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Farydak is a brand name for Panobinostat. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent.
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with Farydak should be initiated by a physician experienced in the use of anti-cancer therapies. 2 Posology The recommended starting dose of panobinostat is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10 and 12 of a 21-day cycle.
Patients should be treated initially for eight cycles. It is recommended that patients with clinical benefit continue the treatment for eight additional cycles. The total duration of treatment is up to 16 cycles (48 weeks). Panobinostat is administered in combination with bortezomib and dexamethasone, as shown in Tables 1 and 2.
The bortezomib and dexamethasone prescribing information should be consulted prior to the start of the combination treatment to assess whether a dose reduction is required. 3 mg/m2 given as an injection. The recommended dose of dexamethasone is 20 mg taken orally on a full stomach.
Table 1 Recommended dosing schedule of panobinostat in combination with bortezomib and dexamethasone (cycles 1-8) Cycles 1-8 (3-week cycles) Week 1 Days Week 2 Days Week 3 Farydak 1 3 5 8 10 12 Rest period Bortezomib 1 4 8 11 Rest period Dexamethasone 1 2 4 5 8 9 11 12 Rest period Table 2 Recommended dosing schedule of panobinostat in combination with bortezomib and dexamethasone (cycles 9-16) Cycles 9-16 (3-week cycles) Week 1 Days Week 2 Days Week 3 Farydak 1 3 5 8 10 12 Rest period Bortezomib 1 8 Rest period Dexamethasone 1 2 8 9 Rest period Monitoring recommendations Blood cell counts A complete blood cell count must be performed before initiating treatment with panobinostat.
0 x 109/l. e. 4). 4). g. on days 15 and/or 18, especially in patients ≥65 years and patients with a baseline platelet count below 150 x 109/l. 4). Therefore an ECG should be recorded prior to the start of therapy and repeated periodically before each treatment cycle.
4). Blood electrolytes Blood electrolytes, especially potassium, magnesium and phosphorus, should be measured at baseline and monitored periodically as clinically indicated, especially in patients with diarrhoea. 4). 4). 4). g. free T4 and TSH) as clinically indicated.
Dose adjustments Modification of the treatment dose and/or schedule may be required based on individual tolerability. Clinical judgement on how to continue the treatment should be exercised when a patient experiences an adverse drug reaction.
Summary of the safety profile The safety data of panobinostat have been assessed from a total of 451 patients with multiple myeloma treated with panobinostat in combination with bortezomib and dexamethasone and from a total of 278 patients treated with panobinostat as a single agent.
The safety data reported below are based on the phase III clinical study (Panorama 1) in 381 patients with multiple myeloma treated with 20 mg panobinostat once a day three times per week, on a 2 weeks on and 1 week off dosing regimen in combination with bortezomib and dexamethasone.
0 months. 7% of patients were exposed to study treatment for ≥48 weeks. The most common non-haematological adverse reactions were diarrhoea, fatigue, nausea and vomiting. Treatment-emergent haematological toxicities included thrombocytopenia, anaemia, neutropenia and lymphopenia.
8% of patients. No patient had an absolute QTcF >500 msec. 4%, respectively. 2% of patients. 3%). 2% of placebo + bortezomib + dexamethasone-treated patients. Tabulated list of adverse drug reactions from clinical studies Adverse drug reactions from the phase III study (Panorama 1) are shown in Table 7.
Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness.
In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from available data).
Table 7 includes adverse drug reactions that occur due to the addition of panobinostat to the bortezomib and dexamethasone combination. e. panobinostat + bortezomib + dexamethasone. For adverse drug reactions that are related to bortezomib or dexamethasone treatment, please refer to the relevant SmPC.
Panobinostat is used in combination treatment, therefore the prescribing information of bortezomib and dexamethasone should be consulted prior to initiation of treatment with panobinostat. Decrease in blood cell count Haematological adverse drug reactions, including severe thrombocytopenia, neutropenia and anaemia (CTC grade 3 to 4) were reported in patients treated with panobinostat.
Therefore a complete blood count must be performed before initiating therapy with panobinostat, with frequent monitoring during treatment (in particular before each injection of bortezomib as per bortezomib SmPC). 0 x 109/l prior to initiation of treatment.
2). In the phase III study, thrombocytopenia typically recovered to baseline by the start of the next 21-day cycle (see Figure 1). The median time to onset for grade 3 and 4 thrombocytopenia was one month and the median time to recovery was 12 days.
8 Figure 1 Median platelet counts over time (Study D2308, Safety set, cycles 1-8) PAN=panobinostat BTZ= bortezomib Dex = dexamethasone In patients with CTC grade 3 thrombocytopenia (platelet count <50 x 109/l with bleeding) panobinostat may need to be temporarily withheld and/or the subsequent dose may need to be reduced.
8). Haemorrhage Haemorrhage has been reported in patients during treatment with panobinostat. 2% of patients, including cases of gastrointestinal and pulmonary haemorrhage with fatal outcomes. Therefore, physicians and patients should be aware of the increased risk of thrombocytopenia and the potential for haemorrhage, especially in patients with coagulation disorders or in those who are receiving chronic anti-coagulation therapy.
Infection Localised and systemic infections, including pneumonia, other bacterial infections, invasive fungal infections such as aspergillosis or candidiasis, and viral infections including hepatitis B virus and herpes simplex, have been reported in patients taking panobinostat.
1. 6).
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e. from 20 mg to 15 mg or from 15 mg to 10 mg). The dose should not be reduced below 10 mg and the same treatment schedule (3-week treatment cycle) should be kept. e. on days 1, 4, 8 and 11 of cycles 1-8, see Table 1, and on days 1 and 8 of cycles 9-16, see Table 2).
If patients experience thrombocytopenia, panobinostat may need to be temporarily withheld and the subsequent dose may need to be reduced (see Table 3). In patients with platelet count <50 x 109/l (complicated by bleeding) or <25 x 109/l, Farydak therapy should be withheld and resumed at a reduced dose upon recovery to platelet count ≥50 x 109/l.
Platelet counts should be monitored at least twice a week until ≥50 x 109/l. 4). Discontinuation of treatment may be considered if thrombocytopenia does not improve despite the treatment modifications described below and/or the patient requires repeated platelet transfusions.
Additionally, dose adjustment of bortezomib may be considered (see bortezomib SmPC and Table 3). Table 3 Recommended dose modifications for thrombocytopenia Thrombocytopenia grade on day of treatment Modification of panobinostat starting dose Panobinostat dose on recovery to grade 2 thrombocytopenia (≥50 x 109/l) Modification of bortezomib starting dose Bortezomib dose on recovery to grade 2 thrombocytopenia (≥50 x 109/l) 1 dose omitted More than 1 dose omitted Grade 3 Platelets <50 x 109/l with bleeding Omit dose Resume at reduced dose Omit dose Resume at same dose Resume at reduced dose Grade 4 Platelets <25 x 109/l Omit dose Resume at reduced dose Omit dose Resume at same dose Resume at reduced dose Gastrointestinal toxicity Gastrointestinal toxicity is very common in patients treated with panobinostat.
Patients who experience diarrhoea and nausea or vomiting may require temporary dose discontinuation or dose 4 reduction as outlined in Table 4. Table 4 Recommended dose modifications for gastrointestinal toxicity Adverse drug reaction Grade on day of treatment Modification of panobinostat starting dose Panobinostat […]
Table 7 Panobinostat adverse drug reactions observed in multiple myeloma patients in the phase III study System Organ Class Frequency Adverse reaction Infections and infestations Very common Upper respiratory tract infection, pneumonia Common Septic shock, urinary tract infection, viral infection, oral herpes, Clostridium difficile colitis, otitis media, cellulitis, sepsis, gastroenteritis, lower respiratory tract infection, candidiasis Uncommon Pneumonia fungal, hepatitis B, aspergillosis Blood and lymphatic system disorders a Very common Pancytopenia, thrombocytopenia, anaemia, leukopenia, neutropenia, lymphopenia Endocrine disorders Common Hypothyroidism Metabolism and nutrition disorders Very common Decreased appetite, hypophosphataemia a, hyponatraemia a, hypokalaemia a Common Hyperglycaemia, dehydration, hypoalbuminaemia, fluid retention, hyperuricaemia, hypocalcaemia, hypomagnesaemia Psychiatric disorders Very common Insomnia Nervous system disorders Very common Dizziness, headache Common Haemorrhage intracranial, syncope, tremor, dysgeusia Eye disorders Common Conjunctival haemorrhage 14 Cardiac disorders Common Bradycardia, atrial fibrillation, sinus tachycardia, tachycardia, palpitation Uncommon Myocardial infarction Vascular disorders Very common Hypotension Common Hypertension, haematoma, orthostatic hypotension Uncommon Shock haemorrhagic Respiratory, thoracic and mediastinal disorders Very common Cough, dyspnoea Common Respiratory failure, rales, wheezing, epistaxis Uncommon Pulmonary haemorrhage, haemoptysis Gastrointestinal disorders Very common Diarrhoea, nausea, vomiting, abdominal pain, dyspepsia Common Gastrointestinal haemorrhage, haematochezia, gastritis, cheilitis, abdominal distension, dry mouth, flatulence Uncommon Colitis, haematemesis, gastrointestinal pain Hepatobiliary disorders Common Hepatic function abnormal, hyperbilirubinaemia a Skin and subcutaneous disorders Common Skin lesions, rash, erythema Uncommon Petechiae Musculoskeletal and connective tissue disorders Common Joint swelling Renal and urinary disorders Common Renal failure, haematuria, urinary incontinence General disorders and administration site conditions Very common Fatigue, oedema peripheral, pyrexia, asthenia Common Chills, malaise Investigations Very common Weight decreased Common Blood urea increased, glomerular filtration rate decreased, blood alkaline phosphatase increased, electrocardiogram QT prolonged, blood creatinine increased a, SGPT alanine transaminase (ALT) increased a, SGOT aspartate transaminase (AST) increased a a Frequency is based on laboratory values Description of selected adverse drug reactions Gastrointestinal Gastrointestinal toxicity, primarily diarrhoea, nausea and vomiting, is among the most frequently reported adverse reactions.
5% and nausea and […]
g. g. 8). 8). Physicians and patients should be aware of the increased risk of infection with panobinostat. Farydak treatment should not be initiated in patients with active infections. Pre-existing infections should be treated prior to initiation of the therapy.
Patients should be monitored for signs and symptoms of infections during treatment with panobinostat; if a diagnosis of infection is made, appropriate anti-infective treatment should be instituted promptly and interruption or discontinuation of Farydak considered.
If a diagnosis of invasive systemic fungal infection is made, panobinostat should be discontinued and appropriate anti-fungal therapy instituted. 8). 2). g. prochlorperazine) may be considered at the discretion of the physician and in accordance with local medical practice.
5). g. loperamide) or any additional treatment in accordance with local treatment guidelines. Replacement intravenous fluids and electrolytes may be used as appropriate. Medicinal products with laxative properties should be used with caution because of the potential for exacerbation of diarrhoea.
Patients should be advised to contact their physician to discuss the use of any laxative product. Electrocardiographic changes Panobinostat may prolong cardiac ventricular repolarisation (QT interval). No episodes of QTcF prolongation >500 msec were reported with the dose of 20 mg Farydak in the phase III clinical study, in combination with bortezomib and dexamethasone.
Pooled clinical data from over 500 patients treated with panobinostat alone in multiple indications and at different dose levels have shown that the incidence of CTC grade 3 QTc prolongation (QTcF >500 msec) was approximately 1% overall and 5% or more at a dose of 60 mg or higher; no episodes of torsades de pointes were observed.
2). QTcF should be <480 msec prior to initiation of treatment with Farydak. g. potassium, magnesium and phosphorus) and ECG […]