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The following adverse reactions are described in detail in other sections of the label:

  • Diarrhea [see WARNINGS AND PRECAUTIONS]
  • Cardiac Toxicities [see WARNINGS AND PRECAUTIONS]
  • Hemorrhage [see WARNINGS AND PRECAUTIONS]
  • Myelosuppression [see WARNINGS AND PRECAUTIONS]
  • Infections [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience

The safety data reflect subject exposure to FARYDAK from a clinical trial, in which 758 subjects with relapsed multiple myeloma received FARYDAK in combination with bortezomib and dexamethasone or placebo in combination with bortezomib and dexamethasone (referred to as the control arm). The median duration of exposure to FARYDAK was 5 months with 16% of patients exposed to study treatment for > 48 weeks.

Serious adverse events (SAEs) occurred in 60% of patients in the FARYDAK, bortezomib, and dexamethasone compared to 42% of patients in the control arm. The most frequent ( ≥ 5%) treatment-emergent SAEs reported for patients treated with FARYDAK were pneumonia (18%), diarrhea, (11%), thrombocytopenia (7%), fatigue (6%), and sepsis (6%).

Adverse reactions that led to discontinuation of FARYDAK occurred in 36% of patients. The most common adverse reactions leading to treatment discontinuations were diarrhea, fatigue, and pneumonia.

Deaths occurred in 8% of patients in the FARYDAK arm versus 5% on the control arm. The most frequent causes of death were infection and hemorrhage.

Table 4 summarizes the adverse reactions occurring in at least 10% of patients with ≥ 5% greater incidence in the FARYDAK arm, and Table 5 summarizes the treatment-emergent laboratory abnormalities.

Table 4: Adverse Reactions ( ≥ 10% Incidence and ≥ 5% Greater Incidence in FARYDAK-Arm) in Patients with Multiple Myeloma

Primary System Organ Class
Preferred term
FARYDAK, BTZ1, Dex2
N=381 All grades %
FARYDAK, BTZ1, Dex2
N=381 Grade 3/4 %
Placebo, BTZ1, Dex 2
N=377 All grades %
Placebo, BTZ1, Dex 2
N=377 Grade 3/4 %
Cardiac disorders
Arrhythmia3 12 3 5 2
Gastrointestinal disorders
Diarrhea 68 25 42 8
Nausea 36 6 21 1
Vomiting 26 7 13 1
General disorders and administration site conditions
Fatigue4 60 25 42 12
Peripheral edema 29 2 19 < 1
Pyrexia 26 1 15 2
Investigations
Weight decreased 12 2 5 1
Metabolism and nutrition disorders
Decreased appetite 28 3 12 1
1 BTZ = bortezomib
2 Dex = dexamethasone
3 Arrhythmia includes the terms: arrhythmia, arrhythmia supraventricular, atrial fibrillation, atrial flutter, atrial tachycardia, bradycardia, cardiac arrest, cardio-respiratory arrest, sinus bradycardia, sinus tachycardia, supraventricular extra-systoles, tachycardia, ventricular arrhythmia, and ventricular tachycardia
4 Fatigue includes the terms: fatigue, malaise, asthenia, and lethargy

Other Adverse Reactions

Other notable adverse drug reactions of FARYDAK not described above, which were either clinically significant, or occurred with a frequency less than 10% but had a frequency in the FARYDAK arm greater than 2% over the control arm in the multiple myeloma clinical trial are listed below:

Infections and infestations: hepatitis B.

Endocrine disorders: hypothyroidism.

Metabolism and nutrition disorders: hyperglycemia, dehydration, fluid retention, hyperuricemia, hypomagnesemia.

Nervous system disorders: dizziness, headache, syncope, tremor, dysgeusia.

Cardiac disorders: palpitations.

Vascular disorders: hypotension, hypertension, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders: cough, dyspnea, respiratory failure, rales, wheezing.

Gastrointestinal disorders: abdominal pain, dyspepsia, gastritis, cheilitis, abdominal distension, dry mouth, flatulence, colitis, gastrointestinal pain.

Skin and subcutaneous disorders: skin lesions, rash, erythema.

Musculoskeletal and connective tissue disorders: joint swelling.

Renal and urinary disorders: renal failure, urinary incontinence.

General disorders and administration site conditions: chills.

Investigations: blood urea increased, glomerular filtration rate decreased, blood alkaline phosphatase increased.

Psychiatric disorders: insomnia.

Table 5: Treatment-emergent Laboratory Abnormalities ( ≥ 10% Incidence and ≥ 5% Greater Incidence in FARYDAK-arm) in Patients with Multiple Myeloma

Investigations FARYDAK, BTZ1, Dex2
N=381 Any grade %
FARYDAK, BTZ1, Dex2
N=381 Grade 3/4 %
Placebo, BTZ1, Dex2
N=377 Any grade %
Placebo, BTZ1, Dex2
N=377 Grade 3/4 %
Hematology
Thrombocytopenia 97 67 83 31
Anemia 62 18 52 19
Neutropenia 75 34 36 11
Leukopenia 81 23 48 8
Lymphopenia 82 53 74 40
Chemistry
Blood creatinine increased 41 1 23 2
Hypokalemia 52 18 36 7
Hypophosphatemia 63 20 45 12
Hyponatremia 49 13 36 7
Hyperbilirubinemia 21 1 13 < 1
Hypocalcemia 67 5 55 2
Hypoalbuminemia 63 2 38 2
Hyperphosphatemia 29 2 20 < 1
Hypermagnesemia 27 5 14 1
1 BTZ = bortezomib
2 Dex = dexamethasone

Fatigue and Asthenia

Grade 1 to Grade 4 asthenic conditions (fatigue, malaise, asthenia, and lethargy) were reported in 60% of the patients in the FARYDAK arm compared to 42% of patients in the control arm. Grade ≥ 3 asthenic conditions were reported in 25% of the patients in the FARYDAK arm compared to 12% of patients in the control arm. Asthenic conditions led to treatment discontinuation in 6% of patients in the FARYDAK arm versus 3% of patients in the control arm.

The prespecified sub-group upon which the efficacy and safety of FARYDAK was based had a similar adverse reaction profile to the entire safety population of patients treated with FARYDAK, bortezomib, and dexamethasone.