Yulareb

ABEMACICLIB (YULAREB) — CLINICIAN SUMMARY

🔴 RED FLAG (IMPORTANT) INFORMATION

(Main things to consider when prescribing and monitoring)

• Diarrhoea is very common and can be severe — early loperamide and dose interruption are essential.

• Neutropenia and infection risk — check FBC regularly; febrile neutropenia can occur.

• Hepatotoxicity — monitor ALT/AST closely; severe liver injury possible.

• Interstitial lung disease / pneumonitis — new cough or dyspnoea requires urgent assessment and discontinuation if confirmed.

• Venous thromboembolism (VTE) — increased risk; monitor for leg swelling, chest pain, SOB.

• CYP3A interactions are clinically significant — strong inhibitors require dose reduction; inducers reduce efficacy.

• Creatinine rise is common but not true renal failure — due to transporter inhibition.

1. BASIC INFORMATION

Generic name: Abemaciclib
Brand name: YULAREB
Drug class: CDK4/6 inhibitor
Formulation: Oral film-coated tablets
Strengths: 50 mg, 100 mg, 150 mg, 200 mg

2. INDICATIONS

HR-positive, HER2-negative breast cancer

Early breast cancer:

• High-risk, node-positive disease

• Used with endocrine therapy

Advanced / metastatic breast cancer:

• First-line with aromatase inhibitor

• After progression with fulvestrant

• Monotherapy after endocrine therapy and chemotherapy failure

3. DOSING & ADMINISTRATION

Combination therapy (with AI or fulvestrant):

• 150 mg twice daily

Monotherapy:

• 200 mg twice daily

Fulvestrant (if used):

• 500 mg IM on Days 1, 15, 29, then monthly

Administration:

• Oral, with or without food

• Swallow tablets whole (do not crush or split)

• If a dose is missed, skip and take the next scheduled dose

• Do not double doses

4. DOSE MODIFICATIONS

Dose levels:

Starting dose

• Combination therapy: 150 mg twice daily

• Monotherapy: 200 mg twice daily

1st dose reduction

• Combination: 100 mg twice daily

• Monotherapy: 150 mg twice daily

2nd dose reduction

• Combination: 50 mg twice daily

• Monotherapy: 100 mg twice daily

3rd dose reduction

• Combination: Discontinue

• Monotherapy: 50 mg twice daily

If unable to tolerate lowest dose:

• Permanently discontinue

5. CO-MEDICATIONS

Required combinations:

• Aromatase inhibitor or fulvestrant

• Add GnRH agonist in pre- or perimenopausal patients

Supportive care commonly required:

• Antidiarrhoeals (e.g. loperamide)

• Antiemetics as needed

6. CONTRAINDICATIONS

• Hypersensitivity to abemaciclib or excipients

• Pregnancy and breastfeeding

• Concomitant use with strong CYP3A inhibitors (e.g. ketoconazole) if dose adjustment not possible

7. MONITORING REQUIREMENTS

Baseline and during treatment:

FBC:

• Baseline

• Every 2 weeks for first 2 months

• Monthly thereafter

Liver function tests (ALT, AST, bilirubin):

• Baseline and regularly

Renal function:

• Baseline and periodically

• Expect creatinine rise without true renal impairment

Clinical monitoring:

• Diarrhoea severity

• Signs of infection or febrile neutropenia

• New or worsening cough/dyspnoea (ILD)

• Signs of VTE (leg swelling, chest pain, shortness of breath)

8. SIDE EFFECTS

Very common (>10%):

• Diarrhoea

• Neutropenia, leukopenia

• Nausea, vomiting

• Fatigue

• ALT/AST elevation

Common (1–10%):

• Rash

• Alopecia

• Headache, dizziness

• Decreased appetite

• Weight loss

• Infections (URTI, UTI)

Serious (<5%):

• Interstitial lung disease / pneumonitis

• Venous thromboembolism

• Febrile neutropenia

• Severe hepatotoxicity (rare)

9. DRUG INTERACTIONS

CYP3A inhibitors (e.g. ketoconazole, clarithromycin):

• Increase abemaciclib levels → dose reduction required

CYP3A inducers (e.g. rifampicin, carbamazepine, phenytoin):

• Reduce efficacy → avoid

Avoid grapefruit and grapefruit juice.

Compatible with:

• Letrozole

• Anastrozole

• Fulvestrant

• Tamoxifen

10. USE IN SPECIAL POPULATIONS

Pregnancy / breastfeeding: Contraindicated

Hepatic impairment:

• Severe impairment → reduce dosing frequency to once daily

Renal impairment:

• No dose adjustment required

Pre- or perimenopausal patients:

• Use GnRH agonist with endocrine therapy

Men:

• May impair fertility

11. DURATION OF USE / WHEN TO STOP

Continue treatment until:

• Disease progression, or

• Unacceptable toxicity

Permanently discontinue if:

• Recurrent Grade 3 or any Grade 4 toxicity despite dose reduction

• Confirmed ILD/pneumonitis

• ALT/AST >20 × ULN or bilirubin >3 × ULN

• Inability to tolerate 50 mg twice daily

12. TOXICITY MANAGEMENT (SIMPLIFIED)

Diarrhoea:

• Grade 1: Supportive care

• Grade 2: Loperamide; hold dose if >24 hours

• Grade 3: Hold, restart at reduced dose when resolved

• Grade 4: Discontinue permanently

Neutropenia:

• Grade 1–2: Continue, monitor

• Grade 3: Hold until recovery, reduce dose

• Grade 4 or febrile: Discontinue if persistent

ALT / AST elevation:

• Grade 1: Monitor

• Grade 2: Consider dose adjustment if persistent

• Grade 3: Hold, restart at reduced dose

• Grade 4: Discontinue permanently

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2024/11/Yulareb_approved_ZA_PIL_28-October-2024.pdf