Drug Action
Panobinostat is a histone deacetylase inhibitor, which promotes cell-cycle arrest and apoptosis of tumour cells via multiple pathways.
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Drug reference
Panobinostat is a histone deacetylase inhibitor, which promotes cell-cycle arrest and apoptosis of tumour cells via multiple pathways.
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Treatment of relapsed or refractory multiple myeloma (in combination with bortezomib and dexamethasone), in patients who have received at least two prior regimens, including bortezomib and an immunomodulatory agent ▶BY MOUTH ▶Adult 18–74 years: 20 mg once daily, on days 1, 3, 5, 8, 10 and 12 of a 21-day cycle for 8 cycles. Patients with clinical benefit should continue treatment for 8 additional cycles; total duration 16 cycles (48 weeks), for doses of dexamethasone and bortezomib, or dose adjustment due to side-effects—consult product literature ▶Adult 75 years and over: 20 mg once daily, on days 1, 3, 5, 8, 10 and 12 of a 21-day cycle for 8 cycles. Patients with clinical benefit should continue treatment for 8 additional cycles; total duration 16 cycles (48 weeks), alternatively initially 15 mg once daily, on days 1, 3, 5, 8, 10 and 12 of a 21-day cycle for 1 cycle, increased if tolerated to 20 mg once daily, on days 1, 3, 5, 8, 10 and 12 of a 21-day cycle for 7 subsequent cycles, patients with clinical benefit should continue treatment for 8 additional cycles; total duration 16 cycles (48 weeks), lower dose may be used for the first cycle depending on patient’s condition and co-morbidities, for doses of dexamethasone and bortezomib, or dose adjustment due to side-effects—consult product literature
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DUE TO INTERACTIONS ▶Manufacturer advises reduce dose to 10 mg with concurrent use of potent inhibitors of CYP3A4; if the potent inhibitor of CYP3A4 is to be continued, consider increasing the dose to 15 mg if tolerated. ▶Manufacturer advises avoid potent inhibitors of CYP3A4 if possible in patients taking a reduced panobinostat dose due to side-effects, or in those with hepatic impairment. Immune system and malignant disease
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Coagulation disorders. elderly. QT-interval prolongation. risk factors for QT-interval prolongation CAUTIONS, FURTHER INFORMATION ▶Risk factors for QT-interval prolongation Patients at risk of developing QT-interval prolongation include those with long QT syndrome, or uncontrolled or significant cardiac disease.
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NICE decisions ▶Panobinostat for treating multiple myeloma after at least 2 previous treatments (January 2016) NICE TA380 Panobinostat, in combination with bortezomib and dexamethasone, is recommended as an option for treating relapsed or refractory multiple myeloma in patients who have received at least 2 prior regimens including bortezomib and an immunomodulatory agent when the manufacturer provides panobinostat with the discount agreed in the patient access scheme. www.nice.org.uk/guidance/ta380
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RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES See Cytotoxic drugs p. 938.
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→Appendix 1: panobinostat
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▶Common or very common Anaemia. antibiotic associated colitis. appetite decreased. arrhythmias. asthenia. cheilitis. chills. cough. decreased leucocytes. diarrhoea. dizziness. dry mouth. dyspnoea. electrolyte imbalance. fever. fluid imbalance. gastrointestinal discomfort. gastrointestinal disorders. haemorrhage. headache. hepatic disorders. hyperbilirubinaemia. hyperglycaemia. hypertension. hyperuricaemia. hypoalbuminaemia. hypotension. hypothyroidism. increased risk of infection. insomnia. intracranial haemorrhage. joint swelling. malaise. nausea. neutropenia. palpitations. pancytopenia . peripheral oedema. QT interval prolongation. renal failure. respiratory disorders. sepsis. skin reactions. syncope. taste altered. thrombocytopenia. tremor. urinary incontinence. vomiting. weight decreased ▶Uncommon Haemorrhagic shock. myocardial infarction SIDE-EFFECTS, FURTHER INFORMATION Side-effects are reported when used in combination with bortezomib and dexamethasone. Gastro-intestinal disorders Manufacturer advises that patients are treated with anti-diarrhoeals, or any additional treatment, in accordance with local treatment guidelines at the first sign of abdominal cramping or onset of diarrhoea.
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Manufacturer advises exclude pregnancy before starting treatment in women of child-bearing potential, and ensure highly effective contraception used during treatment and for 3 months after last dose. Women using hormonal contraceptives should also use a barrier method of contraception. Highly effective contraception also required for men and their female partners during treatment and for 6 months after last dose.
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Manufacturer advises avoid unless potential benefit outweighs risk—toxicity in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Manufacturer advises avoid—no information available.
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Manufacturer advises caution in mild and moderate impairment (risk of increased exposure); avoid in severe impairment (no information available). Dose adjustments In mild impairment, manufacturer advises dose reduction to 15 mg for the first treatment cycle, dose may be increased to 20 mg based on patient tolerability; in moderate impairment, manufacturer advises dose reduction to 10 mg for the first treatment cycle, dose may be increased to 15 mg based on patient tolerability.
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▶Manufacturer advises monitor full blood count before treatment, then frequently during treatment; reduce dose or interrupt treatment if thrombocytopenia or neutropenia occur—consult product literature. ▶Manufacturer advises monitor ECG before treatment and repeat periodically before each treatment cycle; QTcF should be <480 milliseconds before treatment initiation— Immune system and malignant disease consult product literature. ▶Manufacturer advises monitor electrolytes before treatment and periodically as clinically indicated, especially in patients with diarrhoea; monitor thyroid and pituitary function (free T4 and TSH) as clinically indicated; monitor hepatic function before treatment and regularly during treatment as clinically indicated. ▶Manufacturer advises monitor patients over 65 years more frequently, especially for thrombocytopenia and gastro- intestinal toxicity.
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There can be variation in the licensing of different medicines containing the same drug. Capsule CAUTIONARY AND ADVISORY LABELS 25 ▶Farydak (Novartis Pharmaceuticals UK Ltd) A Panobinostat (as Panobinostat lactate anhydrous) 10 mg Farydak 10mg capsules | 6 capsule P £3,492.00 Panobinostat (as Panobinostat lactate anhydrous) 15 mg Farydak 15mg capsules | 6 capsule P £3,492.00 Panobinostat (as Panobinostat lactate anhydrous) 20 mg Farydak 20mg capsules | 6 capsule P £4,656.00
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Manufacturer advises that patients and their carers should be told to seek medical advice if severe gastro-intestinal toxicity occurs. Missed doses Manufacturer advises if a dose is missed, it can be taken up to 12 hours after the specified dose time. Driving and skilled tasks Dizziness may affect performance of skilled tasks (e.g. driving).
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20 mg once daily, on days 1, 3, 5, 8,
First-line fragment. Read the complete Indications and Dose section above.
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20 mg once daily, on days 1, 3,
First-line fragment. Read the complete Indications and Dose section above.
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