RILUZOLE Drug Interactions: What You Need to Know

INTERACTIONS · Strong to moderate CYP1A2 inhibitors: Coadministration may increase riluzole -associated adverse reactions ( 7.1 ) · Strong to moderate CYP1A2 inducers: Coadministration may result in decreased efficacy ( 7.2 ) · Hepatotoxic drugs: Riluzole -treated patients that take other hepatotoxic drugs may be at increased risk for hepatotoxicity ( 7.3 )

7.1 Agents that may Increase Riluzole Blood Concentrations CYP1A2 inhibitors Co-administration of riluzole (a CYP1A substrate) with CYP1A2 inhibitors was not evaluated in a clinical trial; however, in vitro findings suggest an increase in riluzole exposure is likely. The concomitant use of strong or moderate CYP1A2 inhibitors (e.g., ciprofloxacin, enoxacin, fluvoxamine, methoxsalen, mexiletine, oral contraceptives, thiabendazole, vemurafenib, zileuton) with riluzole may increase the risk of riluzole-associated adverse reactions [ see Clinical Pharmacology (12.3) ] .

7.2 Agents that may Decrease Riluzole Plasma Concentrations CYP1A2 inducers Co-administration of riluzole (a CYP1A substrate) with CYP1A2 inducers was not evaluated in a clinical trial; however, in vitro findings suggest a decrease in riluzole exposure is likely. Lower exposures may result in decreased efficacy [ see Clinical Pharmacology (12.3)] .

7.3 Hepatotoxic Drugs Clinical trials in ALS patients excluded patients on concomitant medications which were potentially hepatotoxic (e.g., allopurinol, methyldopa, sulfasalazine). Riluzole-treated patients who take other hepatotoxic drugs may be at an increased risk for hepatotoxicity [ see Warnings and Precautions (5.1) ] .

Riluzole tablets is contraindicated in patients with a history of severe hypersensitivity reactions to riluzole or to any of its components (anaphylaxis has occurred) [see Adverse Reactions ( 6.1 )] . Patients with a history of severe hypersensitivity reactions to riluzole tablets or to any of its components ( 4 )

AND PRECAUTIONS Hepatic injury: Use of TIGLUTIK is not recommended in patients with baseline elevations of serum aminotransferases greater than 5 times the upper limit of normal; discontinue TIGLUTIK if there is evidence of liver dysfunction ( 5.1 ) Neutropenia: Advise patients to report any febrile illness ( 5.2 ) Interstitial lung disease: Discontinue TIGLUTIK if interstitial lung disease develops ( 5.3 )

5.1 Hepatic Injury TIGLUTIK can cause liver injury. Cases of drug-induced liver injury, some of which were fatal, have been reported in patients taking riluzole. Asymptomatic elevations of hepatic transaminases have also been reported, and in some patients have recurred upon re-challenge with riluzole. In clinical studies, the incidence of elevations in hepatic transaminases was greater in riluzole-treated patients than placebo-treated patients. The incidence of elevations of ALT above 5 times the upper limit of normal (ULN) was 2% in riluzole-treated patients. Maximum increases in ALT occurred within 3 months after starting riluzole.

About

50% and 8% of riluzole-treated patients in pooled controlled efficacy studies (Studies 1 and 2) had at least one elevated ALT level above ULN and above 3 times ULN, respectively [see Clinical Studies (14) ]. Monitor patients for signs and symptoms of hepatic injury, every month for the first 3 months of treatment, and periodically thereafter. The use of TIGLUTIK is not recommended if patients develop hepatic transaminases levels greater than 5 times the ULN. Discontinue TIGLUTIK if there is evidence of liver dysfunction (e.g., elevated bilirubin). Concomitant use with other hepatotoxic drugs may increase the risk for hepatotoxicity [see Drug Interactions (7.3) ] .

5.2 Neutropenia TIGLUTIK can cause neutropenia. Cases of severe neutropenia (absolute neutrophil count less than 500 per mm 3 ) within the first 2 months of riluzole treatment have been reported. Advise patients to report febrile illnesses.

5.3 Interstitial Lung Disease TIGLUTIK can cause interstitial lung disease, including hypersensitivity pneumonitis. Discontinue TIGLUTIK immediately if interstitial lung disease develops.