Koselugo

Koselugo offers two different specifications of products, with the 10mg specification containing 60 tablets, priced at approximately 2800 RMB; 

The 25mg specification also includes 60 tablets, which is approximately 5500 RMB.

Koselugo is used to treat type I neurofibromatosis (NF1) in children aged 3 years and older with symptomatic and inoperable plexiform neurofibromatosis (PN). This approval further expands the scope of application of sematinib and brings good news to domestic patients.

1.Main components

Koselugo

2.Adapt to the population

Koselugo is suitable for treating children aged 2 years and above with type 1 neurofibromatosis.

3.Medication for special populations

3.1Pregnancy

Based on findings from animal studies and its mechanism of action, Koselugo can cause fetal harm when administered to a pregnant woman. There are no available data  on the use of Koselugo in pregnant women to evaluate drug-associated risk. In animal reproduction studies, administration of Koselugo to mice during organogenesis caused reduced fetal weight, adverse  structural defects, and effects on embryofetal survival at exposures approximately>5 times the human  exposure at the clinical dose of 25 mg/m2 twice daily. Advise pregnant women of the potential  risk to the fetus.

3.2Lactation

There are no data on the presence of Koselugo or its active metabolite in human milk or their effects on  the breastfed child or milk production. Koselugo and its active metabolite were present in the milk of lactating mice. Due to the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Koselugo and for 1 week after the last dose.

3.3Females and Males of Reproductive Potential

Koselugo can cause fetal harm when administered to a pregnant woman.

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating Koselugo.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment and for 1 week  after the last dose.

Males

Advise male patients with female partners of reproductive potential to use effective contraception during  treatment with Koselugo and for 1 week after the last dose.

3.4Pediatric Use

The safety and effectiveness have been established in pediatric patients 2 years of age and older with NF1 who have inoperable PN and the information on this use is discussed throughout the labeling. The safety and effectiveness of Koselugo have not been established in pediatric patients younger than 2 years of  age.

3.5Geriatric Use

Clinical studies did not include patients 65 years of age and older.

3.6Renal Impairment

No dose adjustment is recommended in patients with renal impairment or those with End Stage Renal  Disease.

3.7Hepatic Impairment

Koselugo exposures increased in patients with moderate or severe hepatic impairment. Reduce the dose of Koselugo for patients with moderate hepatic impairment (Child-Pugh B). A recommended dosage of Koselugo for use in patients with severe hepatic  impairment (Child-Pugh C)has not been established.

4.Drug overdose

Dialysis is not helpful as Koselugo is highly protein bound and is extensively metabolized.

5.Drug storage

Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F). 

Dispense in original bottle. Keep the bottle tightly closed. Do not remove desiccant. Protect from  moisture.

6.Pharmacokinetics

The mean absolute oral bioavailability of Koselugo was 62% in healthy adults. The median time to peak plasma concentrations (Tmax) at steady-state in pediatric patients was 1 to 1.5 hours.

from FDA，2024.01