Teriflunomide

Avoid smoking tobacco (CYP1A2 inducer) and avoid concomitant use of erlotinib with moderate CYP1A2 inducers (e.g., teriflunomide, rifampin, or phenytoin).

Avoid smoking tobacco (CYP1A2 inducer) and avoid concomitant use of erlotinib tablets with moderate CYP1A2 inducers (e.g., teriflunomide, rifampin, or phenytoin).

When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating fingolimod [see Warnings and Precautions ( 5.2 )] .

When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating fingolimod [see Warnings and Precautions ( 5.2 )].

When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating TASCENSO ODT [see Warnings and Precautions (5.2) ].

Teriflunomide increased rosuvastatin exposure more than 2.5-fold, increasing the risk of myopathy and rhabdomyolysis. Do not exceed rosuvastatin 10 mg once daily.

Teriflunomide increases rosuvastatin exposure more than 2.5-fold, increasing risk of myopathy and rhabdomyolysis. Do not exceed 10 mg rosuvastatin once daily.

Teriflunomide may decrease peak INR by approximately 25%. Close monitoring of INR is required.

Teriflunomide may reduce exposure of alosetron. Monitor patients and adjust dose as required.

For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking teriflunomide tablets [see Clinical Pharmacology (12.3) ] .

Teriflunomide may increase exposure of cefaclor. Monitor patients and adjust dose as required.

Teriflunomide may increase exposure of cimetidine. Monitor patients and adjust dose as required.

Teriflunomide may increase exposure of ciprofloxacin. Monitor patients and adjust dose as required.

Teriflunomide may reduce exposure of duloxetine. Monitor patients and adjust dose as required.

Teriflunomide may increase systemic exposure of ethinylestradiol. Consideration should be given to the type or dose of contraceptives used.

Teriflunomide may increase exposure of furosemide. Monitor patients and adjust dose as required.

Teriflunomide may increase exposure of ketoprofen. Monitor patients and adjust dose as required.

7 DRUG INTERACTIONS Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Drug interaction studies have been conducted with both ARAVA (leflunomide) and with its active metabolite, teriflunomide, where the metabolite was directly administered to the test subjects. Drugs metabolized by CYP2C8 and OAT3 transporters: Monitor patients because teriflunomide may increase exposure of these drugs.

Teriflunomide may increase systemic exposure of levonorgestrel. Consideration should be given to the type or dose of contraceptives used.

Teriflunomide may increase exposure of methotrexate via OAT3 and OATP inhibition. Monitor patients and adjust dose as required.

Teriflunomide may increase exposure of mitoxantrone. Consider reducing dose and monitor patients closely.

Teriflunomide may increase exposure of nateglinide. Consider reducing dose and monitor patients closely.

Concomitant use may cause additive immunosuppressive effects. Consider duration and mode of action when switching from teriflunomide to OCREVUS.

Concomitant use may increase risk of additive immunosuppressive effects due to prolonged immune effects of teriflunomide. Consider duration and mode of action when switching to ocrelizumab.

Teriflunomide may increase exposure of paclitaxel. Monitor patients and adjust dose as required.

Teriflunomide may increase exposure of penicillin G. Monitor patients and adjust dose as required.

Teriflunomide may increase exposure of pioglitazone. Monitor patients and adjust dose as required.

For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking teriflunomide tablets [see Clinical Pharmacology (12.3) ] .

Teriflunomide may increase exposure of repaglinide. Monitor patients and adjust dose as required.

Teriflunomide may increase exposure of rifampin. Consider reducing dose and monitor patients closely.

Teriflunomide may increase exposure of rosiglitazone. Monitor patients and adjust dose as required.

7 DRUG INTERACTIONS Moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox and teriflunomide) increase exposure to the active metabolite of selexipag.

For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking teriflunomide tablets [see Clinical Pharmacology (12.3) ] .

Teriflunomide may reduce exposure of theophylline. Monitor patients and adjust dose as required.

Teriflunomide may reduce exposure of tizanidine. Monitor patients and adjust dose as required.

OAT3 inhibitor may increase vadadustat AUC, increasing risk of adverse reactions. Monitor for rapid hemoglobin increase and adverse effects.

Teriflunomide may increase exposure of zidovudine. Monitor patients and adjust dose as required.

7 DRUG INTERACTIONS Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Drug interaction studies have been conducted with both leflunomide and with its active metabolite, teriflunomide, where the metabolite was directly administered to the test subjects. Concomitant use of leflunomide tablets and rifampin, a potent inducer of CYP and transporters, increased the plasma concentration of teriflunomide by 40%.

In patients taking teriflunomide tablets, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased.