Methadone dose optimisation is vital when treating people on opioid substitution programmes for tuberculosis (TB) and other conditions, according to new research.
Researchers at Aston University’s School of Pharmacy, in partnership with Addaction, looked at how methadone interacts with drugs used to treat other medical conditions. Anti-TB drug rifampicin is known to increase the breakdown of methadone in the body, meaning that methadone levels need to be gradually increased and then decreased after the TB treatment ends. A wide range of medications for HIV and epilepsy, along with some antibiotics, can cause similar interactions, meaning that it’s ‘critical’ to fully understand the clinical implications, the study says.
The researchers found their ‘virtual’ clinical trial – using a mathematical computer modelling technique to analyse previous studies – to be almost 95 per cent effective in ensuring that patients avoided withdrawal symptoms or relapse while undergoing TB treatment. According to the World Health Organization (WHO), TB remains one of the top ten causes of death worldwide, with England seeing more than 5,000 cases in 2017. Of these, 13 per cent will have had at least one ‘social risk factor’, such as a history of substance use, time spent in prison, or homelessness.
‘We found that rifampicin significantly alters the level of methadone in the blood and necessitates dose adjustments, with daily doses of almost double those commonly used in clinical practice required for optimal levels of methadone in the blood,’ said lecturer in pharmacokinetics at Aston University Dr Raj K. Singh Badhan. ‘This interaction has wider implications – drugs that are routinely used for epilepsy, HIV and some antibiotics may also result in a similar phenomenon occurring and this research hopes to illustrate the clinical implications of this interaction and offer some approaches to mitigating clinical risk.’
‘We know that when people are taking methadone for opioid dependency and rifampicin for tuberculosis at the same time, this can be challenging,’ added Roz Gittins, Addaction’s director of pharmacy. ‘We know that there has been a lack of information to advise prescribers on how to change the doses of medication in this situation. Using computer modelling, we have looked at how doses of these medicines may be changed to get the best possible patient outcomes.
‘We plan to apply this research in the “real world” and hope that in the next year we will be able to carry out similar work with other medications that are used in mental health and substance misuse services.’
Read the study at: https://www.sciencedirect.com/science/article/pii/S0376871619301450