Action and Spectrum

Actions and Spectrum 

selpercatinib has shown activity in preclinical studies against a variety of cancer types, including NSCLC and MTC. In clinical trials, selpercatinib has demonstrated efficacy in patients with RET-mutant NSCLC and MTC, with a response rate of approximately 70% in both indications. It is currently being evaluated in ongoing clinical trials for the treatment of other types of cancer as well. 

In terms of its spectrum of activity, selpercatinib has been specifically designed to target cancers with RET mutations. It is not active against cancers that do not have these mutations and may not be effective in the treatment of these types of cancer. It is important for patients to discuss with their healthcare provider whether selpercatinib is an appropriate treatment option for their specific type of cancer. 

Drug Interaction

Adverse Reaction

Frequency Defined  

>10%   

Increased glucose (44%)  

Increased ALT (45%)  

Decreased leukocytes (43%)  

Decreased calcium (41%)  

Decreased albumin (42%)  

Dry mouth (39%)  

Increased creatinine (37%)  

Increased AST (51%)  

Diarrhea (37%)  

Increased alkaline phosphatase (36%)  

Fatigue (35%)  

Hypertension (35%)  

Edema (33%)  

Increased total cholesterol (31%)  

Decreased platelets (33%)  

Rash (27%)  

Constipation (25%)  

Decreased sodium (27%)  

Decreased magnesium (24%)  

Nausea (23%)  

Increased potassium (24%)  

Abdominal pain (23%)  

Increased bilirubin (23%)  

Headache (23%)  

Black Box Warning

Contraindication / Caution

Contraindications/ Cautions  

• It is contraindicated in patients who have had a severe allergic reaction to selpercatinib or any of its components.  
• There are several cautions to be aware of when taking selpercatinib. It can cause serious side effects, including liver damage, high blood pressure, and bleeding.   
• It is important for patients to have regular blood tests to monitor for these and other potential side effects.   
• selpercatinib can also cause fetal harm, and therefore it is important for women who are pregnant or planning to become pregnant to use effective contraception while taking this medication.   
• selpercatinib may also interact with other medications, and it is important for patients to inform their healthcare provider about all the medications they are taking.  

Pregnancy / Lactation

Pregnancy warnings:     

US FDA pregnancy category: N/A 

Lactation:   

Excreted into human milk is unknown  

Pregnancy Categories:         

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 available 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:  

Selpercatinib (brand name: Retevmo) is a selective inhibitor of the intracellular tyrosine kinases RET, ROS1, and TRK. These kinases are involved in the growth and proliferation of cancer cells, and selpercatinib works by blocking their activity, which may help to slow down the growth of cancer cells. 

Pharmacodynamics:  

The pharmacodynamics of selpercatinib is specifically indicated for the treatment of adults with RET-mutant medullary thyroid cancer that is locally advanced or has spread to other parts of the body (metastasized) and who have received prior treatment with at least one other drug. It is also indicated for the treatment of adults with RET fusion-positive non-small cell lung cancer that has spread to other parts of the body (metastasized) and who have received prior treatment with at least one other drug. In clinical studies, selpercatinib has demonstrated an ability to shrink tumors and slow the growth of cancer cells in patients with these types of cancer.  

Pharmacokinetics:  

Absorption   

It is absorbed well in the body, with an absolute bioavailability of 73%. This means that about 73% of the drug reaches systemic circulation and is available to be used by the body.   

Distribution   

selpercatinib reaches peak plasma concentration (the highest level of the drug in the blood) in about 2 hours after administration and has a plasma half-life (the time it takes for the drug to be reduced to half its original concentration) of 32 hours. This means that it stays in the body for a relatively long time, allowing for once-daily dosing.   

Metabolism   

selpercatinib is metabolized predominantly by the enzyme CYP3A4   

Elimination and excretion  

Eliminated mainly through the feces, with about 69% of the drug being excreted in the feces and 24% being excreted in the urine. It is important to note that the above pharmacokinetic parameters may vary depending on individual factors such as age, weight, and liver and kidney function.  

Adminstartion

Administration:  

selpercatinib is a medication used to treat certain types of cancer, including non-small cell lung cancer, thyroid cancer, and other types of tumors that have a specific genetic alteration called RET fusion or mutation. It is typically taken orally as a capsule and is usually taken once daily.   

The recommended dose of selpercatinib varies depending on the specific condition being treated and other factors such as the patient’s age and weight. It is important to take selpercatinib exactly as directed by a healthcare provider.   

The capsules should be swallowed whole with water and should not be opened, crushed, or chewed. selpercatinib should be taken at the same time each day, either with or without food.   

Storage:  

Keep at 20-25oC (68-77oF); excursions are allowed to 15-30oC (59-86oF).  

Patient Information Leaflet

Patient information leaflet 

Generic Name: selpercatinib  

Why do we use selpercatinib? 

selpercatinib is a medication that is used to treat certain types of cancer that have a specific genetic alteration called RET fusion or mutation. RET is a protein that is involved in the growth and development of cells in the body. When there is a genetic alteration in the RET gene, it can cause cells to grow and divide in an uncontrolled way, leading to the development of cancer.  

selpercatinib is a type of cancer treatment called a tyrosine kinase inhibitor, which means it works by blocking the activity of a group of proteins called tyrosine kinases. These proteins play a role in the growth and division of cancer cells, and by blocking their activity, selpercatinib can help to slow or stop the growth of cancer cells.  

selpercatinib is used to treat non-small cell lung cancer, thyroid cancer, and other types of tumors that have RET fusion or mutation. It is typically used when other treatments, such as surgery, chemotherapy, or radiation therapy, have not been successful or are not suitable for the patient.