AURO-NINTEDANIB

1 Dosing Considerations • Treatment should be initiated by physicians experienced in the diagnosis and treatment of conditions for which Auro-Nintedanib is indicated. , at each patient visit) or as clinically indicated. Conduct liver function tests promptly in patients who reports symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.

1 Pregnant Women). 2 Recommended Dose and Dosage Adjustment • The recommended dose of Auro-Nintedanib is 150 mg twice daily administered approximately 12 hours apart. • Dose adjustments due to adverse reactions o In addition to symptomatic treatment if applicable, the management of adverse reactions of Auro-Nintedanib could include dose reduction (to 100 mg twice daily) and temporary interruption of Auro-Nintedanib treatment until the specific adverse reaction has resolved to levels that allow continuation of therapy.

Auro-Nintedanib treatment may be resumed at the full recommended dose (150 mg twice daily) or a reduced dose (100 mg twice daily). If a patient does not tolerate 100 mg twice daily, treatment with Auro-Nintedanib should be discontinued (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

o Cases of drug-induced liver injury (DILI), have been reported in patients treated with nintedanib. In the majority of cases, the DILI was reversible when the dose was reduced or treatment was stopped. ▪ Treatment interruption or dose reduction to 100 mg twice daily is recommended for patients whose transaminase (AST or ALT) are measured greater than 3 times to less than 5 times the upper limit of normal (ULN) without signs of liver damage.

These patients should be monitored closely. Alternative causes of the liver enzyme elevations should be investigated. Once transaminases have returned to baseline values, treatment with Auro-Nintedanib may be reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full recommended dose (150 mg twice daily) (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

▪ Treatment with Auro-Nintedanib should be permanently discontinued 1) if transaminase (AST or ALT) elevations are greater than 5 times ULN, or 2) if transaminase (AST or ALT) elevations are greater than 3 times ULN with clinical signs or symptoms of liver injury which may include fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

). o Cases of drug-induced liver injury (DILI), have been reported in patients treated with nintedanib. In the majority of cases, the DILI was reversible when the dose was reduced or treatment was stopped. ▪ Treatment interruption or dose reduction to 100 mg twice daily is recommended for patients whose transaminase (AST or ALT) are measured greater than 3 times to less than 5 times the upper limit of normal (ULN) without signs of liver damage.

These patients should be monitored closely. Alternative causes of the liver enzyme elevations should be investigated. Once transaminases have returned to baseline values, treatment with Auro-Nintedanib may be reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full recommended dose (150 mg twice daily) (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

▪ Treatment with Auro-Nintedanib should be permanently discontinued 1) if transaminase (AST or ALT) elevations are greater than 5 times ULN, or 2) if transaminase (AST or ALT) elevations are greater than 3 times ULN with clinical signs or symptoms of liver injury which may include fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

• Hepatic impairment o Mild hepatic impairment: In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Auro-Nintedanib is 100 mg twice daily approximately 12 Auro-Nintedanib Capsules 100 mg and 150 mg Page 6 of 53 hours apart.

Treatment interruption or discontinuation for management of adverse reactions should be considered. o Moderate and severe hepatic impairment: Treatment of patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment with Auro-Nintedanib is not recommended.

The safety and efficacy of nintedanib have not been investigated in patients with hepatic impairment classified as Child Pugh B and C. 3 Pharmacokinetics). • Renal impairment o Adjustment of the recommended dose (150 mg twice daily) in patients with mild to moderate renal impairment is not required.

• Auro-Nintedanib is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including peanut or soya, or any non-medicinal ingredient, or component of the container. For a complete listing, (see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).

1 Pregnant Women).