PERT Program: Tip of the Month

PERT Program

Tip of the Month: May 2004

AN OVERVIEW OF THE ANALGESIC METHADONE

Although many experts caution against the use of methadone in older adults¹, it is increasingly being used in both community and long-term care settings. Part of the reason for this trend is that some reimbursement sources (e.g., WA State DSHS) are covering only generic morphine or methadone as the preferred first-line opioids to treat chronic, non-malignant pain conditions such as osteoarthritis.

Several advantages to this medication that also contribute to its increased use are²: Ultralow cost (generally pennies a pill), especially when compared with other opioids with extended dosing intervals (e.g., MSContin®, OxyContin®) Lack of known active metabolites Availability in multiple formulations, including liquid which may be particularly useful in frail, older adults Predominantly fecal excretion—does not accumulate with renal impairment NMDA receptor antagonist properties, which may increase its effectiveness in opioid resistant and neuropathic pain Appears to cause less constipation than morphine³

Despite these advantages, methadone must be used with caution because of its long half-life and the potential for subsequent drug buildup. The elimination phase ranges from 15–60 hours, yet the duration of analgesia is only 6–12 hours.^{4, 5} The drug’s toxicity cannot be fully evaluated for up to 7 days after its initiation. For example, if too high a dose is administered on Day 1 or 2, the resident may have good pain control and no visible side effects. But the resident might become oversedated or even obtunded on Day 4 or 5 if the dose is maintained and the drug accumulates. Unfortunately there are very few guidelines for the use of methadone in older adults—most of the work has been done in younger cancer patients.

Additional potential disadvantages include² Stigma related to its traditional use in the management of opioid addiction Subcutaneous infusion may cause site irritation; co-administration with dexamethasone can decrease this side effect Difficulties in converting to methadone from other opioids because of the significant individual variation in response to methadone. Unlike what is typically expected, there seems to be an increased incidence of significant side effects in those patients that have been on high doses of other opioids, than in patients who have received low doses Multiple drug interactions that can either 1) increase serum levels causing sedation and respiratory depression, or 2) decrease serum levels causing withdrawal symptoms or poor pain control. This is of particular importance due to the delayed elimination of methadone from the body. Drug interactions may not be observed until several days after their initiation

Drugs that have the potential to increase serum levels of methadone²	Drugs that have the potential to decrease serum levels of methadone²
Select antibiotics: erythomycin and other macrolides ketoconazole and other imidazoles ciprofloxacin and other quinolones	Anticonvulsants: phenytoin carbamazepine phenobarbital
Antidepressants: amitriptyline SSRIs, in particular fluvoxamine (Luvox)	rifampacin
diazepam	corticosteroids
Antiviral drugs: ritonavir nevirapine
Grapefruit juice⁴

For these reasons, we would suggest that methadone should only be used in consultation with a clinician who is experienced in using methadone for chronic pain and/or a pharmacist familiar with its use and conversion. The common standards for equianalgesic dose conversion, incomplete cross-tolerance dose modification, and titration based on frequency of breakthrough medication do not apply when using methadone. Because of its unique and complex pharmacology, methadone has its own set of prescribing and titration guidelines. It is important for nurses in the clinical setting to be aware of safe and acceptable dosing and titration regimens for this medication. There are particular challenges regarding the use of methadone in the long-term care setting. Nursing assessment and close resident monitoring are critical when using this drug.

We plan to focus on methadone for the next few months. Check back in June for information on starting methadone in the resident who has been on another strong opioid. July’s tip will teach conversion to methadone in the resident who has not previously been on opioids.

Questions or comments? We’d love to hear from you. Please contact us via the PERT Advisor. We’ll make certain your communication is forwarded to the appropriate experts and their responses posted on this site.

This series is authored by Anna Du Pen, ARNP and Beth Miller Kraybill, RN with review and consultation by Polly Mazanec, MSN, APRN, BC, AOCN and Elizabeth Ford Pitorak, MSN, RN, CHPN.

References

American Geriatrics Society. The management of persistent pain in older persons. J Am Geriatr Soc. 2002;50((Supple, No. 6)):1-20.
Bruera E, Sweeney C. Methadone use in cancer patients with pain: a review. Journal of Palliative Medicine. 2002;5(1):127-138.
Mercadante S, Casuccio A, Fulfaro F, et al. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. Journal of Clinical Oncology. 2001;19(11):2898-2904.
Gazelle G, Fine PG. Fast facts and concepts #75. Methadone for the treatment of pain. End-of-Life Physician Education Resource Center. Available at: www.eperc.mcw.edu. Accessed Jun 7, 2004.
von Gunten CF. Fast facts and concepts #86. Methadone: Starting dosing information. End-of-Life Physician Education Resource Center. Available at: www.eperc.mcw.edu.