Anamorelin (ADLUMIZ): GHS-R1a Agonist for Cancer Cachexia—Mechanism, Use, and Safety Boundaries

　　Anamorelin hydrochloride(brand:ADLUMIZ)is an oral,selective agonist of the growth hormone secretagogue receptor type 1a(GHS-R1a),also known as the ghrelin receptor.Developed by Ono Pharmaceutical,it mimics endogenous ghrelin:it acts on hypothalamic appetite centers to stimulate food intake and on the pituitary to promote growth hormone secretion,helping counteract the weight loss,reduced lean body mass,and anorexia seen in cancer cachexia.

　　Not for every cancer patient with weight loss

　　The approved indication is narrow.It is used for cancer cachexia associated with unresectable,advanced,or recurrent:

　　non-small cell lung cancer

　　gastric cancer

　　pancreatic cancer

　　colorectal cancer

　　Patients must also meet specific criteria:inadequate response to nutritional therapy;≥5%body weight loss within 6 months plus anorexia;and at least two of the following—fatigue or malaise,generalized muscle weakness,or abnormal labs(CRP>0.5 mg/dL,hemoglobin<12 g/dL,or albumin<3.2 g/dL).

　　Those who cannot eat orally or have impaired digestion/absorption are not appropriate candidates.

　　Dosing and response evaluation

　　Typical adult dose is 100 mg(two 50 mg tablets)once daily on an empty stomach.No food should be taken within 1 hour after dosing to avoid reduced absorption.

　　Reassess after about 3 weeks:if no weight gain or appetite improvement is observed,discontinuation is generally recommended.Clinical experience beyond 12 weeks is limited,so continuation should be reviewed regularly using body weight,appetite assessment,and lab markers.

　　Contraindications and high-risk groups

　　The drug should usually not be used in:

　　patients with hypersensitivity to anamorelin

　　congestive heart failure,myocardial infarction,or angina

　　severe cardiac conduction disorders such as complete AV block

　　moderate-to-severe hepatic impairment(Child-Pugh B or C)

　　patients taking strong CYP3A4 inhibitors(clarithromycin,itraconazole,voriconazole,ritonavir,cobicistat,etc.)

　　patients unable to take food orally or with significant malabsorption

　　Safety monitoring

　　Because anamorelin has sodium-channel inhibitory effects,it can affect cardiac conduction.Baseline and periodic ECG,pulse,blood pressure,and electrolytes are needed to watch for PR/QRS/QT prolongation,AV block,or arrhythmias.

　　Blood glucose should be monitored,as hyperglycemia or worsening diabetes may occur.Liver function tests should be checked periodically.Common adverse reactions include nausea,fatigue,diarrhea,abdominal pain,edema,rash,and dry mouth.

　　Interactions and storage

　　Anamorelin is mainly metabolized by CYP3A4:

　　Avoid strong CYP3A4 inhibitors(raised drug exposure)

　　Use caution with beta-blockers,antiarrhythmics,QT-prolonging drugs,and cardiotoxic chemotherapy

　　Avoid grapefruit juice(raises levels)and St.John's wort(lowers efficacy)

　　Store protected from light,heat,and moisture,and keep out of reach of children.