Milnacipran (even at concentrations 25 times higher than the average) does not affect the system of microsomal oxidation in hepatocytes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 / 5), so there is no interaction expected with inducers and inhibitors of microsomal oxidation.
Carbamazepine, fluoxetine, lorazepam - no interaction with milnacipran.
Clomipramine - when transferring patients with clomipramine (75 mg / day) to milnacipran (100 mg / day), there was no significant change in the pharmacokinetic parameters of the latter. At the same time, in these cases, patients need more careful observation, since with such a transfer (without a period of washing), there are more frequent euphoria and postural hypotension, and the risk of developing a serotonin syndrome increases.
Non-selective MAO inhibitors (iproniazide) - the risk of serotonin syndrome increases. After the termination of treatment with an MAO inhibitor, a break of 2 weeks is necessary before starting the treatment with milnacipran, and a break after the end of treatment with milnacipran and before starting the MAO inhibitor should be at least 1 week.
Selective MAO inhibitor type B (selegiline) - the risk of a sudden increase in blood pressure increases. After the termination of treatment with a selective MAO B inhibitor, a break of 2 weeks is necessary before the start of the treatment with milnacipran, and the interval after the end of treatment with milnacipran and before the commencement of the intake of the selective MAO inhibitor of type B should be at least 1 week.
Agonists of 5-HT1D serotonin receptors (including sumatriptan) increase the risk of a pronounced increase in blood pressure, spasm of the coronary arteries as a result of cumulation of serotonergic action of the drugs. It is necessary to take a break between the end of treatment with milnacipran and the start of the course of therapy with agonists of 5-HT1D serotonin receptors for a period of 1 week.
Cardiac glycosides (including digoxin) - the risk of increasing the severity of the action on the CAS is increased (especially with the parenteral route of administration of digoxin).
Diuretics - increase the risk of hyponatremia.
Lithium preparations increase the risk of developing serotonin syndrome, while milnacipran does not affect the pharmacokinetics of lithium preparations.
Milnacipran should not be used concurrently with the following drugs:
- epinephrine, norepinephrine (parenteral administration) - a sharp increase in the risk of BP elevation with the likelihood of heart rhythm disturbances (inhibition of the capture of catecholamines by sympathetic nerve fibers);
- clonidine and other drugs with a similar mechanism of action - a decrease in the hypotensive effect of clonidine (antagonism with adrenergic receptors);
- selective MAO inhibitors type A (moclobemide, toloxaton) - a sharp increase in the risk of developing serotonin syndrome.
