Methadone: Safe Prescribing for Chronic Pain

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.