Ofev

Adults:

Treatment should be initiated by physicians experienced in the management of diseases for which Ofev is approved.

Paediatric patients:

Treatment should be initiated only after involvement of a multidisciplinary team (physicians, radiologists, pathologists) experienced in the diagnosis and treatment of fibrosing interstitial lung diseases (ILDs). Posology Adults • Idiopathic pulmonary fibrosis (IPF) • Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype • Systemic sclerosis associated interstitial lung disease (SSc-ILD) The recommended dose is 150 mg nintedanib twice daily administered approximately 12 hours apart.

The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose. If a dose is missed, administration should resume at the next scheduled time at the recommended dose. If a dose is missed the patient should not take an additional dose.

The recommended maximum daily dose of 300 mg should not be exceeded. 8) could include dose reduction and temporary interruption until the specific adverse reaction has resolved to levels that allow continuation of therapy. Ofev treatment may be resumed at the full dose (150 mg twice daily in adult patients) or a reduced dose (100 mg twice daily in adult patients).

If an adult patient does not tolerate 100 mg twice daily, treatment with Ofev should be discontinued. If diarrhoea, nausea and/or vomiting persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required.

The treatment may be resumed at a reduced dose (100 mg twice daily in adult patients) or at the full dose (150 mg twice daily in adult patients). 4). 8). For specific dose reduction recommendations for the management of adverse reactions in paediatric population, see Table 1.

Children and adolescents from 6 to 17 years old • Treatment of clinically significant, progressive fibrosing interstitial lung diseases (ILDs) • Treatment of systemic sclerosis associated interstitial lung disease (SSc-ILD) Growth must be regularly monitored, and evaluation of epiphyseal growth plate alteration via annual bone imaging is recommended in patients with open epiphyses.

Summary of the safety profile In clinical trials and during the post-marketing experience, the most frequently reported adverse reactions associated with the use of nintedanib included diarrhoea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.

4. Tabulated list of adverse reactions Table 2 provides a summary of the adverse drug reactions (ADRs) by MedDRA System Organ Class (SOC) and frequency category using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data).

1), diarrhoea was the most frequent gastro-intestinal event reported. In most patients, the event was of mild to moderate intensity. More than two thirds of patients experiencing diarrhoea reported its first onset already during the first three months of treatment.

4). 6% of patients treated with Ofev and placebo, respectively. 7% of patients treated with Ofev and placebo, respectively. 1% of patients treated with Ofev and placebo, respectively. Elevations of liver enzymes were reversible and not associated with clinically manifest liver disease.

2, respectively. 3% for SENSCIS). Non-serious epistaxis was the most frequent bleeding event reported. 7% for SENSCIS). 4). 0% for SENSCIS). Nephrotic syndrome has not been reported in clinical trials. Very few cases of nephrotic range proteinuria with or without renal function impairment have been reported post-marketing.

Histological findings in individual cases were consistent with glomerular microangiopathy with or without renal thrombi. Reversal of the symptoms has been observed after Ofev was discontinued, with residual proteinuria in some cases.

Treatment interruption should be considered in patients who […]

8). In most patients, the adverse reaction was of mild to moderate intensity and occurred within the first 3 months of treatment. Serious cases of diarrhoea leading to dehydration and electrolyte disturbances have been reported in the post-marketing.

g. loperamide, and may require dose reduction or treatment interruption. 2). In case of persisting severe diarrhoea despite symptomatic treatment, therapy with Ofev should be discontinued. 8). In most patients with nausea and vomiting, the event was of mild to moderate intensity.

4% of patients. If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required. 2 Dose adjustments). In case of persisting severe symptoms therapy with Ofev should be discontinued.

Hepatic function The safety and efficacy of Ofev has not been studied in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. 2). Based on increased exposure, the risk for adverse reactions may be increased in patients with mild hepatic impairment (Child Pugh A).

2). Cases of drug-induced liver injury have been observed with nintedanib treatment, including severe liver injury with fatal outcome. The majority of hepatic events occur within the first three months of treatment. Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Ofev.

g. at each patient visit or as clinically indicated. 8) and bilirubin were reversible upon dose reduction or interruption in the majority of cases. If transaminase (AST or ALT) elevations > 3× ULN are measured, dose reduction or interruption of the therapy with Ofev is recommended and the patient should be monitored closely.

2 Dose adjustments). g. jaundice, treatment with Ofev should be permanently discontinued. Alternative causes of the liver enzyme elevations should be investigated. Adult patients with low body weight (< 65 kg), Asian and female patients have a higher risk of elevations of liver enzymes.

1.