Methadone withdrawal

A protracted abstinence syndrome may follow the acute opioid withdrawal syndrome and last for many weeks (Martin et al. 1973). In one study ofher-oin addicts detoxified with methadone, withdrawal distress peaked at day 20,... 

Nervirapine is an HIV drug that is a CYP3A4 inducer in a small sample, nevirapine caused a 50% reduction in methadone blood levels, resulting in complaints of methadone withdrawal symptoms in patients receiving methadone maintenance may need to increase methadone dose in patients who have nevirapine added to their drug regimen. 

Unnecessary detoxification with drugs should be avoided if possible (e.g., if symptoms are tolerable). Heroin withdrawal reaches a peak within 36 to 72 hours, and methadone withdrawal peak is reached at 72 hours. 

Gossop M, Griffiths P, Bradley M Strang J (1989). Opiate withdrawal symptoms in response to 10-day and 21-day methadone withdrawal programmes. British Journal of Psychiatry, 154, 360-3... 

Since nevirapine is metabolized by the cytochrome P-450 system and induces 3A4 and 2B6, other drugs that are also metabolized by these isoenzymes will have low plasma levels when given in combination. It also increases the clearance of methadone and results in methadone withdrawal. Nevirapine decreases the plasma concentrations of norethindrone, ethinyl estradiol and protease inhibitors (HIV). 

Four patients with methadone withdrawal psychosis have been described (SEDA-20, 79). 

Enzyme-inducing drugs, such as rifampicin, enhance the metabolism of methadone, leading to lower serum methadone concentrations (59). This interaction is thought to have caused acute methadone withdrawal symptoms in two patients with AIDS (SEDA-16, 81). 

Since methadone is partly metabolized by CYP3A4, the interaction of efavirenz with methadone has been investigated prospectively in 11 patients taking stable methadone maintenance therapy (28). Efavirenz reduced the steady-state methadone AUC by 50%. However, patients generally only needed a 22% increase in their methadone dose to eliminate the symptoms of methadone withdrawal, and the full basis of the interaction is not understood. 

When methadone is used in HIV infection (for pain or treatment of opioid dependence) nevirapine given simultaneously can reduce methadone blood concentrations, the effect being sufficient to cause methadone withdrawal symptoms (24,25). 

Heelon MW, Meade LB. Methadone withdrawal when starting an antiretroviral regimen including nevirapine. Pharmacotherapy 1999 19(4) 471-2. 

Narcotics Methadone Rifampin and rifapentine use may require methadone dose increase rifabutin infrequently causes methadone withdrawal. 

Treatment with the NNRTIs efavirenz and nevirapine was noted to cause methadone withdrawal symptoms in patients with HIV [66, 52], Subsequently, both NNRTIs were shown to induce drug-metabolizing enzymes in cultured hepatocytes due to activation of CAR and weak activation of PXR [37]. 

Because nevirapine induces CYP3A4, this drug may lower plasma concentrations of coadministered CYP3A4 substrates. Methadone withdrawal has been reported in patients receiving nevirapine, presumably as a consequence of enhanced methadone clearance. Plasma ethinyl estradiol and norethindrone concentrations decrease by 20% with nevirapine, and alternative methods of birth control are advised. Nevirapine also can reduce concentrations of some coadministered HIV protease inhibitors. 

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. ... 

In contrast, a study found no evidence of any change in the pharmacokinetics of methadone in HIV-positive patients taking methadone 14 days after they started zidovudine 200 mg every 4 hours. No methadone withdrawal symptoms occurred. Another study in 16 patients taking methadone found that a single-dose of a fixed combination of zidovudine 300 mg with lamivudine 150 mg (Combivir) had no effect on the pharmacokinetics of methadone, and there was no evidence of withdrawal or toxicity. ... 

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... 

In a pharmacokinetic study, 8 patients taking methadone 30 to 120 mg daily had methadone levels measured before and 14 days after starting an antiretroviral regimen including nevirapine 200 mg daily. The methadone AUC decreased by 52%, and the maximum level by 36%. Six patients complained of symptoms of methadone withdrawal, and required a mean increase in methadone dose of 16%. ... 

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. ... 

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