Comprehensive Guide to Everolimus: Uses, Dosage, Side Effects, and More
What is Everolimus?
Overview of Everolimus
Generic Name: Everolimus
Brand Name: Afinitor, Zortress, generics
Drug Group: mTOR inhibitor (immunosuppressant, antineoplastic)
Commonly Used For
- Treat advanced cancers.
- Prevent organ transplant rejection.
- Manage tuberous sclerosis complex (TSC).
Key Characteristics
Form: Oral tablets (2.5 mg, 5 mg, 10 mg) or dispersible tablets (e.g., Afinitor Disperz) (detailed in Dosage section).
Mechanism: Inhibits mTOR, reducing cell proliferation and immune activity.
Approval: FDA-approved (2009 for Afinitor, 2010 for Zortress) and EMA-approved for multiple indications.
Indications and Uses of Everolimus
Everolimus is indicated for a wide range of conditions, leveraging its mTOR inhibition to control cell growth and immune responses:
Advanced Renal Cell Carcinoma (RCC): Treats advanced RCC after failure of sunitinib or sorafenib, improving progression-free survival, per oncology guidelines.
Pancreatic Neuroendocrine Tumors (PNET): Manages unresectable or metastatic PNET, reducing tumor size, supported by clinical trials.
Breast Cancer (HR+/HER2-): Treats advanced hormone receptor-positive, HER2-negative breast cancer with exemestane, enhancing response rates, per oncologic research.
Subependymal Giant Cell Astrocytoma (SEGA) with TSC: Controls SEGA in TSC patients, reducing seizure frequency, used in pediatric neurology.
Renal Angiomyolipoma with TSC: Treats renal angiomyolipomas in TSC, preventing hemorrhage, supported by nephrology studies.
Kidney Transplant Rejection Prevention: Prevents acute rejection in kidney transplant recipients, used with reduced cyclosporine doses, per transplant protocols.
Heart Transplant Rejection Prevention: Manages rejection in heart transplant patients, reducing vasculopathy risk, with cardiology evidence.
Lung Transplant Rejection Prevention: Investigated off-label to prevent rejection in lung transplants, improving graft survival, supported by pulmonology research.
Hepatocellular Carcinoma (HCC): Explored off-label for advanced HCC, stabilizing disease in select patients, with hepatology data.
Lymphangioleiomyomatosis (LAM): Treats LAM associated with TSC, improving lung function, with emerging pulmonology evidence.
Gastrointestinal Stromal Tumors (GIST): Used off-label in imatinib-resistant GIST, enhancing control, supported by gastrointestinal oncology studies.
Meningioma: Investigated off-label for recurrent meningioma, reducing tumor growth, with neurosurgery research.
Dosage of Everolimus
Dosage for Adults
Advanced RCC or PNET:
- 10 mg once daily, with or without food, adjusted for tolerability.
Breast Cancer (HR+/HER2-):
- 10 mg once daily with exemestane, with dose reduction if needed.
SEGA or Renal Angiomyolipoma with TSC:
- 10 mg once daily or titrated to maintain trough levels (5–15 ng/mL).
Kidney Transplant Rejection Prevention:
- Initial: 0.75 mg twice daily (1.5 mg total), adjusted to target trough levels (3–8 ng/mL).
Dosage for Children
SEGA with TSC (1–17 years):
- 4.5 mg/m² once daily, titrated to maintain trough levels (5–15 ng/mL), under pediatric specialist supervision.
Not recommended under 1 year.
Dosage for Pregnant Women
Pregnancy Category C: Avoid unless benefits outweigh risks (e.g., life-threatening cancer). Consult an obstetrician, with fetal monitoring.
Dosage Adjustments
Renal Impairment: No adjustment needed; monitor in severe cases (CrCl <30 mL/min).
Hepatic Impairment: Mild (Child-Pugh A): Reduce to 7.5 mg/day; moderate (Child-Pugh B): 5 mg/day; severe (Child-Pugh C): 2.5 mg/day or avoid.
Elderly: Start with 5 mg once daily; increase cautiously with monitoring.
Concomitant Medications: Adjust if combined with CYP3A4 inducers/inhibitors (e.g., rifampin, ketoconazole), altering levels.
Additional Considerations
- Take this active ingredient consistently with or without food, using a glass of water.
- Monitor trough levels regularly to optimize efficacy and minimize toxicity.
How to Use Everolimus
Administration:
- Swallow tablets whole with water, with or without food; disperse tablets in water for patients unable to swallow (e.g., Afinitor Disperz).
- Take at the same time daily for consistency.
Timing: Use once daily, preferably in the morning or evening, as directed.
Monitoring: Watch for stomatitis, infections, or signs of pneumonitis (e.g., cough).
Additional Tips:
- Store at 20–25°C (68–77°F), protecting from moisture and light.
- Keep out of reach of children due to toxicity risk.
- Report severe rash, shortness of breath, or signs of infection immediately.
Contraindications for Everolimus
Hypersensitivity: Patients with a known allergy to Everolimus or mTOR inhibitors.
Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to toxicity risk.
Active Infections: Avoid in untreated systemic infections.
Warnings & Precautions for Everolimus
General Warnings
Immunosuppression: Risk of infections (e.g., pneumonia, TB); use prophylaxis if needed.
Non-Infectious Pneumonitis: Risk of interstitial lung disease; monitor respiratory symptoms.
Stomatitis: Frequent oral ulcers; use alcohol-free mouthwash.
Renal Failure: Risk in transplant patients; monitor kidney function.
Angioedema: Risk with ACE inhibitors; discontinue if swelling occurs.
Additional Warnings
Hyperlipidemia: Increases cholesterol/triglycerides; manage with statins if needed.
Thrombotic Events: Rare risk of deep vein thrombosis; assess mobility.
Wound Healing Complications: Delayed healing post-surgery; time administration.
Skin Reactions: Rash or acneiform dermatitis; use topical treatments.
Hypersensitivity Reactions: Rare anaphylaxis; discontinue if severe.
Use in Specific Populations
Pregnancy: Category C; avoid unless critical; use contraception.
Breastfeeding: Avoid due to potential toxicity; monitor infant.
Elderly: Higher risk of toxicity; start with lower doses.
Children: Limited to 1+ years for TSC; supervise closely.
Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.
Additional Precautions
- Inform your doctor about liver disease, infections, or recent surgery before starting this medication.
- Avoid grapefruit juice, which inhibits CYP3A4 metabolism.
Overdose and Management of Everolimus
Overdose Symptoms
- Nausea, diarrhea, or stomatitis.
- Severe cases: Pneumonitis, renal failure, or immunosuppression-related infections.
- Fatigue, headache, or rash as early signs.
- Seizures with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer IV fluids, monitor vital signs, and treat infections.
Specific Treatment: No antidote; manage symptoms and adjust dose; consider temporary discontinuation.
Monitor: Check lung function, kidney parameters, and blood counts for 48–72 hours.
Additional Notes
- Overdose risk is low; store securely.
- Report persistent symptoms (e.g., cough, swelling) promptly.
Side Effects of Everolimus
Common Side Effects
- Stomatitis (20–40%, managed with oral care)
- Rash (15–30%, relieved with moisturizers)
- Fatigue (10–25%, decreases with rest)
- Diarrhea (10–20%, controlled with diet)
- Nausea (5–15%, reduced with antiemetics)
These effects may subside with dose adjustment.
Serious Side Effects
Seek immediate medical attention for:
- Pulmonary: Non-infectious pneumonitis or pulmonary fibrosis.
- Infectious: Opportunistic infections or sepsis.
- Renal: Acute kidney injury or proteinuria.
- Metabolic: Hyperlipidemia, hyperglycemia, or hypophosphatemia.
- Allergic: Rash, angioedema, or anaphylaxis.
Additional Notes
- Regular monitoring for lung function, kidney health, and lipid levels is advised.
- Report any unusual symptoms (e.g., persistent cough, yellow skin) immediately to a healthcare provider.
Drug Interactions with Everolimus
This active ingredient may interact with:
- CYP3A4 Inhibitors/Inducers: Alters levels (e.g., ketoconazole, rifampin); adjust dose.
- P-Glycoprotein Inhibitors: Increases exposure (e.g., verapamil); monitor.
- Antifungals: Enhances toxicity (e.g., itraconazole); reduce dose.
- Statins: Increases myopathy risk; use alternatives.
- Vaccines: Reduces efficacy of live vaccines; avoid.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this mTOR inhibitor as prescribed for cancer or transplant, following the exact schedule.
Monitoring: Report stomatitis, cough, or signs of infection immediately.
Lifestyle: Avoid sun exposure; use sunscreen and protective clothing.
Diet: Take with or without food; avoid grapefruit or pomegranate juice.
Emergency Awareness: Know signs of pneumonitis or kidney issues; seek care if present.
Follow-Up: Schedule regular check-ups every 1–3 months to monitor drug levels, lung, and kidney health.
Pharmacokinetics of Everolimus
Absorption: Well-absorbed orally (peak at 1–2 hours); enhanced with food (high-fat meals increase exposure).
Distribution: Volume of distribution ~128 L; 74% protein-bound.
Metabolism: Hepatic via CYP3A4 to inactive metabolites.
Excretion: Primarily fecal (80%) as metabolites; renal (5%); half-life 30 hours.
Half-Life: 30 hours, with steady-state achieved in 7 days.
Pharmacodynamics of Everolimus
This drug exerts its effects by:
Inhibiting mTOR complex 1 (mTORC1), blocking cell cycle progression and angiogenesis.
Suppressing T-cell proliferation, preventing transplant rejection.
Reducing tumor growth in cancers like RCC and PNET.
Exhibiting dose-dependent risks of pneumonitis and immunosuppression.
Storage of Everolimus
- Temperature: Store at 20–25°C (68–77°F); protect from moisture and light.
- Protection: Keep in original container, away from heat sources.
- Safety: Store in a locked container out of reach of children due to toxicity risk.
- Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Everolimus treat?
A: This medication treats cancers and prevents transplant rejection.
Q: Can this active ingredient cause mouth sores?
A: Yes, stomatitis may occur; use mouthwash.
Q: Is Everolimus safe for children?
A: Yes, for 1+ years with TSC, with a doctor’s guidance.
Q: How is this drug taken?
A: Orally as tablets once daily, as directed.
Q: How long is Everolimus treatment?
A: Varies by condition, often long-term.
Q: Can I use Everolimus if pregnant?
A: No, avoid unless critical; consult a doctor.
Regulatory Information for Everolimus
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 2009 (Afinitor) for RCC, 2010 (Zortress) for transplant, with expansions for PNET, breast cancer, and TSC.
European Medicines Agency (EMA): Approved for multiple indications including cancer and transplant.
Other Agencies: Approved globally for oncology and immunosuppression; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Afinitor (Everolimus) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Everolimus Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Everolimus: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Everolimus.
- WHO’s consideration of Everolimus for cancer and transplant therapy.
- Journal of Clinical Oncology. (2022). Everolimus in Neuroendocrine Tumors.
- Peer-reviewed article on Everolimus efficacy (note: access may require a subscription).
