Methadone dosage

The initial dose of buprenorphine should be given at least 12-24 hours after the last heroin dose, 24 hours after the last methadone dose, or 48 hours after the last LAAM dose (see Table 2-3). The methadone dosage of methadone maintenance patients should be reduced to 30 mg/day before the transfer to buprenorphine is attempted. Ideally patients should show clear evidence of opiate withdrawal before receiving the first dose of buprenorphine, to avoid the risk that buprenorphine will precipitate more severe withdrawal. For the first day, sublingual buprenorphine/naloxone doses of 2/0.5-4/1 mg can be given every 2-4 hours, up to a maximum total dose of 8/2 mg/day. On the... 

Finally, it should be stressed again that certainly not all benzodiazepine prescribing to opioid maintenance patients need be long term. McDuff et al. (1993) reported on detoxification from alprazolam, the benzodiazepine most commonly used by their methadone subjects. With methadone dosage usually remaining the same, patients were offered a set reducing course of alprazolam over 11 weeks. Of 22 patients, four refused the treatment and 12 out of 18 subsequently completed detoxification, although timescales in practice proved variable. In a comparative study by Weizman et al. (2003) just over a quarter of benzodiazepine-dependent methadone maintenance patients remained free of benzodiazepines... 

Individuals who have been misusing pharmaceutical opioids pose a particular problem, as any straight conversion from claimed average usage tends to result in methadone dosages which appear excessively high. In practice, such users can usually be given doses of... 

Client assessed for methadone (Dosage level established)... 

Coller JK, Barratt DT, Dahlen K, Loennechen MH, Somogyi AA (2006) ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Clin Pharmacol Ther 80 682-690... 

A 1 997 Dutch study showed that up to 90 % of clients on an average daily dose of 50 mg methadone also used cocaine and heroin, and 70 % used alcohol. First results of a study, initiated by the ministerfor health, into the effect of different methadone dosages on experimental groups show that the group receiving a higher dose became more stable, their health and social skills deteriorated less frequently and even improved somewhat more often. 

Two patients who had methadone withdrawal symptoms while taking phenjdoin 300 to 400 mg daily, and one of them later when taking car-bamazepine 600 mg daily, became free from withdrawal symptoms when they were given valproate instead. It was also found possible to virtually halve their daily methadone dosage. ... 

Information is limited but the interaction between methadone and these enzyme-inducing antiepileptics appears to be established and of clinical importance. Anticipate the need to increase the methadone dosage in patients taking carbamazepine, phenytoin or phenobarbital. It may be necessary to give the methadone twice daily to prevent withdrawal symptoms appearing towards the end of the day. It seems probable that primidone will interact similarly because it is metabolised to phenobarbital. Also be aware of the need to reduce the methadone dose if any enzyme-inducing antiepileptic is stopped. Valproate appears not to interact. 

Methadone effects reduced or unaffected. A drug abuser with AIDS needed an increase in his levomethadone (7 -methadone) dosage from 40 to 60 mg daily, within a month of starting to take zidovudine 1 g daily. ... 

In a pharmacokinetic study, 11 patients taking methadone 35 to 100 mg daily were given efavirenz with two nucleoside analogues. Nine of the patients developed methadone withdrawal symptoms and needed dose increases of 15 to 30 mg (mean 22%). A pharmacokinetic study of these patients found that 3 weeks after starting efavirenz their mean methadone AUCs were reduced by 57% and their maximum plasma levels by 48%. Similar results were found in another study in 5 HIV-positive patients taking methadone 4 patients experienced opioid withdrawal symptoms and a mean methadone dose increase of 52% was required. In another retrospective study, 6 out of 7 patients needed methadone dosage increases of 8% to 200% within 2 weeks to 8 months of starting an efavirenz-based... 

A study in 24 HI V-positive patients taking methadone found that after taking rifabutin 300 mg daily for 13 days the pharmacokinetics of the methadone were minimally changed. However 75% of the patients reported at least one mild symptom of methadone withdrawal, but this was not enough for any of them to withdraw from the study. Only 3 of them asked for and received an increase in their methadone dosage. The authors offered the opinion that over-reporting of withdrawal symptoms was likely to be due to the warnings that the patients had received. ... 

Other cases of this interaction have been reported. Some patients needed two to threefold increases in the methadone dosage while taking rifampicin to control the withdrawal symptoms. ... 

Rifabutin appears to interact to a very mueh lesser extent so that fewer, if any, patients are likely to need a methadone dosage inerease. 

This seems to be the only report of this interaction but it would appear to be of clinical importance. Care is needed if ciprofloxacin and methadone are given concurrently, especially if there are other factors such as smoking or the use of other enzyme inhibitors, which may also contribute to the interaction. Be alert for the need to change the methadone dosage. Consider also Quinolones + Opioids , p.338. 

Information is limited, but it indicates that the effects of starting or stopping fluvoxamine should be monitored in patients taking methadone, being alert for the need to adjust the methadone dosage. Although the increase in methadone levels with sertraline and paroxetine, and possibly also fluoxetine, is unlikely to have clinical effects in most patients, the possibility should be borne in mind, especially if high doses of methadone... 

Fetotoxicity Exposure to opioids in utero can lead to the development of the neonatal abstinence syndrome, especially in infants born to mothers who have misused these drugs. Neonatal abstinence syndrome in neonates bom to mothers taking treatment has been investigated in 68 neonates. Pre-delivery higher doses of maternal methadone were associated with an increased incidence of treatment for withdrawal and with longer episodes of neonatal abstinence syndrome. There was a dose-response relationship— for every 1 mg increase in last maternal methadone dosage before delivery, an extra 0.18 days of infant treatment for neonatal abstinence syndrome were required furthermore, breastfeeding reduced the duration of neonatal abstinence syndrome by 7.76 days [261. 

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