June 29, 2016
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Faslodex

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Faslodex




Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

  • Risk of Bleeding [see WARNINGS AND PRECAUTIONS]
  • Increased Exposure in Patients with Hepatic Impairment [see WARNINGS AND PRECAUTIONS]
  • Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]

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.

Monotherapy

Comparison of FASLODEX 500 mg and FASLODEX 250 mg

The following adverse reactions (ARs) were calculated based on the safety analysis of Study 1 comparing the administration of FASLODEX 500 mg intramuscularly once a month with FASLODEX 250 mg intramuscularly once a month. 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 Study 1.7

Table 1: Adverse Reactions in Study 1 ( ≥ 5% in Either Treatment Group)

Body System and Adverse Reaction Number (%) of Patients
Fulvestrant 500 mg
N=361
Fulvestrant 250 mg
N=374
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)
Vascular System
Hot Flash 24 (6.6) 22 (5.9)
Digestive System
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)
Musculoskeletal System
Bone Pain 34 (9.4) 28 (7.5)
Arthralgia 29 (8.0) 29 (7.8)
Musculoskeletal Pain 20 (5.5) 12 (3.2)
Respiratory System
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 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: Adverse Reactions in Studies 2 and 3 ( ≥ 5% from Combined Data)

Body System and Adverse Reaction FASLODEX 250 mg
N=423 (%)
Anastrozole 1 mg
N=423 (%)
Body as a Whole 68.3 67.6
Asthenia 22.7 27.0
Pain 18.9 20.3
Headache 15.4 16.8
Back Pain 14.4 13.2
Abdominal Pain 11.8 11.6
Injection Site Pain1 10.9 6.6
Pelvic Pain 9.9 9.0
Chest Pain 7.1 5.0
Flu Syndrome 7.1 6.4
Fever 6.4 6.4
Accidental Injury 4.5 5.7
Cardiovascular System 30.3 27.9
Vasodilatation 17.7 17.3
Digestive System 51.5 48.0
Nausea 26.0 25.3
Vomiting 13.0 11.8
Constipation 12.5 10.6
Diarrhea 12.3 12.8
Anorexia 9.0 10.9
Hemic and Lymphatic Systems 13.7 13.5
Anemia 4.5 5.0
Metabolic and Nutritional Disorders 18.2 17.7
Peripheral Edema 9.0 10.2
Musculoskeletal System 25.5 27.9
Bone Pain 15.8 13.7
Arthritis 2.8 6.1
Nervous System 34.3 33.8
Dizziness 6.9 6.6
Insomnia 6.9 8.5
Paresthesia 6.4 7.6
Depression 5.7 6.9
Anxiety 5.0 3.8
Respiratory System 38.5 33.6
Pharyngitis 16.1 11.6
Dyspnea 14.9 12.3
Cough Increased 10.4 10.4
Skin and Appendages 22.2 23.4
Rash 7.3 8.0
Sweating 5.0 5.2
Urogenital System 18.2 14.9
Urinary Tract Infection 6.1 3.5
1 All patients on FASLODEX received injections, but only those anastrozole patients who were in the North American Study 2 received placebo injections.

Combination Therapy with Palbociclib

The safety of FASLODEX (500 mg) plus palbociclib (125 mg/day) versus FASLODEX plus placebo was evaluated in Study 4. The data described below reflect exposure to FASLODEX plus palbociclib in 345 out of 517 patients with HR-positive, HER2-negative advanced or metastatic breast cancer who received at least 1 dose of treatment in Study 4.

No dose reduction was allowed for FASLODEX in Study 4. Dose reductions of palbociclib due to an adverse reaction of any grade occurred in 36% of patients receiving FASLODEX plus palbociclib.

Permanent discontinuation associated with an adverse reaction occurred in 19 of 345 (6%) patients receiving FASLODEX plus palbociclib, and in 6 of 172 (3%) patients receiving FASLODEX plus placebo. Adverse reactions leading to discontinuation for those patients receiving FASLODEX plus palbociclib included fatigue (0.6%), infections (0.6%), and thrombocytopenia (0.6%).

The most common adverse reactions ( ≥ 10%) of any grade reported in patients in the FASLODEX plus palbociclib arm were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia.

The most frequently reported serious adverse reactions in patients receiving FASLODEX plus palbociclib were infections (3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%).

Adverse reactions reported in patients who received FASLODEX plus palbociclib in Study 4 are listed in Table 3, and laboratory abnormalities are listed in Table 4.

Table 3: Adverse Reactions in Study 4

Adverse Reaction FASLODEX plus palbociclib
(N=345)
FASLODEX plus placebo
(N=172)
All Grades % Grade 3 % Grade 4 % All Grades % Grade 3 % Grade 4 %
Infections and infestations
Infectionsa 47 3 1 31 3 0
Blood and lymphatic system disorders
Febrile neutropenia 1 1 0 1 0 1
Neutropenia 83 55 11 4 1 0
Leukopenia 53 30 1 5 1 1
Anemia 30 3 0 13 2 0
Thrombocytopenia 23 2 1 0 0 0
Eye disorders
Vision blurred 6 0 0 2 0 0
Lacrimation increased 6 0 0 1 0 0
Dry eye 4 0 0 2 0 0
Metabolism and nutrition disorders
Decreased appetite 16 1 0 8 1 0
Nervous system disorders
Headache 26 1 0 20 0 0
Dysgeusia 7 0 0 3 0 0
Respiratory, thoracic and mediastinal disorders
Epistaxis 7 0 0 2 0 0
Gastrointestinal disorders
Nausea 34 0 0 28 1 0
Stomatitisb 28 1 0 13 0 0
Diarrhea 24 0 0 19 1 0
Constipation 20 0 0 16 0 0
Vomiting 19 1 0 15 1 0
Skin and subcutaneous tissue disorders
Alopecia 18c N/A N/A 6d N/A N/A
Rashe 17 1 0 6 0 0
Dry skin 6 0 0 1 0 0
General disorders and administration site conditions
Fatigue 41 2 0 29 1 0
Pyrexia 13 < 1 0 5 0 0
Asthenia 8 0 0 5 1 0
Grading according to CTCAE 4.0.
CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients; N/A=not applicable.
a Most common infections ( > 1%) include: nasopharyngitis, upper respiratory infection, urinary tract infection, influenza, bronchitis, rhinitis, conjunctivitis, pneumonia, sinusitis, cystitis, oral herpes, respiratory tract infection.
b Stomatitis includes: aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, stomatitis.
c Grade 1 events – 17%; Grade 2 events – 1%.
d Grade 1 events – 6%.
e Rash includes: rash, rash maculo-papular, rash pruritic, rash erythematous, rash papular, dermatitis, dermatitis acneiform, toxic skin eruption.

Table 4: Laboratory Abnormalities in Study 4

Laboratory Abnormality FASLODEX plus palbociclib
(N=345)
FASLODEX plus placebo
(N=172)
All Grades % Grade 3 % Grade 4 % All Grades % Grade 3 % Grade 4 %
WBC decreased 99 45 1 26 0 1
Neutrophils decreased 96 56 11 14 0 1
Anemia 78 3 0 40 2 0
Platelets decreased 62 2 1 10 0 0
N=number of patients; WBC=white blood cells.

Postmarketing Experience

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%).

Read the Faslodex (fulvestrant) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

There are no known drug-drug interactions. Although, fulvestrant is metabolized by CYP 3A4 in vitro, drug interactions studies with ketoconazole or rifampin did not alter fulvestrant pharmacokinetics. Dose adjustment is not needed in patients co-prescribed CYP 3A4 inhibitors or inducers [see CLINICAL PHARMACOLOGY].

Read the Faslodex Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 3/9/2016

Side Effects
Interactions

Faslodex - User Reviews

Faslodex User Reviews

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