Recommended Topic Related To:

Afinitor

"In women at high risk for breast cancer, a long-term drug treatment can cut the risk of developing the disease in half. Researchers supported by the National Institutes of Health have now identified two gene variants that may predict which wom"...

Afinitor

Afinitor

Afinitor Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Afinitor (everolimus) is used to treat advanced kidney cancer, and is usually given after sorafenib (Nexavar) or sunitinib (Sutent) have been tried without successful treatment of symptoms. It is an antineoplastic agent (cancer medication). Common side effects include diarrhea, nausea/vomiting, decreased appetite, changes in taste, nosebleeds, dry skin, headache, or pain or sores in the mouth and throat.

The recommended dose of Afinitor is 10 mg, taken once daily. Afinitor may interact with aminoglutethimide, aprepitant, bosentan, conivaptan, dexamethasone, diclofenac, enoxacin, imatinib, isoniazid, phenylbutazone, St. John's wort, antidepressants, antibiotics, barbiturates, heart or blood pressure medications, HIV or AIDS medications, medicines to treat narcolepsy, or seizure medications. Tell your doctor all medications you use. Afinitor is not recommended for use during pregnancy. It may harm a fetus. Use at least 2 forms of birth control (such as condoms, birth control pills) while taking this medication and for 8 weeks after stopping treatment. If you become pregnant or think you may be pregnant, tell your doctor. It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended.

Our Afinitor (everolimus) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Afinitor in Detail - Patient Information: Side Effects

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

Stop using Afinitor and call your doctor at once if you have a serious side effect such as:

  • new or worsening cough, wheezing, feeling short of breath;
  • stabbing chest pain, cough with yellow or green mucus;
  • seizure (convulsions);
  • white patches or sores inside your mouth or on your lips;
  • swelling, rapid weight gain, urinating less than usual or not at all;
  • fever, chills, sore throat, body aches, flu symptoms, feeling weak or tired;
  • pain or burning when you urinate;
  • pain or fullness in your ear, hearing problems;
  • pale skin, feeling light-headed, rapid heart rate, trouble concentrating;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin; or
  • nausea, pain in your upper stomach, itching, joint pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of your skin or eyes).

Less serious side effects may include:

  • diarrhea, constipation, mild nausea or vomiting, weight loss;
  • dry skin, acne, mild itching or skin rash;
  • cold symptoms such as stuffy nose, sneezing, sore throat;
  • unusual taste in your mouth;
  • headache; or
  • pain in your arms and legs.

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 Afinitor (Everolimus Tablets) »

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.

Afinitor Overview - Patient Information: Side Effects

SIDE EFFECTS: Diarrhea, nausea/vomiting, decreased appetite, weight loss, changes in taste, nosebleeds, dry skin, dizziness, and headache may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Pain or sores in the mouth and throat may occur. Brush your teeth carefully/gently and avoid using mouthwash that contains alcohol, iodine, peroxide, or thyme. Rinse your mouth frequently with cool water mixed with baking soda or salt. It may also be best to eat soft, moist foods.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Many people using this medication have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.

Tell your doctor right away if you have any serious side effects, including: swelling hands/ankles/feet, missed/heavy/painful periods, easy bruising/bleeding, unusual tiredness, mental/mood changes, wound problems (such as slowed wound healing).

Everolimus has rarely caused very serious (possibly fatal) kidney disease. Tell your doctor right away if you develop symptoms of kidney disease, such as a change in the amount of urine.

This medication has caused very serious (rarely fatal) lung problems. Tell your doctor right away if you have symptoms of lung problems, such as shortness of breath, chest pain.

This medication may infrequently make your blood sugar level rise, which can cause or worsen diabetes. Tell your doctor immediately if you develop symptoms of high blood sugar, such as increased thirst and urination. If you already have diabetes, be sure to check your blood sugars regularly. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

This medication may cause your cholesterol/triglycerides to increase. You may need to have your cholesterol/triglycerides checked periodically and/or take another medication to control your cholesterol/triglycerides.

Everolimus may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as fever, chills, persistent sore throat, cough).

Everolimus may rarely cause serious (possibly fatal) liver disease in people who have hepatitis B virus. Get medical help right away if you have any symptoms of liver damage, including: dark urine, persistent nausea/vomiting/loss of appetite, stomach/abdominal pain, yellow eyes/skin.

This medication may increase your risk of getting a rare but very serious (sometimes fatal) brain infection (progressive multifocal leukoencephalopathy-PML). Get medical help right away if any of these rare but very serious side effects occur: clumsiness, loss of coordination, weakness, sudden change in your thinking (such as confusion, difficulty concentrating), difficulty moving your muscles, problems with speech, seizure, vision changes.

This medication can decrease sperm production, an effect that may lower male fertility. Consult your doctor for more details.

Everolimus can commonly cause a mild rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Therefore, get medical help right away if you develop any rash.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Afinitor (Everolimus Tablets)»

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Afinitor FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in another section of the label [see WARNINGS AND PRECAUTIONS]:

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.

Clinical Study Experience In Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

The efficacy and safety of AFINITOR (10 mg/day) plus exemestane (25 mg/day) (n=485) versus placebo plus exemestane (25 mg/day) (n=239) was evaluated in a randomized, controlled trial in patients with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The median age of patients was 61 years (range 28-93 years), and 75% were Caucasian. Safety results are based on a median follow-up of approximately 13 months.

The most common adverse reactions (incidence ≥ 30%) were stomatitis, infections, rash, fatigue, diarrhea, and decreased appetite. The most common Grade 3/4 adverse reactions (incidence ≥ 2%) were stomatitis, infections, hyperglycemia, fatigue, dyspnea, pneumonitis, and diarrhea. The most common laboratory abnormalities (incidence ≥ 50%) were hypercholesterolemia, hyperglycemia, increased aspartate transaminase (AST), anemia, leukopenia, thrombocytopenia, lymphopenia, increased alanine transaminase (ALT), and hypertriglyceridemia. The most common Grade 3/4 laboratory abnormalities (incidence ≥ 3%) were lymphopenia, hyperglycemia, anemia, decreased potassium, increased AST, increased ALT, and thrombocytopenia.

Fatal adverse reactions occurred more frequently in patients who received AFINITOR plus exemestane (2%) compared to patients on the placebo plus exemestane arm (0.4%). The rates of treatment-emergent adverse events resulting in permanent discontinuation were 24% and 5% for the AFINITOR plus exemestane and placebo plus exemestane treatment groups, respectively. Dose adjustments (interruptions or reductions) were more frequent among patients in the AFINITOR plus exemestane arm than in the placebo plus exemestane arm (63% versus 14%).

Table 2 compares the incidence of treatment-emergent adverse reactions reported with an incidence of ≥ 10% for patients receiving AFINITOR 10 mg daily versus placebo.

Table 2: Adverse Reactions Reported ≥ 10% of Patients with Advanced HR+ BC*

  AFINITOR (10 mg/day)
+ exemestanea
N=482
Placebo
+ exemestanea
N=238
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Any adverse reaction Gastrointestinal disorders 100 41 9 90 22 5
  Stomatitisb 67 8 0 11 0.8 0
  Diarrhea 33 2 0.2 18 0.8 0
  Nausea 29 0.2 0.2 28 1 0
  Vomiting 17 0.8 0.2 12 0.8 0
  Constipation 14 0.4 0 13 0.4 0
  Dry mouth 11 0 0 7 0 0
General disorders and administration site conditions
  Fatigue 36 4 0.4 27 1 0
  Edema peripheral 19 1 0 6 0.4 0
  Pyrexia 15 0.2 0 7 0.4 0
  Asthenia 13 2 0.2 4 0 0
Infections and infestations
  Infectionsc 50 4 1 25 2 0
Investigations
  Weight decreased 25 1 0 6 0 0
Metabolism and nutrition disorders
  Decreased appetite 30 1 0 12 0.4 0
  Hyperglycemia 14 5 0.4 2 0.4 0
Musculoskeletal and connective tissue disorders
  Arthralgia 20 0.8 0 17 0 0
  Back pain 14 0.2 0 10 0.8 0
  Pain in extremity 9 0.4 0 11 2 0
Nervous system disorders
  Dysgeusia 22 0.2 0 6 0 0
  Headache 21 0.4 0 14 0 0
Psychiatric disorders
  Insomnia 13 0.2 0 8 0 0
Respiratory, thoracic and mediastinal disorders
  Cough 24 0.6 0 12 0 0
  Dyspnea 21 4 0.2 11 0.8 0.4
  Epistaxis 17 0 0 1 0 0
  Pneumonitisd 19 4 0.2 0.4 0 0
Skin and subcutaneous tissue disorders
  Rash 39 1 0 6 0 0
  Pruritus 13 0.2 0 5 0 0
  Alopecia 10 0 0 5 0 0
Vascular disorders
  Hot flush 6 0 0 14 0 0
  Median duration of treatment® 23.9 weeks 13.4 weeks
Grading according to CTCAE Version 3.0
*160 patients (33.2%) were exposed to AFINITOR therapy for a period of ≥ 32 weeks)
a Exemestane (25 mg/day)
b Includes stomatitis, mouth ulceration, aphthous stomatitis, glossodynia, gingival pain, glossitis and lip ulceration
c Includes all preferred terms within the 'infections and infestations' system organ class, the most common being nasopharyngitis (10%), urinary tract infection (10%), upper respiratory tract infection (5%), pneumonia (4%), bronchitis (4%), cystitis (3%), sinusitis (3%), and also including candidiasis ( < 1%), and sepsis ( < 1%), and hepatitis C ( < 1%).
d Includes pneumonitis, interstitial lung disease, lung infiltration, and pulmonary fibrosis
e Exposure to AFINITOR or placebo

Key observed laboratory abnormalities are presented in Table 3.

Table 3: Key Laboratory Abnormalities Reported in ≥ 10% of Patients with Advanced HR+ BC

  AFINITOR (10 mg/day)
+ exemestanea
N=482
Placebo
+ exemestanea
N=238
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Hematologyb
  Hemoglobin decreased 68 6 0.6 40 0.8 0.4
  WBC decreased 58 1 0 28 5 0.8
  Platelets decreased 54 3 0.2 5 0 0.4
  Lymphocytes decreased 54 11 0.6 37 5 0.8
  Neutrophils decreased 31 2 0 11 0.8 0.8
Clinical chemistry
  Glucose increased 69 9 0.4 44 0.8 0.4
  Cholesterol increased 70 0.6 0.2 38 0.8 0.8
  Aspartate transaminase (AST) increased 69 4 0.2 45 3 0.4
  Alanine transaminase (ALT) increased 51 4 0.2 29 5 0
  Triglycerides increased 50 0.8 0 26 0 0
  Albumin decreased 33 0.8 0 16 0.8 0
  Potassium decreased 29 4 0.2 7 1 0
  Creatinine increased 24 2 0.2 13 0 0
Grading according to CTCAE Version 3.0
a Exemestane (25 mg/day)
b Reflects corresponding adverse drug reaction reports of anemia, leukopenia, lymphopenia, neutropenia, and thrombocytopenia (collectively as pancytopenia), which occurred at lower frequency.

Clinical Study Experience In Advanced Pancreatic Neuroendocrine Tumors

In a randomized, controlled trial of AFINITOR (n=204) versus placebo (n=203) in patients with advanced PNET the median age of patients was 58 years (range 20-87), 79% were Caucasian, and 55% were male. Patients on the placebo arm could cross over to open-label AFINITOR upon disease progression.

The most common adverse reactions (incidence ≥ 30%) were stomatitis, rash, diarrhea, fatigue, edema, abdominal pain, nausea, fever, and headache. The most common Grade 3-4 adverse reactions (incidence ≥ 5%) were stomatitis and diarrhea. The most common laboratory abnormalities (incidence ≥ 50%) were decreased hemoglobin, hyperglycemia, alkaline phosphatase increased, hypercholesterolemia, bicarbonate decreased, and increased aspartate transaminase (AST). The most common Grade 3-4 laboratory abnormalities (incidence ≥ 3%) were hyperglycemia, lymphopenia, decreased hemoglobin, hypophosphatemia, increased alkaline phosphatase, neutropenia, increased aspartate transaminase (AST), potassium decreased, and thrombocytopenia. Deaths during double-blind treatment where an adverse event was the primary cause occurred in seven patients on AFINITOR and one patient on placebo. Causes of death on the AFINITOR arm included one case of each of the following: acute renal failure, acute respiratory distress, cardiac arrest, death (cause unknown), hepatic failure, pneumonia, and sepsis. There was one death due to pulmonary embolism on the placebo arm. After cross-over to open-label AFINITOR, there were three additional deaths, one due to hypoglycemia and cardiac arrest in a patient with insulinoma, one due to myocardial infarction with congestive heart failure, and the other due to sudden death. The rates of treatment-emergent adverse events resulting in permanent discontinuation were 20% and 6% for the AFINITOR and placebo treatment groups, respectively. Dose delay or reduction was necessary in 61% of everolimus patients and 29% of placebo patients. Grade 3-4 renal failure occurred in six patients in the everolimus arm and three patients in the placebo arm. Thrombotic events included five patients with pulmonary embolus in the everolimus arm and one in the placebo arm as well as three patients with thrombosis in the everolimus arm and two in the placebo arm.

Table 4 compares the incidence of treatment-emergent adverse reactions reported with an incidence of ≥ 10% for patients receiving AFINITOR 10 mg daily versus placebo.

Table 4: Adverse Reactions Reported ≥ 10% of Patients with Advanced PNET

  AFINITOR
N=204
Placebo
N=203
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Any adverse reaction Gastrointestinal disorders 100 49 13 98 32 8
  Stomatitisa 70 7 0 20 0 0
  Diarrheab 50 5 0.5 25 3 0
  Abdominal pain 36 4 0 32 6 1
  Nausea 32 2 0 33 2 0
  Vomiting 29 1 0 21 2 0
  Constipation 14 0 0 13 0.5 0
  Dry mouth 11 0 0 4 0 0
General disorders and administration site conditions
  Fatigue/malaise 45 3 0.5 27 2 0.5
  Edema (general and peripheral) 39 1 0.5 12 1 0
  Fever 31 0.5 0.5 13 0.5 0
  Asthenia 19 3 0 20 3 0
Infections and infestations
  Nasopharyngitis/ rhinitis/ URI 25 0 0 13 0 0
  Urinary tract infection 16 0 0 6 0.5 0
Investigations
  Weight decreased 28 0.5 0 11 0 0
Metabolism and nutrition disorders
  Decreased appetite 30 1 0 18 1 0
  Diabetes mellitus 10 2 0 0.5 0 0
Musculoskeletal and connective tissue disorders
  Arthralgia 15 1 0.5 7 0.5 0
  Back pain 15 1 0 11 1 0
  Pain in extremity 14 0.5 0 6 1 0
  Muscle spasms 10 0 0 4 0 0
Nervous system disorders
  Headache/migraine 30 0.5 0 15 1 0
  Dysgeusia 19 0 0 5 0 0
  Dizziness 12 0.5 0 7 0 0
Psychiatric disorders
  Insomnia 14 0 0 8 0 0
Respiratory, thoracic and mediastinal disorders
  Cough/ productive cough 25 0.5 0 13 0 0
  Epistaxis 22 0 0 1 0 0
  Dyspnea/ dyspnea exertional 20 2 0.5 7 0.5 0
  Pneumonitisc 17 3 0.5 0 0 0
  Oropharyngeal pain 11 0 0 6 0 0
Skin and subcutaneous disorders
  Rash 59 0.5 0 19 0 0
  Nail disorders 22 0.5 0 2 0 0
  Pruritus/ pruritus generalized 21 0 0 13 0 0
  Dry skin/ xeroderma 13 0 0 6 0 0
Vascular disorders
  Hypertension 13 1 0 6 1 0
  Median duration of treatment (wks) 37 16
Grading according to CTCAE Version 3.0
a Includes stomatitis, aphthous stomatitis, gingival pain/swelling/ulceration, glossitis, glossodynia, lip ulceration, mouth ulceration, tongue ulceration, and mucosal inflammation.
b Includes diarrhea, enteritis, enterocolitis, colitis, defecation urgency, and steatorrhea.
c Includes pneumonitis, interstitial lung disease, pulmonary fibrosis and restrictive pulmonary disease.

In female patients aged 18 to 55 years, irregular menstruation occurred in 5 of 46 (11%) AFINITOR-treated females and none of the 33 females in the placebo group.

Key observed laboratory abnormalities are presented in Table 5.

Table 5: Key Laboratory Abnormalities Reported in ≥ 10% of Patients with Advanced PNET

Laboratory parameter AFINITOR
N=204
Placebo
N=203
All grades% Grade 3-4% All grades % Grade 3-4%
Hematology
  Hemoglobin decreased 86 15 63 1
  Lymphocytes decreased 45 16 22 4
  Platelets decreased 45 3 11 0
  WBC decreased 43 2 13 0
  Neutrophils decreased 30 4 17 2
Clinical chemistry
  Alkaline phosphatase increased 74 8 66 8
  Glucose (fasting) increased 75 17 53 6
  Cholesterol increased 66 0.5 22 0
  Bicarbonate decreased 56 0 40 0
  Aspartate transaminase (AST) increased 56 4 41 4
  Alanine transaminase (ALT) increased 48 2 35 2
  Phosphate decreased 40 10 14 3
  Triglycerides increased 39 0 10 0
  Calcium decreased 37 0.5 12 0
  Potassium decreased 23 4 5 0
  Creatinine increased 19 2 14 0
  Sodium decreased 16 1 16 1
  Albumin decreased 13 1 8 0
  Bilirubin increased 10 1 14 2
  Potassium increased 7 0 10 0.5
Grading according to CTCAE Version 3.0

Clinical Study Experience In Advanced Renal Cell Carcinoma

The data described below reflect exposure to AFINITOR (n=274) and placebo (n=137) in a randomized, controlled trial in patients with metastatic renal cell carcinoma who received prior treatment with sunitinib and/or sorafenib. The median age of patients was 61 years (range 27-85), 88% were Caucasian, and 78% were male. The median duration of blinded study treatment was 141 days (range 19-451 days) for patients receiving AFINITOR and 60 days (range 21-295 days) for those receiving placebo.

The most common adverse reactions (incidence ≥ 30%) were stomatitis, infections, asthenia, fatigue, cough, and diarrhea. The most common Grade 3-4 adverse reactions (incidence ≥ 3%) were infections, dyspnea, fatigue, stomatitis, dehydration, pneumonitis, abdominal pain, and asthenia. The most common laboratory abnormalities (incidence ≥ 50%) were anemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, lymphopenia, and increased creatinine. The most common Grade 3-4 laboratory abnormalities (incidence ≥ 3%) were lymphopenia, hyperglycemia, anemia, hypophosphatemia, and hypercholesterolemia. Deaths due to acute respiratory failure (0.7%), infection (0.7%), and acute renal failure (0.4%) were observed on the AFINITOR arm but none on the placebo arm. The rates of treatment-emergent adverse events (irrespective of causality) resulting in permanent discontinuation were 14% and 3% for the AFINITOR and placebo treatment groups, respectively. The most common adverse reactions (irrespective of causality) leading to treatment discontinuation were pneumonitis and dyspnea. Infections, stomatitis, and pneumonitis were the most common reasons for treatment delay or dose reduction. The most common medical interventions required during AFINITOR treatment were for infections, anemia, and stomatitis.

Table 6 compares the incidence of treatment-emergent adverse reactions reported with an incidence of ≥ 10% for patients receiving AFINITOR 10 mg daily versus placebo. Within each MedDRA system organ class, the adverse reactions are presented in order of decreasing frequency.

Table 6: Adverse Reactions Reported in at Least 10% of Patients with RCC and at a Higher Rate in the AFINITOR Arm than in the Placebo Arm

  AFINITOR 10 mg/day
N=274
Placebo
N=137
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Any adverse reaction 97 52 13 93 23 5
Gastrointestinal disorders
  Stomatitisa 44 4 < 1 8 0 0
  Diarrhea 30 1 0 7 0 0
  Nausea 26 1 0 19 0 0
  Vomiting 20 2 0 12 0 0
Infections and infestationsb 37 7 3 18 1 0
General disorders and administration site conditions
  Asthenia 33 3 < 1 23 4 0
  Fatigue 31 5 0 27 3 < 1
  Edema peripheral 25 < 1 0 8 < 1 0
  Pyrexia 20 < 1 0 9 0 0
  Mucosal inflammation 19 1 0 1 0 0
Respiratory, thoracic and mediastinal disorders
  Cough 30 < 1 0 16 0 0
  Dyspnea 24 6 1 15 3 0
  Epistaxis 18 0 0 0 0 0
  Pneumonitisc 14 4 0 0 0 0
Skin and subcutaneous tissue disorders
  Rash 29 1 0 7 0 0
  Pruritus 14 < 1 0 7 0 0
  Dry skin 13 < 1 0 5 0 0
Metabolism and nutrition disorders
  Anorexia 25 1 0 14 < 1 0
Nervous system disorders
  Headache 19 < 1 < 1 9 < 1 0
  Dysgeusia 10 0 0 2 0 0
Musculoskeletal and connective tissue disorders
  Pain in extremity 10 1 0 7 0 0
  Median duration of treatment (d) 141 60
Grading according to CTCAE Version 3.0
a Stomatitis (including aphthous stomatitis), and mouth and tongue ulceration.
b Includes all preferred terms within the 'infections and infestations' system organ class, the most common being nasopharyngitis (6%), pneumonia (6%), urinary tract infection (5%), bronchitis (4%), and sinusitis (3%), and also including aspergillosis ( < 1%), candidiasis ( < 1%), and sepsis ( < 1%).
c Includes pneumonitis, interstitial lung disease, lung infiltration, pulmonary alveolar hemorrhage, pulmonary toxicity, and alveolitis.

Other notable adverse reactions occurring more frequently with AFINITOR than with placebo, but with an incidence of < 10% include:

Gastrointestinal disorders: Abdominal pain (9%), dry mouth (8%), hemorrhoids (5%), dysphagia (4%)

General disorders and administration site conditions: Weight decreased (9%), chest pain (5%), chills (4%), impaired wound healing ( < 1%)

Respiratory, thoracic and mediastinal disorders: Pleural effusion (7%), pharyngolaryngeal pain (4%), rhinorrhea (3%)

Skin and subcutaneous tissue disorders: Hand-foot syndrome (reported as palmar-plantar erythrodysesthesia syndrome) (5%), nail disorder (5%), erythema (4%), onychoclasis (4%), skin lesion (4%), acneiform dermatitis (3%)

Metabolism and nutrition disorders: Exacerbation of pre-existing diabetes mellitus (2%), new onset of diabetes mellitus ( < 1%)

Psychiatric disorders: Insomnia (9%)

Nervous system disorders: Dizziness (7%), paresthesia (5%)

Eye disorders: Eyelid edema (4%), conjunctivitis (2%)

Vascular disorders: Hypertension (4%), deep vein thrombosis ( < 1%)

Renal and urinary disorders: Renal failure (3%)

Cardiac disorders: Tachycardia (3%), congestive cardiac failure (1%)

Musculoskeletal and connective tissue disorders: Jaw pain (3%)

Hematologic disorders: Hemorrhage (3%)

Key laboratory abnormalities are presented in Table 7.

Table 7: Key Laboratory Abnormalities Reported in Patients with RCC at a Higher Rate in the AFINITOR Arm than the Placebo Arm

Laboratory parameter AFINITOR 10 mg/day
N=274
Placebo
N=137
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Hematologya
  Hemoglobin decreased 92 12 1 79 5 < 1
  Lymphocytes decreased 51 16 2 28 5 0
  Platelets decreased 23 1 0 2 0 < 1
  Neutrophils decreased 14 0 < 1 4 0 0
Clinical chemistry
  Cholesterol increased 77 4 0 35 0 0
  Triglycerides increased 73 < 1 0 34 0 0
  Glucose increased 57 15 < 1 25 1 0
  Creatinine increased 50 1 0 34 0 0
  Phosphate decreased 37 6 0 8 0 0
  Aspartate transaminase (AST) increased 25 < 1 < 1 7 0 0
  Alanine transaminase (ALT) increased 21 1 0 4 0 0
  Bilirubin increased 3 < 1 < 1 2 0 0
Grading according to CTCAE Version 3.0
a Reflects corresponding adverse drug reaction reports of anemia, leukopenia, lymphopenia, neutropenia, and thrombocytopenia (collectively pancytopenia), which occurred at lower frequency.

Clinical Study Experience In Renal Angiomyolipoma With Tuberous Sclerosis Complex

The data described below are based on a randomized (2:1), double-blind, placebo-controlled trial of AFINITOR in 118 patients with renal angiomyolipoma as a feature of TSC (n=113) or sporadic lymphangioleiomyomatosis (n=5). The median age of patients was 31 years (range 18 to 61 years), 89% were Caucasian, and 34% were male. The median duration of blinded study treatment was 48 weeks (range 2 to 115 weeks) for patients receiving AFINITOR and 45 weeks (range 9 to 115 weeks) for those receiving placebo.

The most common adverse reaction reported for AFINITOR (incidence ≥ 30%) was stomatitis. The most common Grade 3-4 adverse reactions (incidence ≥ 2%) were stomatitis and amenorrhea. The most common laboratory abnormalities (incidence ≥ 50%) were hypercholesterolemia, hypertriglyceridemia, and anemia. The most common Grade 3-4 laboratory abnormality (incidence ≥ 3%) was hypophosphatemia.

The rate of adverse reactions resulting in permanent discontinuation was 3.8% in the AFINITOR-treated patients. Adverse reactions leading to permanent discontinuation in the AFINITOR arm were hypersensitivity/angioedema/bronchospasm, convulsion, and hypophosphatemia. Dose adjustments (interruptions or reductions) due to adverse reactions occurred in 52% of AFINITOR-treated patients. The most common adverse reaction leading to AFINITOR dose adjustment was stomatitis.

Table 8 compares the incidence of adverse reactions reported with an incidence of ≥ 10% for patients receiving AFINITOR and occurring more frequently with AFINITOR than with placebo. Laboratory abnormalities are described separately in Table 9.

Table 8: Adverse Reactions Reported in ≥ 10% of AFINITOR-treated Patients with Renal Angiomyolipoma

  AFINITOR
N=79
Placebo
N=39
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Any adverse reaction 100 25 5 97 8 5
Gastrointestinal disorders
  Stomatitisa 78 6 0 23 0 0
  Vomiting 15 0 0 5 0 0
  Diarrhea 14 0 0 5 0 0
General disorders and administration site conditions
  Peripheral edema 13 0 0 8 0 0
Infections and infestations
  Upper respiratory tract infection 11 0 0 5 0 0
Musculoskeletal and connective tissue disorders
  Arthralgia 13 0 0 5 0 0
Respiratory, thoracic and mediastinal disorders
  Cough 20 0 0 13 0 0
Skin and subcutaneous tissue disorders
  Acne 22 0 0 5 0 0
Grading according to CTCAE Version 3.0
a Includes stomatitis, aphthous stomatitis, mouth ulceration, gingival pain, glossitis, and glossodynia.

Amenorrhea occurred in 15% of AFINITOR-treated females (8 of 52) and 4% (1 of 26) of females in the placebo group. Other adverse reactions involving the female reproductive system were menorrhagia (10%), menstrual irregularities (10%), and vaginal hemorrhage (8%).

The following additional adverse reactions occurred in less than 10% of Afinitor-treated patients: epistaxis (9%), decreased appetite (6%), otitis media (6%), depression (5%), abnormal taste (5%), increased blood luteinizing hormone (LH) levels (4%), increased blood follicle stimulating hormone (FSH) levels (3%), hypersensitivity (3%), and pneumonitis (1%).

Table 9: Key Laboratory Abnormalities Reported in AFINITOR-treated Patients with Renal Angiomyolipoma

  AFINITOI
N=79
Placebo
N=39
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Hematology
  Anemia 61 0 0 49 0 0
  Leucopenia 37 0 0 21 0 0
  Neutropenia 25 0 1 26 0 0
  Lymphopenia 20 1 0 8 0 0
  Thrombocytopenia 19 0 0 3 0 0
Clinical chemistry
  Hypercholesterolemia 85 1 0 46 0 0
  Hypertriglyceridemia 52 0 0 10 0 0
  Hypophosphatemia 49 5 0 15 0 0
  Alkaline phosphatase increased 32 1 0 10 0 0
  Elevated aspartate transaminase (AST) 23 1 0 8 0 0
  Elevated alanine transaminase (ALT) 20 1 0 15 0 0
  Fasting hyperglycemia 14 0 0 8 0 0
Grading according to CTCAE Version 3.0

Clinical Study Experience In Subependymal Giant Cell Astrocytoma With Tuberous Sclerosis Complex

The data described below are based on a randomized (2:1), double-blind, placebo-controlled trial (Study 1) of AFINITOR in 117 patients with subependymal giant cell astrocytoma (SEGA) and tuberous sclerosis complex (TSC). The median age of patients was 9.5 years (range 0.8 to 26 years), 93% were Caucasian, and 57% were male. The median duration of blinded study treatment was 52 weeks (range 24 to 89 weeks) for patients receiving AFINITOR and 47 weeks (range 14 to 88 weeks) for those receiving placebo.

The most common adverse reactions reported for AFINITOR (incidence ≥ 30%) were stomatitis and respiratory tract infection. The most common Grade 3-4 adverse reactions (incidence ≥ 2%) were stomatitis, pyrexia, pneumonia, gastroenteritis, aggression, agitation, and amenorrhea. The most common key laboratory abnormalities (incidence ≥ 50%) were hypercholesterolemia and elevated partial thromboplastin time. The most common Grade 3-4 laboratory abnormality (incidence ≥ 3%) was neutropenia.

There were no adverse reactions resulting in permanent discontinuation. Dose adjustments (interruptions or reductions) due to adverse reactions occurred in 55% of AFINITOR-treated patients. The most common adverse reaction leading to AFINITOR dose adjustment was stomatitis.

Table 10 compares the incidence of adverse reactions reported with an incidence of ≥ 10% for patients receiving AFINITOR and occurring more frequently with AFINITOR than with placebo. Laboratory abnormalities are described separately in Table 11.

Table 10: Adverse Reactions Reported in ≥ 10% of AFINITOR-treated Patients with SEGA in Study 1

  AFINITOR
N=78
Placebo
N=39
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Any adverse reaction 97 36 3 92 23 3
Gastrointestinal disorders
  Stomatitisa 62 9 0 26 3 0
  Vomiting 22 1 0 13 0 0
  Diarrhea 17 0 0 5 0 0
  Constipation 10 0 0 3 0 0
Infections and infestations
  Respiratory tract infectionb 31 1 1 23 0 0
  Gastroenteritisc 10 4 1 3 0 0
  Pharyngitis streptococcal 10 0 0 3 0 0
General disorders and administration site conditions
  Pyrexia 23 6 0 18 3 0
  Fatigue 14 0 0 3 0 0
Psychiatric disorders
  Anxiety, aggression or other behavioral disturbanced 21 5 0 3 0 0
Skin and subcutaneous tissue disorders
  Rashe 21 0 0 8 0 0
  Acne 10 0 0 5 0 0
Grading according to CTCAE Version 3.0
a Includes mouth ulceration, stomatitis, and lip ulceration
b Includes respiratory tract infection, upper respiratory tract infection, and respiratory tract infection viral
c Includes gastroenteritis, gastroenteritis viral, and gastrointestinal infection
d Includes agitation, anxiety, panic attack, aggression, abnormal behavior, and obsessive compulsive disorder
e Includes rash, rash generalized, rash macular, rash maculo-papular, rash papular, dermatitis allergic, and urticaria

Amenorrhea occurred in 17% of AFINITOR-treated females aged 10 to 55 years (3 of 18) and none of the females in the placebo group. For this same group of AFINITOR-treated females, the following menstrual abnormalities were reported: dysmenorrhea (6%), menorrhagia (6%), metrorrhagia (6%), and unspecified menstrual irregularity (6%).

The following additional adverse reactions occurred in less than 10% of AFINITOR-treated patients: nausea (8%), pain in extremity (8%), insomnia (6%), pneumonia (6%), epistaxis (5%), hypersensitivity (3%), increased blood luteinizing hormone (LH) levels (1%) and pneumonitis (1%).

Table 11: Key Laboratory Abnormalities Reported in AFINITOR-treated Patients with SEGA in Study 1

  AFINITOR N=78 Placebo N=39
All grades % Grade 3 % Grade 4 % All grades % Grade 3 % Grade 4 %
Hematology
  Elevated partial thromboplastin time 72 3 0 44 5 0
  Neutropenia 46 9 0 41 3 0
  Anemia 41 0 0 21 0 0
Clinical chemistry
  Hypercholesterolemia 81 0 0 39 0 0
  Elevated aspartate transaminase (AST) 33 0 0 0 0 0
  Hypertriglyceridemia 27 0 0 15 0 0
  Elevated alanine transaminase (ALT) 18 0 0 3 0 0
  Hypophosphatemia 9 1 0 3 0 0
Grading according to CTCAE Version 3.0

Longer-term follow-up of 34.2 months (range 4.7 to 47.1 months) from a non-randomized, open-label, 28-patient trial resulted in the following additional notable adverse reactions and key laboratory abnormalities: cellulitis (29%), hyperglycemia (25%), and elevated creatinine (14%).

Postmarketing Experience

The following adverse reactions have been identified during post approval use of AFINITOR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency or establish a causal relationship to drug exposure: acute pancreatitis, cholecystitis, cholelithiasis, arterial thrombotic events and reflex sympathetic dystrophy.

Read the entire FDA prescribing information for Afinitor (Everolimus Tablets) »

A A A

Afinitor - User Reviews

Afinitor User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Afinitor sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Cancer

Get the latest treatment options.

Health Resources
advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations