Ribociclib is a CDK (cyclin-dependent kinase) 4 and 6 inhibitor drug. Cyclin-dependent kinase 4 and 6 are activated upon binding to Dcyclins and play an important role in signaling pathways which lead to cell cycle progression and cellular proliferation.
This drug is used in combination with other drugs to treat patients suffering from hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)- negative advanced or metastatic breast cancer in postmenopausal women. Ribociclib is the active ingredient in the medicine with inactive ingredients colloidal silicon dioxide, crospovidone, hydroxypropyl cellulose, magnesium stearate, and microcrystalline cellulose.
Administration and Dosage
Ribociclib comes as tablets of 200 mg to administer orally. The general recommended dosage of Ribociclib is 600 mg (three 200 mg tablets) taken orally, once a day for 21 consecutive days, followed by 7 days off treatment resulting in a complete cycle of 28 days. Patients can take Ribociclib medicine with or without food. Healthcare professionals recommend co-administering Ribociclib with letrozole 2.5 mg once a day throughout the 28-day cycle.
Before administering this medicine to a patient, acknowledge the doctor about the patient's medical history. According to the doctor's prescription, one should take this medicine only to avoid adverse side effects or overdose.
Drug Interactions
Drugs which affect Ribociclib 200 mg Plasma Concentrations
CYP3A inhibitors:
A drug interaction trial was conducted with ritonavir (a strong CYP3A inhibitor). Compared to Ribociclib alone, ritonavir increased Ribociclib Cmax and AUCinf by 1.7-fold and 3.2-fold, following a single dose of 400 mg Ribociclib. Cmax and AUC for LEQ803 were reduced by 96% and 98%. A moderate CYP3A4 inhibitor (erythromycin) increases Ribociclib Cmax and AUC by 1.3-fold and 1.9-fold.
CYP3A inducers:
A drug interaction trial was conducted with rifampicin (a strong CYP3A4 inducer). Compared to Ribociclib alone, rifampicin decreased Ribociclib Cmax and AUCinf by 81% and 89%, following a single dose of Ribociclib 600 mg. LEQ803 Cmax increased 1.7-fold, and AUCinf reduced by 27%. Efavirenz, a moderate CYP3A inducer is predicted to reduce Ribociclib Cmax and AUC by 37% and 60%.
Drugs That Are Affected By Ribociclib
CYP3A4 and CYP1A2 substrates:
A drug interaction trial was conducted as a cocktail study with midazolam and caffeine. Compared to midazolam and caffeine alone, Ribociclib multiple doses of increased midazolam Cmax and AUCinf by 2.1- fold and 3.8-fold. Administration of Ribociclib at 600 mg(Ribociclib 200 mg tablets) once a day is predicted to increase midazolam Cmax and AUC by 2.4-fold and 5.2-fold. The effect of multiple doses of Ribociclib 400 mg on caffeine was minimal, with Cmax reduced by 10% and AUCinf increased by 20%. Only the weak inhibitory effects on CYP1A2 substrates were seen at 600 mg Ribociclib once a day dose.
Gastric pH-elevating agents: Ribociclib, when coadministered with drugs that elevate the gastric pH, was not evaluated in a clinical trial; however, altered Ribociclib absorption was not identified in a population PK analysis and was not predicted using physiology-based PK models.
Letrozole: The data from a clinical trial in patients having breast cancer and population PK analysis showed no drug interaction between Ribociclib and letrozole following the coadministration of the drugs.
Anastrozole: The data from a clinical trial in patients with breast cancer showed no clinically relevant drug interaction between Ribociclib and anastrozole following the coadministration of the drugs.
Exemestane: The data from a clinical trial in patients with breast cancer showed no clinically relevant drug interaction between Ribociclib and exemestane following the coadministration of the drugs.
In vitro Studies
Effect of Ribociclib 200 mg on CYP enzymes: In vitro, Ribociclib was a CYP1A2, CYP2E1, and CYP3A4/5 reversible inhibitor, and it is a time-dependent inhibitor of CYP3A4/5 at clinically relevant concentrations. In vitro evaluations showed that this medication has no potential to stop the activities of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6 at clinically relevant concentrations. It has no capacity for time-dependent inhibition of CYP1A2, CYP2C9, and CYP2D6.
Effect of Ribociclib on transporters: In vitro evaluations showed that Ribociclib has a low potential to inhibit the activities of drug transporters P-gp, OATP1B1/B3, OCT1, MATEK2 at clinically relevant concentrations. Ribociclib may stop BCRP, OCT2, MATE1, and human BSEP at clinically relevant concentrations.
Effect of transporters on Ribociclib: Based on in vitro data, P-gp and BCRP mediated transport are unlikely to affect the extent of oral absorption of Ribociclib at therapeutic doses.