Levomethadyl

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

If transferring from levomethadyl to methadone, the nurse should wait 48 hours after the last dose of levomethadyl before administering the first dose of methadone or other narcotic. 

LAAM (L-a-acetylmethadol or levomethadyl acetate) is a full agonist at the i opioid receptor with pharmacologic properties similar to those of methadone. A number of studies have demonstrated that treatment with LAAM results in reduction of opioid use and beneficial effects comparable to those achieved with methadone (Ling et al. 1978 Tennant et al. 1986 Zangwell et al. 1986). However, retention rates are higher in patients who take methadone doses of 80—100 mg/day. 

Johnson RE, Chutuape MA, Strain EC, et al A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N EnglJ Med 343 1290-1297, 2000... 

Schobelock, M.f. (2003) Product Discontinuation Notice — Orlaam (Levomethadyl Hydrochloride Acetate) Oral Solution 10 mg/mL, CII, FDA, Columbus, OH. 

Orlaam(tm) (Levomethadyl hydrochloride acetate) was discontinued in the spring of 2004 because it caused severe cardiac toxicity, including Q-T prolongation, Torsade des pointes and cardiac arrest. See http //www.fda.gov/cder/drug/ shortages / orlaam.htm. 

ORLAAM (Levomethadyl hydrochloride acetate) Roxane Laboratories... 

Product Discontinuation Notice, CRLAAM (Levomethadyl hydrochloride acetate) Oral Solution, 10 mg/ml. Oil, http //www.fda.gov/ cder/drug/sh ortages/orlaam. h tm. 

Respiratory depression Accidental overdose with long-acting opioids (eg, methadone, levomethadyl) may result in prolonged respiratory depression. While nalmefene has a longer duration of action than naloxone in fully reversing doses, be aware that a recurrence of respiratory depression is possible. Observe patients until there is no reasonable risk of recurrent respiratory depression. 

Itraconazole contraindicated in patients with evidence of ventricular dysfunction (CHF) or a history of CHF Itraconazole is also a potent inhibitor of cytochrome P450 3A4 isoenzyme, which may increase plasma concentrations of drugs metabolized by this pathway. Serious cardiovascular events have occurred in patients taking cisapride, pimozide, levomethadyl, or quinidine concomitantly with itraconazole. 

Edwards G, Marshall EJ Cook CCH (2003). The Treatment of Drinking Problems A Guide for the Helping Professions, 4th ed. Cambridge Cambridge University Press Eissenberg T, Bigelow GE, Strain EC, Walsh SL, Brooner RK, Stitzer ML Johnson RE (1997). Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. Journal of the American Medical Association, 111, 1945-51... 

Designated synthetic drugs levomethadyl (Orlaam), meperidine (Demerol), methadone, levorphanol (Levo-Dromoran), fentanyl (Sublimaze, Duragesic, Actiq), alphaprodine, alfentanil (Alfenta), sufentanil (Sufenta), remifentanil (Ultiva)... 

Scheme 5 Variations of methadone. Levomethadyl acetate, levomethadone ...

Opioid receptor binding Levomethadyl acetate has a moderate affinity for opioid receptors with selectivity for the p-type. Higher binding affinity is induced by the active metabolites /-alpha-nor-acetylmethadol, nor-methadol and methadol (Walczak et al., 1981 Carroll, 1976). 

Analgesic efficacy and clinical use Levomethadyl acetate, a methadone derivative, is a long-acting opioid analgesic, which is mostly used for the treatment of opioid dependence (Blaine etal., 1978 Ling, 1978)... 

Pharmacokinetic properties Levomethadyl acetate is well absorbed from the intestinal tract and is extensively metabolized to various active metabolites, which contribute to the long duration of action. The metabolites nor-acytylmethadol, di-nor-acetylmethadol, nor-methadol, and methadol are formed by N-demethylation and hydrolytic cleavage of the ester bond (Moody et al., 1997)... 

Side-effects Levomethadyl acetate induces opioid-type side-effects with respiratory depression, bradycardia and impairment of cardiac contractility (Wolven and Archer, 1976). The compound increases the QT-interval and may induce Torsade de pointes (Deamer et al., 2001). Because of the cardiovascular side effects (Q/T interval prolongation) Levomethadyl acetate was recently withdrawn from the market in most of the european countries. 

Deamer, R.L., Wilson, D.R., Clark, D.S., Prichard, J.G. Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM), J. Addict. Dis. 2001, 20, 7-14. 

Ethoxy- S-Mepheny- Rosiglitazone 0 Phenytoin Moclobemide 4-Nitrophenol Brofaromine Amlodipine Domperidone Levomethadyl Rosuvastatin... 

Alverine, azapropazone, benzhexol, diamphenethide, diethyltryptamine (-> yellow), dihydrocodeine, guai-phenesin, hordenine, levomethadyl acetate, normorphine, oxyphencyclimine, papaverine, terbutaline... 

Clomiphene, diethazine, levomethadyl acetate (— grey-green), methoxamine (- > green)... 

Gas Chromatography-Mass Spectrometry. In plasma, whole blood or tissues levomethadyl acetate and demethylated metabolites, sensitivity 5 ng/ml—T. A. Jennison et al., J. chromatogr. Sci., 1979, 17, 64-74. 

High Pressure Liquid Chromatography. In plasma or urine levomethadyl acetate and metabolites, sensitivity 6 ng/ml for levomethadyl acetate, L-a-noracetylmethadol and methadol, 10 ng/ml for L-a-dinoracetylmethadol, normethadol, and dinor-methadol—C.- H. Kiang et al., J. Chromat., 1981, 222 Biomed. AppL, 11, 81-93. 

After a single oral dose of 60 mg given to 5 subjects, peak plasma concentrations of 0.09 to 0.16 pg/ml (mean 0.13) of levomethadyl acetate and 0.04 to 0.05 pg/ml of L-a-noracetylmethadol were attained in about 2 to 4 hours and 2 to 6 hours, respectively following chronic oral treatment with 85 mg three times a week for three months to 3 subjects, peak plasma concentrations were levomethadyl acetate 0.16 to 0.23 pg/ml (mean 0.20), L-a-noracetylmethadol 0.15 to 0.30pg/ml (mean 0.24), and L-a-dinoracetylmethadol, mean 0.27 pg/ml (G. L. Henderson et al., Clin. Pharmac. Ther., 1977, 21, 16-25). 

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