Faslodex
- Generic Name: fulvestrant
- Brand Name: Faslodex
- Drug Class: How Do Antineoplastic Estrogen Receptor Antagonists Work?
Faslodex (Fulvestrant) side effects drug center
Faslodex Side Effects Center
What Is Faslodex?
Faslodex (fulvestrant) Injection is an estrogen receptor antagonist used to treat some hormone-related breast cancer. Faslodex is also used in postmenopausal women whose breast cancer has progressed after treatment with other anti-estrogen medication.
What Are Side Effects of Faslodex?
Common side effects of Faslodex include:
- injection site reactions (pain, swelling, redness),
- nausea,
- vomiting,
- loss of appetite,
- constipation,
- diarrhea,
- upset stomach,
- dizziness,
- headache,
- tiredness,
- weakness,
- headache,
- back pain,
- joint pain,
- muscle pain,
- pain in your arms or legs,
- other body aches/pains,
- flushing and sweating (hot flushes/hot flashes),
- tiredness,
- cough,
- trouble sleeping, or
- trouble breathing.
Tell your doctor if you have serious side effects of Faslodex including:
- burning/painful/frequent urination,
- numbness/tingling/swelling of the hands or feet,
- bone/pelvis/hip pain,
- signs of infection (e.g., fever, persistent sore throat),
- persistent cough,
- persistent vaginal bleeding,
- mental/mood changes (e.g., anxiety, depression), or
- chest pain.
Dosage for Faslodex
The recommended dose of Faslodex is 500 mg to be administered intramuscularly into the buttocks slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter.
What Drugs, Substances, or Supplements Interact with Faslodex?
Faslodex may interact with a blood thinner such as warfarin. Other drugs may interact with Faslodex. Tell your doctor all prescription and over-the-counter medications and supplements you use. Faslodex is used mainly in women after menopause.
Faslodex During Pregnancy and Breastfeeding
This medication should not be used during pregnancy. It may cause miscarriage, or harm to a fetus. Women of childbearing age should use non-hormonal birth control during treatment. Consult your doctor. It is unknown if this drug passes into breast milk. Because of the potential risk to the infant, breastfeeding while using this drug is not recommended.
Additional Information
Our Faslodex (fulvestrant) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Faslodex Consumer Information
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
- signs of nerve damage--numbness, tingling, weakness, or burning pain in your buttocks, back, or leg.
Common side effects may include:
- pain where the medicine was injected;
- headache;
- pain in your arms, legs, feet, or back;
- bone pain, joint pain, muscle pain;
- nausea, vomiting, loss of appetite;
- diarrhea, constipation;
- weakness, feeling tired;
- cough, feeling short of breath;
- hot flashes; or
- abnormal liver function tests.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Faslodex (Fulvestrant)
Faslodex Professional Information
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]
- Injection Site Reaction [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 (CONFIRM)
The following adverse reactions (ARs) were calculated based on the safety analysis of CONFIRM 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 FASLODEX 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 FASLODEX 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 CONFIRM.
Table 1: Adverse Reactions in CONFIRM (≥5% in Either Treatment Group)
| Adverse Reactions | FASLODEX 500 mg N=361 % | FASLODEX 250 mg N=374 % |
| Body as a Whole | ||
| Injection Site Pain1 | 12 | 9 |
| Headache | 8 | 7 |
| Back Pain | 8 | 11 |
| Fatigue | 8 | 6 |
| Pain in Extremity | 7 | 7 |
| Asthenia | 6 | 6 |
| Vascular System | ||
| Hot Flash | 7 | 6 |
| Digestive System | ||
| Nausea | 10 | 14 |
| Vomiting | 6 | 6 |
| Anorexia | 6 | 4 |
| Constipation | 5 | 4 |
| Musculoskeletal System | ||
| Bone Pain | 9 | 8 |
| Arthralgia | 8 | 8 |
| Musculoskeletal Pain | 6 | 3 |
| Respiratory System | ||
| Cough | 5 | 5 |
| Dyspnea | 4 | 5 |
| 1. Including moresevere injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy. | ||
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 500 mg And Anastrozole 1 mg (FALCON)
The safety of FASLODEX 500 mg versus anastrozole 1 mg was evaluated in FALCON. The data described below reflect exposure to FASLODEX in 228 out of 460 patients with HR-positive advanced breast cancer in postmenopausal women not previously treated with endocrine therapy who received at least one (1) dose of treatment in FALCON.
Permanent discontinuation associated with an adverse reaction occurred in 4 of 228 (1.8%) patients receiving FASLODEX and in 3 of 232 (1.3%) patients receiving anastrozole. Adverse reactions leading to discontinuation for those patients receiving FASLODEX included drug hypersensitivity (0.9%), injection site hypersensitivity (0.4%), and elevated liver enzymes (0.4%).
The most common adverse reactions (≥10%) of any grade reported in patients in the FASLODEX arm were arthralgia, hot flash, fatigue, and nausea.
Adverse reactions reported in patients who received FASLODEX in FALCON at an incidence of ≥5% in either treatment arm are listed in Table 2, and laboratory abnormalities are listed in Table 3.
Table 2: Adverse Reactions in FALCON
| Adverse Reactions | FASLODEX 500 mg N=228 | Anastrozole 1 mg N=232 | ||
| All Grades % | Grade 3 or 4 % | All Grades % | Grade 3 or 4 % | |
| Vascular Disorders | ||||
| Hot flash | 11 | 0 | 10 | 0 |
| Gastrointestinal Disorders | ||||
| Nausea | 11 | 0 | 10 | <1 |
| Diarrhea | 6 | 0 | 6 | <1 |
| Musculoskeletal and Connective Tissue Disorders | ||||
| Arthralgia | 17 | 0 | 10 | 0 |
| Myalgia | 7 | 0 | 3 | 0 |
| Pain in extremity | 6 | 0 | 4 | 0 |
| Back pain | 9 | <1 | 6 | 0 |
| General Disorders and Administration Site Conditions | ||||
| Fatigue | 11 | <1 | 7 | <1 |
Table 3: Laboratory Abnormalities in FALCON1
| Laboratory Parameters | FASLODEX 500 mg N=228 | Anastrozole 1 mg N=232 | ||
| All Grades % | Grade 3 or 4 % | All Grades % | Grade 3 or 4 % | |
| Alanine aminotransferase increased (ALT) | 7 | 1 | 3 | 0 |
| Aspartate aminotransferaseincreased (AST) | 5 | 1 | 3 | <1 |
| 1. In FALCON, post-baselineincreasesof≥1CTCgradein eitherAST, ALT, or alkaline phosphatase were observed in >10% of patients receiving FASLODEX. Grade 3-4 increases were observed in 1%-3% of patients. | ||||
Comparison Of FASLODEX 250 mg And Anastrozole 1 mg In Combined Trials (Studies 0020 And 0021)
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 given the single 5 mL injection (Study 0020) and in 27% of patients given the 2 x 2.5 mL injections (Study 0021) in the two clinicaltrials that compared FASLODEX 250 mg and anastrozole 1 mg.
Table 4 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 4:AdverseReactionsinStudies0020 and0021 (≥5% fromCombinedData)
| Adverse Reactions | FASLODEX 250 mg N=423 % | Anastrozole 1 mg N=423 % |
| Body as a Whole | 68 | 68 |
| Asthenia | 23 | 27 |
| Pain | 19 | 20 |
| Headache | 15 | 17 |
| Back Pain | 14 | 13 |
| Abdominal Pain | 12 | 12 |
| Injection Site Pain1 | 11 | 7 |
| Pelvic Pain | 10 | 9 |
| Chest Pain | 7 | 5 |
| Flu Syndrome | 7 | 6 |
| Fever | 6 | 6 |
| Accidental Injury | 5 | 6 |
| Cardiovascular System | 30 | 28 |
| Vasodilatation | 18 | 17 |
| Digestive System | 52 | 48 |
| Nausea | 26 | 25 |
| Vomiting | 13 | 12 |
| Constipation | 13 | 11 |
| Diarrhea | 12 | 13 |
| Anorexia | 9 | 11 |
| Hemic and Lymphatic Systems | 14 | 14 |
| Anemia | 5 | 5 |
| Metabolic and Nutritional Disorders | 18 | 18 |
| Peripheral Edema | 9 | 10 |
| Musculoskeletal System | 26 | 28 |
| Bone Pain | 16 | 14 |
| Arthritis | 3 | 6 |
| Nervous System | 34 | 34 |
| Dizziness | 7 | 7 |
| Insomnia | 7 | 9 |
| Paresthesia | 6 | 8 |
| Depression | 6 | 7 |
| Anxiety | 5 | 4 |
| Respiratory System | 39 | 34 |
| Pharyngitis | 16 | 12 |
| Dyspnea | 15 | 12 |
| Cough Increased | 10 | 10 |
| Skin and Appendages | 22 | 23 |
| Rash | 7 | 8 |
| Sweating | 5 | 5 |
| Urogenital System | 18 | 15 |
| Urinary Tract Infection | 6 | 4 |
| 1. Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy. All patients on FASLODEX received injections, but only those anastrozole patients who were in Study 0021 received placebo injections. | ||
Combination Therapy
Combination Therapy with Palbociclib (PALOMA-3)
The safety of FASLODEX 500 mg plus palbociclib 125 mg/day versus FASLODEX plus placebo was evaluated in PALOMA-3. 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 PALOMA-3. The median duration of treatment for FASLODEX plus palbociclib was 10.8 months while the median duration of treatment for FASLODEX plus placebo arm was 4.8 months.
No dose reduction was allowed for FASLODEX in PALOMA-3. 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 pluspalbociclib 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 by descending frequency were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia.
The most frequently reported Grade ≥3 adverse reactions (≥5%) in patients receiving FASLODEX plus palbociclib in descending frequency were neutropenia and leukopenia.
Adverse reactions (≥10%) reported in patients who received FASLODEX plus palbociclib or FASLODEX plus placebo in PALOMA-3 are listed in Table 5, and laboratory abnormalities are listed in Table 6.
Table 5: Adverse Reactions (≥10%) in PALOMA-3
| Adverse Reactions | 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 | ||||||
| Infections1 | 472 | 3 | 1 | 31 | 3 | 0 |
| Blood and Lymphatic System Disorders | ||||||
| Neutropenia | 83 | 55 | 11 | 4 | 1 | 0 |
| Leukopenia | 53 | 30 | 1 | 5 | 1 | 1 |
| Anemia | 30 | 4 | 0 | 13 | 2 | 0 |
| Thrombocytopenia | 23 | 2 | 1 | 0 | 0 | 0 |
| Metabolism and Nutrition Disorders | ||||||
| Decreased appetite | 16 | 1 | 0 | 8 | 1 | 0 |
| Gastrointestinal Disorders | ||||||
| Nausea | 34 | 0 | 0 | 28 | 1 | 0 |
| Stomatitis3 | 28 | 1 | 0 | 13 | 0 | 0 |
| Diarrhea | 24 | 0 | 0 | 19 | 1 | 0 |
| Vomiting | 19 | 1 | 0 | 15 | 1 | 0 |
| Skin and Subcutaneous Tissue Disorders | ||||||
| Alopecia | 184 | N/A | N/A | 65 | N/A | N/A |
| Rash6 | 17 | 1 | 0 | 6 | 0 | 0 |
| General Disorders and Administration Site Conditions | ||||||
| Fatigue | 41 | 2 | 0 | 29 | 1 | 0 |
| Pyrexia | 13 | <1 | 0 | 5 | 0 | 0 |
| Grading according to CTCAEv.4.0. CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients; N/A=notapplicable. 1. Infections includes all reported preferred terms (PTs) that are part of the System Organ Class Infections and infestations. 2. Most common infections (≥1%)include: nasopharyngitis, upper respiratory infection, urinary tract infection, influenza, bronchitis, rhinitis, conjunctivitis, pneumonia, sinusitis, cystitis, oral herpes, respiratory tract infection, gastroenteritis, tooth infection, pharyngitis, eye infection, herpes simplex, paronychia. 3. Stomatitis includes: aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, stomatitis. 4. Grade 1 events – 17%; Grade 2 events – 1%. 5. Grade 1 events – 6%. 6. Rash includes: rash, rash maculo-papular, rash pruritic, rash erythematous, rashpapular, dermatitis, dermatitis acneiform, toxic skin eruption. | ||||||
Additional adverse reactions occurring at an overall incidence of <10.0% of patients receiving FASLODEX plus palbociclib in PALOMA-3 included asthenia (7.5%), aspartate aminotransferase increased (7.5%), dysgeusia (6.7%), epistaxis (6.7%), lacrimation increased (6.4%), dry skin (6.1%), alanine aminotransferase increased (5.8%), vision blurred (5.8%), dry eye (3.8%), and febrile neutropenia (0.9%).
Table 6: Laboratory Abnormalities in PALOMA-3
| Laboratory Parameters | 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 |
| Aspartate aminotransferase increased | 43 | 4 | 0 | 48 | 4 | 0 |
| Alanine aminotransferase increased | 36 | 2 | 0 | 34 | 0 | 0 |
| N=number of patients; WBC=white blood cells. | ||||||
Combination Therapy With Abemaciclib (MONARCH 2)
The safety of FASLODEX (500 mg) plus abemaciclib (150 mg twice daily) versus FASLODEX plus placebo was evaluated in MONARCH 2. The data described below reflect exposure to FASLODEX in 664 patients with HR-positive, HER2-negative advanced breast cancer who received at least one dose of FASLODEX plus abemaciclib or placebo in MONARCH 2.
Median duration of treatment was12months forpatients receivingFASLODEXplus abemacicliband 8 months for patients receiving FASLODEX plus placebo.
Dose reductions due to an adverse reaction occurred in 43% of patients receiving FASLODEX plus abemaciclib. Adverse reactions leading to dose reductions ≥5% of patients were diarrhea and neutropenia. Abemaciclib dose reduction due to diarrhea of any grade occurred in 19% of patients receiving FASLODEX plus abemaciclib compared to 0.4% of patients receiving FASLODEX plus placebo. Abemaciclib dose reductions due to neutropenia of any grade occurred in 10% of patients receiving FASLODEX plus abemaciclib compared to no patients receiving FASLODEX plus placebo.
Permanent study treatment discontinuation due to an adverse event was reported in 9% of patients receiving FASLODEX plus abemaciclib and in 3% of patients receiving FASLODEX plus placebo. Adverse reactions leading to permanent discontinuation for patients receiving FASLODEX plus abemaciclib were infection (2%), diarrhea (1%), hepatotoxicity (1%), fatigue (0.7%), nausea (0.2%), abdominal pain (0.2%), acute kidney injury (0.2%), and cerebral infarction (0.2%).
Deaths during treatment or during the 30-day follow up, regardless of causality, were reported in 18 cases (4%) of FASLODEX plus abemaciclib treated patients versus 10 cases (5%) of FASLODEX plus placebo treated patients. Causes of death for patients receiving FASLODEX plus abemaciclib included: 7 (2%)patient deaths due to underlying disease, 4 (0.9%) due to sepsis, 2 (0.5%) due to pneumonitis, 2 (0.5%) due to hepatotoxicity, and one (0.2%) due to cerebral infarction.
The most common adverse reactions reported (≥20%) in the FASLODEX plus abemaciclib arm were diarrhea, fatigue, neutropenia, nausea, infections, abdominal pain, anemia, leukopenia, decreased appetite, vomiting, and headache (Table 7). The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were neutropenia, diarrhea, leukopenia, anemia, and infections.
Table 7: Adverse Reactions ≥10% of Patients Receiving FASLODEX Plus Abemaciclib and ≥2% Higher Than FASLODEX Plus Placebo in MONARCH 2
| Adverse Reactions | FASLODEX plus Abemaciclib N=441 | FASLODEX plus Placebo N=223 | ||||
| All Grades % | Grade 3 % | Grade 4 % | All Grades % | Grade 3 % | Grade 4 % | |
| Gastrointestinal Disorders | ||||||
| Diarrhea | 86 | 130 | 1 | 25 | <1 | 0 |
| Nausea | 45 | 3 | 0 | 23 | 1 | 0 |
| Abdominal pain1 | 35 | 2 | 0 | 16 | 1 | 0 |
| Vomiting | 26 | <1 | 0 | 10 | 2 | 0 |
| Stomatitis | 15 | <1 | 0 | 10 | 0 | 0 |
| Infections and Infestations | ||||||
| Infections2 | 43 | 5 | <1 | 25 | 3 | <1 |
| Blood and Lymphatic System Disorders | ||||||
| Neutropenia3 | 46 | 24 | 3 | 4 | 1 | <1 |
| Anemia4 | 29 | 7 | <1 | 4 | 1 | 0 |
| Leukopenia5 | 28 | 9 | <1 | 2 | 0 | 0 |
| Thrombocytopenia6 | 16 | 2 | 1 | 3 | 0 | <1 |
| General Disorders and Administration Site Conditions | ||||||
| Fatigue7 | 46 | 3 | 0 | 32 | <1 | 0 |
| Edema peripheral | 12 | 0 | 0 | 7 | 0 | 0 |
| Pyrexia | 11 | <1 | <1 | 6 | <1 | 0 |
| Metabolism and Nutrition Disorders | ||||||
| Decreased appetite | 27 | 1 | 01 | 2 | <1 | 0 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||||||
| Cough | 13 | 0 | 0 | 11 | 0 | 0 |
| Skin and Subcutaneous Tissue Disorders | ||||||
| Alopecia | 16 | 0 | 0 | 2 | 0 | 0 |
| Pruritus | 13 | 0 | 0 | 6 | 0 | 0 |
| Rash | 11 | 1 | 0 | 4 | 0 | 0 |
| Nervous System Disorders | ||||||
| Headache | 20 | 1 | 0 | 15 | <1 | 0 |
| Dysgeusia | 18 | 0 | 0 | 3 | 0 | 0 |
| Dizziness | 12 | 1 | 0 | 6 | 0 | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 13 | 4 | <1 | 5 | 2 | 0 |
| Aspartate aminotransferase increased | 12 | 2 | 0 | 7 | 3 | 0 |
| Creatinine increased | 12 | <1 | 0 | <1 | 0 | 0 |
| Weight decreased | 10 | <1 | 0 | 2 | <1 | 0 |
| 1. Includes abdominalpain, abdominalpain upper, abdominal pain lower, abdominal discomfort, abdominal tenderness. 2. Includesupper respiratory tract infection, urinary tract infection, lunginfection, pharyngitis, conjunctivitis, sinusitis, vaginal infection, sepsis. 3. Includesneutropenia, neutrophil countdecreased. 4. Includes anemia, hematocrit decreased, hemoglobin decreased, red blood cell count decreased. 5. Includes leukopenia, white blood cell count decreased. 6. Includes platelet count decreased, thrombocytopenia. 7. Includes asthenia, fatigue. | ||||||
Additional adverse reactions in MONARCH 2 include venous thromboembolic events (deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian vein thrombosis, axillary vein thrombosis, and DVT inferior vena cava), which were reported in 5% of patients treated with FASLODEX plus abemaciclib as compared to 0.9% of patients treated with FASLODEX plus placebo.
Table 8: Laboratory Abnormalities ≥10% in Patients Receiving FASLODEXPlus Abemacicliband ≥2% Higher Than FASLODEX Plus Placebo in MONARCH 2
| Laboratory Parameters | Fulvestrant plus Abemaciclib N=441 | Fulvestrant plus Placebo N=223 | ||||
| All Grades % | Grade 3 % | Grade 4 % | All Grades % | Grade 3 % | Grade 4 % | |
| Creatinine increased | 98 | 1 | 0 | 74 | 0 | 0 |
| White blood cell decreased | 90 | 23 | <1 | 33 | <1 | 0 |
| Neutrophil count decreased | 87 | 29 | 4 | 30 | 4 | <1 |
| Anemia | 84 | 3 | 0 | 33 | <1 | 0 |
| Lymphocyte count decreased | 63 | 12 | <1 | 32 | 2 | 0 |
| Platelet count decreased | 53 | <1 | 1 | 15 | 0 | 0 |
| Alanine aminotransferase increased | 41 | 4 | <1 | 32 | 1 | 0 |
| Aspartate aminotransferase increased | 37 | 4 | 0 | 25 | 4 | <1 |
Combination Therapy With Ribociclib (MONALEESA-3)
The safety of FASLODEX 500 mg plus ribociclib 600 mg versus FASLODEX plus placebo was evaluated in MONALEESA-3. The data described below reflect exposure to FASLODEX plus ribociclib in483outof724postmenopausalpatientswithHR-positive,HER2-negative advancedormetastatic breast cancer for initial endocrine based therapy or after disease progression on endocrine therapy who received at least one dose of FASLODEX plus ribociclib or placebo in MONALEESA-3. Median duration oftreatmentwas 15.8 months for FASLODEX plus ribociclib and12 months for FASLODEX plus placebo.
Dose reductions due to adverse reactions occurred in 32% of patients receiving FASLODEX plus ribociclib and in 3% of patients receiving FASLODEX plus placebo. Among patients receiving FASLODEX plus ribociclib, 8% were reported to have permanently discontinued both FASLODEX plus ribociclib, and 9% were reported to have discontinued ribociclib alone due to ARs. Among patients receiving FASLODEX plus placebo, 4% were reported to have permanently discontinued both FASLODEX and placebo and 2% were reported to have discontinued placebo alone due to ARs.
Adverse reactions leading to treatment discontinuation of FASLODEX plus ribociclib (as compared to FASLODEXplus placebo) were ALT increased (5% vs. 0%), AST increased (3% vs. 0.6%), and vomiting (1% vs. 0%).
The most common adverse reactions (reported at a frequency ≥20% on the FASLODEX plus ribociclib arm and ≥2% higher than FASLODEX plus placebo) were neutropenia, infections, leukopenia, cough, nausea, diarrhea, vomiting, constipation, pruritus, and rash. The most frequently reported Grade 3/4 adverse reactions (reported at a frequency ≥5%) in patients receiving FASLODEX plus ribociclib in descending frequency were neutropenia, leukopenia, infections, and abnormal liver function tests.
Adverse reactions and laboratory abnormalities occurring in patients in MONALEESA-3 are listed in Table 9 and Table 10, respectively.
Table 9: Adverse Reactions Occurring in ≥10% and ≥2% higher than FASLODEX plus Placebo Arm in MONALEESA-3 (All Grades)
| Adverse Reactions | FASLODEX plus Ribociclib N=483 | FASLODEX plus Placebo N=241 | ||||
| All Grades % | Grade 3 % | Grade 4 % | All Grades % | Grade 3 % | Grade 4 % | |
| Infections and Infestations | ||||||
| Infections1 | 42 | 5 | 0 | 30 | 2 | 0 |
| Blood and Lymphatic System Disorders | ||||||
| Neutropenia | 69 | 46 | 7 | 2 | 0 | 0 |
| Leukopenia | 27 | 12 | <1 | <1 | 0 | 0 |
| Anemia | 17 | 3 | 0 | 5 | 2 | 0 |
| Metabolism and Nutrition Disorders | ||||||
| Decreased appetite | 16 | <1 | 0 | 13 | 0 | 0 |
| Nervous System Disorders | ||||||
| Dizziness | 13 | <1 | 0 | 8 | 0 | 0 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||||||
| Cough | 22 | 0 | 0 | 15 | 0 | 0 |
| Dyspnea | 15 | 1 | <1 | 12 | 2 | 0 |
| Gastrointestinal Disorders | ||||||
| Nausea | 45 | 1 | 0 | 28 | <1 | 0 |
| Diarrhea | 29 | <1 | 0 | 20 | <1 | 0 |
| Vomiting | 27 | 1 | 0 | 13 | 0 | 0 |
| Constipation | 25 | <1 | 0 | 12 | 0 | 0 |
| Abdominal pain | 17 | 1 | 0 | 13 | <1 | 0 |
| Skin and Subcutaneous Tissue Disorders | ||||||
| Alopecia | 19 | 0 | 0 | 5 | 0 | 0 |
| Pruritus | 20 | <1 | 0 | 7 | 0 | 0 |
| Rash | 23 | <1 | 0 | 7 | 0 | 0 |
| General Disorders and Administration Site Conditions | ||||||
| Edema peripheral | 15 | 0 | 0 | 7 | 0 | 0 |
| Pyrexia | 11 | <1 | 0 | 7 | 0 | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 15 | 7 | 2 | 5 | <1 | 0 |
| Aspartate aminotransferase increased | 13 | 5 | 1 | 5 | <1 | 0 |
| Grading according to CTCAE4.03. CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients 1. Infections; urinary tract infections; respiratory tract infections; gastroenteritis; sepsis (<1%). | ||||||
Additional adverse reactions in MONALEESA-3 for patients receiving FASLODEX plus ribociclib included asthenia (14%), dyspepsia (10%), thrombocytopenia (9%), dry skin (8%), dysgeusia (7%), electrocardiogram QT prolonged (6%),dry mouth (5%), vertigo (5%), dry eye (5%), lacrimation increased (4%), erythema (4%), hypocalcemia (4%), blood bilirubin increased (1%), and syncope (1%).
Table 10: Laboratory Abnormalities Occurring in ≥10% of Patients in MONALEESA-3
| Laboratory parameters | FASLODEX plus Ribociclib N=483 | FASLODEX plus Placebo N=241 | ||||
| All Grades % | Grade 3 % | Grade 4 % | All Grades % | Grade 3 % | Grade 4 % | |
| Hematology | ||||||
| Leukocyte count decreased | 95 | 25 | <1 | 26 | <1 | 0 |
| Neutrophil count decreased | 92 | 46 | 7 | 21 | <1 | 0 |
| Hemoglobin decreased | 60 | 4 | 0 | 35 | 3 | 0 |
| Lymphocyte count decreased | 69 | 14 | 1 | 35 | 4 | <1 |
| Platelet count decreased | 33 | <1 | 1 | 11 | 0 | 0 |
| Chemistry | ||||||
| Creatinine increased | 65 | <1 | <1 | 33 | <1 | 0 |
| Gamma-glutamyl transferase increased | 52 | 6 | 1 | 49 | 8 | 2 |
| Aspartate aminotransferase increased | 49 | 5 | 2 | 43 | 3 | 0 |
| Alanine aminotransferase increased | 44 | 8 | 3 | 37 | 2 | 0 |
| Glucose serum decreased | 23 | 0 | 0 | 18 | 0 | 0 |
| Phosphorous decreased | 18 | 5 | 0 | 8 | <1 | 0 |
| Albumin decreased | 12 | 0 | 0 | 8 | 0 | 0 |
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of FASLODEX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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 entire FDA prescribing information for Faslodex (Fulvestrant)
&Copy; Faslodex Patient Information is supplied by Cerner Multum, Inc. and Faslodex Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.