Fulvestrant

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Common side effects may include:

• headache;
• bone pain, joint pain, muscle pain;
• nausea, vomiting, loss of appetite, constipation;
• weakness, feeling tired;
• cough, trouble breathing;
• abnormal liver function tests;
• hot flashes; or
• pain where the medicine was injected.

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.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• a blood thinner--warfarin, Coumadin, Jantoven.

This list is not complete. Other drugs may interact with fulvestrant, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Before you receive fulvestrant, tell your doctor:

• if you are allergic to fulvestrant or any other medications
• if you have or have ever had any bleeding problems (low level of platelets in your blood or bleed easily)
• if you have liver disease
• about any other medical conditions you have
• if you are pregnant or breastfeeding

Tell your doctor about the medicines you take including prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products. 

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Fulvestrant falls into category D. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Contraindications

• Known hypersensitivity to fulvestrant or any ingredient in the formulation (e.g., benzyl alcohol).1 4

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including urticaria and angioedema, reported.1

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm;1 teratogenicity and embryolethality demonstrated in animals.1

Avoid pregnancy during therapy.1 If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.1

Hematologic Disorders

Use with caution in patients with bleeding diatheses or thrombocytopenia and in those receiving anticoagulant therapy because of IM administration.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Distributed into milk in rats; not known whether fulvestrant is distributed into human milk.1 Discontinue nursing or the drug.1

Used in a limited number of girls 1–8 years of age with progressive precocious puberty associated with McCune-Albright syndrome†; however, efficacy not established.1 Common adverse effects included injection site reactions (e.g., inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, vasodilation (hot flush), extremity pain, and vomiting.1 Effects on bone mineral density not elucidated.1

Slightly lower objective response rates in patients ≥65 years of age than in younger adults.1 No substantial difference in pharmacokinetics relative to younger adults.1

Systemic exposure increased in patients with moderate hepatic impairment (Child-Pugh class B).1 (See Hepatic Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics). Safety and efficacy not established in patients with severe hepatic impairment (Child-Pugh class C).1

Not studied in patients with renal impairment; however plasma fulvestrant concentrations in women with Clcr ≥30 mL/minute were similar to those in women with normal renal function.1

Common Adverse Effects

Adverse GI effects1 2 7 (e.g., nausea,1 5 6 vomiting,1 5 6 constipation,1 5 6 diarrhea,1 5 6 abdominal pain1 5 6 ), headache,1 5 6 pain1 5 6 (e.g., back pain,1 5 bone pain,1 5 6 musculoskeletal pain,1 extremity pain,1 pelvic pain1 5 ), asthenia,1 5 6 vasodilation (hot flushes),1 2 5 6 7 pharyngitis,1 5 6 dyspnea,1 5 injection site reactions7 (e.g., pain1 5 ), increased cough,1 5 anorexia,1 5 6 peripheral edema,1 5 rash,1 5 chest pain,1 flu syndrome,1 dizziness,1 5 insomnia,1 5 fever,1 5 paresthesia,1 5 urinary tract infection,1 depression,1 anxiety,1 sweating,1 fatigue,1 arthralgia,1 joint disorder.5 6 7

• An estrogen antagonist; a 7α-alkylsulfinyl analog of estradiol.1 2

• Does not possess estrogen-agonist activity.1

• Competitively binds to and down-regulates estrogen receptors in human breast cancer cells.1 2 Reductions in estrogen-receptor levels, as well as associated reductions in progesterone-receptor levels and associated antiproliferative effects, appear to be dose related.1 12

• Inhibits the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer (MCF-7) cell lines in vitro and in vivo.1 2

• May block the uterotropic action of estradiol.1 2

• Does not exhibit peripheral steroidal effects in postmenopausal women.1

• Faslodex

Store in original carton at 2°C to 8°C (36°F to 46°F). Protect from light.

Adverse reactions reported with 500 mg dose.

>10%:

Central nervous system: Fatigue (8% to 29%), headache (8% to 20%)

Gastrointestinal: Nausea (10% to 28%), diarrhea (19%), constipation (5% to 16%), stomatitis (13%)

Hematologic & oncologic: Anemia (13% to 40%; grade 3: 2%)

Hepatic: Increased liver enzymes (>15%; grades 3/4: 1% to 2%)

Infection: Infection (31%; including nasopharyngitis, upper respiratory infection, urinary tract infection, influenza, bronchitis, rhinitis, conjunctivitis, pneumonia, sinusitis, cystitis, oral herpes, respiratory tract infection)

Local: Pain at injection site (12%; including neuralgia, peripheral neuropathy, sciatica)

1% to 10%:

Dermatologic: Alopecia (6%), skin rash (6%), xeroderma (1%)

Endocrine & metabolic: Hot flash (7%)

Gastrointestinal: Decreased appetite (8%), anorexia (6%), vomiting (6%), dysgeusia (3%)

Hematologic & oncologic: Decreased platelet count (10%), leukopenia (5%; grade 3: 1%; grade 4: 1%), neutropenia (4%; grade 3: 1%), febrile neutropenia (1%; grade 4: 1%)

Neuromuscular & skeletal: Ostealgia (9%), arthralgia (8%), back pain (8%), limb pain (7%), musculoskeletal pain (6%), weakness (5% to 6%)

Ophthalmic: Blurred vision (2%), dry eye syndrome (2%), increased lacrimation (1%)

Respiratory: Cough (5%), dyspnea (4%), epistaxis (2%)

<1% (Limited to important or life-threatening; reported with 250 or 500 mg dose): Hepatic failure, hepatitis, hypersensitivity reaction, thrombosis, vaginal hemorrhage

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity reactions, including urticaria and angioedema, have been reported.

• Injection-site related events: Events related to injection site, including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy, have been reported with fulvestrant administration. Due to the proximity of underlying sciatic nerve, use caution if administering at the dorsogluteal site.

Disease-related concerns:

• Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia) and/or patients on anticoagulant therapy; bleeding/hematoma may occur from IM administration.

• Hepatic impairment: Exposure is increased and dosage adjustment is recommended in patients with moderate impairment. Safety and efficacy have not been established in severe impairment.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Adverse events were observed in animal reproduction studies. Based on the mechanism of action, fulvestrant may cause fetal harm if administered during pregnancy. For females of reproductive potential, pregnancy testing is recommended within 7 days prior to initiation of fulvestrant and effective contraception should be used during treatment and for 1 year after the last fulvestrant dose. Animal data suggest that fulvestrant may affect female and male fertility (although not approved for use in men).

You should not receive fulvestrant if you are pregnant.

Avoid getting pregnant or breast-feeding a baby for at least 1 year after you stop using this medicine.

Fulvestrant is given as two injections into a muscle of your buttock. Your doctor, nurse, or other healthcare provider will give you this injection.

Each injection must be given slowly, and can take up to 2 minutes to complete.

Fulvestrant is usually given once every 2 weeks at first, and then once a month. Do not miss any scheduled appointments.

When treatment also includes taking palbociclib capsules, you will most likely take your palbociclib dose once daily with food for 21 days in a row, followed by 7 days off the medicine. Follow your doctor's dosing instructions very carefully.

If you are a woman using fulvestrant together with palbociclib, tell your doctor if you are going through menopause (you have symptoms such as irregular menstrual periods, hot flashes, night sweats, or vaginal dryness). You may need to be treated with an additional hormone medication.

This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using fulvestrant.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Usual Adult Dose for Breast Cancer:

Initial dose: 500 mg IM on days 1, 15, and 29, then once a month thereafter.