phoselin Selinexor Tablets

[Drug Name] Selinexor Tablets

[English Name] Selinexor Tablets

[Specification] 20 mg; 32 tablets/box

[Manufacturer] State Pharmaceutical Factory No. 2, Lao People's Democratic Republic

[Indications]

Selinexor Tablets are used for the treatment of multiple myeloma in adults.

Selinexor Tablets are used in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma (RRMM).

Selinexor Tablets may also be used for the treatment of certain types of diffuse large B-cell lymphoma in adults.

[Dosage and Administration]

1. Selinexor Tablets are typically taken only two days per week, in combination with dexamethasone. Please strictly follow your doctor's instructions regarding dosage and schedule; take the medication at the same time on each scheduled dosing day. Your doctor will determine the duration of your treatment with Selinexor Tablets and dexamethasone.

2. Swallow Selinexor Tablets whole with a full glass of water; do not crush or chew the tablets.

3. If you vomit shortly after taking Selinexor Tablets, do not take an additional dose. Wait until your next scheduled dose time to take the medication.

4. Usual Adult Dosage for Multiple Myeloma: 80 mg taken orally on Day 1 and Day 3 of each week, continuing until disease progression or unacceptable toxicity occurs.

5. The recommended starting dose for dexamethasone is 20 mg, to be taken concurrently with Selinexor Tablets.

[Adverse Reactions]

Allergic reactions: Hives, difficulty breathing, swelling of the face, lips, tongue, or throat.

Selinexor Tablets may cause serious or life-threatening side effects. Some side effects may not appear until several days or weeks after you begin taking this medication. If you experience any of the following side effects, please contact your doctor immediately:

Persistent and severe nausea, vomiting, or diarrhea.

Loss of appetite, inability to eat, leading to weight loss.

Confusion, dizziness, fainting, or changes in mental status.

Easy bruising, unusual bleeding, or purple or red spots under the skin (petechiae). Signs of infection: Fever, chills, flu-like symptoms, cough with mucus, sores in the mouth and throat, rapid heart rate, feeling short of breath, or a blistering rash accompanied by tingling or pain on one side of the body.

Low red blood cell count (anemia): Pale skin, unusual tiredness, feeling dizzy, or cold hands and feet.

Low sodium levels: Headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, or feeling unsteady.

Common side effects of Xpovio (selinexor) tablets may include:

Fatigue, anemia, bruising or bleeding, fever, infection, cold or flu-like symptoms, low sodium levels, nausea, vomiting, loss of appetite, diarrhea, constipation, weight loss, or shortness of breath.

[Contraindications]

This product is contraindicated in patients with a known severe hypersensitivity to Xpovio (selinexor) tablets or any of their components.

[Precautions]

Thrombocytopenia: Xpovio (selinexor) tablets can cause thrombocytopenia, potentially leading to fatal bleeding. Thrombocytopenia was reported as an adverse reaction in 74% of patients; severe (Grade 3 or 4) thrombocytopenia occurred in 61% of patients treated with Xpovio. The median time to the first onset of thrombocytopenia was 22 days. Bleeding occurred in 23% of patients with thrombocytopenia; clinically significant bleeding occurred in 5% of patients with thrombocytopenia, and fatal bleeding occurred in <1% of patients. Monitor platelet counts at baseline, during treatment, and as clinically indicated. Increase the frequency of platelet count monitoring during the first two months of treatment. Administer platelet transfusions and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt and/or reduce the dose, or discontinue the drug, based on the severity of the adverse reaction.

Neutropenia: Xpovio (selinexor) tablets can cause neutropenia, potentially increasing the risk of infection. Neutropenia was reported as an adverse reaction in 34% of patients; severe (Grade 3 or 4) neutropenia occurred in 21% of patients treated with Xpovio. The median time to the first occurrence of this adverse reaction was 25 days. Febrile neutropenia was reported in 3% of patients. Monitor neutrophil counts at baseline, during treatment, and as clinically indicated. Increase the frequency of monitoring during the first two months of treatment. Monitor patients for signs and symptoms of concurrent infection and evaluate promptly. Consider supportive measures, including the use of antimicrobial agents for signs of infection and growth factors (e.g., G-CSF). Interrupt and/or reduce the dose, or discontinue the drug, based on the severity of the adverse reaction.

Gastrointestinal Toxicity: Gastrointestinal toxicity may occur in patients treated with Selinexor tablets. Nausea/vomiting was reported in 72% of patients; Grade 3 nausea occurred in 9% of patients treated with Selinexor tablets. The median time to the first onset of nausea was 3 days. Vomiting was reported in 41% of patients; Grade 3 vomiting occurred in 4% of patients treated with Selinexor tablets. The median time to the first onset of vomiting was 5 days. Administer prophylactic 5-HT3 antagonists and/or other anti-nausea medications prior to and during treatment with Selinexor tablets. Manage nausea/vomiting through dose interruption, dose reduction, and/or discontinuation of the drug. Administer intravenous fluids and electrolyte replacement to prevent dehydration in patients at risk. Use additional anti-nausea medications as clinically indicated. Diarrhea was reported in 44% of patients; Grade 3 diarrhea occurred in 6% of patients treated with Selinexor tablets. The median time to the onset of diarrhea was 15 days. Manage diarrhea through dose adjustment and/or standard anti-diarrheal agents; administer intravenous fluids to patients at risk to prevent dehydration. Anorexia/weight loss was reported in 53% of patients; Grade 3 anorexia occurred in 5% of patients treated with Selinexor tablets. The median time to the onset of anorexia was 8 days. Weight loss was reported in 47% of patients; Grade 3 weight loss occurred in 1% of patients treated with Selinexor tablets. The median time to the onset of this adverse reaction was 15 days. Monitor patient weight at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Manage anorexia and weight loss through dose adjustments, appetite stimulants, and nutritional support.

Hyponatremia: Xelinisuo tablets can cause hyponatremia; 39% of patients treated with Xelinisuo tablets experienced hyponatremia, and 22% experienced Grade 3 or 4 hyponatremia. The median time to the first onset of this adverse reaction was 8 days. Monitor sodium levels at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Correct sodium levels in the presence of concomitant hyperglycemia (serum glucose >150 mg/dL) and elevated serum paraprotein levels. Treat hyponatremia according to clinical guidelines (intravenous saline and/or salt tablets), including dietary adjustments. Interrupt and/or reduce the dose, or discontinue the drug, based on the severity of the adverse reaction.

Infections: Among patients treated with Xelinisuo tablets, 52% experienced infections of varying severity. The incidence of upper respiratory tract infections of any grade was 21%, pneumonia was 13%, and sepsis was 6%. Twenty-five percent of patients reported Grade ≥3 infections, and 4% of patients died due to infection. The most common Grade ≥3 infection was pneumonia (in 9% of patients), followed by sepsis (in 6% of patients). The median time to onset for pneumonia and sepsis was 54 days and 42 days, respectively. Most infections were not associated with neutropenia.

Neurotoxicity: Thirty percent of patients treated with Xelinisuo tablets experienced neurologic adverse reactions, including dizziness, syncope, decreased level of consciousness, and altered mental status (including confusion); 9% of patients experienced severe (Grade 3–4) adverse reactions. The median time to the first onset of a neurologic adverse reaction was 15 days. Optimize hydration status, hemoglobin levels, and concomitant medications to avoid exacerbating dizziness or altered mental status.

Embryo-Fetal Toxicity: Based on data from animal studies and its mechanism of action, Xelinisuo tablets may cause fetal harm when administered to a pregnant woman. Administration of Selinexor tablets to pregnant animals during organogenesis resulted in malformations; growth was also impaired following exposure to doses lower than the recommended clinical dose. Pregnant women are advised to be aware of the potential risks to the fetus. Women and men of reproductive potential are advised to use effective contraception during treatment with Selinexor tablets and for one week after the last dose.

[Storage]

Store below 30°C.

[Mechanism of Action]

Selinexor tablets are an orally available selective inhibitor of nuclear export. In non-clinical studies, Selinexor reversibly inhibits the nuclear export of tumor suppressor proteins (TSPs), growth regulators, and oncoprotein mRNAs by blocking Exportin 1 (XPO1). Inhibition of XPO1 by Selinexor leads to the accumulation of TSPs within the cell nucleus, a reduction in several oncoproteins (such as c-Myc and Cyclin D1), cell cycle arrest, and apoptosis of cancer cells. Selinexor has demonstrated in vitro pro-apoptotic activity in multiple myeloma cell lines, patient tumor samples, and mouse xenograft models.

[Efficacy and Safety]

The multicenter, single-arm SADAL trial evaluated 134 patients who had previously received 2 to 5 lines of systemic therapy regimens; these patients received oral Selinexor 60 mg on Days 1 and 3 of each week. The median time from the last systemic therapy to the initiation of Selinexor treatment was 5.4 months, and for patients with refractory disease, the median time was 3.6 months. Among the 134 patients, the overall response rate was 29%, with a complete response rate of 13% (18 patients). Of the 39 patients who achieved a partial or complete response, 38% maintained their response for at least 6 months, and 15% maintained their response for at least 12 months.

The Phase 2b SADAL trial was an open-label, randomized study in which investigators compared the efficacy of Selinexor monotherapy administered twice weekly (on a 28-day cycle) at doses of 60 mg versus 100 mg in this patient population. Initial data, presented at the 2018 ASH Annual Meeting, suggested an overall response rate (ORR) of 29.6% and a complete response (CR) rate of 9.6%. The response rate was 34.0% for patients with the GCB subtype and 21.1% for those with the non-GCB subtype. In the modified intention-to-treat (mITT) population, the median overall survival (OS) was 9.1 months; however, for patients who achieved a CR or partial response (PR), the median survival was improved at 29.7 months.

According to Sino-Medical, a specialized agency for international medical services, patients demonstrated profound and durable responses regardless of their DLBCL subtype. Among the 59 patients with GCB histology, the ORR was 33.9%; among the 63 patients with the non-GCB subtype, the ORR was 20.6%. Of the remaining 5 patients whose disease subtype was unclassified, one achieved a CR and two achieved a PR. Responses were typically achieved rapidly, with a median duration of response (DOR) of 9.2 months. In the overall population, the median OS was 9 months. Among patients who achieved a response, the median OS has not yet been reached.