Panobinostat oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of panobinostat.
Drugs List
Therapeutic Indications
Uses
Relapsed/refractory multiple myeloma in combination: Third line treatment
Treatment of adult patients with relapsed and/or refractory multiple myeloma in combination with bortezomib and dexamethasone, who have received at least two prior regimens.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
The recommended starting dose of panobinostat is 20mg once daily on days 1, 3, 5, 8, 10 and 12 of a 21 day cycle. Treatment should continue for 8 cycles. Patients with clinical benefit may continue treatment for a further 8 cycles (a total of 16 cycles).
Elderly
Patients over 75
A reduced starting dose of 15mg should be considered for the first cycle if this is well tolerated the dose can be escalated to 20mg in the second cycle.
Patients under 75
(See Dosage; Adult)
Patients with Hepatic Impairment
Mild hepatic impairment
A reduced starting dose of 15mg should be considered for the first cycle if this is well tolerated the dose can be escalated to 20mg in the second cycle.
Moderate hepatic impairment
A reduced starting dose of 10mg should be considered for the first cycle if this is well tolerated the dose can be escalated to 15mg in the second cycle.
Additional Dosage Information
Strong CYP3A4 inhibitors and P-gp inhibitors
In patients taking concomitant strong CYP3A4 and/or P-gp inhibitors reduce dose of panobinostat to 10mg. If continuous treatment with a strong CYP3A4 inhibitor is required, consider increasing the dose of panobinostat from 10mg to 15mg depending on patient tolerability.
Tolerability
If a dose reduction is required due to individual tolerability, the dose of panobinostat should be reduced in 5mg steps (i.e. from 20mg to 15mg and from 15mg to 10mg). The dose should not be reduced below 10mg.
Thrombocytopenia
Grade 3: Platelets less than 50 x 10 to the power of 9/l with bleeding: Interrupt treatment until recovery to grade 2 then resume at reduced dose.
Grade 4: Platelets less than 25 x 10 to the power of 9/l: Interrupt treatment until recovery to grade 2 then resume at reduced dose.
Gastrointestinal toxicity
Grade 2 diarrhoea despite anti-diarrhoeal treatment: Interrupt treatment until recovery to grade 1 then resume at prior dose.
Grade 3 diarrhoea despite anti-diarrhoeal treatment: Interrupt treatment until recovery to grade 1 then resume at reduced dose.
Grade 4 diarrhoea despite anti-diarrhoeal treatment: Permanently discontinue.
Grade 3 nausea despite anti-emetic treatment: Interrupt treatment until recovery to grade 1 then resume at reduced dose.
Grade 3 or 4 vomiting despite anti-emetic treatment: Interrupt treatment until recovery to grade 1 then resume at reduced dose.
Neutropenia
Grade 3: Neutrophils less than 1 to 0.5 x 10 to the power of 9/l: Interrupt treatment until recovery to grade 2 then resume at prior dose.
Grade 4: Neutrophils less than 0.5 x 10 to the power of 9/l: Interrupt treatment until recovery to grade 2 then resume at reduced dose.
Febrile neutropenia: Neutrophils less than 1 x 10 to the power of 9/l with fever greater than 38.5 degrees C: Interrupt treatment until recovery to grade 2 then resume at reduced dose.
QTc prolongation
QTc is greater than 480 msec or above 60 msec from baseline: Interrupt treatment until recovery. If recovery occurs within 7 days resume at prior dose for first incidence or at reduced dose if recurrent. If unresolved within 7 days discontinue treatment.
QTcF above 500 msec: Permanently discontinue.
Other adverse drug reactions
CTC grade 2 toxicity recurrence: Interrupt treatment until recovery to grade 1 then resume at reduced dose.
CTC grade 3 or 4 toxicity: Interrupt treatment until recovery to grade 1 then resume at reduced dose.
CTC grade 3 or 4 recurrence: A further dose reduction could be considered following recovery to grade 1.
Contraindications
Children under 18 years
Infection
Neutrophil count below 1.0 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9 / L at baseline
Breastfeeding
Long QT syndrome
Pregnancy
Severe hepatic impairment
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Females of childbearing potential
Patients over 65 years
QT interval greater than 480 milliseconds at baseline
Cardiac disorder
Coagulopathy
Congestive cardiac failure
Electrolyte imbalance
History of torsade de pointes
Mild hepatic impairment
Recent myocardial infarction
Severe bradycardia
Unstable angina
Correct electrolyte disorders before treatment
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Blood counts should be performed before and periodically during treatment
Exclude pregnancy prior to initiation of treatment
Monitor hepatic function before treatment and regularly during treatment
Consider monitoring ECG in patients at risk of QT prolongation
Monitor periodically for signs of fluid or electrolyte imbalance
Monitor pituitary function as clinically indicated
Monitor serum electrolytes
Monitor thyroid function where clinically indicated
Advise patient to report diarrhoea and / or vomiting
Advise patient to report symptoms of infection immediately
Consider G-CSF in severe neutropenia / agranulocytosis
Consider the use of anti-emetics before and during therapy
Discontinue permanently if grade 4 diarrhoea occurs
Discontinue treatment if QTc exceeds 500msec
Suspend treatment and reduce dose if febrile neutropenia occurs
Suspend treatment and reduce dose if grade 4 neutropenia occurs
Suspend treatment and/or reduce dose for grade 3 thrombocytopenia
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Suspend treatment if grade 2 diarrhoea occurs
Suspend treatment if grade 3 neutropenia occurs
Suspend treatment if grade 3 or greater nausea unresponsive to antiemetics
Suspend treatment if grade 3 vomiting unresponsive to antiemetic occurs
Suspend treatment if infection occurs
Suspend treatment if QTc > 480 msec or > 60 msec from baseline
Reduce dose and/or alter dose interval in elderly patients
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Advise patient to avoid pomegranate products
Advise patient to avoid star fruit
Male: May cause infertility
Female: Contraception required during and for 3 months after treatment
Female: Two reliable methods of contraception should be used simultaneously
Male: Contraception required during and for 6 months after treatment
Advise patient of risk of bleeding
Pregnancy and Lactation
Pregnancy
Panobinostat is contraindicated during pregnancy.
The manufacturer advises panobinostat should only be used during pregnancy if the expected benefits outweigh the potential risks to the foetus. If it is used during pregnancy or if the patient becomes pregnant while using it, the patient must be informed of the potential risk to the foetus.
At the time of writing there are no clinical studies on the use of panobinostat in pregnancy.
Animal studies have shown embryo-foetal toxicity.
The effect of concurrent therapies must also be considered.
Lactation
Panobinostat is contraindicated during breastfeeding.
The manufacturer advises given its cytostatic/cytotoxic mode of action, breastfeeding is contraindicated during panobinstat treatment.
It is not known whether this agent or its metabolites are excreted in human breast milk.
The effect of concurrent therapies must also be considered.
Side Effects
Abdominal distension
Abdominal pain
Anaemia
Aspergillosis
Asthenia
Atrial fibrillation
Blood urea increased
Bradycardia
Candidiasis
Cellulitis
Cheilitis
Chills
Colitis
Conjunctival haemorrhage
Cough
Decreased appetite
Dehydration
Diarrhoea
Dizziness
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Epistaxis
Erythema
Fatigue
Flatulence
Fluid retention
Gastritis
Gastro-enteritis
Gastro-intestinal haemorrhage
Gastro-intestinal pain
Haematemesis
Haematochezia
Haematoma
Haematuria
Haemoptysis
Haemorrhagic shock
Headache
Hepatic impairment
Hepatitis
Hyperbilirubinaemia
Hyperglycaemia
Hypertension
Hyperuricaemia
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Hypothyroidism
Increase in alkaline phosphatase
Increase in serum ALT/AST
Insomnia
Intracranial bleeding
Joint swelling
Leukopenia
Lower respiratory tract infection
Lymphopaenia
Malaise
Myocardial infarction
Nausea
Neutropenia
Oral herpes
Orthostatic hypotension
Otitis media
Palpitations
Pancytopenia
Peripheral oedema
Petechiae
Pneumonia
Pneumonitis
Prolongation of QT interval
Pulmonary haemorrhage
Pyrexia
Rales
Rash
Renal failure
Renal impairment
Respiratory failure
Sepsis
Septic shock
Serum creatinine increased
Sinus tachycardia
Skin lesions
Syncope
Tachycardia
Thrombocytopenia
Tremor
Upper respiratory tract infection
Urinary incontinence
Urinary tract infections
Viral infection
Vomiting
Weight loss
Wheezing
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2019
Reference Sources
Summary of Product Characteristics: Farydak capsules: Novartis Pharmaceuticals Ltd. Revised June 2018.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 24 July 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.