Nexpovio (Tablets) Instructions for Use

Marketing Authorization Holder

Stemline Therapeutics B.V. (Netherlands)

Manufactured By

Catalent CTS LLC (USA)

ATC Code

L01XX66 (Selinexor)

Active Substance

Selinexor

Dosage Form

Nexpovio

Film-coated tablets, 20 mg

Dosage Form, Packaging, and Composition

Film-coated tablets

2 pcs. – blister packs (4 pcs.) – cardboard packs (8 pcs.) – Not specified
3 pcs. – blister packs (4 pcs.) – cardboard packs (12 pcs.) – Not specified
4 pcs. – blister packs (4 pcs.) – cardboard packs (16 pcs.) – Not specified
5 pcs. – blister packs (4 pcs.) – cardboard packs (20 pcs.) – Not specified
8 pcs. – blister packs (4 pcs.) – cardboard packs (32 pcs.) – Not specified

Pharmacotherapeutic Group

Antineoplastic agents; other antineoplastic agents

Pharmacological Action

Selinexor is a reversible covalent selective inhibitor of nuclear export (SINE) that specifically blocks exportin 1 (XPO1).

XPO1 is the main mediator of the nuclear export of many transport proteins, including tumor suppressor proteins (TSP), growth regulators, and mRNAs of proteins that stimulate cell growth (oncogenic proteins).

Inhibition of XPO1 by selinexor leads to significant accumulation of TSP in the cell nucleus, cell cycle arrest, reduction in the levels of several oncogenic proteins such as c-Myc and cyclin D1, and apoptosis of tumor cells.

The combined use of selinexor with dexamethasone and/or bortezomib demonstrated synergism of cytotoxic effects in multiple myeloma in vitro and increased antitumor activity in multiple myeloma xenograft models in vivo, including those resistant to proteasome inhibitors.

Pharmacokinetics

After oral administration of selinexor, C_max in plasma is reached within 4 hours.

The binding of selinexor to human plasma proteins is 95%.

In a population pharmacokinetic analysis of cancer patients, the apparent V_d of selinexor was 133 L.

Selinexor is metabolized with the involvement of the CYP3A4 isoenzyme, numerous UDP-glucuronosyltransferases (UGT), and glutathione-S-transferase.

After a single dose of selinexor 80 mg, the mean T_1/2 is 6-8 hours.

In a population pharmacokinetic analysis of cancer patients, the apparent total clearance of selinexor was 18.6 L/h.

Indications

Treatment of patients with multiple myeloma who have received at least one prior line of therapy (in combination with bortezomib and dexamethasone); for the treatment of patients with multiple myeloma who have previously received at least four lines of therapy, and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have documented disease progression on the last line of therapy (in combination with dexamethasone).

Dosage Regimen

Administer Nexpovio orally once weekly on the same day each week, as part of combination therapy.

Take tablets with water. Swallow tablets whole; do not break, crush, or chew.

For combination therapy with bortezomib and dexamethasone, the recommended dose is 100 mg once weekly on Day 1 of each week for the first 4 weeks of each 5-week cycle. Continue until disease progression or unacceptable toxicity.

For combination therapy with dexamethasone, the recommended dose is 80 mg once weekly on Day 1 and Day 3 of each week. Continue until disease progression or unacceptable toxicity.

Administer prior to or after concomitant medications as directed. Adhere strictly to the prescribed schedule for all combination agents.

Take antiemetic prophylaxis as prescribed, prior to and during treatment. Maintain adequate hydration and nutritional intake.

Manage toxicity using dose modifications, which may include interruption, reduction, or discontinuation. For Grade 3 or 4 non-hematological toxicity, interrupt treatment until toxicity resolves to Grade ≤1 or baseline, then consider resuming at a reduced dose.

For Grade 4 hematological toxicity, interrupt treatment until toxicity resolves to Grade ≤1 or baseline, then consider resuming at a reduced dose. Provide supportive care, including growth factors or transfusions, as clinically indicated.

Do not take a missed dose within 72 hours of the next scheduled dose. Resume dosing at the next scheduled time.

Monitor blood counts, weight, and clinical status regularly, with increased frequency during the initial months of therapy.

Adverse Reactions

Infections and infestations very common – pneumonia, upper respiratory tract infection, bronchitis, nasopharyngitis; common – sepsis, lower respiratory tract infection.

Blood and lymphatic system disorders very common – thrombocytopenia, anemia, neutropenia; common – leukopenia, lymphopenia.

Metabolism and nutrition disorders very common – decreased appetite; common – hyponatremia, dehydration, hypokalemia, hypocalcemia, hypophosphatemia, hyperkalemia, hypomagnesemia.

Psychiatric disorders very common – insomnia; common – confusion.

Nervous system disorders very common – peripheral neuropathy, dizziness, headache; common – syncope, amnesia, balance disorder, dysgeusia, ageusia.

Eye disorders very common – cataract, blurred vision.

Ear and labyrinth disorders common – vertigo.

Cardiac disorders common – tachycardia, arterial hypotension.

Respiratory, thoracic and mediastinal disorders very common – cough; common – dyspnea, epistaxis.

Gastrointestinal disorders very common – nausea, diarrhea, vomiting, constipation; common – abdominal pain, dyspepsia, dry mouth, stomach gas accumulation.

Skin and subcutaneous tissue disorders common – alopecia, night sweats, pruritus; uncommon – night sweats.

Musculoskeletal and connective tissue disorders common – hypercreatininemia.

Renal and urinary disorders common – acute kidney injury.

General disorders and administration site conditions very common – fatigue, pyrexia, asthenia.

Investigations very common – weight decreased; common – increased AST and ALT.

Injury, poisoning and procedural complications common – fall, contusion.

Contraindications

Hypersensitivity to selinexor, pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Women of childbearing potential and male patients with reproductive potential should be advised to use effective contraception or abstain from sexual activity to prevent pregnancy during selinexor therapy and for at least 1 week after the last dose.

Use in Hepatic Impairment

Dose adjustment of selinexor is not required in patients with mild hepatic impairment. There is insufficient data on the use in patients with moderate or severe hepatic impairment to provide dosing recommendations.

Use in Renal Impairment

Dose adjustment of selinexor is not required in patients with mild, moderate, or severe renal impairment. There is no data on the use in patients with end-stage renal disease or on hemodialysis for dosing recommendations.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

No dose adjustment is required in patients over 65 years of age.

Special Precautions

Before starting treatment, it is necessary to familiarize yourself with the Summary of Product Characteristics (SmPC) of the medicinal products prescribed in combination with selinexor, including special warnings and precautions for use, as well as recommended concomitant therapy.

Patients should be advised to maintain adequate fluid and caloric intake throughout treatment. Patients at risk of dehydration should consider intravenous hydration.

Prophylactic concomitant therapy with a serotonin 5-HT3 receptor antagonist and/or other antiemetic drugs should be administered before and during treatment with selinexor.

A complete blood count should be performed at baseline, during treatment, and as clinically indicated. During the first two months of treatment, blood counts should be monitored more frequently.

Management of thrombocytopenia can include therapy interruption, dose modification, platelet transfusion, and/or other treatments as clinically indicated. Patients should be monitored for signs and symptoms of bleeding and evaluated promptly.

Management of neutropenia can include therapy interruption, dose modification, and administration of colony-stimulating factors according to medical guidelines.

Nausea, vomiting, and diarrhea, which in some cases can be severe and require the prescription of antiemetic and antidiarrheal drugs.

Body weight, nutritional status, and food intake should be monitored at baseline, during treatment, and as clinically indicated. During the first 2 months of treatment, these parameters should be monitored more frequently. Patients with new or worsening symptoms of decreased appetite and weight may require dose modification, appetite stimulants, and nutritional counseling.

Patients should be advised to avoid situations where dizziness or confusion could be problematic and not to take other medications that may cause dizziness or confusion on their own.

Sodium levels should be monitored at baseline, during treatment, and as clinically indicated. During the first two months of treatment, this parameter should be monitored more frequently.

In case of concomitant hyperglycemia (serum glucose greater than 150 mg/dL) and high serum paraprotein levels, sodium correction should be performed. Hyponatremia should be treated according to medical guidelines (intravenous sodium chloride solution), including dietary review. Interruption of selinexor therapy and/or dose modification may be required.

An ophthalmological examination may be performed if clinically indicated. Cataract treatment should be carried out according to medical guidelines, including surgical treatment if warranted.

Patients at high risk of tumor lysis syndrome (TLS) should be closely monitored. TLS should be treated immediately according to institutional guidelines.

Effect on ability to drive and use machines

Selinexor may cause fatigue, confusion, and dizziness. Patients should be advised to avoid activities where dizziness or confusion could have negative consequences, including driving vehicles and operating machinery.

Drug Interactions

Concomitant use of selinexor with potent inducers of the CYP3A4 isoenzyme may lead to a decrease in selinexor exposure.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.