Does the particular formulation or brand of methadone make a difference?

As with many medications, there are several forms of methadone to make dispensing and administration more convenient. Pharmacologically – that is, the way they work in the body – the different formulations must be equivalent to be approved by the FDA.

Some patients may perceive that one formulation is easier on the stomach or seemingly more rapid acting. This may be due to individual differences in absorption and metabolism; but is not due to differences in the essential methadone ingredient. It also could be due to how the liquid or dispersible tablets are diluted (e.g., with juice versus plain water). Finally, the preservatives or fillers – inactive ingredients – used in the various formulations may differ and some persons can be sensitive to one of those compounds for unknown reasons.

Practitioners and patients have often debated whether methadone liquid, tablets, or dispersible tablets are more potent. Patients sometimes bitterly complain when switched to a different formulation, but pharmacologic advantages of one formulation over another are not supported by the research.

Investigators at Albert Einstein College of Medicine, Bronx, NY (Gourevitch et al. 1999), enrolled MMT patients in an experiment whereby each received either methadone liquid, tablets, or dispersible tablets for a period of 3 weeks. Each subject was then switched to one of the other formulations for a similar period of time.

There were no significant differences in methadone blood levels among the 3 formulations during a 24-hour dosing period (see graph). Additionally, patient-reported subjective opioid-withdrawal symptoms did not differ at any time by methadone formulation.

The researchers concluded that patient intolerance to changes in methadone formulation appear to have no basis in the pharmacologic action of methadone itself, whether in liquid or solid forms. Any difficulties attributed solely to a particular methadone formulation may be due more to patient-specific psychosocial factors. However, this is not to say that patient comments about particular formulations working better for them than others should be dismissed as meaningless. The very real placebo effect of merely “believing” that one formulation is better than the other can be a strong influence. And, in rare cases, a patient might indeed digest a particular formulation of solid methadone differently than the liquid; so, possible variable effects of different formulations cannot be entirely discounted.

Furthermore, there is sometimes a misperception that Methadose ® and methadone are different drugs, potentially having different effects. It is important to understand that Methadose is simply an FDA-approved brand name of the generic product – methadone HCl – produced by Mallinckrodt, Inc. of St. Louis, MO, and used for marketing purposes. At equivalent doses, both the branded product and the generic version have the same potency and effects – that is, 10 mg Methadose ® should have exactly the same pharmacologic action and effect as 10 mg of generic methadone. Similarly, Tylenol® (McNeil-PPC, Inc.) is a brand name for the generic medication acetaminophen, Vicodin® (Abbott Laboratories) is a brand name for generic hydrocodone bitartrate and acetaminophen, and so forth.

Sources:

Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone. Implications for the treatment of opioid dependence. Clin Pharmacokinet. 2002;41(14)1153-1193.