Pharmacokinetics of fingolimod (FTY720) and a combined oral contraceptive coadministered in healthy women: drug-drug interaction study results.
BACKGROUND
Fingolimod has a novel mechanism of action in multiple sclerosis, being a first-in-class sphingosine 1-phosphate receptor modulator. Because of a potential risk of fetal toxicity based on animal studies, women of childbearing potential are advised to take effective contraceptive measures during and for 2 months after stopping fingolimod therapy. To assess whether the efficacy of a combined oral contraceptive (OC) could be compromised during fingolimod therapy, a steady-state, drug-drug interaction study of fingolimod with ethinylestradiol/levonorgestrel was performed in healthy female volunteers.


OBJECTIVE
To assess the interaction between fingolimod 0.5 mg once daily and ethinylestradiol 30 μg/ levonorgestrel 150 μg once daily at a steady state.


METHODS
31 healthy women received the combined OC only on Days 1 - 14, followed by OC plus fingolimod on Days 15 - 28.


RESULTS
In the presence of fingolimod, ethinylestradiol pharmacokinetics were unchanged, and levonorgestrel maximum plasma concentration at steady state and area under the concentration-time curve during a dosing interval increased by factors of 1.10 (90% CI 1.05 - 1.16) and 1.22 (90% CI 1.18 - 1.27), respectively.


CONCLUSIONS
Fingolimod therapy does not alter the pharmacokinetics of the combined OC ethinylestradiol/ levonorgestrel to a clinically significant degree. Ethinylestradiol/levonorgestrel does not alter the pharmacokinetics of fingolimod. Women receiving fingolimod therapy are able to use a combined OC as a means of effective birth control.
Novartis Institute for Biomedical Research, Basel, Switzerland. olivier.david@novartis.com
Olivier J
OJ
David
Magdalena
M
Ocwieja
Karin
K
Meiser
Corinne
C
Emotte
Annamaria
A
Jakab
Johan
J
Wemer
Izaak
I
den Daas
Robert
R
Schmouder
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016912:Levonorgestrel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine