Abstract
Methadone hydrochloride is an effective, inexpensive, and relatively safe opioid to use in treatment of patients with chronic pain. Because it is the only long-acting analgesic available in liquid form, methadone is especially valuable in management of pain during the final stages of life. However, because methadone has an inherently long duration of action with wide variations, a possibility of accumulation and overdosage exists. Therefore, physicians must be judicious and conscientious when prescribing this opioid. Physicians must also closely monitor patients during the titration phase and educate them with regard to basic pharmacologic properties and potential side effects. A plan to start at low doses and proceed slowly is applicable to methadone.
Chronic pain, one of the most common conditions for which people seek medical treatment, affects more than 85 million Americans.
1 In end-of-life care, in which the primary focus is a reduction or elimination of suffering, many patients still endure uncontrolled pain. In recent years, healthcare consumers have become more sophisticated, demanding better pain control. Thus, physicians need to be familiar and competent with various treatment options including pharmacotherapy to manage their patients' chronic pain.
Although the primary responsibility of physicians is to nurture the physical and psychological well-being of their patients, it is also important that they serve as stewards of financial resources. A resurgence in the understanding of pharmacologic and pharmacokinetic properties of methadone hydrochloride coupled with its low cost has led to increased use of this agent in management of chronic pain.
Methadone, a synthetic opioid agonist developed in the late 1940s, has been used for more than 40 years to treat patients who are addicted to narcotics. Although substantial information exists regarding such use of methadone, only limited data are available with respect to pain management. It is only within the past decade that there has been a renewed focus on its use in treatment of patients with chronic pain. The National Guideline Clearinghouse guideline titled “VA/DoD clinical practice guideline for the management of opioid therapy for chronic pain”
2 recommends use of an agent with a long duration of action, such as a controlled-release morphine or methadone, when initiating a trial of opioid therapy for continuous pain.
Initial interest in methadone for pain management emerged in caring for terminally ill cancer patients, but recent attention now includes management of nonmalignant pain. Methadone is achieving greater acceptance in end-of-life care because it is the sole long-acting opioid in liquid form. It is highly lipophilic and readily absorbed through buccal mucosa. Methadone has a wide spectrum of absorption and formulations that allows administration via multiple routes: oral, sublingual, rectal, subcutaneous, intramuscular, intravenous, epidural, intrathecal, and percutaneous endoscopic gastrostomy (PEG) tube.
The process of switching from another opioid to methadone, especially when high doses are being used, is more complex. Several conversion protocols are available.
13-15 One example is:
Example—If prior daily opioid dose equals 150 mg of oral morphine sulfate equivalent per day; then, use 15 mg of methadone hydrochloride every 3 hours as needed. (Note: This is not a 1:10 ratio unless only one dose is given in 24 hours: 1:10 ratio would be 15 mg/d, not 15 mg per dose.)
On day 6, calculate total amount of methadone taken during previous 48 hours and convert to twice-daily methadone dose. If the patient actually took the 15 mg dose every 3 hours on days 4 and 5, then the correct dosing would be 60 mg every 12 hours.
Example—Patient is taking 600 mg of oral morphine sulfate equivalent per day. Because the oral morphine equivalent is greater than 300 mg/d, use 30 mg of methadone hydrochloride as initial fixed dose after terminating morphine administration and give 30 mg of methadone hydrochloride every 3 hours as needed. If the patient requires eight doses of 30 mg each for a total of 240 mg days 4 and 5 (120 mg/d); then, on day 6, adjust methadone dose to 40 mg orally every 8 hours or 60 mg every 12 hours.
14,15
Figure 3 provides a list of additional print and Web site resources.
A 46-year-old man with head and neck cancer status post radical dissection is taking the following medications:
fentanyl transdermal system, 100 μg, three patches every 72 hours
oxycodone hydrochloride, 20-mg tablets, three every 12 hours
oxycodone hydrochloride with acetaminophen tablets (5 mg/325 mg), two every 4 hours
morphine sulfate immediate release (MSIR), 20 mg every 2 hours
The approach to pain control in this patient would be as follows:
Total equianalgesic dose equals 1000 mg per 24 hours
In the patient described in the case scenario, pain control was initiated with administration of methadone hydrochloride, 15 mg every 8 hours, with four 8-mg tablets of hydromorphone hydrochloride (32 mg) every 2 hours as needed for pain. The patient utilized 10 doses of hydromorphone daily for 2 days, then 5 to 8 doses per 24 hours for the next 3 days. After the fifth day, his pain was well controlled with 3 doses of hydromorphone daily.
Methadone is gaining recognition in the arsenal of pain management. With appropriate knowledge and initial, cautious titration, physicians can readily give consideration to administration of methadone as they would to extended-release formulations of morphine, oxycodone, hydromorphone, and fentanyl. The efficacy, long-acting liquid formulations, multiple routes of administration, and low cost make methadone a noteworthy contender in treatment of patients with chronic pain.
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