Contraindications : התוויות נגד

4          CONTRAINDICATIONS
•     ZEPATIER is contraindicated in patients with known hypersensitivity to elbasvir, grazoprevir, or to any of the excipients listed in section 11.
•     ZEPATIER is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) due to the expected significantly increased grazoprevir plasma concentration and the increased risk of alanine aminotransferase (ALT) elevations [see Warnings and Precautions (5.2), Use in Specific Populations (8.9), and Clinical Pharmacology (12.3)].
•     ZEPATIER is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of hepatic decompensation due to the risk of hepatic decompensation [see Warnings and Precautions (5.3), Use in Specific Populations (8.9)].
•     ZEPATIER is contraindicated with inhibitors of organic anion transporting polypeptides 1B1/3 (OATP1B1/3), that are known or expected to significantly increase grazoprevir plasma concentrations, strong inducers of cytochrome P450 3A (CYP3A), and efavirenz [see Warnings and Precautions (5.5), Drug Interactions (7), and Clinical Pharmacology (12.3)].
•     If ZEPATIER is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen. Refer to the ribavirin prescribing information for a list of contraindications for ribavirin.

Table 2 lists drugs that are contraindicated with ZEPATIER.

Table 2: Drugs that are Contraindicated with ZEPATIER
Drug(s) within Class
Drug Class         that are Contraindicated                Clinical Comment* 
Anticonvulsants                 Phenytoin                      May lead to loss of virologic response to Carbamazepine                  ZEPATIER due to significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction.


Antimycobacterials              Rifampin                       May lead to loss of virologic response to ZEPATIER due to significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction.

Herbal Products                 St. John’s Wort (Hypericum     May lead to loss of virologic response to perforatum)                    ZEPATIER due to significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction.

HIV Medications                 Efavirenz†                     May lead to loss of virologic response to ZEPATIER due to significant decreases in elbasvir and grazoprevir plasma concentrations caused by CYP3A induction.

HIV Medications                 Atazanavir                     May increase the risk of ALT elevations due to a Darunavir                      significant increase in grazoprevir plasma Lopinavir                      concentrations caused by OATP1B1/3
Saquinavir                     inhibition.
Tipranavir

Immunosuppressants              Cyclosporine                   May increase the risk of ALT elevations due to a significant increase in grazoprevir plasma



concentrations caused by OATP1B1/3 inhibition.

*This table is not a comprehensive list of all drugs that strongly induce CYP3A. This table may not include all OATP1B1/3 inhibitors that significantly increase grazoprevir plasma concentrations.
†Efavirenz is included as a strong CYP3A inducer in this table, since co-administration reduced grazoprevir exposure by 
≥80% [see Table 8].