Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction
Sympathomimetics and other vasopressor agents
Concomitant treatment with sympathomimetics and other vasoconstrictive substances such as reserpine, guanethidine, tricyclic antidepressants, antihistamines, thyroid hormones and MAO-inhibitors, including treatments that are available without prescription, should be avoided as a pronounced increase in blood pressure may occur.


Alpha-adrenergic antagonists
As with other specific α-adrenergic agonists, the effect of midodrine hydrochloride is blocked by α-adrenergic antagonists such as prazosin and phentolamine.


Heart rate reducing drugs
Monitoring is recommended if midodrine hydrochloride is combined with other drugs that directly or indirectly reduce the heart rate.


Glycosides
Simultaneous use of digitalis preparations is not recommended, as the heart rate reducing effect may be potentiated by midodrine hydrochloride and heart block may occur.


Corticosteroid preparations
Midodrine hydrochloride may potentiate or enhance the hypertensive effects of corticosteroid preparations. Patients being treated with midodrine hydrochloride in combination with mineralocorticoids or glucocorticoids (e.g. fludrocortisone) may be at increased risk of glaucoma/increased intraocular pressure, and should be carefully monitored.


Potential pharmacokinetic interactions
The potential for pharmacokinetic interaction is limited as the metabolic pathways do not involve cytochrome P450 enzymes (see section 5.2). However, decreased clearance of medicinal products metabolised by CYP2D6 (e.g. promethazine) has been reported.


Potential effect of other drugs on midodrine
No studies to evaluate the effect of other drugs on the pharmacokinetics of midodrine or the active metabolite desglymidodrine have been conducted. In vitro data indicate that desglymidodrine is a substrate of CYP2D6. Concomitant administration of drugs that inhibit this enzyme (e.g. quinidine, paroxetine, fluoxetine and bupropion) may cause increased plasma levels of desglymidodrine with a potential risk of increased adverse events.

Potential effect of midodrine on other drugs
Midodrine is an inhibitor of CYP2D6 and may affect the metabolism of other drugs.
This may be of clinical relevance for active substances that are mainly metabolized by CYP2D6, e.g. tricyclic antidepressants, beta blockers, selective serotonin reuptake inhibitors (SSRI), antiarrhythmics (including class 1A, 1B and 1C) and monoamine oxidase inhibitors (MAO inhibitors) type B, especially if the active substance also has a narrow therapeutic index.

Falsely elevated plasma metanephrine
Patients taking midodrine may have falsely elevated plasma metanephrine as a result of analytical interference when measured by HILIC-based HPLC-MS/MS. This potential for interference should be considered in cases where patients taking midodrine require biochemical investigation for potential phaeochromocytomas and paragangliomas.