Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.
Comparison of FASLODEX 500 mg and FASLODEX 250 mg
The following frequency categories for adverse reactions (ARs) were calculated based on the safety analysis of Study 1 that compared FASLODEX 500 mg with FASLODEX 250 mg. The most frequently reported adverse reactions in the fulvestrant 500 mg group were injection site pain (11.6% of patients), nausea (9.7% of patients) and bone pain (9.4% of patients); the most frequently reported adverse reactions in the fulvestrant 250 mg group were nausea (13.6% of patients), back pain (10.7% of patients) and injection site pain (9.1% of patients).
Table 1 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from the controlled clinical trial Study 1 comparing the administration of FASLODEX 500 mg intramuscularly once a month with FASLODEX 250 mg intramuscularly once a month.
Table 1: Summary of Most Commonly Reported Adverse Reactions in Study 1 ( ≥ 5% in either treatment group): Safety Population
|Body System and Adverse Reaction||Number (%) of Patients|
|Fulvestrant 500 mg
|Fulvestrant 250 mg
|Body as a Whole|
|Injection Site Pain||42 (11.6)||34 (9.1)|
|Headache||28 (7.8)||25 (6.7)|
|Back Pain||27 (7.5)||40 (10.7)|
|Fatigue||27 (7.5)||24 (6.4)|
|Pain in Extremity||25 (6.9)||26 (7.0)|
|Asthenia||21 (5.8)||23 (6.1)|
|Hot Flash||24 (6.6)||22 (5.9)|
|Nausea||35 (9.7)||51 (13.6)|
|Vomiting||22 (6.1)||21 (5.6)|
|Anorexia||22 (6.1)||14 (3.7)|
|Constipation||18 (5.0)||13 (3.5)|
|Bone Pain||34 (9.4)||28 (7.5)|
|Arthralgia||29 (8.0)||29 (7.8)|
|Musculoskeletal Pain||20 (5.5)||12 (3.2)|
|Cough||19 (5.3)||20 (5.3)|
|Dyspnea||16 (4.4)||19 (5.1)|
In the pooled safety population (N=1127) from clinical trials comparing FASLODEX 500 mg to FASLODEX 250 mg, post-baseline increases of ≥ 1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in > 15% of patients receiving FASLODEX. Grade 3-4 increases were observed in 1-2% of patients. The incidence and severity of increased hepatic enzymes (ALT, AST, ALP) did not differ between the 250 mg and the 500 mg FASLODEX arms.
Comparison of FASLODEX 250 mg and Anastrozole 1 mg in Combined Trials (Studies 2 and 3)
The most commonly reported adverse reactions in the FASLODEX and anastrozole treatment groups, regardless of the investigator's assessment of causality, were gastrointestinal symptoms (including nausea, vomiting, constipation, diarrhea and abdominal pain), headache, back pain, vasodilatation (hot flashes), and pharyngitis.
Injection site reactions with mild transient pain and inflammation were seen with FASLODEX and occurred in 7% of patients (1% of treatments) given the single 5 mL injection (predominantly European Trial Study 3) and in 27% of patients (4.6% of treatments) given the 2 x 2.5 mL injections (North American Trial Study 2).
Table 2 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from the two controlled clinical trials comparing the administration of FASLODEX 250 mg intramuscularly once a month with anastrozole 1 mg orally once a day.
Table 2: Combined Data from Studies 2 and 3, Adverse Reactions ≥ 5%
|Body System and Adverse Reactiona||FASLODEX 250 mg
|Body as a Whole||68.3||67.6|
|Injection Site Painb||10.9||6.6|
|Hemic and Lymphatic Systems||13.7||13.5|
|Metabolic and Nutritional Disorders||18.2||17.7|
|Skin and Appendages||22.2||23.4|
|Urinary Tract Infection||6.1||3.5|
|aA patient may have more than one adverse reaction.
bAll patients on FASLODEX received injections, but only those anastrozole patients who were in the North American Study 2 received placebo injections.
For FASLODEX 250 mg, other adverse reactions reported as drug-related and seen infrequently ( < 1%) include thromboembolic phenomena, myalgia, vertigo, leukopenia, and hypersensitivity reactions including angioedema and urticaria.
Vaginal bleeding has been reported infrequently ( < 1%), mainly in patients during the first 6 weeks after changing from existing hormonal therapy to treatment with FASLODEX. If bleeding persists, further evaluation should be considered.
Elevation of bilirubin, elevation of gamma GT, hepatitis, and liver failure have been reported infrequently ( < 1%).