Drug Drug Interactions with VICTRELIS® (boceprevir) Informative ...

Class of
Drug
24
IMMUNOSUPPRESSANTS
Substrate
class
Drug Brand name
(non exhaustive
list, generics
not listed). For
a complete list,
please consult
www.bcfi.be or
www.cbip.be
Sirolimus Rapamune ® Potential
Interaction
Methyl-
prednisolone
Prednisone/
Prednisolone
Beclamethasone
Medrol ® , Depo-Medrol
® , Solu-Medrol ®
Liverpool University (*) /
Extra-information
Potential
interaction
Lodotra ® Potential
interaction
Clipper ® , Beclophar
® , Qvar ® ,
Ecobec ®
Budesonide Budenofalk ® , Entocort
®
Not Clinically
Significant
Potential
Interaction
Azathioprine Imuran ® Not Clinically
Significant
Coadministration
is expected to
increase sirolimus
concentrations*
May [methylprednisolone]*
Prednisone AUC
by 22% and
Cmax by 1%
Prednisolone
AUC and Cmax
by 37% and
16% †
May
[Budesonide]*
Recommendations SmPC/
Scientific Literature
Close monitoring of sirolimus
blood
concentrations is
recommended and frequent
assessments of renal function
and sirolimus-related side
effects †
The dose of methylprednisolone
may need to be titrated
to avoid steroid toxicity*
No dose adjustment is necessary
when co-administered
with BOC. Patients receiving
prednisone and BOC should
be monitored appropriately †
Vigilance is recommended in
transplant patients, dosage
modifications are probably
not necessary but the occurrence
of a cushing syndrome
could suggest an increase in
Prednisolone concentrations ‡
Avoid coadministration,
particularly for extended
durations*
smpc: Blood concentrations of sirolimus are
expected to
increase significantly when administered
with BOC. Close monitoring of sirolimus
blood concentrations is recommended and
frequent assessments of renal function and
sirolimus-related side effects. Burger et al.,
Journal of hepatology 2013: There are no
data on the use of other immunosuppressant
such as sirolimus and everolimus, but it’s
expected that the effect are similar to those
with tacrolimus.
smpc: No dose adjustment is necessary
when co-administered with BOC. Patients
receiving prednisone and BOC should
be monitored appropriately. abstract:
No dosage adjustment of Prednisone is
necessary when coadministered with BOC.
However, because of the long-term nature
of corticosteroid therapy, patients receiving
concomitant prednisone and BOC should be
monitored appropriately for the Aes of prolonged
increases in prednisolone exposure. a
Burger et al., Journal of hepatology
2013: There are data available suggesting
that beclomethasone can be used safely in
patients on strong CYP3A4 inhibitors and
consequently this could be the corticosteroid
of choice for patients on HCV protease
inhibitors
CYP pathway(s)
(www.cbip/bcfi.be)
(www.mims.com.au)
CYP3A4
Substrate/
Inhibitor/
Inducer
CYP3A4 Substrate +
Inhibitor
CYP3A4 Substrate
CYP3A4 a Substrate a
CYP3A4 Substrate
a P.Jumes et al., Pharmacokinetic interaction between the hepatitis C Virus Protease Inhibitor Boceprevir and Prednisone in healthy volunteers - Presented at the 63rd Annual meeting of the AASLD, November 9-13, 2012, Boston, MA, USA. ‡ Recommendation based on Pr. Colle experience.