Oral Hormone receptor positive, HER2-negative locally advanced carcinoma of breast, Hormone receptor positive, HER2-negative metastatic carcinoma of breast
Adult: In combination with an aromatase inhibitor, or in combination with fulvestrant in postmenopausal women: 600 mg once daily preferably in the morning for 21 days followed by 7-days off to complete 28 days cycle. Pre/perimenopausal women should be treated with luteinising hormone-releasing hormone (LHRH) agonist. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). Management of adverse reactions adjustment:1st reduction: 400 mg once daily; 2nd dose: 200 mg once daily; discontinue if dose reduction below 200 mg once daily is required.
Special Patient Group
Patient taking potent CYP3A inhibitors: Reduce dose to 400 mg once daily for 21 days, followed by 7 days off, to complete 28-days cycle.
Moderate to severe (Child-Pugh class B or C): Reduce dose to 400 mg once daily for 21 days, followed by 7 days off, to complete 28 days cycle.
May be taken with or without food. Take at the same time each day, preferably in the morning. Swallow whole, do not chew/crush/split.
Pregnancy and lactation.
Severe renal and hepatic impairment.
Significant: Prolongation of QT interval, hepatotoxicity, neutropenia, leucopenia, anaemia, lymphopenia, thrombocytopenia. Cardiac disorders: Dyspnoea. Eye disorders: Increased lacrimation, dry eye. Gastrointestinal disorders: Nausea, diarrhoea, vomiting, constipation, stomatitis, abdominal pain, dry mouth, dyspepsia, oropharyngeal pain. General disorders and admin site conditions: Fatigue, asthenia, pyrexia. Infections and infestations: Infections. Investigations: Abnormal liver function tests, increased blood creatinine, blood bilirubin increased. Metabolism and nutrition disorders: Decreased appetite, peripheral oedema, hypocalcaemia, hypokalaemia, hypophosphataemia. Musculoskeletal and connective tissue disorders: Back pain. Nervous system disorders: Headache, dizziness, vertigo, dysgeusia. Respiratory, thoracic and mediastinal disorders: Cough. Skin and subcutaneous tissue disorders: Alopecia, rash, pruritus, erythema, dry skin, vitiligo. Vascular disorders: Syncope.
Patient Counseling Information
This drug may cause fatigue, dizziness or vertigo, if affected, do not drive or operate machinery.
Monitor CBC and LFTs before treatment, every 2 weeks for the 1st 2 cycles, then prior to each 4 cycles, and as clinically indicated; ECG assessment before treatment, then prior to each 1st 2 cycle, and as clinically indicated; serum electrolytes. Perform pregnancy test prior to initiation of therapy.
Increased risk of QT prolongation with antiarrhythmic drugs (e.g. amiodarone, disopyramide) and other drugs which are known to prolong QT interval (e.g. chloroquine, bepridil, pimozide, moxifloxacin, tamoxifen). May increase the plasma concentration and risk of toxicity with strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole, nefazodone) and increase plasma concentration of CYP3A4 substrates (e.g. ergotamine, quinidine, cisapride). May decrease efficacy with CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine).
Increase toxicity and serum concentration with grapefruit or grapefruit juice. Decreased serum concentration with St John’s wort.
Description: Ribociclib selectively inhibits cyclin-dependent kinases (CDK) 4 and 6 which are involved in cell proliferation. The interaction between cyclin D and CDK 4 and 6 is blocked, preventing the phosphorylation of tumour suppressor protein retinoblastoma and the progression of cell cycle from G1 into S phase thereby inhibiting cancer cell growth. Pharmacokinetics: Absorption: Time to peak plasma concentration: 1-4 hours. Distribution: Volume of distribution: 1090 L. Plasma protein binding: Approx 70%. Metabolism: Extensively metabolised in the liver mainly by CYP3A4, undergoes oxidation to major metabolites M13 (CCl284, N-hydroxylation), M4 (LEQ803, N-demethylation), and M1 (secondary glucuronide). Excretion: Via urine (23%; 12% unchanged drug, 4% M1, ≤3% other metabolites), faeces (69%; 17% unchanged drug, 14% M1, ≤3% other metabolites). Terminal elimination half-life: Approx 30-55 hours.
Store between 20-25°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration and disposal. Any unused portions should be disposed of in accordance with local requirements.
L01EF02 - ribociclib ; Belongs to the class of cyclin-dependent kinase (CDK) inhibitors. Used in the treatment of cancer.
Anon. Ribociclib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 27/02/2019.Anon. Ribociclib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/02/2019.Buckingham R (ed). Ribociclib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www..medicinescomplete.com. Accessed 27/02/2019.Kisqali (Novartis Pharmaceuticals Corp). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 27/02/2019.