Valdoxan Drug Interactions

Potential interactions affecting VALDOXAN (agomelatine): VALDOXAN (agomelatine) is metabolised mainly by cytochromes CYP1A2 (90%) and CYP2C9/19 (10%). Medicines that interact with these isoenzymes may decrease or increase the bioavailability of VALDOXAN (agomelatine).
Co-administration of VALDOXAN (agomelatine) with potent CYP1A2 inhibitors such as fluvoxamine and ciprofloxacin are contraindicated. Fluvoxamine, a potent CYP1A2 and moderate CYP2C9 inhibitor, has been shown to markedly inhibit the metabolism of VALDOXAN (agomelatine) resulting in a 60-fold (range 12-412) increase in agomelatine exposure.
Combination of VALDOXAN (agomelatine) with estrogens (moderate CYP1A2 inhibitors) results in a several fold increased exposure of VALDOXAN (agomelatine). While there was no specific safety signal in the 800 patients treated in combination with estrogens, caution should be exercised when prescribing VALDOXAN (agomelatine) with other moderate CYP1A2 inhibitors (e.g. propranolol) until more experience has been gained.
Rifampicin an inducer of all three cytochromes involved in the metabolism of agomelatine may decrease the bioavailability of agomelatine.
Fluconazole, a potent CYP2C9 and CYP2C19 inhibitor, has been shown not to affect the pharmacokinetics of VALDOXAN (agomelatine). (See Table 13.)

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As the decrease in VALDOXAN (agomelatine) exposure in cigarette smokers due to induction of CYP1A2 is not clinically relevant, no dose adjustment is necessary because a patient is a cigarette smoker (see Pharmacology: Pharmacokinetics under Actions).
Use with other antidepressants: VALDOXAN (agomelatine) should not be combined with fluvoxamine as fluvoxamine is a potent inhibitor of the metabolism of VALDOXAN (agomelatine) (see Contraindications). Caution should be taken when administering VALDOXAN (agomelatine) with other antidepressants as the safety and efficacy of VALDOXAN (agomelatine) in combination with other antidepressants has not been studied in randomised clinical trials.
There is no pharmacokinetic or pharmacodynamic interaction between VALDOXAN (agomelatine) and paroxetine.
Lithium: There is no pharmacokinetic or pharmacodynamic interaction between VALDOXAN (agomelatine) and lithium.
Benzodiazepines (lorazepam): There is no pharmacokinetic or pharmacodynamic interaction between VALDOXAN (agomelatine) and lorazepam.
Potential for VALDOXAN (agomelatine) to affect other medicinal products: VALDOXAN (agomelatine) inhibits neither CYP1A2 in vivo nor the other CYP450 in vitro and does not induce CYP450 isoenzymes in vivo. Therefore, VALDOXAN (agomelatine) will not modify exposure to medicines metabolised by CYP450. In healthy volunteers VALDOXAN (agomelatine) did not modify the kinetics of theophylline, a CYP1A2 substrate.
Drugs highly bound to plasma protein: VALDOXAN (agomelatine) does not modify free concentrations of drugs highly bound to plasma proteins (e.g. zolpidem, diazepam, sertraline, warfarin, estrogen and salicylic acid) or vice versa.