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Afinitor (Everolimus) - Side Effects and Adverse Reactions



The following serious adverse reactions are discussed in greater detail in another section of the label:

  • Non-infectious pneumonitis  [see Warnings and Precautions].
  • Infections  [see Warnings and Precautions].

6.1 Clinical S tudies E xperience

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.

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) for patients receiving AFINITOR and 60 days (range 21-295) 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 1 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 1      Adverse Reactions Reported in at least 10% of Patients and at a Higher Rate in the AFINITOR Arm than in the Placebo Arm
AFINITOR 10 mg/day
All grades Grade 3 Grade 4 All grades Grade 3 Grade 4
% % % % % %
Any Adverse R eaction 97 52 13 93 23 5
Gastrointestinal D isorders
      Stomatitis a444<1800
Infections and I nfestations b 37731810
General Disorders and Administration Site C onditions
      Edema peripheral25<108<10
      Mucosal inflammation1910100
Respiratory, Thoracic and Mediastinal D isorders
      Pneumonitis c1440000
Skin and Subcutaneous Tissue D isorders
      Dry skin13<10500
Metabolism and Nutrition D isorders
Nervous S ystem D isorders
Musculoskeletal and Connective Tissue D isorders
      Pain in extremity1010700
Medi an Duration of T reatment (d) 141 60
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%)

      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%)

      Nervous system disorders: Insomnia (9%), dizziness (7%), paresthesia (5%)

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

      Vascular disorders: Hypertension (4%)

      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 treatment-emergent laboratory abnormalities are presented in Table 2.

Table 2      Key Laboratory Abnormalities Reported at a Higher rate in the AFINITOR Arm than the Placebo Arm
Laboratory P arameter AFINITOR 10 mg/day
All grades Grade 3 Grade 4 All grades Grade 3 Grade 4
% % % % % %
Hematology a
      Hemoglobin decreased92121795<1
      Lymphocytes decreased511622850
      Platelets decreased231020<1
      Neutrophils decreased140<1400
Clinical C hemistry
      Cholesterol increased77403500
      Triglycerides increased73<103400
      Glucose increased5715<12510
      Creatinine increased50103400
      Phosphate decreased3760800
      Aspartate transaminase (AST) increased25<1<1700
      Alanine transaminase (ALT) increased2110400
      Bilirubin increased3<1<1200
CTCAE Version 3.0
a Includes reports of anemia, leukopenia, lymphopenia, neutropenia, pancytopenia, thrombocytopenia.


Below is a sample of reports where side effects / adverse reactions may be related to Afinitor. The information is not vetted and should not be considered as verified clinical evidence.

Possible Afinitor side effects / adverse reactions in 69 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-03

Patient: 69 year old female

Reactions: Erythema Multiforme

Suspect drug(s):

Possible Afinitor side effects / adverse reactions in 71 year old female

Reported by a physician from Belgium on 2011-10-06

Patient: 71 year old female

Reactions: Weight Decreased, Malaise, Fatigue, Pain in Extremity, Drug Intolerance, Microcytic Anaemia

Suspect drug(s):
    Dosage: 10 mg
    Indication: Pancreatic Neuroendocrine Tumour
    Start date: 2011-07-13
    End date: 2011-09-21

    Dosage: 5 mg
    Start date: 2011-09-22

Possible Afinitor side effects / adverse reactions in 57 year old female

Reported by a consumer/non-health professional from France on 2011-10-12

Patient: 57 year old female

Reactions: Carbohydrate Antigen 15-3 Increased, Metastatic Pain, Metastases TO Spine, Thrombocytopenia

Suspect drug(s):

See index of all Afinitor side effect reports >>

Drug label data at the top of this Page last updated: 2009-04-07

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