Capmatinib 200 mg (Capmaxen) | 56 Tablets | Everest Pharma

Capmatinib 200 mg (Capmaxen) general approval has been granted for adult patients as detected by an FDA test  with metastatic non-small cell lung cancer with a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping on 10 August 2022.

On May 6, 2020, the FDA initially granted approval based on overall response rate and duration of response observed in the GEOMETRY mono-1 trial. The subsequent regular approval was supported by data from 63 additional patients and 22 more months of follow-up, which confirmed response durability and verified clinical benefit.

This approval information was cited on the Capmatinib Approval page of the FDA website. 

Composition

Each film coated tablet contains Capmatinib Hydrochloride INN, which is equivalent to Capmatinib 200 mg.

Clinical Pharmacology

Mechanism of Action

Capmatinib 200 mg (Capmatinib) is a tyrosine kinase inhibitor that targets MET, including the mutant variant built with exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that decreases its negative regulation leading to increased resulting MET signaling. Capmatinib, targeting a mutant MET variant, reduced anti-tumor activity at clinically attainable levels and in xenograft murine models of MET exon 14 skipping or MET amplification driven by human lung tumors. Capmatinib anti-phosphorylated MET at and beyond the level of HGF, MET amplification, and at subsequent levels in MET-dependent cancer cells.

Absorption

When Capmatinib 400 mg is taken orally by patients with metastatic non-small cell lung cancer, the highest blood concentration is usually reached within 1 to 2 hours, and its absorption after administration is estimated to exceed 70%.

Distribution

Capmatinib 200 mg (Capmaxen) plasma protein binding is 96%, independent of capmatinib concentration. The visible mean volume of distribution at steady-state is 164 L. The blood-to-plasma ratio was 1.5, but decreased at higher concentrations to 0.9.

Dosing Information Mentioned in the FDA website

The general recommended dosage of Capmaxen for adults is 400 mg taken by mouth twice a day, with or without food. Tablets should be swallowed whole with water and not broken or split. Its safety and effectiveness in children have not been established in any clinical trials.

The dose may differ from person to person, follow the prescription instructions properly mentioned by a licensed health care professional.

Missed Dose

Take the missed dose as soon as possible or skip the dose if it is close to the next dose. Do not take a combined dose to make up the missed dose. Medical attention is required for missed dose and overdose.

Side Effects of the Medication

The below adverse reactions were seen in less than 10% of the patients who took Capmatinib 200 mg tablets in GEOMETRY mono-1.

•       Edema: edema (swelling of the body’s outer parts with fluid) peripheral, generalized edema, face edema, localized edema, edema genital, eyelid edema, peripheral swelling, scrotal edema, and penile edema.
•       Musculoskeletal pain: Musculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, pain in jaw and spinal pain.
•       Fatigue: It includes regular fatigue and asthenia.
•       Pyrexia: It includes increased body temperature.
•       Weight decreased
•       Nausea
•       Vomiting
•       Constipation
•       Diarrhea
•       Dyspnea
•       Cough: Upper airway cough syndrome and productive cough
•       Pneumonia: It includes pneumonia aspiration, pneumonia influenzal, pneumonia bacterial, lower respiratory tract infection and lung abscess.
•       Decreased Appetite
•       Rash: Pimples like rash, rash maculo-papular, eczema, erythema multiforme, rash macular, dermatitis.
•       Dizziness: It includes dizziness, vertigo and vertigo positional.

Warnings and Precautions

Interstitial Lung Disease (ILD)/Pneumonia

Fatal pneumonia can occur in patients who are going to be treated with Capmatinib 200 mg. Evidence of pneumonia was found in 4.8% patients treated with the medication. Monitoring is required for new or pulmonary symptoms indicative of pneumonia including dyspnea, fever and cough.

Hepatotoxicity

Monitor liver function test including ALT, AST and bilirubin prior to the start of the medication and every two weeks during the first 3 months of treatment, then once in a month or as clinically indicated, with more frequently testing who develop increased transaminases or bilirubin. With the severity of the adverse reaction withhold, dose reduce or permanently discontinue in accordance with prescribing information.

Pancreatic Toxicity

Monitor digestive enzymes (Amylase and lipase) at baseline and regularly during treatment with Capamatinib. Based on the severity of the adverse drug reaction temporarily withhold, dose reduce or discontinue permanently with the help of a healthcare professional.

Risk of photosensitivity

Based on the findings from animal studies, there is a potential risk of photosensitivity reaction with Capamatinib. In GEOMETRY mono-1, it was recommended that patients use precautionary measures against ultraviolet exposure such as use of sunscreen or proactive clothing during treatment. It is advised to limit direct ultraviolet exposure during the treatment.

Embryo-Fetal Toxicity

Based on the findings from animal studies and mechanism of action, Capamatinib can cause fetal harm when administered to a pregnant woman. Oral administration of Capamatinib to pregnant rats and rabbits during the period of organogenesis resulted in malformation at exposure less than the human exposure based on the area under the curve at the 400 mg twice daily clinical dose. Female reproductive potentials should use effective contraception during treatment with Capmaxen and for one week after the last dose. It is advised for the both, females and males with reproductive potentials to use effective contraception during treatment with Capmaxen for one week after the last dose.

Drug Interactions

Effects of other drug on Capamatinib

Strong CYP3A inhibitors: Co-administration of Capamatinib with a strong CYP3A inhibitor increases the exposure of the medication, which may increase the severity of the adverse reaction. Patients should be monitored closely for any adverse reactions during co-administration with a CYP3A inhibitor.

Strong and moderate CYP3A inducers: Co-administration with strong and moderated CYP3A inducers decreases the exposure of the Capamatinib.

Effects of Capamatinib on other drugs

CYP1A2 Substrates:Using Capmatinib 200 mg alongside CYP1A2 substrates can raise the risk of side effects from those substrates. If taking both medicines together cannot be avoided and even small changes in concentration could cause adverse effects, the dosage of the CYP1A2 substrate should be reduced as recommended in its prescribing guidelines.

P-glycoprotein (P-gp) and Breast Cancer resistance protein (BCRP) substrates: Co-administration of P-gp and BCRP with Capmatinib can increase the exposure that may increase the adverse reaction of the substrates. If co-administration is unavoidable where minimal concentration changes may lead to adverse reaction, decrease the doses of the substrates in accordance with approved prescribing information.

MATE1 and MATE2 substrates:Taking Capmatinib together with MATE1 or MATE2 substrates may raise their levels in the body, potentially increasing the risk of side effects. If co-administration cannot be avoided and even small changes in concentration could cause adverse effects, the doses of these substrates should be reduced according to their approved prescribing guidelines.

Uses in specific population

Pregnancy

Based on findings from animal studies and its mechanism of action, it can cause fetal harm when it is administered to a pregnant woman. Currently, there are no clinical data on the use of Capmatinib in pregnant women. In animal studies, oral administration to rats and rabbits during organ development caused malformations at exposure levels lower than those seen in humans at the 400 mg twice-daily dose based on AUC.

Lactation

No information is available on whether Capmatinib 200 mg (Capmaxen) or its metabolites pass into human or animal breast milk, or on their potential impact on nursing infants or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Capmatinib and for 1 week after the last dose.

Female and Male Reproductive Potential

Based on animal data Capmaxen 200 mg can cause malformation at doses less than human exposure based on AUC at the 400 mg twice daily clinical dose. Verify pregnancy status for females of reproductive potential prior to starting treatment with Capmatinib tablet. Advise females of reproductive potential to use effective contraception during treatment with the medication and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with the medication and for 1 week after the last dose. 

Pediatric Use

Safety and effectiveness of the pediatric use of Capmatinib tablets has not been established. 

Geriatric Use

In the GEOMETRY mono-1 study, 61% of the 373 participants were aged 65 or older, and 18% were 75 or older. The study found no significant differences in safety or effectiveness between these older patients and younger participants.

Renal Impairment

For patients with mild to moderate kidney impairment, no dose adjustment of Capmatinib is necessary. Its use has not been evaluated in individuals with severe renal impairment, so medical guidance should be sought before use in such cases.

Manufacturer and Supplier Information

Capmaxen 200 mg (Capmatinib) is manufactured by the Everest Pharmaceutical LTD. You can access this medication through Onus Pharma.

 Disclaimer: Information above is not for using as an alternative to medical information. The information above has been collected from https://www.novartis.com/us-en/sites/novartis_us/files/tabrecta.pdf and,

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capmatinib-metastatic-non-small-cell-lung-cancer

Sharing information about approval and uses of Capmatinib.