Afatinib(Gilotrif)

Afatinib is an irreversible inhibitor of tyrosine kinase (TK) developed by Boehringer Ingelheim Pharmaceuticals. The specification is 40mg * 30Tablets.

Afatinib was approved by the US FDA for marketing in the United States on July 12, 2013, under the trade name Gilotrif.

Afatinib exerts its effects by irreversibly blocking ErbB family receptors (including EGFR, HER2, etc.), thereby shutting down cancer cell signaling pathways and inhibiting tumor growth.

1.Main components

Afatinib

2.Adapt to the population

Afatinib is suitable for EGFR mutation positive metastatic non-small cell lung cancer.

3.Medication for special populations

3.1Pregnancy

Based on findings from animal studies and its mechanism of action, Afatinib can cause fetal harm when administered to a pregnant woman. There are no available data on the  use of Afatinib in pregnant women.

3.2Lactation

There are no data on the presence of afatinib in human milk or its effects on the breastfed infant or on milk  production.Because of the potential for serious adverse reactions in breastfed infants from Afatinib, advise women not to breastfeed during treatment with  Afatinib and for 2 weeks after the final dose.

3.3Females and Males of Reproductive Potential

Females 

Afatinib can cause fetal harm when administered to a pregnant woman. Advise females of reproductive  potential to use effective contraception during treatment with Afatinib and for at least 2 weeks after the last  dose of Afatinib.

3.4Pediatric Use

Safety and effectiveness of Afatinib in pediatric patients have not been established.

3.5Geriatric Use

No overall differences in safety were observed between patients 65 years and older and  younger patients.

3.6Renal Impairment

Patients with severe renal impairment have a higher exposure to afatinib than patients with normal renal function. Afatinib has not been studied in patients with eGFR <15 mL/min/1.73 m2 or on dialysis.

3.7Hepatic Impairment

Afatinib has not been studied in patients with severe (Child Pugh C) hepatic impairment.Closely monitor patients with severe hepatic  impairment and adjust Afatinib dose if not tolerated.

4.Drug overdose

Overdose was reported in 2 healthy adolescents each of whom ingested 360 mg of Afatinib (as part of a  mixed-drug ingestion) resulting in nausea, vomiting, asthenia, dizziness, headache, abdominal pain, and  elevated amylase [<1.5 times upper limit of normal (ULN)]. Both subjects recovered.

5.Drug storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). Dispense medication in the original container to protect from exposure to high humidity and light.

6.Pharmacokinetics

Following oral administration of Afatinib tablets, time to peak afatinib plasma concentrations (T_max) is 2 to 5 hours. Maximum concentration (Cmax) and area under the concentration-time curve from time zero to infinity  (AUC0-INF) values increased slightly more than dose proportional in the range of 20 to 50 mg. The geometric mean relative bioavailability of 20 mg Afatinib tablets was 92% as compared to an oral solution. Steady-state plasma concentrations are achieved within 8 days of repeat dosing of Afatinib resulting in an accumulation of 2.8-fold for AUC and 2.1-fold for C_max.

from FDA，2022.04