selinexor

Action and Spectrum

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All grades 

SVd 

Lymphocyte count decreased (77%) 

Glucose increase (62%) 

Fatigue (59%) 

Sodium decrease (58%) 

Nausea (50%) 

BUN increase (41%) 

Peripheral neuropathy (32%) 

Platelet count decrease (92%) 

Phosphate increase (61%) 

Calcium decrease (55%) 

Neutrophil count decrease (48%) 

ALT increase (33%) 

Diarrhea (32%) 

Hemoglobin decrease (71%) 

Sd 

Fatigue (73%) 

Anemia (59%) 

Weight decreased (47%) 

Vomiting (41%) 

Neutropenia (34%) 

Constipation (25%) 

Thrombocytopenia (74%) 

Decreased appetite (53%) 

Diarrhea (44%) 

Hyponatremia (39%) 

Leukopenia (28%) 

Dyspnea (24%) 

Nausea (72%)  

DLBCL 

Nausea (57%) 

Appetite decrease (37%) 

Constipation (29%) 

Pyrexia (22%) 

Edema (17%) 

Fatigue (63%) 

Diarrhea (37%) 

Weight decrease (30%) 

Vomiting (28%) 

Cough (18%)  

Grade 3 or 4 

SVd 

Lymphocyte count decrease (38%) 

Phosphate decrease (23%) 

Sodium decrease (14%) 

Sd H5 

Thrombocytopenia (61%) 

Platelet count decrease (43%) 

Fatigue (28%) 

Hemoglobin decrease (17%) 

Neutrophil count decrease (12%)  

1-10% 

All grades 

Sd 

Headache (10%) 

Vision blurred (10%)  

DLBCL 

Dyspnea (10%) 

Urinary tract infection (10%) 

Hemorrhage (10%) 

Abdominal pain (10%) 

Pneumonia (10%) 

Peripheral neuropathy, sensory (10%) 

Grade 3 or 4 

SVd 

Mental status changes (9%) 

Diarrhea (6%) 

BUN increase (5%) 

Vomiting (4.1%) 

Cataract (9%) 

Potassium decrease (6%) 

Peripheral neuropathy (4.6%) 

Potassium increase (4.1%) 

Nausea (8%)  

Sd 

Nausea (9%) 

Mental status changes (7%) 

Diarrhea (6%) 

Vomiting (3.5%) 

Pneumonia (9%) 

Hyperglycemia (7%) 

Decreased appetite (4.5%) 

Lymphopenia (10%)  

DLBCL 

Pneumonia (6%) 

Appetite decrease (3.7%) 

Diarrhea (3%) 

Hypotension (3%) 

Nausea (6%) 

Pyrexia (4.5%) 

Mental status changes (3.7%) 

Urinary tract infection (3%) 

Edema (2.2%)  

<1% 

Grade 3 or 4 

SVd 

Blurred vision 

Magnesium decrease 

Dizziness 

Albumin decreased 

Sd 

Pyrexia 

Vision blurred 

Weight decreased 

Epistaxis  

DLBCL 

Dizziness 

Blurred vision 

Hemorrhage 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Actions and Spectrum: 

Mechanism of Action:  

• selinexor exerts its anticancer effects by explicitly inhibiting the nuclear export protein exportin 1 (XPO1), also known as chromosome region maintenance 1 (CRM1). XPO1 is responsible for the export of numerous tumor-suppressor proteins, messenger RNAs (mRNAs), and microRNAs from the cell nucleus to the cytoplasm. 
• By inhibiting XPO1, selinexor blocks the nuclear export of these tumor-suppressor proteins and other molecules, accumulating them in the nucleus. This accumulation disrupts the cancer cell’s normal regulatory processes, including cell cycle control, DNA repair, and apoptosis (programmed cell death). Ultimately, it impairs cancer cell growth and survival. 

Spectrum of Activity: 

selinexor has demonstrated activity against various cancer types, including solid tumors and hematological malignancies. It has shown promising efficacy in the following cancers: 

• Hematological Malignancies: selinexor has been studied and approved for treating certain hematological malignancies, including relapsed or refractory multiple myeloma. It has also shown activity in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and other lymphomas. 
• Solid Tumors: selinexor has shown activity against several solid tumor types, including but not limited to non-small cell lung cancer (NSCLC), ovarian cancer, bladder cancer, breast cancer, prostate cancer, and colorectal cancer. It has also demonstrated activity in rare tumors such as sarcomas and neuroendocrine tumors. 

Pregnancy / Lactation

Pregnancy consideration: selinexor has the potential to harm the developing fetus. It should not be used during pregnancy 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

selinexor is a selective inhibitor of nuclear export (SINE) compound that exhibits its pharmacological effects through its interaction with exportin 1 (XPO1), also known as chromosome region maintenance 1 (CRM1) 

Pharmacodynamics: 

The pharmacodynamics of selinexor involves interacting with the nuclear export protein XPO1/CRM1, leading to changes in cellular processes and signaling pathways. The critical aspects of the pharmacodynamics of selinexor: 

• Inhibition of Nuclear Export: selinexor binds to the cysteine residue in the cargo-binding pocket of XPO1/CRM1, preventing the interaction between XPO1 and its nuclear export signal (NES) cargoes. This inhibition disrupts the average nuclear export of various tumor-suppressor proteins, mRNAs, and microRNAs, resulting in their nuclear accumulation. 
• Nuclear Retention of Tumor-Suppressor Proteins: By preventing the export of tumor-suppressor proteins, such as p53 and p21, selinexor increases their nuclear concentration. This leads to enhanced transcriptional activity of these proteins, which can contribute to cell cycle arrest, DNA repair, and apoptosis, ultimately inhibiting cancer cell growth and survival. 
• Altered Gene Expression: The nuclear retention of specific mRNAs and microRNAs by selinexor can influence gene expression patterns. The altered gene expression can impact cellular processes in cancer progression, including cell cycle regulation, DNA repair, and apoptosis. 
• Disruption of Oncogenic Signaling Pathways: selinexor’s inhibition of XPO1 can affect multiple dysregulated signaling pathways in cancer cells. For example, selinexor has been shown to modulate the nuclear localization of proteins involved in the nuclear factor kappa B (NF-κB) pathway, resulting in decreased NF-κB activity. This can lead to inhibition of pro-survival and anti-apoptotic signaling in cancer cells. 
• Anti-Angiogenic Effects: selinexor has been reported to exert anti-angiogenic effects by inhibiting the nuclear export of hypoxia-inducible factor 1-alpha (HIF-1α), a key regulator of angiogenesis. The nuclear accumulation of HIF-1α can disrupt the expression of pro-angiogenic factors, potentially inhibiting tumor angiogenesis. 

Pharmacokinetics: 

Absorption 

selinexor is administered orally in the form of tablets. It is rapidly absorbed from the gastrointestinal tract after oral ingestion. The specific details of its absorption, such as bioavailability and absorption rate, may depend on various factors, including formulation and individual patient characteristics. 

Distribution 

selinexor exhibits moderate plasma protein binding, primarily to albumin. It distributes throughout the body, including to tissues and organs. The volume of distribution (Vd) of selinexor is approximately 9.1 L, indicating that it distributes widely in the extravascular space. 

Metabolism 

selinexor undergoes metabolism primarily through hepatic biotransformation. The main enzyme involved in the metabolism of selinexor is cytochrome P450 3A4 (CYP3A4), although other CYP enzymes may contribute to a lesser extent. The metabolites of selinexor are primarily formed through oxidative metabolism. The specific metabolites and their activities are the subject of ongoing research. 

Elimination and Excretion 

selinexor and its metabolites are eliminated mainly through feces, with a smaller portion eliminated through urine. The exact percentages of excretion routes and the specific metabolites excreted are not widely reported.The elimination half-life of selinexor is approximately 8 to 10 hours. This indicates that it takes around 8 to 10 hours for the concentration of selinexor in the body to decrease by 50%. 

Adminstartion

Administration: 

The administration of selinexor: 

• Dosing schedule: selinexor is usually taken once or twice weekly. The treating physician will determine the dosing schedule, including the frequency and duration of treatment cycles, based on the specific indication and the patient’s condition. 
• Timing of Dose: selinexor should be taken consistently at the same time(s) on the designated days to ensure optimal dosing. It is essential to follow the prescribed schedule closely. 
• Oral administration: selinexor tablets should be swallowed whole with water without chewing or crushing them. As the healthcare provider instructs, taking tablets with or without food is recommended. 
• Dose Adjustments: The dose of selinexor may be adjusted based on individual patient factors, such as tolerability and treatment response. Any dose adjustments should only be made under the guidance of a healthcare professional. 
• Concomitant Medications: The use of concomitant medications, including other anticancer agents or supportive therapies, should be discussed with the healthcare provider. Some medications may interact with selinexor, and adjustments may be necessary. 
• Compliance: It is essential to adhere to the prescribed dosing schedule and complete the entire course of treatment unless otherwise directed by the healthcare professional. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: selinexor 

Why do we use selinexor? 

selinexor is a medication that has been approved for the treatment of specific types of cancer. 

• Multiple Myeloma: Patients with recurrent or refractory multiple myeloma who have had at least four previous treatments and have no other viable therapy alternatives are treated with selinexor and dexamethasone. 
• selinexor is authorized to treat Diffuse Large B-Cell Lymphoma (DLBCL), including DLBCL resulting from follicular lymphoma, that has relapsed or is resistant to at least two previous systemic therapy.