Unlike other opioids, Methadone has significant ability to inhibit the NMDA receptor(n-methyl-d-aspartate receptor) at therapeutic doses (Davis, Walsh (2001) Support Care Cancer; 9:73-76). Activation of the NMDA receptor produces central nervous system sensitization, so this pharmacological effect makes Methadone a much more effective drug for neuropathic pain than other opioids. There is also evidence that inhibitory activity at the NMDA receptor sites reduces the possibility of tolerance to Methadone when compared to that exhibited by other opioids (Hewitt (2000) Clin J Pain; 16:S73-79).
In addition to being a long-acting opioid that may be dosed at 8 to 12 hour intervals, Methadone is available in a variety of dosage forms:
Methadone is well absorbed by the sublingual route which may be of critical importance in patients that are unable to swallow and in whom infusion therapy is not feasible (Coluzzi (1998) J Pain & Symptom Management; 16:184-192). Although oral morphine solution is often administered by the sublingual route, there is evidence to suggest that it is poorly absorbed because of its low lipid solubility (Coluzzi (1998) J Pain & Symptom Management; 16:184-192). Methadone may offer distinct advantages over oral morphine solution when the sublingual route of administration is indicated.
One of the most impressive advantages to this unique opioid is its very low cost compared with other potent opioid drugs. Methadone is about one-tenth of the cost of an equivalent dose of the Fentanyl patch (generic) and one-seventh the cost of Morphine extended release tablets (generic).
Methadone is appropriate for treating chronic severe pain, including cancer pain and neuropathic pain. It is an excellent choice when rotating a patient from other opioid therapy which may be either ineffective or causing intolerable side effects. A study of cancer patients who had uncontrolled pain and/or intolerable adverse effects showed 80% of the patients reported improvement in pain control and reduction of adverse effects following rotation to Methadone (Mercadante, et al. (2001) J Clin Oncology; 19:2898-2904). Morphine has been associated with a variety of adverse effects including pseudo-allergy (itching, flushing, sweating) and tremors. Methadone is synthetic and belongs to a distinctly different structural class than Morphine, making it a good alternative to patients exhibiting the pseudo-allergy symptoms.
In patients receiving Morphine who have renal impairment, an active metabolite, Morphine-3-glucuronide can accumulate and is thought to be associated with neurotoxic symptoms (myoclonus, allodynia, and hyperalgesia). (Anderson, et al. (2003) J. Pain & Symptom Management; 25: 74-91). There is also evidence that Morphine-3-glucuronide may actually antagonize the analgesic effect of Morphine itself. (Anderson, et al. (2003) J. Pain & Symptom Management; 25: 74-91). Since Methadone does not have any active metabolites and the dosage does not need to be adjusted for renal impairment, it is ideal for the patient with renal impairment or for a patient on Morphine that is exhibiting neurotoxic side effects.
There are a variety of potential drug interactions with Methadone. Many of the potential interactions cited in the literature have not been associated with documented clinical effects, even though alterations in Methadone plasma concentrations may be statistically significant. This may be due to the pharmacodynamics of the drug, specifically; long half-life, extensive distribution, and extensive tissue binding. These factors may blunt the clinical impact of some potentially interacting drugs that may induce or inhibit inactivation of Methadone in the liver. Refer to the drug interaction table for details. There are various strategies for managing drug interactions, however, if the combination of interacting drugs cannot be avoided a general rule of thumb is to adjust the Methadone dose by 25%; upwards if the interacting drug has been shown to result in decreased Methadone clinical effects or down if the interacting drug has been shown to result in increased Methadone clinical effects. Dosage adjustment may not be necessary for drugs which have the potential for altering enzymatic metabolism of Methadone, yet have not been shown to result in a change in the clinical status of patients. The clinician, however, should be alert to possible changes in the clinical picture when any potentially interacting drug is added or removed.
Clinically Significant Drug Interactions
|Increased Methadone||Ciprofloxacin(Cipro), Diazepam(Valium), Fluconazole(Diflucan), ethanol(acute use)|
|Decreased Methadone Effects (reduced effects)||Phenytoin(Dilantin), Phenobarbital, Rifampin, Nelfinavir(Viracept), Ritonavir(Novir)|
Possible Methadone Drug Interactions
|(Clinical effects not documented in literature)|
|Increased Methadone blood levels||Cimetidine(Tagamet), Fluoxetine(Prozac), Paroxetine(Paxil), grapefruit juice|
|Decreased Methadone blood levels||Carbamazepine(Tegretol)|
Methadone is a valuable analgesic with distinct advantages over other opioids that make it a viable option for treatment of chronic severe pain. Clinicians who prescribe Methadone need to be familiar with its unique pharmacokinetics and the dosing ramifications for safe and effective use of the drug.
Outcome Resources is dedicated to supporting hospices in the utilization of methadone and provides consultations and education programs geared toward this and other palliative appropriate medications. Call today to learn more about how we can assist your hospice by providing cutting-edge clinical support services including a direct line to experienced pharmacists.
|You need to be straight with him. Ask him what is more iratmopnt the drugs or ur family? If he can not confidently say ur family end it with him. You and ur kids do not deserve that. It is best for them to be as far away from him as possible. If he can honestly say the family (try to ask him when hes straight) then tell him he needs to get help or he is going to lose the best thing he could ever have. Don't use it as a threat just be honest with him. The treatments won't help him unless he lets them help him. Try to be understanding to what he is going through be supportive but at the same time be strong and firm and smart. Do what is best for you and your children. Most addicts are abusers. Theres a very good chance that he will become violent. Do you really want your children growing up around that?! They are so young, so impressionable. If they see him acting this way they will grow up to think it is ok. If he begins being violent or abusive in any manner and you tolerate it they will think that all women should accept being treated like that. My father was an alcoholic/drug addict, and he could get violent. I am his only child. When she saw what hed become she got rid of him. I saw him once when I was 6 for a visitation and I remember everything was fine then towards the end he became very irrate and i remember him and my mom arguing. And she put me in the car and he grabbed me out he was all sweaty and I was terrified and screaming my mom got me off of him and i remember him putting his sweaty face close to mine and saying something to me i couldnt understand. at the time i didnt no what was going on, but now it makes me so angry to no that he came to see me high!!! and the argument was he watned to stop the visit and go get high then come back to finish the visit he reallly needed it. It makes me sick. I love my mother everyday for getting rid of him and doing everything in her power to keep him away from me (not that it was really hard half the time he forgot i existed) I saw him about 7 yrs ago i was 14 he didnt recognize me i didnt recognize him. My sis told me who it was and when it was brought to my attention i saw he looked just like me .or i looked like him whatever.the point is dont make your children live through that hell.
Posted 2/15/2013 02:53:52 AM
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