Section 4.2 Posology and method of administration
HCV/Human immunodeficiency virus type (HIV)‑1 co‑infection
HCV/HIV‑1 co‑infected patients should be treated in the same way as HCV mono‑infected patients. Drug interactions need to be carefully taken into account, see sections 4.4 and 4.5. Patients on an efavirenz‑based regimen must receive INCIVO 1,125 mg every 8 hours. For outcomes obtained in HIV co‑infected patients, see section 5.1.
Section 4.5 Special warnings and precautions for use
HCV/HIV (human immunodeficiency virus) co‑infection
INCIVO in combination with peginterferon alfa and ribavirin was evaluated in 60 HIV‑infected, HCV treatment‑naïve patients who were either not on HIV antiretroviral therapy or were being treated with efavirenz or atazanavir/ritonavir in combination with tenofovir disoproxil fumarate and emtricitabine or lamivudine (see sections 4.8 and 5.1). Please refer to section 4.5 for relevant interactions with HIV‑antiviral agents.
Interactions between telaprevir and HIV antiretroviral agents are frequent, and the recommendations in table 2, section 4.5, should be carefully followed.
Among HIV regimens that can be used (not limited to those below) the following should be taken into account:
Atazanavir/ritonavir: this combination is associated with a high frequency of hyperbilirubinaemia/icterus. In Study HPC3008 (see sections 4.8 and 5.1), transient grade 3 (2.5 to ≤5 X ULN) and grade 4 (>5 X ULN) bilirubin increases during INCIVO treatment were seen in 39% and in 22% of the 59 patients on atazanavir/ritonavir, respectively.
Efavirenz: with this combination the telaprevir dose must be increased to 1125 mg three times per day (q8h).
4.5 Interaction with other medicinal products and other forms of interaction
AUC 0.80 (0.76‑0.85)
Cmax 0.79 (0.74‑0.84)
Cmin 0.85 (0.75‑0.98)
AUC 1.17 (0.97‑1.43)
Cmax 0.85 (0.73‑0.98)
Cmin 1.85 (1.40‑2.44)
inhibition of CYP3A by telaprevir
Hyperbilirubinaemia is frequent with this combination. Clinical and laboratory monitoring for hyperbilirubinaemia is recommended (see section 4.4 and 4.8).
4.8 Undesirable effects
Patients Co‑infected with HIV‑1
The overall safety profile of INCIVO in HCV/HIV‑1 co‑infected patients
(n = 38) (either not on antiretroviral therapy or being treated with efavirenz in combination with tenofovir disoproxil fumarate and emtricitabineon antiretroviral therapy) was similar to the safety profile in mono‑infected HCV patients, except for patients receiving atazanavir/ritonavirin in the INCIVO combination treatment group and in the peginterferon alfa and ribavirin group who frequently experienced a transient increase in indirect bilirubin levels (including grades 3 to 4) through week 2, returning to near baseline by week 12 (see section 4.4).
5. PHARMACOLOGICAL PROPERTIES
Trial information updated in section 5