methadone for this patient should be about 60 mg/day.
Although G.G. is relatively young, has been using opioids for some time, and has severe pain (quantified at 8/10), a methadone dose of 20 mg Q 8 hr (i.e., 60 mg/day) might be excessive. She should be treated with 15 mg of methadone PO Q 8 hr (45 mg/day), and the dose increased, if needed, based on her clinical response. This smaller initial dose would accommodate for some incomplete cross-tolerance from the morphine and fentanyl, and for any fentanyl that remains in her system over the next several days. Patients who have been on much higher doses of opioids, alternatively, can be converted over a period of several days (e.g., converting one-third of the previous daily dose of opioid every 3 days). This is an especially useful method for converting opioid doses for thin, cachectic patients who have been on multiple transdermal patches. A clinician should be in touch with G.G. frequently during the first several days after her conversion to methadone. A telephone call should be made 2 to 4 hours after the first dose to assess for efficacy and toxicity (primarily somnolence, confusion, or nausea). If pain relief does not last for the entire dosing interval, it can be adjusted, or G.G. can be instructed to take an extra dose of methadone.
An added benefit in changing to methadone for G.G. is a financial one for the hospice. Outpatient prices for long-acting opioids based on AWP are very steep and significantly add to hospice costs. The prudent use of methadone can improve overall pain management and keep costs in check. When methadone is not appropriate, generic extended-release morphine is a good second choice. Transdermal fentanyl should be reserved for patients who cannot take oral medication or for when there are significant compliance issues. OxyContin should be used only when patients cannot tolerate morphine or have other contraindications to its use. By converting to methadone, G.G.'s daily cost for the opioid alone will decrease from $33.41/day (i.e., $16.86 for Kadian and $16.55 for Duragesic) to $0.48 or less based on the AWP prices listed in the table.
| Average Wholesale Price (AWP) of Long-Acting Opioids38 for 1-Day Supply (Equivalent to Oral Morphine 150 mg/day) | |
| OxyContin 120 mg (40-mg tablets × 3) | $17.61 |
| Kadian 150 mg (50-mg capsules × 3) | $16.86 |
| Duragesic 75 mcg ($49.65/patch / 3 = 1 day's dose) | $16.55 |
| Avinza 150 mg (60 mg + 90 mg, one capsule of each) | $15.63 |
| Fentanyl transdermal 75 mcg ($40.23 / 3) | $13.41 |
| MS Contin 75 mg BID (15 mg + 60 mg, two of each) | $10.94 |
| Morphine-ER 75 mg BID (15 mg + 60 mg, two of each) | $8.40 |
| Methadone 30 mg (10 mg × 3) | $0.48 |
| From RED BOOK for Windows, Thompson Micromedex, Vol. 44, April 2007. | |
G.G. will also need something for breakthrough pain. Some practitioners use small doses of methadone, 2.5 mg or 5 mg, as often as Q 3 hr. This is a good choice in a well-supervised (i.e., inpatient) setting with nurses familiar with the use of methadone. However, if caregivers treat methadone as if it were morphine, which is much more commonly used for breakthrough pain, the risk of overmedicating the patient is very real. This can have disastrous consequences, especially in frail, elderly patients. Because G.G. tolerated morphine well in the past, 30 mg or 1.5 mL of OMS 20 mg/mL can be prescribed Q 2-4 hr PRN for breakthrough pain because she is not in an inpatient setting
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