Adverse effects methadone

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

In Table 1.3 I have included the areas of physical and psychological health, which often do not feature in reviews. Methadone has significant adverse effects, as discussed below, and by no means do all patients report subjective improvements in health on the drug, as opposed to when taking street heroin or other opiates. However, if methadone treatment is adhered to, there is normalization of various circadian rhythms and endocrine effects... 

There are a range of more minor adverse effects, however, which are often not mentioned in formal reviews of methadone treatment but which are discussed more in practical handbooks. In clinical practice these can be very problematic, variously leading to distress for individuals, limitations in compliance and requests for alternative treatments, and the most troublesome such effects are listed in Table 1.4. 

In the course of clinical treatment with methadone, certain situations relating to adverse effects are characteristic. Nausea is a general opiate effect, but complaints most frequently relate to the methadone mixture. This preparation does have a syrupy consistency, but the problem for clinicians is that the alternatives - sugar-free mixture or methadone tablets - are both more injectable, and therefore requests or implied requirements for these are often manipulative. So are requests for the antiemetic cyclizine tablets, which are crushed and injected by drug misusers along with injected methadone. As indicated in Chapter 4, thankfully these particular claims have become less common now that guidelines are much more discouraging of any use of methadone tablets. 

As indicated, buprenorphine can offer a quicker option than methadone, with a three-day course reported to be effective for withdrawal from heroin (Cheskin et al. 1994). The side-effects of clonidine which render it unsuitable for community treatment can be manageable in the inpatient setting, although the drug is being superseded by lofexidine where that is available. Controlled studies have found clonidine and lofexidine to be equally effective in alleviating withdrawal symptoms in inpatient detoxification from heroin (Lin et al. 1997) and from methadone (Khan et al. 1997), with lofexidine resulting in less hypotension and fewer adverse effects. Another double-blind controlled study found lofexidine to be broadly as effective as a ten-day methadone detoxification in inpatient opiate withdrawal (Bearn et al. 1996). 

When we reviewed the limited evidence regarding treatment, it appeared that personality disorder was associated with worse results in the treatments aimed at abstinence, but had not so marked an effect in methadone maintenance (Gill et al. 1992, Darke et al. 1994b). That pattern of findings, with personality impairment seemingly exerting a less adverse effect in maintenance than various other treatments, has been demonstrated further (van den Bosch Verheul 2007), even to the point where in populations in which methadone maintenance is the main approach, few overall differences in response are found (Havens Strathdee 2005, Welch 2007). 

This is the goal of methadone maintenance programs. Apparently, when properly administered, these have had considerable worldwide success in countering the adverse effects of heroin addiction. Nevertheless, as a matter of public policy, they have been controversial in the United States partly because they are thought merely to replace one addiction with another (Lowinson et al. 1997 Kreek and Reisinger 1997). 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

In addition to knowledge about the clinical efficacy, adverse effect profile, and likelihood of emergence of resistance, the physician caring for an HIV-infected patient must be well versed in basic pharmacokinetics as well. Such patients are frequently taking multiple medications, including combinations of antiretroviral agents, prophylaxis or treatment for opportunistic infections, and opioid pain medications or methadone for maintenance therapy. 

Adverse effects Methadone can produce dependence like that of morphine. The withdrawal syndrome is much milder but is more protracted (days to weeks) than with opiates. 

In the second study there were 174 patients in two similar experimental groups in whom injectable rather than inhaled heroin was used (5). A response to treatment was defined as at least a 40% improvement in physical, mental, or social domains of quality of life, if not accompanied by a substantial (over 20%) increase in the use of another illicit drug, such as cocaine or amphetamines. After 12 months those who took methadone and heroin (smoked or injected) had significantly better outcomes. The incidences of adverse effects (constipation and drowsiness) were similar in all the groups. However, owing to the limitations of the study and the complex nature of drug dependence, the therapeutic outcomes could not be justifiably and solely attributed to the specific drug(s). 

In a prospective, open, uncontrolled study 50 patients with a history of cancer taking daily oral morphine (90-800 mg) but with uncontrolled pain with or without severe opioid adverse effects were switched to oral 8-hourly methadone in a dose ratio of 1 4 for patients receiving less than 90 mg of morphine daily, 1 8 for patients receiving 90-300 mg daily, and 1 12 for patients receiving more than 300 mg daily (5). Methadone was effective in 80% of the patients when comparing analgesic... 

In a prospective uncontrolled study of intrathecal methadone in 24 patients with a history of intractable chronic non-malignant pain, methadone was a better analgesic than morphine, with improved quality of life and no adverse effects in 13 patients (6). The final rates of methadone infusion were 20% higher than the preceding morphine rates. 

An analysis of the balance of benefit to harm during methadone maintenance treatment for diamorphine dependence has shown lower mortality and morbidity with improvement in quality of life (7). The risks of methadone treatment include an increased risk of opiate overdosage during induction into treatment, and adverse effects of methadone in some patients. However, with careful management the benefits of prescribing methadone outweigh the risks. 

The combinations of methadone + carbamazepine and buprenorphine + carbamazepine have been compared in the treatment of mood disturbances during the detoxification of 26 patients with co-morbidities (30). The buprenorphine combination had more of an effect. More patients taking the methadone combination dropped out of the study (58% versus 36%). However, both regimens were considered safe and without unexpected adverse effects. The results of this study need to be interpreted with caution because of the small sample size. 

In a randomized, double-bhnd, placebo-controlled trial of the efficacy of intravenous methylnaltrexone (0.015-0.095 mg/kg) in treating chronic methadone-induced constipation in 22 patients attending a methadone maintenance program (oral methadone linctus 30-100 mg/day), methylnaltrexone induced immediate bowel movements in all subjects (32). There were no opioid withdrawal symptoms or significant adverse effects. 

The role of opioid rotation in cancer pain management has been described, highlighting the limitations of equianalgesic tablets and the need for monitoring and individualization of dose. This is particularly important when methadone is used as the opioid for conversion. The authors referred to a greater than expected potency of methadone, with excessive sedation and opioid-related adverse effects, if the switch is done on a one-to-one basis. They suggested that the calculated equianalgesic dose of methadone should be reduced by 75-90% and the dose then titrated upwards if necessary (47,48). 

Methadone has been used for intrathecal administration. Although this route can provide prolonged analgesia, the adverse effects have been reported to be unacceptable (SEDA-16, 81). 

Methadone maintenance treatment is considered to be a medically safe treatment with relatively few and minimal adverse effects. However, the danger of serious adverse effects and death with the increasing use of methadone as maintenance therapy in drug addicts has been highlighted. It must be emphasized that a daily maintenance dose of 50-100 mg is toxic in a non-tolerant adult and as little as 10 mg can be fatal in a child. There is an increasing number of reports of the deaths of children of mothers on maintenance therapy from inadvertent ingestion. 

GRAPEFRUIT JUICE METHADONE t plasma concentrations and t risk of adverse effects. Interaction is considered to be of rapid onset but of minor clinical significance Methadone is metabolized by intestinal CYP3A4, which is inhibited by grapefruit juice Prudent to be aware and warn users and carers... 

Although thromboprophylaxis of microvascular anastomoses seems advisable theoretically, there is little clinical evidence to support the use of dextran for this purpose. The pulmonary edema in these cases was thought to be non-cardiogenic, similar to that caused by heroin, methadone, propoxyphene, and salicylates, due to a direct adverse effect on the pulmonary vasculature, rather than anaphylaxis, cardiac pump failure, or volume overload. 

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