Cipla Everolimus Rolimus 10mg

[Drug Name]

Generic Name: Everolimus Tablets

Brand Name: Everolimus Tablets (Afinitor)

English Name: Everolimus Tablets

Full Pinyin Code: YiWeiMoSiPian (FeiNiTuo)

[Main Ingredient] Everolimus.

[Composition]

Chemical Name: 40-O-(2-hydroxyethyl)-rapamycin

Molecular Formula: C53H83NO14

[Description] This product is a white or slightly yellowish tablet.

[Indications/Therapeutic Uses]

Renal Cell Carcinoma: Everolimus is indicated for patients with advanced renal cell carcinoma, particularly those whose disease has progressed following prior treatment with sunitinib or sorafenib. By inhibiting the mTOR signaling pathway, it blocks the growth, proliferation, and angiogenesis of tumor cells, thereby exerting an anti-tumor effect and extending the patient's progression-free survival.

Pancreatic Neuroendocrine Tumors: For unresectable, locally advanced, or metastatic pancreatic neuroendocrine tumors—specifically when tumor growth is evident or symptoms are present—everolimus serves as an effective treatment option. It controls the metabolism and proliferation of tumor cells, stabilizes the disease, improves the patient's quality of life, and extends survival time.

Gastrointestinal or Lung Neuroendocrine Tumors: Everolimus may be used to treat unresectable, locally advanced, or metastatic neuroendocrine tumors of gastrointestinal or pulmonary origin. For these tumors, which originate from neuroendocrine cells, everolimus modulates cellular signaling to inhibit tumor growth and dissemination, thereby providing an effective therapeutic intervention for patients.

Breast Cancer: Everolimus, in combination with exemestane, is indicated for the treatment of advanced breast cancer in postmenopausal women with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) disease, particularly in patients whose disease has progressed following treatment with letrozole or anastrozole. It helps overcome resistance to endocrine therapy by inhibiting the mTOR pathway and blocking the downstream signaling of estrogen receptors, thereby suppressing the growth of tumor cells. Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA): For patients with TSC accompanied by SEGA who do not require immediate surgical intervention, Everolimus may be used for treatment. It inhibits the abnormal cell proliferation associated with TSC, reduces tumor volume, alleviates symptoms, and lowers the need for—as well as the risks associated with—surgery.

TSC-Associated Renal Angiomyolipoma: Everolimus may be used to treat TSC-associated renal angiomyolipoma in patients who do not require immediate surgical intervention. It inhibits the growth of tumor cells, controls tumor progression, reduces tumor-related complications, preserves renal function, and improves the patient's quality of life.

[Specifications] 10 mg × 10 tablets

[Dosage and Administration]

Administration

Everolimus is generally administered orally. It is available in various tablet strengths, including 1 mg, 2.5 mg, 5 mg, and 10 mg. Tablets should be swallowed whole and must not be chewed or crushed. For patients unable to swallow tablets, the tablets may be dispersed in water or apple juice; stir gently until completely dispersed, then consume immediately.

Dosage

Advanced Renal Cell Carcinoma; Pancreatic Neuroendocrine Tumors; Gastrointestinal or Lung Neuroendocrine Tumors

The recommended dosage is 10 mg once daily. It should be taken at the same time each day, with or without food.

Breast Cancer

When used in combination with Exemestane, the recommended dosage of Everolimus is also 10 mg once daily.

TSC-Associated Subependymal Giant Cell Astrocytoma (SEGA)

The initial dosage is determined based on the patient's body surface area (BSA), typically 4.5 mg/m² once daily. Dosage adjustments should be made based on the drug's trough concentration, with a target trough concentration range of 5–10 ng/mL.

TSC-Associated Renal Angiomyolipoma

The recommended initial dosage is 10 mg once daily. Dose adjustment should also be guided by trough concentrations, with a target trough concentration of 5–10 ng/mL.

**Dose Adjustment**

**Renal Impairment:** No dose adjustment is required for patients with mild renal impairment; for patients with moderate renal impairment, the recommended starting dose is 5 mg/day; for patients with severe renal impairment or those undergoing dialysis, the recommended starting dose is 2.5 mg/day, which may subsequently be adjusted based on individual tolerability and therapeutic response.

**Hepatic Impairment:** For patients with mild hepatic impairment, the recommended starting dose is 7.5 mg/day; for patients with moderate hepatic impairment, the recommended starting dose is 5 mg/day; use in patients with severe hepatic impairment is not recommended unless the potential benefits outweigh the risks.

**Adverse Reactions:** If adverse reactions occur during treatment, it may be necessary to temporarily interrupt administration, reduce the dose, or permanently discontinue the drug. In the event of non-hematologic adverse reactions, depending on severity, a dose reduction to 5 mg/day or 2.5 mg/day may be considered; in the event of hematologic adverse reactions, dose adjustment or temporary interruption of treatment is also required based on the specific clinical situation.

**[Adverse Reactions]** 1. **Advanced RCC:** The most common adverse reactions (incidence ≥30%) are stomatitis, infections, asthenia, fatigue, cough, and diarrhea. 2. **SEGA:** The most common adverse reactions (incidence ≥30%) are stomatitis, upper respiratory tract infection, sinusitis, otitis media, and pyrexia.

**[Contraindications]** Hypersensitivity to everolimus, to other rapamycin derivatives, or to any component of the excipients.

**[Precautions]** 1. **Non-infectious Pneumonitis:** Monitor for clinical symptoms or radiologic changes; fatal cases have occurred. Manage by reducing the dose or discontinuing the drug until symptoms resolve, and consider the use of corticosteroids. 2. **Infections:** Increased risk of infection; some cases have been fatal. Monitor for signs and symptoms, and treat promptly. 3. **Oral Ulceration:** Oral ulcers, stomatitis, and oral mucositis are common. Management includes the use of alcohol-free or peroxide-free mouthwashes and topical treatments. 4. Laboratory Test Changes: Elevations in serum creatinine, blood glucose, and lipids may occur. Decreases in hemoglobin, neutrophils, and platelets may also occur. Monitor renal function, blood glucose, lipids, and hematologic parameters prior to treatment and periodically thereafter. 5. Immunizations: Avoid live vaccines and close contact with individuals who have recently received live vaccines. 6. Use in Pregnancy: Fetal harm may occur when administered to pregnant women. Advise women of the potential risk to the fetus. Please read the package insert carefully and use strictly as directed by a physician.

[Pediatric Use] Not established.

[Geriatric Use] Not established.

[Use in Pregnant and Lactating Women] Discontinue the drug or discontinue nursing, taking into account the importance of the drug to the mother.

[Drug Interactions] 1. Strong CYP3A4 Inhibitors: Avoid concomitant use. 2. Moderate CYP3A4 and/or PgP Inhibitors: If concomitant use is necessary, use with caution and reduce the dose of AFINITOR. 3. Strong CYP3A4 Inducers: Avoid concomitant use. If concomitant use cannot be avoided, increase the dose of AFINITOR.

[Overdosage] Not established.

[Pharmacology and Toxicology] Not established.

[Pharmacokinetics] Not established.

[Storage] Keep tightly closed.

[Packaging] 10 tablets per box.

[Shelf Life] 24 months.

Product Specifications

Product Name: Cipla Finitor (Everolimus Tablets) 10mg x 10 Tablets [Everolimus / Rolimus 10mg]

Common Name: Finitor

Composition: The active ingredient of this product is Everolimus.

Dosage Form: Tablets

Specification: 10 tablets

Manufacturer: Cipla Pharmaceuticals

Indications: Everolimus is indicated for the treatment of the following patients:

1. Adult patients with advanced renal cell carcinoma whose disease has progressed despite prior treatment with sunitinib or sorafenib.

2. Adult patients with unresectable, locally advanced or metastatic, well-differentiated (moderately differentiated or highly differentiated) progressive pancreatic neuroendocrine tumors. 3. Adult and pediatric patients with Tuberous Sclerosis Complex (TSC)-associated Subependymal Giant Cell Astrocytoma (SEGA) who require therapeutic intervention but are not candidates for surgical resection. The efficacy of this product is primarily demonstrated by durable objective response (i.e., reduction in SEGA tumor volume). It has not been demonstrated whether patients with TSC-associated SEGA experience improvement in disease-related symptoms or increased overall survival.

**Dosage and Administration:** Treatment with this product should be initiated and supervised by a physician experienced in the management of oncology or Tuberous Sclerosis Complex.

**Advanced Renal Cell Carcinoma and Advanced Pancreatic Neuroendocrine Tumors**

**Recommended Dose:**

The recommended dose of this product is 10 mg once daily.

This product is administered orally once daily, taken at the same time each day, and may be taken with or without food (see [Pharmacokinetics]).

The tablets should be swallowed whole with a glass of water; they should not be chewed or crushed. For patients unable to swallow tablets, place the tablet in a glass of water (approximately 30 mL) immediately prior to administration, and gently stir until completely dispersed (this takes approximately 7 minutes); administer immediately. Rinse the glass with the same volume of water and drink the rinse completely to ensure that the full dose is administered.

Treatment should be continued as long as clinical benefit is observed or until intolerable toxicity occurs.

**Dose Adjustment:**

**Management of Adverse Reactions**

Management of severe and/or intolerable adverse reactions may require temporary dose reduction and/or interruption of treatment with this product. If dose reduction is required, the recommended dose is approximately half of the previously administered dose (see [Precautions]). If the dose is reduced below the lowest available tablet strength, alternate-day dosing should be considered.

Table 1 summarizes recommendations for dose reduction, interruption, or discontinuation of treatment with this product in patients experiencing adverse reactions, along with recommendations for routine management. Management should be guided by an individual patient's benefit-risk assessment and the clinical judgment of the treating physician.

**Severity Grading:** Grade 1 = Mild symptoms; Grade 2 = Moderate symptoms; Grade 4 = Life-threatening symptoms. If a dose reduction is required, the recommended dose is approximately 50% of the previously administered dose.

Activities of Daily Living (ADL): When managing stomatitis, avoid using products containing hydrogen peroxide, iodine, or thyme derivatives, as these ingredients may exacerbate oral ulcers.

Renal Impairment: Clinical studies of this product have not been conducted in patients with reduced renal function. Renal impairment is not expected to affect drug exposure; therefore, dose adjustment of everolimus is not recommended in patients with renal impairment (see [Pharmacokinetics]).

Hepatic Impairment: Hepatic impairment increases everolimus exposure (see [Precautions]). Dose adjustments should be made as follows:

Mild Hepatic Impairment (Child-Pugh Class A): The recommended dose is 7.5 mg/day; if not well tolerated, the dose may be reduced to 5 mg/day.

Moderate Hepatic Impairment (Child-Pugh Class B): The recommended dose is 5 mg/day; if not well tolerated, the dose may be reduced to 2.5 mg/day.

Severe Hepatic Impairment (Child-Pugh Class C): If the anticipated benefits outweigh the risks, a dose of 2.5 mg once daily may be administered, but this dose should not be exceeded.

During the course of treatment, if the patient's hepatic function status (Child-Pugh classification) changes, the dose should be adjusted accordingly.

CYP3A4 and/or P-glycoprotein (PgP) Inhibitors

Avoid the use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) (see [Precautions] and [Drug Interactions]).

Exercise caution when co-administering with moderate CYP3A4 and/or PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem). If a patient requires concomitant use of moderate CYP3A4 and/or PgP inhibitors, the dose of this product may be reduced to 2.5 mg once daily. It is expected that this reduced dose will adjust the Area Under the Curve (AUC) to within the range observed in the absence of inhibitors. Based on patient tolerability, an increase in the dose of this product from 2.5 mg to 5 mg may be considered. If the moderate inhibitor is discontinued, a washout period of approximately 2–3 days should be allowed before increasing the dose of this product. Upon discontinuation of the moderate inhibitor, the dose of this product should be returned to the level used prior to the concomitant use of the moderate CYP3A4 and/or PgP inhibitor.

During treatment, the consumption of grapefruit, grapefruit juice, and other foods known to inhibit cytochrome P450 and PgP activity should be avoided.

**Strong CYP3A4 Inducers**

Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital) should be avoided. If a patient requires concomitant use of strong CYP3A4 inducers, a dose escalation of this product in 5 mg increments—from 10 mg once daily up to 20 mg once daily—should be considered. Based on pharmacokinetic data, it is expected that this increased dose will adjust the AUC to within the range observed in the absence of inducers. However, there are currently no clinical data regarding dose adjustment in patients receiving strong CYP3A4 inducers. If the strong inducer is discontinued, the dose of this product should be returned to the level used prior to the concomitant use of the strong CYP3A4 inducer (see [Precautions] and [Drug Interactions]).

St. John’s wort (*Hypericum perforatum*) may unexpectedly reduce everolimus exposure and should be avoided.

**Tuberous Sclerosis Complex-Associated Subependymal Giant Cell Astrocytoma (TSC-associated SEGA)**

**Recommended Dosage**

The recommended starting dose is 4.5 mg/m² once daily. This product should be administered under the guidance of a specialist experienced in the treatment of Tuberous Sclerosis Complex and its associated Subependymal Giant Cell Astrocytoma. Dosage is individualized based on Body Surface Area (BSA, m²). BSA is calculated using the Dubois formula, where body weight (W) is measured in kilograms and height (H) is measured in centimeters: BSA = (W⁰.⁴²⁵ × H⁰.⁷²⁵) × 0.007184.

For patients with severe hepatic impairment (Child-Pugh Class C) or those requiring concomitant use of moderate CYP3A4 and/or PgP inhibitors, the recommended starting dose is 2.5 mg/m² once daily (see [Dosage and Administration] "Dose Adjustment"). For patients requiring concomitant use of strong CYP3A4 inducers, the recommended starting dose is 9 mg/m² once daily (see [Dosage and Administration] "Dose Adjustment"). Please round the calculated dose to the nearest available strength of this product.

Subsequent dosing should be guided by therapeutic drug monitoring (see [Dosage and Administration] "Therapeutic Drug Monitoring"). If necessary, the dose may be adjusted at 2-week intervals to achieve a trough concentration of 5–15 ng/mL (see [Dosage and Administration] "Dose Adjustment" and "Therapeutic Drug Monitoring").

Continue treatment until disease progression or the occurrence of intolerable toxicity. The optimal duration of treatment is not yet known.

Therapeutic Drug Monitoring

Routine monitoring of whole blood trough concentrations of everolimus should be performed for all patients. Whenever possible, the same analytical method and laboratory should be used for therapeutic drug monitoring throughout the course of treatment.

Trough concentrations should be assessed approximately 2 weeks after initiating treatment, after any dose adjustment, after initiating or adjusting concomitant CYP3A4 and/or PgP inducers or inhibitors, or following any change in hepatic function. Once a stable dose has been established, trough concentrations should be monitored every 3–6 months during treatment for patients whose body surface area changes; for patients...