Oral methadone

McCaul ME, Bigelow GE, Stitzer ML, et al Short-term effects of oral methadone in methadone maintenance subjects. Clin Pharmacol Ther 31 753-761, 1982... 

Ripamonti C, Groff L, Brunelli C, et al Switching from morphine to oral methadone in treating cancer pain what is the equianalgesic dose ratio J Clin Oncol 16 3216-3221,1998... 

Oral methadone is about one half as potent as parenteral. Oral administration results in a delay of onset, a lower peak, and an increased duration of analgesic effect. Duration of effect increases with repeated use because of cumulative effects. 

Methadone Coadministration increased oral methadone clearance by 22%. An increased methadone dose may be required in a small number of patients. 

Hutchinson SJ, Taylor A, Gruer L, Barr C, Mills C, Elliott L, Goldberg DJ, Scott R Gilchrist G (2000). One-year follow-up of opiate injectors treated with oral methadone in a GP-centred programme. Addiction, 95, 1055-68... 

Strang J, Sheridan J Barber N (1996). Prescribing injectable and oral methadone to opiate addicts results from the 1995 national postal survey of community pharmacies in England and Wales. British Medical Journal, 313, 270-2... 

Strang J, Marsden J, Cummins M, Farrell M, Finch E, Gossop M, Stewart D Welch S (2000). Randomized trial of supervised injectable versus oral methadone maintenance report of feasibility and 6-month outcome. Addiction, 95, 1631-45... 

Mancini, I., Lossignol, D. A., Body, J. J.. Opioid switch to oral methadone in cancer pain, Curr. Opin. Oncol., 2000, 12, 308-312. 

A variety of complications following parenteral selfadministration of oral methadone were noted, including... 

There have been another 11 cases showing a direct link between QT interval prolongation and oral methadone maintenance treatment at doses of 14-360 micrograms/ day (15) (16). QT interval prolongation can lead to arrhythmias such as torsade de pointes, especially when high doses of methadone are given intravenously and associated with concomitant use of cocaine and/or medications that inhibit the hepatic clearance of methadone (e.g. antidepressants and antihistamines). 

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. 

Parenteral self-administration of oral methadone can cause cellulitis, abscess formation, and necrosis of the skin and deeper tissues (10). 

When injectable drugs are prescribed there is currently no way of assessing the truth of an addict s statement that he/she needs x mg of heroin (or other drug), and the dose has to be assessed intuitively by the doctor. This has resulted in addicts obtaining more than they need and selling it, sometimes to initiate new users. The use of oral methadone or other opioid for maintenance by prescription is devised to mitigate this problem. 

In a double-blind, randomized comparison of subUngual buprenorphine tablets with oral methadone in a 6-week trial in 58 patients using a flexible dosing procedure the retention rate was significantly better in those using methadone (90 versus 50%) (22). Those who completed the study had a similar number of opioid-positive urine samples, with a mean stabilization dose of 11 mg/day of buprenorphine and 70 mg/day of methadone. This study had several limitations 6 weeks is too short a period to determine any intermediate or long-term treatment outcomes, the sample size was too small, and the comparison of non-equivalent doses makes interpretation difficult. 

Bagger MA, Nielsen HW, Bechgaard E. Nasal bioavailability of peptide T in rabbits absorption enhancement by sodium glycocholate and glycofurol. Eur ] Pharm Sci 2001 14(1) 69-74. Dale O, Sheffels P, Khorasch ED. Bioavailabilities of rectal and oral methadone in healthy subjects. Br ] Clin Pharmacol 2004 58(2) 156-162. 

Methadone is rapidly absorbed after all routes of exposure. When administered orally, methadone is approximately one-half as potent as when given par-enterally. Oral administration results in a delay of the onset, a lowering of the peak, and an increase in the duration of analgesic effect. It is metabolized primarily in the liver where it undergoes N-demethylation. Protein binding is 85%. Urinary excretion of methadone and its metabolites is dose dependent and comprises the major route of excretion only in doses exceeding 55 mg day It is excreted by glomerular... 

The intensity of symptoms depends both on the drug and on its mode of administration, the dosage that the individual has been using, and the time from abrupt discontinuance. Full agonist opioids used IV, which include heroin, cause the most severe withdrawal symptoms. Management involves administration of oral methadone , buprenorphine, or clonidine, with gradual dose tapering. 

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