FARYDAK SIDE EFFECTS
- Generic Name: panobinostat capsules
- Brand Name: Farydak
- Drug Class: ,
SIDE EFFECTS
The following adverse reactions are described in detail in other sections of the label:
- Diarrhea
- Cardiac Toxicities
- Hemorrhage
- Myelosuppression
- Infections
- Hepatotoxicity
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 1 summarizes the adverse reactions occurring in at least 10% of patients with ≥ 5% greater incidence in the FARYDAK arm, and Table 2 summarizes the treatment-emergent laboratory abnormalities.
Table 1: Adverse Reactions ( ≥ 10% Incidence and ≥ 5% Greater Incidence in FARYDAK-Arm) in Patients with Multiple Myeloma
| Primary System Organ Class Preferred term |
FARYDAK, BTZ [1], Dex [2] N=381 All grades % |
FARYDAK, BTZ [1], Dex [2] N=381 Grade 3/4 % |
Placebo, BTZ [1], Dex [2] N=377 All grades % |
Placebo, BTZ [1], Dex [2] N=377 Grade 3/4 % |
| Cardiac disorders | ||||
| Arrhythmia[3] | 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 | ||||
| Fatigue[4] | 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 |
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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 2: Treatment-emergent Laboratory Abnormalities ( ≥ 10% Incidence and ≥ 5% Greater Incidence in FARYDAK-arm) in Patients with Multiple Myeloma
| Investigations | FARYDAK, BTZ[1], Dex[2] N=381 Any grade % |
FARYDAK, BTZ[1], Dex[2] N=381 Grade 3/4 % |
Placebo, BTZ[1], Dex[2] N=377 Any grade % |
Placebo, BTZ[1], Dex[2] 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 |
| Hyperphosphatem ia | 29 | 2 | 20 | < 1 |
| Hypermagnesemia | 27 | 5 | 14 | 1 |
| 1 BTZ = bortezomib 2 Dex = dexamethasone |
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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.
SRC: NLM .