Active Ingredient: Nintedanib
Nintedanib is indicated in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology after first-line chemotherapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 200 milligrams nintedanib, once every 12 hours, over the duration of 20 days.
The recommended dose of nintedanib is 200 mg twice daily administered approximately 12 hours apart, on days 2 to 21 of a standard 21 day docetaxel treatment cycle.
Nintedanib must not be taken on the same day of docetaxel chemotherapy administration (= day 1). If a dose of nintedanib is missed, administration should resume at the next scheduled time at the recommended dose. The individual daily doses of nintedanib should not be increased beyond the recommended dose to make up for missed doses. The recommended maximum daily dose of 400 mg should not be exceeded.
Patients may continue therapy with nintedanib after discontinuation of docetaxel for as long as clinical benefit is observed or until unacceptable toxicity occurs.
For posology, methods of administration, and dose modifications of docetaxel, please refer to the corresponding product information for docetaxel.
As initial measure for the management of adverse reactions (see Tables 1 and 2) treatment with nintedanib should be temporarily interrupted until the specific adverse reaction has resolved to levels that allow continuation of therapy (to grade 1 or baseline).
Nintedanib treatment may be resumed at a reduced dose. Dose adjustments in 100 mg steps per day (i.e. a 50 mg reduction per dosing) based on individual safety and tolerability are recommended as described in Table 1 and Table 2.
In case of further persistence of the adverse reaction(s), i.e. if a patient does not tolerate 100 mg twice daily, treatment with nintedanib should be permanently discontinued. In case of specific elevations of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) values to >3 × upper limit normal (ULN) in conjunction with an increase of total bilirubin to ≥2 × ULN and alkaline phosphatase (ALKP) <2 × ULN (see Table 2) treatment with nintedanib should be interrupted. Unless there is an alternative cause established, nintedanib should be permanently discontinued.
Table 1. Recommended dose adjustments for nintedanib in case of diarrhoea, vomiting and other non-haematological or haematological adverse reactions:
| CTCAE* Adverse reaction | Dose adjustment |
|---|---|
| Diarrhoea ≥ grade 2 for more than 7 consecutive days despite anti-diarrhoeal treatment OR Diarrhoea ≥ grade 3 despite anti-diarrhoeal treatment | After treatment interruption and recovery to grade 1 or baseline, dose reduction from 200 mg twice daily to 150 mg twice daily and – if a 2nd dose reduction is considered necessary – from 150 mg twice daily to 100 mg twice daily. |
| Vomiting ≥ grade 2 AND/OR Nausea ≥ grade 3 despite anti-emetic treatment | |
| Other non-haematological or haematological adverse reaction of ≥ grade 3 |
* CTCAE: Common Terminology Criteria for Adverse Events
Table 2. Recommended dose adjustments for nintedanib in case of AST and/or ALT and bilirubin elevations:
| AST/ALT and bilirubin elevations | Dose adjustment |
|---|---|
| Elevation of AST and/or ALT values to >2.5 × ULN in conjunction with total bilirubin elevation to ≥1.5 × ULN OR Elevation of AST and/or ALT values to >5 × ULN | After treatment interruption and recovery of transaminase-values to ≤2.5 × ULN in conjunction with bilirubin to normal, dose reduction from 200 mg twice daily to 150 mg twice daily and – if a 2nd dose reduction is considered necessary – from 150 mg twice daily to 100 mg twice daily. |
| Elevation of AST and/or ALT values to >3 × ULN in conjunction with an increase of total bilirubin to ≥2 × ULN and ALKP <2 × ULN | Unless there is an alternative cause established, nintedanib should be permanently discontinued |
AST: Aspartate aminotransferase; ALT: Alanine aminotransferase
ALKP: Alkaline phosphatase; ULN: Upper limit normal
It must be taken orally, preferably with food.
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