Kisqali

Ribociclib succinate

In combination w/ aromatase inhibitor or fulvestrant as initial endocrine-based therapy for patients w/ hormone receptor (HR) +ve, human epidermal growth factor receptor 2 (HER2) -ve locally advanced or metastatic breast cancer, or in patients who have received prior endocrine therapy. In combination w/ LH-releasing hormone (LHRH) agonist in pre- or perimenopausal women or men.

600 mg (as three 200 mg tab) once daily for 21 consecutive days followed by 7 days off treatment (28-day complete cycle) in combination w/ letrozole 2.5 mg or another aromatase inhibitor once daily continuously throughout the 28-day cycle, or w/ fulvestrant 500 mg IM on days 1, 15 & 29, & once mthly thereafter. Dose modification: 1st dose reduction: 400 mg daily (as two 200 mg tab), 2nd dose reduction: 200 mg daily. Concomitant use w/ strong CYP3A4 inhibitor Reduce dose to 400 mg once daily & can be further reduced to 200 mg. Severe renal impairment Initially 200 mg. Moderate (Child-Pugh class B) & severe (Child-Pugh class C) hepatic impairment Initially 400 mg once daily.

May be taken with or without food: Swallow whole, do not chew/crush/split.

Hypersensitivity to ribociclib, peanut or soya.

Discontinue treatment immediately if sign & symptoms of severe cutaneous reactions (eg, progressive widespread skin rash often w/ blisters or mucosal lesions) appear. Avoid in patients at risk of developing QTc prolongation including those w/ long QT syndrome, uncontrolled or significant cardiac disease (eg, recent MI, CHF, unstable angina & bradyarrhythmias), electrolyte abnormalities. Interrupt, reduce, or discontinue treatment based on severity of neutropenia; transaminase elevations; QT prolongation; ILD/pneumonitis. Monitor patients for pulmonary symptoms of ILD/pneumonitis. Patients w/ critical visceral disease; elevated AST/ ALT grade ≥3 at baseline. Perform LFTs before initiating treatment & monitor thereafter; appropriate serum electrolytes monitoring (eg, K, Ca, P & Mg) before initiating treatment, & at the beginning of 1st 6 cycles & correct any abnormality before initiating treatment; further assessment of renal function to exclude renal impairment in case of blood creatinine increase while on treatment. Assess ECG before initiating treatment & repeat thereafter at approx day 14 of 1st cycle & at the beginning of 2nd cycle. Initiate only in patients w/ QTcF values <450 msec. Not recommended in combination use w/ tamoxifen. Avoid QTc interval prolonging drugs &/or strong CYP3A4 inhibitors. Concomitant use w/ sensitive CYP3A4 substrates w/ narrow therapeutic index. May affect ability to drive & use machines. Severe renal impairment. Women of childbearing potential should use effective method of contraception (eg, double barrier contraception) during therapy & for at least 21 days after last dose. Not recommended during pregnancy & in women of childbearing potential not using contraception. Not to breastfeed for at least 21 days after last dose. Childn & adolescents <18 yr.

Infections; neutropenia, leukopenia, anaemia, lymphopenia; decreased appetite; headache, dizziness; cough, dyspnoea; nausea, diarrhoea, vomiting, constipation, abdominal pain, stomatitis, dyspepsia; alopecia, rash, pruritus; back pain; fatigue, peripheral oedema, pyrexia, asthenia; abnormal LFTs. Thrombocytopenia, febrile neutropenia; hypocalcaemia, hypokalaemia, hypophosphataemia; vertigo; increased lacrimation, dry eye; syncope; dysgeusia; hepatotoxicity; dry skin, erythema, vitiligo; oropharyngeal pain, dry mouth; increased blood creatinine, prolonged ECG QT. ILD/pneumonitis; TEN.

Increased exposure & peak conc w/ ritonavir. Concomitant use w/ CYP3A4 inhibitors eg, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, verapamil & voriconazole; sensitive substrates of drug transporters P-gp, BCRP, OATP1B1/1B3, OCT1, OCT2, MATE1 & BSEP w/ narrow therapeutic index eg, digoxin, pitavastatin, pravastatin, rosuvastatin & metformin; OCs. Increased steady-state C_max & AUC w/ erythromycin. Increased exposure w/ grapefruit or grapefruit juice. Decreased AUC_inf, C_max & exposure w/ strong (eg, rifampicin, phenytoin, carbamazepine & St. John's wort (Hypericum perforatum) & moderate (eg, efavirenz) CYP3A4 inducers. Increased exposure of midazolam; sensitive CYP3A4 substrates w/ narrow therapeutic index (eg, alfentanil, ciclosporin, everolimus, fentanyl, sirolimus, tacrolimus); caffeine; tamoxifen. Avoid concomitant use w/ CYP3A4 substrates eg, alfuzosin, amiodarone, cisapride, pimozide, quinidine, ergotamine, dihydroergotamine, quetiapine, lovastatin, simvastatin, sildenafil, midazolam, triazolam; medicinal products w/ known potential to prolong QT interval eg, anti-arrhythmic drugs (eg, amiodarone, disopyramide, procainamide, quinidine & sotalol), & other QT interval prolonging drugs (eg, chloroquine, halofantrine, clarithromycin, ciprofloxacin, levofloxacin, azithromycin, haloperidol, methadone, moxifloxacin, bepridil, pimozide & IV ondansetron).

Targeted Cancer Therapy

L01EF02 - ribociclib ; Belongs to the class of cyclin-dependent kinase (CDK) inhibitors. Used in the treatment of cancer.

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