CO-ARTEMETHER AND TRICYCLICS

The manufacturer of co-artemether notes that in vitro data indicate that lumefantrine significantly inhibits CYP2D6. As a consequence, they contraindicate the use of co-artemether in patients taking any drug that is metabolised by CYP2D6 (they include imipramine, amitriptyline, and clomipramine as examples).
These contraindications seem unnecessarily restrictive, especially since the tricyclics are not contraindicated with other established inhibitors of CYP2D6. Until more is known, it would be prudent to closely monitor the effects of any CYP2D6 substrate in patients for whom co-artemether is considered the antimalarial drug of choice. However, more seriously, note that additive QT- prolonging effects are possible, see drugs that prolong the QT interval.
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