Everolimus

Everolimus (AFINITOR®)

🔴 Red Flag (Important) Information

• Not interchangeable with other everolimus formulations (e.g. transplant products).

• Risk of non-infectious pneumonitis – stop treatment if moderate–severe.

• Immunosuppression → ↑ risk of serious infections (bacterial, fungal, viral).

• Severe stomatitis/mucositis is common – early prophylaxis and dose modification required.

• Avoid strong CYP3A4 inhibitors/inducers – significant exposure changes.

• Monitor glucose and lipids – hyperglycaemia and dyslipidaemia are common.

• Live vaccines contraindicated during treatment.

🔹 1. Basic Information

Generic name: Everolimus
Brand name: AFINITOR®
Drug class: mTOR (mammalian target of rapamycin) inhibitor
Formulation: Oral tablets
Strengths: 2.5 mg, 5 mg, 10 mg

Mechanism of Action:
Everolimus inhibits mTOR, a key regulator of cell growth, proliferation, angiogenesis, and metabolism → results in reduced tumour cell proliferation and angiogenesis.

🔹 2. Oncology Indications (FULL – PI-based)

AFINITOR is indicated for the treatment of adult patients with the following malignancies:

Breast Cancer

• Hormone receptor-positive, HER2-negative advanced breast cancer
  In postmenopausal women, in combination with exemestane,
  after recurrence or progression following prior non-steroidal aromatase inhibitor therapy.

Renal Cell Carcinoma (RCC)

• Advanced renal cell carcinoma,
  in patients whose disease has progressed on or after treatment with VEGF-targeted therapy.

Neuroendocrine Tumours (NETs)

Pancreatic NETs

• Unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours (pNETs)
  in adults with disease progression.

Non-functional Gastrointestinal or Lung NETs

• Unresectable or metastatic, well-differentiated, non-functional neuroendocrine tumours
  of gastrointestinal or lung origin,
  with disease progression.

🔹 3. Dosing & Administration (Oncology)

Standard dose:

• 10 mg orally once daily

Administration:

• Take consistently with or without food

• Swallow tablets whole (do not crush or chew)

• Continue until disease progression or unacceptable toxicity

🔹 4. Dose Modifications

• Stomatitis, pneumonitis, infections, metabolic toxicity:
  → Interrupt treatment ± reduce dose (to 5 mg daily or 5 mg alternate days)

• Severe or recurrent Grade 3 toxicity:
  → Resume at reduced dose after recovery

• Life-threatening toxicity:
  → Permanently discontinue

🔹 5. Contraindications

• Hypersensitivity to everolimus or other rapamycin derivatives

• Pregnancy and breastfeeding

• Concomitant use with live vaccines

🔹 6. Monitoring Requirements

• Full blood count: Baseline and periodically

• Renal function: Baseline and regularly

• Liver function tests: Baseline and regularly

• Fasting glucose & lipids: Baseline and during treatment

• Clinical assessment for pneumonitis: Ongoing

• Infection surveillance: Continuous

🔹 7. Side Effects

Very Common / Common:

• Stomatitis / oral ulcers

• Fatigue

• Rash

• Diarrhoea

• Infections

• Anaemia

• Hyperglycaemia

• Hyperlipidaemia

• Decreased appetite

Serious:

• Non-infectious pneumonitis

• Severe infections / sepsis

• Renal failure

• Haemorrhage (rare)

• Delayed wound healing

🔹 8. Drug Interactions

• Strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin): ↑ toxicity

• Strong CYP3A4 inducers (e.g. rifampicin, carbamazepine): ↓ efficacy

• Avoid grapefruit and grapefruit juice

🔹 9. Use in Special Populations

• Hepatic impairment: Dose reduction required

• Renal impairment: No initial adjustment; monitor closely

• Elderly: No dose adjustment

• Pregnancy: Contraindicated

• Breastfeeding: Contraindicated

🔹 10. Duration of Use / When to Stop

Continue treatment until:

• Disease progression, or

• Unacceptable toxicity

Permanently discontinue if:

• Severe or recurrent pneumonitis

• Life-threatening infection

• Inability to tolerate lowest effective dose

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2022/11/pi-afinitor-28-Oct-2022.pdf