Everolimus

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Generic Name of Everolimus - Learn More

Everolimus

Everolimus Precaution - What You Need to Know

Everolimus is an immunosuppressive drug that is primarily used in the treatment of various cancers, organ transplants, and specific rare conditions like tuberous sclerosis. While it is highly effective, there are several precautions that need to be taken into consideration:

- Pregnancy and breastfeeding: Everolimus is classified as a Category D drug during pregnancy, meaning it may cause harm to a developing fetus. It should not be used during pregnancy unless the potential benefit justifies the risk to the fetus. It is also excreted in breast milk, so breastfeeding is not recommended while using this medication. Women of reproductive age should use effective contraception during treatment and for at least 8 weeks after discontinuation.

- Immunosuppression: As a potent immunosuppressive agent, Everolimus increases the risk of infections, including bacterial, viral, fungal, and opportunistic infections. Regular monitoring of white blood cell counts and signs of infection is essential. In some cases, prophylactic treatment with antimicrobials may be necessary, especially in transplant patients.

- Liver and kidney function: Everolimus is metabolized in the liver, and impaired liver function can increase the concentration of the drug in the body. Dose adjustments may be required for patients with liver impairment. Similarly, caution should be used in patients with renal impairment, and drug levels should be closely monitored.

- Lung toxicity: Pulmonary adverse effects, such as interstitial lung disease (ILD) and pneumonitis, have been reported. Symptoms like cough, dyspnea, or chest pain should be immediately investigated. If lung toxicity is suspected, Everolimus should be discontinued.

- Hyperlipidemia: Everolimus can increase cholesterol and triglyceride levels. Regular monitoring of lipid profiles is recommended during treatment, and statin therapy may be required to manage hyperlipidemia.

- Oral mucositis: Mucositis, particularly oral mucositis, is a common side effect of Everolimus. Patients should be counseled on the proper oral hygiene practices and informed to report any painful oral lesions or ulcers.

Everolimus Indication - Uses and Benefits

Everolimus is approved for the treatment of several conditions, including:

- Cancer treatment: Everolimus is used in combination with other drugs for the treatment of certain types of cancer, including renal cell carcinoma (RCC), breast cancer, neuroendocrine tumors (NETs), and various other malignancies. It is primarily indicated in patients with advanced, metastatic, or refractory cancer where other treatments have failed or are not viable.

- Organ transplantation: It is commonly used as part of immunosuppressive therapy following kidney and liver transplantation to prevent organ rejection. Everolimus works by inhibiting T-cell activation, which is critical for preventing the immune system from attacking the transplanted organ.

- Tuberous sclerosis complex (TSC): Everolimus is approved for the treatment of complications related to TSC, such as renal angiomyolipomas and subependymal giant cell astrocytomas (SEGAs), which are non-cancerous tumors that can cause significant health problems.

- Off-label uses: Some off-label indications for Everolimus include the treatment of other cancers such as gastrointestinal stromal tumors (GIST) and specific types of brain tumors. It may also be used in other rare conditions that involve excessive cell growth or overactive immune responses.

Everolimus Contraindications - Important Warnings

Everolimus should not be used in certain conditions and situations due to the risk of serious complications:

- Hypersensitivity to Everolimus: Patients with a known hypersensitivity or allergy to Everolimus or any of its excipients should not use this drug. Severe allergic reactions may include rash, swelling, or anaphylaxis.

- Severe liver impairment: Everolimus is metabolized in the liver, and patients with severe hepatic impairment may experience increased drug concentrations, leading to toxicity. It is contraindicated in patients with severe liver dysfunction.

- Active infections: Given its immunosuppressive effects, Everolimus should not be used in patients with active infections. The drug can mask symptoms of infection, and further suppression of immune function can worsen the infection.

- Pregnancy: Everolimus is contraindicated in pregnancy due to its teratogenic effects. It can cause birth defects or harm the fetus, so it should be avoided during pregnancy.

- Severe renal impairment: Although mild to moderate renal impairment may be managed with dose adjustments, severe renal impairment (creatinine clearance less than 30 mL/min) is a contraindication for Everolimus due to the risk of accumulation and toxicity.

Everolimus Side Effects - What to Expect

Everolimus has a range of potential side effects, both common and severe:

- Common side effects:
- Mouth sores (oral mucositis): This is one of the most frequent side effects and can lead to painful ulcers or sores in the mouth and throat.
- Increased risk of infections: Due to immunosuppression, patients may develop respiratory, urinary tract, or fungal infections.
- Diarrhea and nausea: Gastrointestinal issues like diarrhea, nausea, and vomiting are commonly observed.
- Fatigue: Many patients report feeling tired or weak during treatment with Everolimus.
- Rash: Skin rashes are frequently seen, including acneiform rashes.

- Serious side effects:
- Pulmonary toxicity: Everolimus has been associated with severe lung problems, including pneumonitis and interstitial lung disease (ILD). Symptoms such as shortness of breath, dry cough, or chest pain should be immediately investigated.
- Liver problems: Hepatic toxicity can occur, evidenced by elevated liver enzymes or jaundice. Liver function should be closely monitored.
- Hyperlipidemia: Everolimus can increase levels of cholesterol and triglycerides, requiring lipid monitoring and management.
- Nephrotoxicity: Kidney function may deteriorate, especially in transplant patients, requiring careful monitoring of renal parameters.
- Severe allergic reactions: Although rare, some patients may experience severe reactions, including anaphylaxis, requiring immediate medical intervention.

Everolimus Pregnancy Category ID - Safety Information

4

Everolimus Mode of Action - How It Works

Everolimus is a potent inhibitor of the mTOR (mechanistic target of rapamycin) pathway, which is critical for cell growth, proliferation, and survival. By binding to the FKBP12 protein, Everolimus forms a complex that inhibits mTOR, which leads to the suppression of protein synthesis and cell cycle progression.

- Pharmacodynamics: Everolimus suppresses the activation of T-cells, thus reducing immune response and preventing organ rejection in transplant patients. Additionally, by inhibiting mTOR, Everolimus stops cancer cells from dividing and growing, making it effective in treating certain types of tumors.

- Pharmacokinetics: Everolimus is absorbed orally and undergoes extensive metabolism in the liver by the CYP3A4 enzyme. Its elimination half-life is around 30 hours, allowing for once-daily dosing in many patients. However, the drug's absorption can be affected by food, and it is advised to take it consistently either with or without food to ensure stable drug levels.

Everolimus Drug Interactions - What to Avoid

Everolimus interacts with several drugs and substances, which can affect its efficacy and safety:

- CYP3A4 inhibitors: Drugs that inhibit the CYP3A4 enzyme, such as ketoconazole, clarithromycin, and grapefruit juice, can increase the concentration of Everolimus in the body. This can lead to an increased risk of toxicity, so the dose of Everolimus should be reduced when used with strong CYP3A4 inhibitors.

- CYP3A4 inducers: Medications that induce CYP3A4, such as rifampin, phenytoin, and St. John’s Wort, can reduce the effectiveness of Everolimus by decreasing its plasma concentration. Dose adjustments may be required to maintain therapeutic levels.

- Live vaccines: Everolimus can reduce the immune system’s ability to respond to live vaccines, making vaccination with live vaccines dangerous during treatment. It is advisable to avoid live vaccinations while on Everolimus therapy.

- Other immunosuppressants: When combined with other immunosuppressants (e.g., cyclosporine, tacrolimus), the immunosuppressive effects may be additive, increasing the risk of infections and organ toxicity. Monitoring for signs of organ rejection, infections, and side effects is essential when using multiple immunosuppressive agents.

- Antiplatelet and anticoagulant drugs: Everolimus may increase the risk of bleeding, especially when combined with antiplatelet drugs like aspirin or anticoagulants such as warfarin. Close monitoring of bleeding times and clotting factors is recommended.

Everolimus Adult Dose - Recommended Dosage

For cancer treatment, the typical dose of Everolimus is 10 mg daily, which may be adjusted based on tolerance and specific tumor type. For organ transplant patients, Everolimus is usually prescribed in combination with other immunosuppressive agents at 0.75 mg to 1.5 mg daily, with adjustments based on blood drug levels and clinical response.

- Renal transplantation: The recommended dose is 0.75 mg daily, adjusted based on serum drug levels.
- Liver transplantation: The starting dose is typically 0.5 mg daily, titrated to maintain adequate immunosuppression without excessive toxicity.

Everolimus Child Dose - Dosage for Children

Everolimus is not recommended for use in children except for specific indications such as tuberous sclerosis complex (TSC). In the treatment of TSC, the typical pediatric dose for children aged 2 years and older is 4.5 mg/m² once daily, with adjustments based on body surface area. Dosing should be guided by blood drug levels and response to treatment.

Everolimus Renal Dose - Dosage for Kidney Conditions

For patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min), dose adjustments are not generally required. However, patients with severe renal impairment (creatinine clearance <30 mL/min) should be closely monitored, as they are at higher risk of Everolimus accumulation and potential toxicity. In such cases, dose reductions and frequent renal function monitoring may be needed.