For Health Care Professionals Outside the US

 
 
 

Dosing modifications

Dose changes may be required for FARYDAK1

The recommended starting dose for FARYDAK is 20 mg, taken orally on assigned days.1

  • If a patient experiences adverse events, dose modification may be required based on individual tolerability1

If a dose reduction for FARYDAK is required:

Dose and/or schedule modifications of FARYDAK may be required if a patient experiences adverse events. The values below are based on the clinical trial protocols for these selected adverse events. The information is intended to help you manage the selected adverse events that may occur in patients treated with FARYDAK/bortezomib (BTZ)/dexamethasone (dex). In the clinical trial, the most common adverse events (nonhaematologic and haematologic) were thrombocytopenia, neutropenia, diarrhoea, and fatigue.1 The labels for BTZ and dex should be consulted if dose modifications are required for these drugs.

For patients >75 years of age, depending on the patient’s general condition and concomitant diseases, an adjustment of the starting doses or schedule of the components of the combination regimen may be considered.1

NOTE: Patients with mild hepatic impairment should be started at a modified dose. View the recommended starting modifications for patients with hepatic impairment.1

  • Platelet transfusions may be required if clinically indicated1
  • Consider discontinuation if thrombocytopenia does not improve with the above treatment modifications and/or the patient requires repeated platelet transfusions

*Grades based on the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Source: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf
Hb=haemoglobin.
IV=intravenous.

In case of Grade 3 or 4 neutropenia:

  • Consider the use of growth factors (eg, granulocyte colony-stimulating factor) according to local guidelines
  • Consider discontinuation if neutropenia does not improve with dose modifications or the addition of growth factor therapy as per local medical practice and treatment guidelines, and/or in case of severe secondary infection

*Grades based on the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Source: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf

  • Consider discontinuation if Grade 4 events persist with antidiarrhoeal medication
  • At the first sign of abdominal cramping, loose stools, or onset of diarrhoea, it is recommended the patient be treated with antidiarrhoeal medication
  • Prophylactic antiemetics should be administered at the discretion of the physician in accordance with local medical practice

*Grades based on the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Source: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf

QTc prolongation

In the event of long QT interval prior to initiation of FARYDAK (QTcF ≥480 msec at baseline), the start of treatment should be delayed until pre-dose average QTcF has returned to <480 msec. In addition any abnormal serum potassium, magnesium, or phosphorus values should be corrected prior to initiation of FARYDAK. In the event of QT prolongation during treatment:

  • The dose should be omitted, if QTcF is ≥480 msec or above 60 msec from baseline
  • If QT prolongation is resolved within 7 days, resume treatment at prior dose for initial occurrence or at reduced dose if QT prolongation is recurrent
  • If QT prolongation is unresolved within 7 days, treatment should be discontinued
  • If any QTcF value is above 500 msec, FARYDAK therapy should be permanently discontinued

Other adverse drug reactions

For patients experiencing severe adverse drug reactions other than thrombocytopenia, gastrointestinal toxicity, neutropenia, or QTc prolongation, the recommendation is the following:

  • CTC Grade 2 toxicity recurrence or CTC Grades 3 and 4: Omit the dose until recovery to CTC Grade ≤1 and resume treatment at a reduced dose
  • CTC Grade 3 or 4 toxicity recurrence: A further dose reduction may be considered once the adverse event has resolved to CTC Grade <1

CTC= Common Terminology Criteria.

Reference:

  1. FARYDAK® (panobinostat). EU Summary of Product Characteristics. Novartis AG; April 2016.

Need more information on AEs? See discontinuation rates