Figet Adverse Reactions

Summary of the Safety Profile: In the pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2,462 Gefitinib-treated patients), the most frequently reported adverse drug reactions (ADRs), occurring in more than 20% of the patients, are diarrhoea and skin reactions (including rash, acne, dry skin and pruritus). ADRs usually occur within the first month of therapy and are generally reversible. Approximately 8% of patients had a severe ADR (common toxicity criteria (CTC) grade 3 or 4).
Approximately 3% of patients stopped therapy due to an ADR.
Interstitial lung disease (ILD) has occurred in 1.3% of patients, often severe (CTC grade 3-4). Cases with fatal outcomes have been reported.
List of adverse reactions: The safety profile presented as follows is based on the Gefitinib clinical development program and post-market experience. Adverse reactions have been assigned to the frequency categories as follows where possible based on the incidence of comparable adverse event reports in a pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2,462 Gefitinib-treated patients).
Frequencies of occurrence of undesirable effects are defined as: 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).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Metabolism and nutrition disorders: Very common: Anorexia mild or moderate (CTC grade 1 or 2).
Eye disorders: Common: Conjunctivitis, blepharitis, and dry eye*, mainly mild (CTC grade 1).
Uncommon: Corneal erosion, reversible and sometimes in association with aberrant eyelash growth, keratitis (0.12%) .
Vascular disorders: Common: Haemorrhage, such as epistaxis and haematuria.
Respiratory, thoracic and mediastinal disorders: Common: Interstitial lung disease (1.3%), often severe (CTC grade 3-4). Cases with fatal outcomes have been reported.
Gastrointestinal disorders: Very common: Diarrhoea, mainly mild or moderate (CTC grade 1 or 2), vomiting, mainly mild or moderate (CTC grade 1 or 2), nausea, mainly mild (CTC grade 1), stomatitis, predominantly mild in nature (CTC grade 1).
Common: Dehydration, secondary to diarrhoea, nausea, vomiting or anorexia, dry mouth*, predominantly mild (CTC grade 1).
Uncommon: Pancreatitis, gastrointestinal perforation.
Hepatobiliary disorders: Very common: Elevations in alanine aminotransferase, mainly mild to moderate.
Common: Elevations in aspartate aminotransferase, mainly mild to moderate, elevations in total bilirubin, mainly mild to moderate.
Uncommon: Hepatitis**.
Skin and subcutaneous tissue disorders: Very common: Skin reactions, mainly a mild or moderate (CTC grade 1 or 2) pustular rash, sometimes itchy with dry skin, including skin fissures, on an erythematous base.
Common: Nail disorder, alopecia, allergic reactions (1.1%), including angioedema and urticaria.
Rare: Bullous conditions including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme, cutaneous vasculitis.
Renal and urinary disorders: Common: Asymptomatic laboratory elevations in blood creatinine, proteinuria, cystitis.
Rare: Haemorrhagic cystitis.
General disorders and administration site conditions: Very common: Asthenia, predominantly mild (CTC grade 1).
Common: Pyrexia.
The frequency of adverse drug reactions relating to abnormal laboratory values is based on patients with a change from baseline of 2 or more CTC grades in the relevant laboratory parameters.
*This adverse reaction can occur in association with other dry conditions (mainly skin reactions) seen with Gefitinib.
**This includes isolated reports of hepatic failure which in some cases, led to fatal outcomes.
Interstitial lung disease (ILD): In the INTEREST trial, the incidence of ILD-type events was 1.4% (10) patients in the Gefitinib group versus 1.1% (8) patients in the docetaxel group. One ILD-type event was fatal, and this occurred in a patient receiving Gefitinib.
In the ISEL trial, the incidence of ILD-type events overall was approximately 1% in both treatment arms. The majority of ILD-type events reported was from patients of Asian ethnicity and the ILD incidence among patients of Asian ethnicity receiving Gefitinib therapy and placebo was approximately 3% and 4% respectively.
One ILD-type event was fatal, and this occurred in a patient receiving placebo.
In a post-marketing surveillance study in Japan (3,350 patients) the reported rate of ILD-type events in patients receiving Gefitinib was 5.8%. The proportion of ILD-type events with a fatal outcome was 38.6%.
In a phase III open-label clinical trial (IPASS) in 1,217 patients comparing Gefitinib to carboplatin/paclitaxel doublet chemotherapy as first-line treatment in selected patients with advanced NSCLC in Asia, the incidence of ILD-type events was 2.6% on the Gefitinib treatment arm versus 1.4% on the carboplatin/paclitaxel treatment arm.