Ribociclib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ribociclib succinate.
Drugs List
Therapeutic Indications
Uses
Hormone receptor +ve, HER2 -ve locally advanced or metastatic breast cancer
Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy.
The endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist in pre- or perimenopausal women.
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 dose is 600mg once daily at the same time each day, preferably in the morning, for 21 days followed by 7 day rest period (28 day cycle).
Patients with Renal Impairment
Starting dose is 400mg once daily in patients with severe renal impairment.
Additional Dosage Information
Dose reductions
First dose reduction: 400mg per day.
Second dose reduction: 200mg per day.
If further dose reduction is required treatment should be discontinued.
Dose modifications for neutropenia
Grade 1 or 2 neutropenia (absolute neutrophil count of between 1000 per cubic millimetre and the lower limit of normal): No adjustment.
Grade 3 neutropenia (absolute neutrophil count of between 500 and 1000 per cubic millimetre): At first occurrence, interrupt treatment until recovery to grade 2 or lower, then resume at the same dose. At second occurrence of grade 3 neutropenia, interrupt treatment until recovery to grade 2 or lower, then resume ribociclib and reduce by one dose level.
Grade 3 febrile neutropenia (neutropenia with a fever above 38.3 degrees Celsius, or a fever of above 38 degrees Celsius sustained for more than one hour and/or concurrent infection: Interrupt treatment until recovery to grade 2 or lower, then resume ribociclib and reduce by one dose level.
Grade 4 neutropenia (absolute neutrophil count of below 500 per cubic millimetre): Interrupt treatment until recovery to grade 2 or lower, then resume ribociclib and reduce by one dose level.
Dose modifications for hepatobiliary toxicity
Grade 1 hepatobiliary toxicity (ALT and/or AST equal to or lower than 3 times the upper limit of normal, ULN, with total bilirubin equal to or below 2 times ULN): No adjustment.
Grade 2 hepatobiliary toxicity (ALT and/or AST between 3 and 5 times ULN, with total bilirubin equal to or below 2 times ULN) with grade 2 ALT/AST values measured at baseline: No adjustment.
Grade 2 hepatobiliary toxicity (ALT and/or AST between 3 and 5 times ULN, with total bilirubin equal to or below 2 times ULN) with lower than grade 2 ALT/AST values measured at baseline:At first occurrence, interrupt treatment until recovery to baseline or lower, then resume at the same dose level. At second occurrence of grade 2 hepatobiliary toxicity, interrupt treatment until recovery to baseline or lower, then resume ribociclib and reduce by one dose level.
Grade 3 hepatobiliary toxicity (ALT and/or AST between 5 and 20 times ULN, with total bilirubin equal to or below 2 times ULN): At first occurrence, interrupt treatment until recovery to baseline or lower, then resume ribociclib at next lower dose level. At second occurrence of grade 3 hepatobiliary toxicity, discontinue treatment.
Grade 4 hepatobiliary toxicity (ALT and/or AST above 20 times ULN, with total bilirubin equal to or below 2 times ULN): Discontinue treatment.
ALT and/or AST above 3 times ULN, with total bilirubin above 2 times ULN (irrespective of baseline grade), in the absence of cholestasis: Discontinue treatment.
Dose modifications for other toxicities
Grade 3 toxicity: At first occurrence, interrupt treatment until recovery to grade 1 or lower, then resume at the same dose level. At second occurrence of grade 3 toxicity, interrupt treatment until recovery to grade 1 or lower, then resume ribociclib at next lower dose level.
Dose modifications for QT prolongation
QTcF interval greater than 480msec, up to and including 500msec: At first occurrence, interrupt treatment until QTcF recovery to below 481msec, then resume at the next lower dose. At second occurrence of a QT interval greater than 480msec, interrupt treatment until QTcF recovery to below 481msec, then resume ribociclib at the next lower dose level.
QTcF interval greater than 500msec on 2 separate ECGs: Interrupt treatment until QTcF recovery to below 481msec, then resume ribociclib at the next lower dose level.
QTcF interval greater than 500msec (or greater than 60msec from baseline), in combination with torsade de pointes, polymorphic ventricular tachycardia or serious arrhythmia symptoms: Discontinue treatment permanently.
Dose modifications for interstitial lung disease (ILD)/pneumonitis
Grade 1 ILD/pneumonitis: No adjustment.
Grade 2 ILD/pneumonitis (asymptomatic): Interrupt treatment until recovery to lower than grade 1, then resume ribociclib at next lower dose level.
Grade 3 or 4 ILD/pneumonitis (severe):Discontinue treatment.
Missed doses
If the patient misses a dose, or vomits after taking a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time.
Contraindications
Children under 18 years
QTcF interval greater than 450msec at baseline
Breastfeeding
History of severe cardiac disorder
Pregnancy
Torsade de pointes
Unstable cardiac disorder
Precautions and Warnings
Family history of long QT syndrome
QTcF interval greater than 480msec
Electrolyte imbalance
History of torsade de pointes
Moderate hepatic impairment
Severe renal impairment
Administration of live vaccines is not recommended
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Combination therapy: refer to information for concomitant agent
Treatment to be initiated by specialist
Contains soya or soya derivative
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Perform ECG before and during treatment
Perform full blood count before treatment
Perform liver function tests before commencing therapy and during therapy
Monitor blood count prior to each cycle and on day 14 of 1st and 2nd cycles
Monitor ECG in patients at risk of QT prolongation
Monitor for signs and symptoms of interstitial lung disease
Monitor for signs and symptoms of pneumonitis
Monitor LFTs prior to each cycle and on day 14 of 1st & 2nd cycles
Monitor serum electrolytes
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report unexplained fever, sore throat, bruising, bleeding
May affect immune response to live vaccines
Discontinue if grade 3 or greater interstitial lung disease occurs
Discontinue if severe skin reaction occurs
Discontinue treatment if grade 3 or greater pneumonitis occurs
Suspend treatment and/or reduce dose if grade 3 or greater neutropenia
Suspend treatment if grade 2 interstitial lung disease occurs
Suspend treatment if grade 2 pneumonitis occurs
Review dose if grade 2 or greater hepatobiliary toxicity
Suspend treatment and/or reduce dose if other toxicity grade 3 or greater
Suspend/review treatment if QTcF interval greater than 480 msec
Advise patient not to take St John's wort concurrently
Advise patient Seville (sour) orange products may increase plasma level
Advise patient that blueberry products may increase plasma level
Advise patient that cranberry products may increase plasma level
Advise patient to avoid grapefruit products
Advise patient to avoid pomegranate products
Female: Contraception required during and at least 21 days after treatment
Breastfeeding: Do not breastfeed during & for 21 days after treatment
Perform ECG before initiation of treatment. Repeat ECG on approximately day 14 of the first treatment cycle, and at the beginning of the second treatment cycle. Perform further ECGs as clinically indicated, and monitor more frequently in patients that display QTcF prolongation during treatment.
Monitor serum electrolytes before initiation of treatment, at the beginning of the first 6 cycles and as clinically indicated.
Pregnancy and Lactation
Pregnancy
Ribociclib succinate is contraindicated during pregnancy.
Use of ribociclib during pregnancy is contraindicated by the manufacturer. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Ribociclib succinate is contraindicated during breastfeeding.
Use of ribociclib when breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of ribociclib in the breast milk, however presence in human breast milk and the effects on exposed infants is unknown.
Side Effects
Abdominal pain
Abnormal liver function tests
Alopecia
Anaemia
Asthenia
Autoimmune hepatitis
Back pain
Constipation
Cough
Decreased appetite
Diarrhoea
Dizziness
Dry eyes
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Dyspnoea
Epistaxis
Erythema
Fatigue
Febrile neutropenia
Gastro-enteritis
Headache
Hepatic failure
Hepatocellular damage
Hepatotoxicity
Hypocalcaemia
Hypokalaemia
Hypophosphataemia
Increase in ALT level
Increase in AST level
Increase in creatinine
Increased lacrimation
Leucopenia
Lymphopenia
Maculopapular rash
Nausea
Neutropenia
Oropharyngeal pain
Peripheral oedema
Prolongation of QT interval
Pruritic rash
Pruritus
Pyrexia
Rash
Respiratory tract infection
Sepsis
Serum bilirubin increased
Stomatitis
Syncope
Thrombocytopenia
Toxic epidermal necrolysis
Urinary tract infections
Vertigo
Vitiligo
Vomiting
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
MHRA Drug Safety Update June 2021
Available at: https://www.mhra.gov.uk
Last accessed: 06 April 2022
Summary of Product Characteristics: Kisqali 200mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2021.
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.