Description

Selcaxen capsule: Each capsule contains Selpercatinib INN 40 mg.

 

Product Features

Product Name	:	Selcaxen
Generic Name	:	Selpercatinib
Formulation	:	Capsule
Available Pack Size	:	30’s Pot
Available Strength	:	400 mg
Registrations	:	Export Only

 

Indication

Selcaxen 40 Mg (Selpercatinib) treats a specific type of non-small cell lung cancer (NSCLC) in adults that have spread to other body parts. It is also used to treat a particular type of thyroid cancer in adults and children 12 years of age and older that has spread to other body parts. Selcaxen 40 Mg is also used to treat thyroid cancer that has spread to other parts of the body in adults and children 12 years of age and older who have been treated unsuccessfully with radioactive iodine. Selcaxen 40 Mg is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.

 

Usage of Selpercatinib

Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

Selpercatinib is indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer(NSCLC). This indication is approved under accelerated approved based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

 

RET-Mutant Medullary Thyroid Cancer

Selpercatinib is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer(MTC) who require systemic therapy.

 

RET Fusion-Positive Thyroid Cancer

Selpercatinib is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory if radioactive iodine is appropriate).

 

Pharmacology of Selpercatinib

Mechanism of Action: Selpercatinib is a kinase inhibitor. Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms as well as VEGFR1 and VEGFR3 with IC50 values ranging from 0.92 nM to 67.8 nM. In other enzyme assays, also inhibited FGFR 1, 2, and 3 at higher concentrations that were still clinically achievable. In cellular assays, inhibited RET at approximately 60-fold lower concentrations than FGFR1 and 2 and approximately 8-fold lower concentration than VEGFR3. 

 

Dosage and Administration

Patient Selection

Select patients for treatment with Selpercatinib based on the presence of a RET gene fusion (NSCLC or thyroid cancer) or specific RET gene mutation (MTC) in tumor specimens or plasma. An FDA-approved test for the detection of RET gene fusions and RET gene mutations is not currently available. Important Administration Instructions
may be taken with or without food unless co-administrated with a proton pump inhibitor (PPI).

 

Recommended Dosage

The recommended dosage based on body weight is: 

• Less than 50 kg: 120 mg 
• 50 kg or greater: 160 mg

Take Selpercatinib orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity. Swallow the capsules whole. Do not crush or chew the capsules. Do not take a missed dose unless it is more than 6 hours until the next scheduled dose. 

If vomiting occurs after Selpercatinib administration, do not take an additional dose and continue to the next scheduled time for the next dose. 

 

Dosage Modifications for Concomitant Use of Acid-Reducing Agents

Avoid concomitant use of a PPI, a histamine-2 (H2) receptor antagonist, or a locally-acting antacid with Selpercatinib. If concomitant use cannot be avoided: 

• Take Selpercatinib with food when co-administered with a PPI. 
• Take Selpercatinib 2 hours before or 10 hours after administration of an H2 receptor antagonist.
• Take Selpercatinib 2 hours before or 2 hours after administration of a locally-acting antacid.

 

Warnings and Precautions

Hepatotoxicity

Serious hepatic adverse reactions occurred in 2.6% of patients treated with Selpercatinib. Monitor ALT and AST prior to initiating Selpercatinib, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue Selpercatinib based on the severity.

 

Hypertension

Hypertension occurred in 35% of patients, including Grade 3 hypertension in 17% and Grade 4 in one (0.1%) patient. Overall, 4.6% had their dose interrupted, and 1.3% had their amount reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications.

Do not initiate Selpercatinib in patients with uncontrolled hypertension. Optimize blood pressure before starting Selpercatinib. Monitor blood pressure after one week, at least monthly after that, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Selpercatinib based on the severity.

 

QT Interval Prolongation

Selpercatinib can cause concentration-dependent QT interval prolongation. An increase in QTCF interval to >500 ms was measured in 6% of patients, and an increase in the QTCF interval of at least 60 ms over baseline was measured in 15% of patients. Selpercatinib has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction.

 

Monitor patients at significant risk of developing QTC prolongation, including patients with known long QT syndromes, clinically substantial bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and TSH at baseline and periodically during treatment, adjusting frequency based upon risk factors, including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia before initiating Selpercatinib and during therapy.

 

Monitor the QT interval more frequently when Selpercatinib is concomitantly administered with potent and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Selpercatinib based on the severity.

 

Hemorrhagic Events

Serious, including fatal hemorrhagic events, can occur with Selpercatinib. Grade 2 3 hemorrhagic events occurred in 2.3% of patients treated with Selpercatinib, including 3 (0.4%) patients with fatal hemorrhagic events, including one case each of cerebral hemorrhage, tracheostomy site hemorrhage, and hemoptysis.

Permanently discontinue Selpercatinib in patients with severe or life-threatening bleeding.

 

Hypersensitivity

Hypersensitivity occurred in 4.3% of patients receiving Selpercatinib, including Grade 3 hypersensitivity in 1.6%. The median time to onset was 1.7 weeks (6 days to 1.5 years). Signs and symptoms of hypersensitivity included fever, rash, and arthralgias or myalgias with concurrent decreased platelets or transaminitis.

And-

• Tell your doctor and pharmacist if you are allergic to Selpercatinib, other medications, or any ingredients in Selpercatinib capsules. Ask your pharmacist for a list of the ingredients.
• If you are taking an H2 blocker medication for indigestion, heartburn, or ulcers, such as cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), or ranitidine (Zantac), take Selpercatinib at least 2 hours before or 10 hours after taking one of these medications.
• If you take an antacid that contains aluminum, magnesium, calcium, or simethicone, or buffered medications such as buffered aspirin, take Selpercatinib at least 2 hours before or at least 2 hours after you take one of these medications.
• If you are taking a proton-pump inhibitor such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex), take each dose of Selpercatinib along with food.
• Tell your doctor what herbal products you take, especially St. John’s wort.
• Tell your doctor if you have had a slow, fast, or irregular heartbeat; a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death); high blood pressure; bleeding problems; or kidney or liver disease.
• Tell your doctor if you are pregnant, plan to become pregnant, or if you plan on fathering a child. It would be best if you did not become pregnant while taking Selpercatinib. If you are female, you will need to take a pregnancy test before you start treatment and use birth control to prevent pregnancy during your treatment with Selpercatinib and for 1 week after your final dose. If you are male, you and your female partner should use birth control during your treatment with Selpercatinib and for 1 week after your last dose. Call your doctor immediately if you or your partner become pregnant while taking Selpercatinib. Selpercatinib can cause fetal harm.
• Tell your doctor if you are breastfeeding. You should not breastfeed while taking Selpercatinib and for 1 week after your final dose.
• You should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking Selpercatinib.
• If you have dental surgery, tell the doctor or dentist that you are taking Selpercatinib. Your doctor may tell you not to take Selpercatinib 7 days before your surgery or procedure and will notify you when you should start taking the medication again.

 

Side Effects

The most common side effects of Selpercatinib are: 

• Higher levels of liver enzymes 
• Higher blood sugar levels 
• Lower white blood cell count 
• Lower protein (albumin) levels in the blood 
• Lower calcium levels in the blood 
• Dry mouth 
• Diarrhea 
• Higher creatinine levels (this measures kidney function) 
• High blood pressure 
• Tiredness 
• Swelling of your arms, legs, hands, and feet (peripheral edema) 
• Lower platelet count 
• Higher cholesterol levels 
• Rash 
• Lower salt (sodium) levels in the blood 
• Constipation  

 

Use in Specific Population

Pregnancy

Risk Summary: Based on findings from animal studies and its mechanism of action, it can cause fetal harm when administered to a pregnant woman. There is no available data on this use in pregnant women to inform a drug-associated risk. Administration of Selpercatinib to pregnant rats during the period of organogenesis resulted in embryolethality and malformations at maternal exposures that were approximately equal to the human exposure at the clinical dose of 160 mg twice daily. Advise pregnant women of the potential risk to a fetus.

 

Lactation

Risk Summary: There are no data on the presence of Selpercatinib or its metabolites in human milk or on their 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 this and for 1 week after the final dose. 

 

Females and Males of Reproductive Potential: Based on animal data, it can cause embryolethality and malformations at doses resulting in  exposures less than or equal to the human exposure at the clinical dose of 160 mg twice daily. 

 

Pregnancy Testing: Verifies pregnancy status in females of reproductive potential prior to initiating it. 

 

Contraception

Females: Advise female patients of reproductive potential to use effective contraception during treatment with Selpercatinib and for 1 week after the final dose. 

Males: Advise males with female partners of reproductive potential to use effective contraception during treatment with Selpercatinib and for 1 week after the final dose. 

Infertility: Selpercatinib may impair fertility in females and males of reproductive potential.  

 

Overdose

Symptoms of overdose have not been established. In the event of suspected overdose, supportive care should be provided. 

 

Pharmaceutical Information

Storage Condition: Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children. 

Selcaxen capsule: Each HDPE container contains 30 capsules (each capsule contains 40 mg Selpercatinib INN) a silica gel desiccant and polyester coil with a child-resistant closure. 

 

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