What are the precautions for Ribociclib?

In clinical studies of Ribociclib (Ribociclib), warnings and precautions such as interstitial lung disease/pneumonitis, severe skin adverse reactions, QT interval prolongation, hepatobiliary toxicity, neutropenia, embryo-fetal toxicity, etc. were found in patients during drug treatment.

1. Interstitial Lung Disease (ILD)/Pneumonitis: ILD/pneumonitis of any grade occurred in patients treated with rebociclib in all clinical trials; additional cases of ILD/pneumonitis were observed in the postmarketing setting, and deaths were reported. Monitor patients for pulmonary symptoms of ILD/pneumonitis, including hypoxia, cough, and dyspnea. If a patient develops new or worsening respiratory symptoms suspected to be caused by ILD or pneumonia, reboxil should be discontinued immediately and the patient evaluated. Rebociclib should be permanently discontinued in patients with recurrent symptomatic or severe ILD/pneumonitis.

2. Serious skin adverse reactions: may include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS). If signs or symptoms of a serious skin reaction occur, ribociclib should be discontinued until the cause of the reaction is determined, and early consultation with a dermatologist is recommended to ensure greater diagnostic accuracy and appropriate management. If SJS, TEN, or DiHS/DRESS is confirmed, permanently discontinue ribociclib and do not reuse ribociclib in patients who develop scarring or other life-threatening skin reactions during treatment.

3. QT interval prolongation: Riboxiclib has been shown to prolong the QT interval in a concentration-dependent manner. Avoid use of reboxil in patients who have QT prolongation or who are at high risk for QT prolongation, including long QT syndrome, uncontrolled or severe cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmias, and electrolyte abnormalities. These ECG changes are reversible upon dose interruption, most occurring during the first four weeks of treatment. No cases of torsade de pointes were reported. Depending on QT prolongation observed during treatment, dose interruption, reduction, or discontinuation of reboxiclib may be necessary; reboxiclib is not indicated for concurrent use with tamoxifen.

4. Hepatobiliary toxicity: In clinical studies of Riboxil, an increase in transaminases was observed, with grade 3 or 4 increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) respectively. Prior to initiating treatment with rebociclib, perform liver function tests (lft) every 2 weeks for the first 2 cycles, then at the beginning of every 4 cycles, and as clinically indicated. Depending on the severity of the transaminase elevation, dose interruption, reduction, or discontinuation of ribociclib may be required. The recommended starting dose of ribociclib in patients with moderate hepatic impairment (Child-Pugh Class B) and severe hepatic impairment (Child-Pugh Class C) is 400 mg once daily.

5. Neutropenia: In studies of reboxil, neutropenia was the most commonly reported adverse reaction (75%). Prior to initiating treatment with rebociclib I, obtain a complete blood count (CBC) during the first 2 cycles and monitor the CBC every 2 weeks as clinically indicated at the beginning of the subsequent 4 cycles. Depending on the severity of neutropenia, dose interruption, reduction, or discontinuation of rebociclib may be required

6. Embryo-fetal toxicity: According to animal research results and mechanism of action, Riboxiclib can cause harm to the fetus when taken by pregnant women. In animal reproduction studies, administration of reboxiclib to pregnant rats and rabbits during organogenesis resulted in maternal exposures that were 0.6 and 1.5 times more embryo-fetal toxic than human clinical exposures, respectively, based on the area under the curve (AUC). Inform pregnant women of potential risks to the fetus. Advise women of childbearing potential to use effective contraception during treatment and for at least 3 weeks after the last dose.

The original drug Riboxil has been launched in China, but due to its short time on the market, its price and purchase methods are not yet known, and it has not yet been included in the scope of medical insurance. The price of the European version of Riboxil's original drug, 200mg*21 tablets, sold overseas may be more than RMB 20,000 per box, while the Indian version of Riboxil's original drug, 200mg*21 tablets, may be priced around RMB 3,000 per box (the price may fluctuate due to exchange rates). The ingredients of the two drugs are basically the same. There are currently no generic versions of Riboxil produced and marketed.