Ribociclib
Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). In vitro, ribociclib decreased pRb phosphorylation leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. In vivo, treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation. In studies using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g., letrozole) resulted in increased tumor growth inhibition compared to each drug alone. Additionally, the combination of ribociclib and fulvestrant resulted in tumor growth inhibition in an estrogen receptor positive breast cancer xenograft model.
Ribociclib tablets are taken orally with or without food in combination with an aromatase inhibitor or fulvestrant.Recommended starting dose: 600 mg orally (three 200 mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment.Dose interruption, reduction, and/or discontinuation may be required based on individual safety and tolerability.
CYP3A4 Inhibitors: Avoid concomitant use of Ribolib with strongCYP3A inhibitors. If strong inhibitors cannot be avoided, reduce Ribolib dose.CYP3A4 Inducers: Avoid concomitant use of Ribolib with strong CYP3A inducers.CYP3A Substrates: The dose of sensitive CYP3A substrates with narrow therapeutic indices may need to be reduced when given concurrently with Ribolib.Drugs Known to Prolong QT Interval: Avoid concomitant use of drugs known to prolong QT interval, such as anti-arrhythmic medicines.
Most common (incidence ≥ 20%) adverse reactions, including laboratory abnormalities, are leukocytes decreased, neutrophils decreased, hemoglobin decreased, lymphocytes decreased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, alanine aminotransferase increased, infections, nausea, creatinine increased, fatigue, platelets decreased, diarrhea, vomiting, headache, constipation, alopecia, cough, rash, back pain, and glucose serum decreased.
Based on findings from animal studies and the mechanism of action, Ribociclib can cause fetal harm when administered to a pregnant woman. It is not known if ribociclib is present in human milk. There are no data on the effects of ribociclib on the breastfed infant or on milk production.
Interstitial Lung Disease (ILD)/Pneumonitis: Patients treated with CDK 4/6 inhibitors should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Interrupt and evaluate patients with new or worsening respiratory symptoms suspected to be due to ILD/pneumonitis. Permanently discontinue Ribolib in patients with recurrent symptomatic or severe ILD/pneumonitis.Severe Cutaneous Adverse Reactions (SCARs): Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), and drug-reaction with eosinophilia and systemic symptoms (DRESS) can occur with Ribolib treatment. Permanently discontinue Ribolib in patients with SCARs or other life-threatening cutaneous reactions.QT Interval Prolongation: Monitor electrocardiograms (ECGs) and electrolytes prior to initiation of treatment with Ribolib. Repeat ECGs at approximately Day 14 of the first cycle and at the beginning of the second cycle, and as clinically indicated. Monitor electrolytes at the beginning of each cycle for 6 cycles, and as clinically indicated. Avoid using Ribolib with drugs known to prolong QT interval and/or strong CYP3A inhibitors.Increased QT Prolongation with Concomitant Use of Tamoxifen: Ribolib is not indicated for concomitant use with tamoxifen.Hepatobiliary Toxicity: Increases in serum transaminase levels have been observed. Perform liver function tests (LFTs) before initiating treatment with Ribolib. Monitor LFTs every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated.Neutropenia: Perform complete blood count (CBC) before initiating therapy with Ribolib. Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated.Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception during therapy.
Targeted Cancer Therapy
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
{'Indications': 'Ribolib is a kinase inhibitor indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with:an aromatase inhibitor as initial endocrine-based therapy; orfulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women or in men'}