Melatonin-SZ (Melatonin-SZ) – instructions for use, composition, drug analogues, dosages, side effects
– It is known that at concentrations significantly higher than therapeutic, melatonin induces CYP3A isoenzyme in vitro. The clinical significance of this phenomenon is not fully understood. In the case of the development of signs of induction, consideration should be given to reducing the dose of simultaneously used drugs;
– at concentrations much higher than therapeutic, melatonin does not induce CYP1A group isoenzymes in vitro. Consequently, the interaction of melatonin with other drugs due to the effect of melatonin on the isoenzymes of the CYP1A group is apparently insignificant;
– melatonin metabolism is mainly mediated by CYP1A isoenzymes. Therefore, melatonin may interact with other drugs due to the effect of melatonin on the isoenzymes of the CYP1A group;
– Care should be taken with patients taking fluvoxamine, which increases the concentration of melatonin (an increase in AUC by 17 times and Cmax by 12 times) due to inhibition of its metabolism by cytochrome P450: CYP1A2 and CYP2C19 isoenzymes. This combination should be avoided;
– caution should be exercised with patients taking 5- and 8-methoxypsoralen, which increases the melatonin concentration due to inhibition of its metabolism;
– care should be taken with patients taking cimetidine (an inhibitor of CYP2D isoenzymes), since it increases the plasma melatonin content by inhibiting the latter;
– smoking can reduce the concentration of melatonin due to the induction of the isoenzyme CYP1A2;
– caution should be exercised in patients taking estrogens (for example, contraceptives or hormone replacement therapy), which increase the concentration of melatonin by inhibiting their metabolism with CYP1A1 and CYP1A2 isoenzymes;
– CYPA2 isoenzyme inhibitors, such as quinolones, can increase the melatonin exposure;
– CYP1A2 isoenzyme inducers, such as carbamazepine and rifampicin, are able to reduce the plasma concentration of melatonin;
– In modern literature there is a wealth of data concerning the effects of adrenergic and opioid receptor agonists / antagonists, antidepressants, PG inhibitors, benzodiazepines, tryptophan and alcohol on the secretion of endogenous melatonin. Studies of the mutual influence of these drugs on the dynamics or kinetics of melatonin was not conducted.
– during the intake of melatonin should not drink alcohol, because it reduces the effectiveness of the drug;
– melatonin potentiates the sedative effect of benzodiazepine and non-benzodiazepine hypnotics, such as zaleplon, zolidem, and zopiclone. During the clinical study, there were clear signs of a transient pharmacodynamic interaction between melatonin and zolpidem an hour after their intake. Combined use may lead to a progressive disorder of attention, memory and coordination in comparison with zolpidem monotherapy;
– In the course of the research, melatonin was administered together with thioridazine and imipramine, drugs that affect the central nervous system. No clinically significant pharmacokinetic interaction was detected in any of the cases. Nevertheless, simultaneous use with melatonin led to an increase in the feeling of calmness and difficulty in performing certain tasks in comparison with imipramine monotherapy, as well as to an increased feeling of turbidity in the head, in comparison with thiordidazine monotherapy.