Introduction to the Chinese instruction manual of nintedanib

1. Name: Nintedanib, Nintedanib, Vegat, Ofev

2. Indications:

Nintedanib is indicated to treat the following conditions:

1. Idiopathic pulmonary fibrosis (IPF): Suitable for the treatment of idiopathic pulmonary fibrosis in adults;

2. Chronic fibrosing interstitial lung disease with progressive phenotype (ILD): It is suitable for the treatment of adult patients with chronic fibrosing interstitial lung disease with progressive phenotype.

3. Systemic sclerosis-related interstitial lung disease (SSc-ILD): It can slow down the decline of lung function in adult patients with systemic sclerosis-related interstitial lung disease.

3. Usage and dosage:

1. Before treatment: Before starting treatment with nintedanib, conduct liver function tests on all patients and conduct a pregnancy test on women of reproductive potential.

2. Recommended dose: Nintedanib is a soft capsule dosage form, the recommended dose is 150 mg, taken orally twice a day, about 12 hours apart.

3. Medication management: Nintedanib capsules should be taken with food and swallowed whole with liquid. The capsules should not be chewed due to the bitter taste, and should not be opened or crushed. If you come into contact with capsule contents, wash your hands immediately and thoroughly. The effect of chewing or crushing the capsule on the pharmacokinetics of nintedanib is unknown.

4. Missed dose: If you miss a dose of nintedanib capsules, you should take the next dose at the next scheduled time. Advise patients not to make up missed doses. Do not exceed the recommended maximum daily dose of 300mg.

5. Dose adjustment: In addition to symptomatic treatment, if applicable, management of nintedanib adverse reactions may require dose reduction or temporary interruption until the specific adverse reaction reduces to a level that allows continued treatment. Treatment with nintedanib may be resumed at full dose (150 mg twice daily) or at a reduced dose (100 mg twice daily) and may subsequently be increased to full dose. If the patient cannot tolerate 100 mg twice daily, discontinue treatment.

4. Adverse reactions:

Common side effects of nintedanib include anorexia, nausea, vomiting, diarrhea, and abdominal pain (stomach pain), gastrointestinal perforation, weight loss, arterial thromboembolism(including myocardial infarction), bleeding, hypothyroidism, elevated liver enzymes and headache; taking nintedanib with food can reduce gastrointestinal side effects.

5. Supply and storage:

Nintedanib soft capsules are available in two common dosages, namely100mg and 150mg. The former is equivalent to 120.40 mg of nintedanib ethanesulfonate, while the latter is equivalent to 180.60mg. In terms of storage, nintedanib should be kept within a temperature range of 20°C to 25°C, with an allowed deviation of 15°C to 30°C. This temperature control requirement is to ensure the stability and effectiveness of the drug. At the same time, nintedanib should be avoided from being exposed to high humidity environments to prevent degradation or failure of the drug.

6. Special groups:

1. Women: Based on the results of animal studies and its mechanism of action, nintedanib can cause fetal harm when used in pregnant women and may reduce the fertility of women of reproductive potential; it is recommended that women of reproductive potential avoid pregnancy while receiving treatment; it is recommended that women of reproductive potential use highly effective contraceptives at the beginning of treatment, during treatment, and for at least3 months after taking the last dose; women are advised not to breastfeed during drug treatment.

2. Smokers: Smoking is associated with reduced exposure to nintedanib, which may alter the efficacy characteristics of nintedanib. Patients are encouraged to quit smoking before treatment with nintedanib and to avoid smoking while taking nintedanib.

7. Mechanism of action:

Nintedanib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases. Nintedanib inhibits the following RTKs: platelet-derived growth factor receptor (PDGFR) alpha and beta, fibroblast growth factor receptor. With the exception of FLT-3, these kinases have been implicated in the pathogenesis of interstitial lung disease (ILD).

Nintedanib competitively binds to the adenosine triphosphate (ATP) binding pocket of these kinases and blocks intracellular signaling cascades that have been shown to be involved in the pathogenesis of fibrotic tissue remodeling in ILD. Nintedanib also inhibits the following nRTKs: Lck, Lyn, and Src kinases. The contribution of FLT-3 and nRTK inhibition to the efficacy of nintedanib in the treatment of ILD is unclear.

8. Overdose:

In theIPF trial, one patient was inadvertently exposed to a dose of 600mg daily for 21 days. During the erroneous dosing period, one non-serious adverse event (nasopharyngitis) occurred and resolved, and no other events were reported. In the oncology study, overdoses were also reported in two patients who were exposed to up to 600 mg twice daily for 8 days. Reported adverse events were consistent with the existing safety profile of nintedanib. Both patients have recovered. In case of overdose, interrupt treatment and institute general supportive measures as appropriate.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da1c9f37-779e-4682-816f-93d0faa4cfc9##