Abemaciclib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of abemaciclib.
Drugs List
Therapeutic Indications
Uses
Hormone receptor +ve, HER2 -ve locally advanced or metastatic breast cancer
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.
In pre or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.
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 150mg twice daily, taken as long as the patient is deriving clinical benefit from therapy, or until unacceptable toxicity occurs.
Additional Dosage Information
Missed dose
If a dose is missed or a patient vomits, administration should resume at the next scheduled time at the appropriate dose.
Dose modifications
First dose reduction
Reduce dose to 100mg twice daily.
Second dose reduction
Reduce dose to 50mg twice daily.
Management of haematologic toxicities
Grade 1 or 2: No dose adjustment required.
Grade 3: Suspend dose. When toxicity resolves to grade 2 or less, resume treatment at the same dose.
Grade 4, or recurrent grade 3: Suspend dose.When toxicity resolves to grade 2 or less, resume treatment at the next lower dose level.
If patient requires administration of blood cell growth factors: Suspend dose for a minimum of 48 hours after the last dose of blood cell growth factors. When toxicity resolves to grade 2 or less, resume treatment at the next lower dose level, unless the dose was already reduced for the toxicity that led to the use of growth factors.
Management of diarrhoea
Grade 1: No dose adjustment required.
Grade 2: If diarrhoea does not resolve to grade 1 or less within 24 hours, suspend dose. When toxicity resolves to grade 1 or less, resume treatment at the same dose.
Grade 3 or above, or grade 2 that persists at the same dose despite supportive measures: Suspend dose. When toxicity resolves to grade 1 or less, resume treatment at the next lower dose level.
Management of elevated alanine aminotransferase (ALT) or aminotransferase (AST)
Grade 1 (3 times the upper limit of normal, ULN, or less): No dose adjustment required.
Grade 2 (above 3 times ULN and up to and including 5 times ULN): No dose adjustment required.
Persistent grade 2, or grade 3 (above 5 times ULN and up to and including 20 times ULN): Suspend dose. When toxicity resolves to grade 1 or less, resume treatment at the next lower dose level.
Elevated AST and/or ALT above 3 times ULN with elevated total bilirubin above 2 times ULN, in the absence of cholestasis: Discontinue treatment.
Grade 4 (above 20 times ULN): Discontinue treatment.
Management of interstitial lung disease (ILD) and pneumonitis
Grade 1 or 2: No dose adjustment required.
Persistent or recurrent grade 2 that does not resolve to baseline or grade 1 within 7 days, despite supportive measures: Suspend dose. When toxicity resolves to grade 1 or less, resume treatment at the next lower dose level.
Grade 3 or 4: Discontinue treatment.
Management of non-haematologic toxicities
Grade 1 or 2: No dose adjustment required.
Persistent grade 2 that does not resolve to baseline or grade 1 within 7 days, despite supportive measures: Suspend dose. When toxicity resolves to grade 1 or less, resume treatment at the next lower dose level.
Grade 3 or 4: Suspend dose. When toxicity resolves to grade 1 or less, resume treatment at the next lower dose level.
Contraindications
Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Precautions and Warnings
Haemoglobin concentration below 8g / dL
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9 / L at baseline
End stage renal disease
Glucose-galactose malabsorption syndrome
Lactose intolerance
Renal dialysis
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Severe renal impairment
Reduce dose in patients with severe hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Maintain adequate hydration during therapy
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor serum transaminases before treatment
Perform full blood count before treatment
Monitor blood counts every 2 weeks for 2 months, then monthly for 2 months
Monitor for signs and symptoms of interstitial lung disease
Monitor for signs and symptoms of pneumonitis
Monitor patient for signs of serious infection
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor transaminases every 2 weeks for 2 months, then monthly for 2 months
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Suspend treatment if transaminases >3 x ULN persists or recurs
Consider dose interruption & reduction in non-haematological toxicity
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if grade 3 or greater interstitial lung disease occurs
Discontinue permanently if AST or ALT level exceeds 20 x ULN
Discontinue treatment if grade 3 or greater pneumonitis occurs
Interrupt treatment if ALT or AST > 5 x ULN
Suspend if persistent/recurrent grade 2 pneumonitis/ILD occurs
Suspend treatment if grade 2 diarrhoea occurs
Suspend treatment if grade 3 or greater haematological toxicity
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Contraception required during and for 3 weeks after treatment
Pregnancy and Lactation
Pregnancy
Abemaciclib is contraindicated during pregnancy.
The manufacturer does not recommend using abemaciclib during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Abemaciclib is contraindicated during breastfeeding.
The manufacturer does not recommend breastfeeding whilst taking abemaciclib. The presence of abemaciclib in human breast milk and the effects on exposed infants are unknown.
Side Effects
Alanine aminotransferase increased
Alopecia
Anaemia
Aspartate aminotransferase increased
Decreased appetite
Diarrhoea
Dizziness
Dry skin
Dysgeusia
Fatigue
Febrile neutropenia
Increased lacrimation
Infections
Interstitial lung disease
Leukopenia
Lymphopenia
Muscle weakness
Nausea
Neutropenia
Pneumonitis
Pruritus
Pyrexia
Rash
Thrombocytopenia
Thromboembolism
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: December 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: Verzenios film-coated tablets. Eli Lilly and Company Limited. Revised October 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.