REDDY-BOSUTINIB

1 Dosing Considerations Concomitant Use With CYP3A Inhibitors Avoid the concomitant use of strong or moderate CYP3A inhibitors with Reddy–Bosutinib as an increase in bosutinib plasma concentration is possible (see 8 DRUG INTERACTIONS, Drug-Drug Interactions and Drug-Food Interactions).

Concomitant Use With CYP3A Inducers Avoid the concomitant use of strong or moderate CYP3A inducers with Reddy–Bosutinib. Based on the large reduction in bosutinib exposure that occurred when Reddy–Bosutinib was co-administered with rifampin, increasing the dose of Reddy–Bosutinib when co-administering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure (see 8 DRUG INTERACTIONS, Drug-Drug Interactions).

3 Pharmacokinetics, Special Populations Serious Warnings and Precautions • Drug interactions with inhibitors or inducers of CYP3A4. The concomitant use of Reddy–Bosutinib with strong or moderate CYP3A4 inhibitors or inducers should be avoided (see 7 WARNINGS AND PRECAUTIONS, 9 DRUG INTERACTIONS, Drug-Drug Interactions, Drug-Food Interactions and 4 DOSAGE AND ADMINISTRATION) • Gastrointestinal toxicity, including diarrhea (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS) • Hepatic toxicity, including Hy’s Law case (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS) • Cardiac failure, including fatal outcomes (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS) • Fluid retention (including pleural effusion, pulmonary edema and pericardial effusion, including fatal outcomes (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS) • Hemorrhage (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS) • QT interval prolongation (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS) Reddy–Bosutinib (bosutinib tablets) Page 7 of 69 and Conditions, Hepatic Impairment).

3 Pharmacokinetics, Special Populations and Conditions, Renal Impairment). 3 Pharmacokinetics, Special Populations and Conditions, Renal Impairment). 3 Pharmacokinetics, Special Populations and Conditions, Renal Impairment). 3 Pharmacokinetics, Special Populations and Conditions, Renal Impairment).

The starting dose recommendation in patients with moderate or severe renal impairment was based on pharmacological modeling; the efficacy and safety of bosutinib have not been investigated in these patients. Initiate Reddy-Bosutinib therapy in these patients only when perceived benefits outweigh the potential risks.

). For a complete listing of ingredients, see the DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph. • Do not use Reddy–Bosutinib in patients with a known history of long QT syndrome or with a persistent QT interval of >480 ms (see 8 ADVERSE REACTIONS).

• Do not use Reddy–Bosutinib in cases of uncorrected hypokalemia or hypomagnesemia (see 8 ADVERSE REACTIONS). Reddy–Bosutinib (bosutinib tablets) Page 6 of 69 • Do not use Reddy–Bosutinib in hepatically impaired patients. 3 Pharmacokinetics, Special Populations and Conditions, Hepatic Impairment).

1 Dosing Considerations Concomitant Use With CYP3A Inhibitors Avoid the concomitant use of strong or moderate CYP3A inhibitors with Reddy–Bosutinib as an increase in bosutinib plasma concentration is possible (see

3 Pharmacokinetics, Special Populations and Conditions, Hepatic Impairment). 1 Dosing Considerations Concomitant Use With CYP3A Inhibitors Avoid the concomitant use of strong or moderate CYP3A inhibitors with Reddy–Bosutinib as an increase in bosutinib plasma concentration is possible (see 8 DRUG INTERACTIONS, Drug-Drug Interactions and Drug-Food Interactions).

Concomitant Use With CYP3A Inducers Avoid the concomitant use of strong or moderate CYP3A inducers with Reddy–Bosutinib. Based on the large reduction in bosutinib exposure that occurred when Reddy–Bosutinib was co-administered with rifampin, increasing the dose of Reddy–Bosutinib when co-administering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure (see 8 DRUG INTERACTIONS, Drug-Drug Interactions).

3 Pharmacokinetics, Special Populations Serious Warnings and Precautions • Drug interactions with inhibitors or inducers of CYP3A4. The concomitant use of Reddy–Bosutinib with strong or moderate CYP3A4 inhibitors or inducers should be avoided (see 7 WARNINGS AND PRECAUTIONS, 9 DRUG INTERACTIONS, Drug-Drug Interactions, Drug-Food Interactions and 4 DOSAGE AND ADMINISTRATION) • Gastrointestinal toxicity, including diarrhea (see 7 WARNINGS AND PRECAUTIONS and

• Do not use Reddy–Bosutinib (bosutinib) in patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. Cases of Grade 3 or 4 drug hypersensitivity were reported in patients treated with bosutinib in single-agent cancer studies.

2%) of Grade 4 drug-related anaphylactic shock were reported in patients treated with bosutinib (see 8 ADVERSE REACTIONS). For a complete listing of ingredients, see the DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.

• Do not use Reddy–Bosutinib in patients with a known history of long QT syndrome or with a persistent QT interval of >480 ms (see 8 ADVERSE REACTIONS). • Do not use Reddy–Bosutinib in cases of uncorrected hypokalemia or hypomagnesemia (see 8 ADVERSE REACTIONS).

Reddy–Bosutinib (bosutinib tablets) Page 6 of 69 • Do not use Reddy–Bosutinib in hepatically impaired patients. 3 Pharmacokinetics, Special Populations and Conditions, Hepatic Impairment).