Table 7 Suspected presence of Adverse Reactions (ADRs) in case reports resulting from methadone-drug interactions (MDIs)

1

Thioridazine

Additive CNS and respiratory depression

A 38-year-old man was diagnosed with drug-induced psychotic disorder with hallucinations and started on thioridazine, flunitrazepam, and trihexyphenidyl for three months. He then experienced anxiety causing hyperventilation, and was consequently treated with midazolam and oxazolam.

2

Chlorpromazine

Additive CNS and respiratory depression

A 31-year-old woman was started on chlorpromazine for insomnia. After three months, she was diagnosed with hyperventilation and tachycardia, which may have been a result of methadone or a methadone-chlorpromazine interaction.

3

Tramadol

May result in withdrawal symptoms

A 48-year-old man was started on tramadol for a month. He then felt anxious, which may have been caused by a methadone-tramadol interaction. Upon discontinuing tramadol, no other symptoms related to anxiety persisted.

Dexamethasone

CYP3A4 strong inducer

This man was started on dexamethasone for intracranial injury. After coadministering methadone with dexamethasone for a month, he started to feel anxious.

4

Tramadol

May result in withdrawal symptoms

A 48-year-old man was prescribed tramadol for a month for fractures of the tibia and fibula. Then, he developed a depressive mood, which may be owing to a methadone-tramadol interaction.

5

Paroxetine

CYP2B6 moderate inhibitor

A 38-year-old man was diagnosed with depression and started on paroxetine for several months. When methadone was coadministered with paroxetine, an anxious feeling persisted.

6

Ketoconazole

CYP3A4 strong inhibitor

A 41-year-old man's foot was infected with mycoses and was started on ketoconazole for two months. He was then diagnosed with angina pectoris, which may be due to a methadone-ketoconazole interaction. Upon stopping ketoconazole, he did not experience any symptoms related to angina.