Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
No in vivo human pharmacokinetic interaction studies have been performed.

Topotecan does not inhibit human P450 enzymes (see section 5.2). In a population study using the intravenous route, the co-administration of granisetron, ondansetron, morphine or corticosteroids did not appear to have a significant effect on the pharmacokinetics of total topotecan (active and inactive form).

Topotecan is a substrate for both ABCB1 (P-glycoprotein) and ABCG2 (BCRP). Inhibitors of ABCB1 and ABCG2 administered with oral topotecan have been shown to increase topotecan exposure.

Cyclosporin A (an inhibitor of ABCB1, ABCC1 [MRP-1], and CYP3A4) administered with oral topotecan increased topotecan AUC to approximately 2 - 2.5-fold of control.

Patients should be carefully monitored for adverse reactions when oral topotecan is administered with a substance known to inhibit ABCB1 or ABCG2 (see section 5.2).

When combining topotecan with other chemotherapy agents, reduction of the doses of each medicinal product may be required to improve tolerability. However, when combining with platinum agents, there is a distinct sequence-dependent interaction depending on whether the platinum agent is given on day 1 or 5 of the topotecan dosing. If either cisplatin or carboplatin is given on day 1 of the topotecan dosing, a lower dose of each agent must be given to improve tolerability compared to the dose of each agent which can be given if the platinum agent is given on day 5 of the topotecan dosing. Currently there is only limited experience in combining oral topotecan with other chemotherapy agents.

The pharmacokinetics of topotecan were generally unchanged when co-administered with ranitidine.