Seleniso Instructions

一.Common name: Seleniso

Product name:Xpovio

All names: selinexor, selinexor, Xpovio

2. Indications:

1.In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma(MM) who have received at least one prior therapy.

2.In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is responsive to at least two proteasome inhibitors, at least two immunomodulators, and an antiCD38monoclonal antibody.

3.For the treatment of patients with relapsed or refractory diffuse largeB cell lymphoma(DLBCL)adult patients, including DLBCL caused by follicular lymphoma, after at least 2 systemic therapies.

Three. Dosage and usage

1.Multiple myeloma in combination with bortezomib and dexamethasone (XVd): The recommended dose of XPOVIO is 100 mg taken orally once weekly in combination with bortezomib and dexamethasone.

2.Multiple myeloma in combination with dexamethasone(Xd): The recommended dose of

3.DLBCL: The recommended dose ofOrally administered 60 mg on day 1 and day 3.

Four. Dosage form and strength

Tablets: 20mg, 40mg, 50mg, 60mg.

Five. Contraindications

None

6. Warnings and Precautions

Thrombocytopenia:Monitor platelet count throughout treatment. Manage with dose interruption or reduction and supportive care.

Neutropenia:Monitor neutrophil counts throughout treatment. Use dose interruption and/or reduction and granulocyte colony-stimulating factor.

Gastrointestinal Toxicity:Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. through dose interruption and/or reduction, antiemetics, and supportive care.

Hyponatremia:Monitor serum sodium levels throughout treatment.

Correction of concurrent hyperglycemia and high serum paraprotein levels. Management of dose interruptions, reductions, or discontinuations, and supportive care. Severe infection: Monitor the infection and treat it promptly.

Neurotoxicity:Patients are advised not to drive or engage in hazardous occupations or activities until the neurotoxicity is resolved. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.

Embryo-Fetal Toxicity:Can cause fetal harm. Inform females of reproductive potential and males with female partners of reproductive potential, potential risks to the fetus, and the use of effective contraception.

Cataracts:Cataracts may develop or worsen. Treatment of cataracts usually requires surgical removal of the cataract.

7. side effects

The most common adverse reactions(≥20%)in patients with multiple myeloma who receivedXVd were fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, weight loss, cataracts, and vomiting.

Grade 3-4laboratory abnormalities(≥10%)are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia.

The most common adverse reactions(≥20%)in patients with multiple myeloma who received

Except for laboratory abnormalities, the most common adverse reactions(incidence≥20%)are fatigue, nausea, diarrhea, decreased appetite, weight loss, constipation, vomiting and fever. Grade 3-4laboratory abnormalities(≥15%)are thrombocytopenia, lymphopenia, neutropenia, anemia and hyponatremia.

8. clinical pharmacology

1.Mechanism of action

In nonclinical studies, selinesol reversibly inhibits the nuclear export of tumor suppressor protein (tsp), growth regulators, and oncogenic protein mRNAs by blocking exportin 1 (XPO1). Selinesolinhibition of XPO1 results in the accumulation of tsp in the nucleus and several oncoproteins(< /span>For example, the reduction of c-myc and cyclin D1), cell cycle arrest and apoptosis of cancer cells. Selinesolhas demonstrated in vitro pro-apoptotic activity in multiple myeloma cells and anti-tumor activity in mouse xenograft models of multiple myeloma and diffuse large Bcell lymphoma. Combinations of selinesol and dexamethasone or bortezomib demonstrated synergistic cytotoxic effects in multiple myeloma in vitro and enhanced antitumor activity in mouse xenograft multiple myeloma models in vivo, including those resistant to proteasome inhibitors.

2.Pharmacodynamics

Increased selinesol exposure is associated with dose adjustments and an increased potential for some adverse reactions.

3.Pharmacokinetics

Absorption

CMaximum is reached within 4 hours after oral administration of XPOVIO.

The influence of food

Concomitantly take a high-fat meal (800 to 1, 000 calories, total dietary calories Approximately50%of content derived from fat)does not have a clinically significant effect onthe pharmacokinetics of selinesol.

DistributionDistribution

Cancer patients The apparent volume of distribution of selinesol is133 L. The protein binding rate of selinesol is 95%.

Elimination

After one dose of XPOVIO, the average half-life is 6 to 8 hours. The apparent total clearance rate of selinesol in cancer patients was 18.6 L/h.

Metabolism

Selenisois metabolized by CYP3A4, multiple UDP-glucuronosyltransferases(UGTs), and glutathione transferases (GSTs).

9. Used by specific groups of people

1.Pregnancy

Based on findings from animal studies and its mechanism of action, XPOVIO can cause fetal harm when administered to pregnant women. There are no data available in pregnant women regarding drug-related risks. In animal reproduction studies, administration of selinesol to pregnant rats during organogenesis resulted in structural abnormalities and growth changes at exposures below clinically recommended doses. Inform pregnant women of the risks to the fetus.

In the general U.S. population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies range from 2% to 4% and 15% to 20%, respectively.

Animal Data: In embryonic-fetal development studies in pregnant rats at doses of 0.75 mg/kg compared to the control group, 0, 0.25, 0.75 or 2 orally administered daily throughout the organogenesis process mg/kg selinesol caused incomplete or delayed ossification, skeletal variations, and reduced fetal weight (approximately 0.08 times the area under the curve in humans at the recommended dose [AUC]). Malformations, including microphthalmia, hydrops fetalis, renal malpositioning, and persistent truncus arteriosus, were observed at doses of 2mg/kg.

2.Breastfeeding

There is no information on the presence of selinesol or its metabolites in breast milk, or on its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with XPOVIO and for 1 week after the last dose.

3.Females and men of reproductive potential

XPOVIO can cause fetal harm when taken by pregnant women[See Use in Certain Populations.Verify the pregnancy status of women of reproductive potential before startingXPOVIO. Advise females of reproductive potential to use effective contraception duringXPOVIOtreatment and for 1 weeks after the last dose. Men with female partners of reproductive potential are advised to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

4.Pediatric use

The safety and effectiveness of XPOVIO in pediatric patients have not been established.

5.Medication for the Elderly

In Boston, patients receiving XPOVIO in combination with bortezomib and dexamethasoneOf the 195 patients with multiple myeloma, 56% were 65 years and older, while 17% were 75 years and older. No overall efficacy differences were observed between these patients and younger patients. When comparing patients aged 65 and older to younger patients, older patients had a higher incidence of discontinuation due to adverse reactions (28% vs. >13%), and the incidence of serious adverse reactions was higher (56% vs. 47%).

Of the 202 multiple myeloma patients treated with XPOVIO in STORM, 49%< /span>of the patients were 65 years old and above, while 11% of the patients were 75 years old and above. Compared with younger patients, there was no difference in overall efficacy in patients 65older (including75older) patients. When comparing patients aged 75 and older to younger patients, older patients had a higher incidence of discontinuation due to adverse reactions (44% vs. 27%) and a higher incidence of serious adverse reactions. High (70% vs. 58%), and the incidence of fatal adverse reactions was higher (17% vs. 9%). The cost of each box of generic drugs is about three to four thousand yuan. For details, please consult overseas pharmaceutical institutions. If you want to get more high-quality information, you can contact YaoDe. YaoDe will do its best to learn more about high-quality overseas drugs for you.

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