Names and pronunciation
(rye-boe-sye′-klib) Kisqali
PDF page 1150
Loading InternPractice…
Drug reference
(rye-boe-sye′-klib) Kisqali
PDF page 1150
Func. class.: Antineoplastic
PDF page 1150
Chem. class.: Protein kinase inhibitors
PDF page 1150
ACTION: A cyclin-dependent kinase (CDK) 4 and 6 inhibitor. Regulates cell- cycle progression through phos phorylation of the retinoblastoma protein. The combination of ribociclib and an antiestrogen such as letrozole inhibited tumor growth more than either agent alone
PDF page 1150
USES: For the initial endocrine-based treatment of hormone receptor (HR)- positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor in post menopausal women
PDF page 1150
CONTRAINDICATIONS: Hyper sensitivity Precautions: Breastfeeding, contracep- tion requirements, hepatic disease, hepa- totoxicity, infertility, neutropenia, preg- nancy, pregnancy testing, reproductive risk, thromboembolic disease
PDF page 1150
SIDE EFFECTS GI: Diarrhea, abdominal pain, anorexia, nausea, vomiting, constipation, stomati- tis, weight loss CNS: Fatigue, headache, insomnia MS: Back pain INTEG: Rash, alopecia HEMA: Leukemia, neutropenia, lymphopenia MISC: Infection
PDF page 1151
INTERACTIONS Increase: QT prolongation—drugs known to prolong QT interval; avoid con- comitant use Increase: ribociclib effect—strong or moderate CYP3A4 inhibitors; avoid con- comitant use; if cannot be avoided, reduce dose Decrease: ribociclib effect—strong or moderate CYP3A4 inducers; avoid con- comitant use Drug/Lab Test Increase: LFTs Drug/Food • Avoid use with pomegranates, pome- granate juice, grapefruit, and grapefruit juice
PDF page 1151
DOSAGE AND ROUTES Hormone receptor (HR)-positive, HER2-negative advanced or meta- static breast cancer in combination with an aromatase inhibitor in post- menopausal women • Adult: 600 mg/day on days 1 to 21, followed by 7 days of rest, in combination with letrozole (2.5 mg daily) or another aromatase inhibitor on days 1 to 28; repeat cycle q28days Therapeutic drug monitoring Neutropenia • ANC ≥1000 cells/mm3 (grade ≤2): no change • ANC 500 cells/mm3 to 999 cells/mm3 (grade 3): hold. For the first occur- rence of grade 3 neutropenia, resume at original dose level when the ANC re- turns to ≥1000 cells/mm3 (grade ≤2); for recurrent grade 3 neutropenia, re- sume at next lower dose level (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg). If further dose reduction be- low 200 mg per day is required, dis- continue • ANC 500 cells/mm3 to 999 cells/mm3 (grade 3 neutropenia) with single epi- sode of fever >38.3°C or >38°C for >1 hr and/or concurrent infection: hold; re- sume at the next lower dose level when ANC returns to ≥1000 cells/mm3 (grade 2 or less) (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg). If further dose reduction below 200 mg per day is required, discontinue QT prolongation • QTcF 481-500 msec and no serious arrhythmia: hold; monitor ECG fre- quently. For the first occurrence, re- sume at the same dose when QTcF prolongation resolves to ≤480 msec; for a recurrence of QTcF >480 msec, resume at the next lower dose level (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg). If further dose reduction below 200 mg/day is re- quired, discontinue • QTcF >500 msec and no serious ar- rhythmia: repeat ECG. If the QTcF >500 msec on at least 2 separate ECGs at the same visit, hold; monitor ECG more fre- quently. Resume at the next lower dose level (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg) when QTcF prolonga- tion resolves to ≤480 msec. If further dose reduction below 200 mg/day is re- quired, discontinue Hepatic dose • Adult: Mild hepatic impairment (Child-Pugh A): no change; moderate to severe hepatic impairment (Child-Pugh B or C): reduce starting dose to 400 mg/ day Renal Dose • Adult: CCr<30 mL/min: use only if ben- efits outweigh risk
PDF pages 1150, 1151
Administer: • Take ribociclib and letrozole at the same time every day, preferably in the morning • Swallow tablets whole; do not chew, crush, or split. Do not take if broken, cracked • If a dose is missed, or if the patient vomits, do not replace the missed dose. Resume with the next scheduled daily dose
PDF page 1151
Assess: • Hepatotoxicity, grade ≥3 was 57 days. Monitor LFTs baseline, q2wk for the first 2 cycles, before the next 4 cycles, and then as needed. A dose interruption, reduction, or discontinuation of therapy may be necessary. • Bone marrow suppression: onset of grade ≥2 neutropenia was 16 days. Moni- tor CBC baseline, q2wk for the first 2 cy- cles, before the next 4 cycles, and then as needed. A dose interruption, reduction, or discontinuation of therapy may be needed in those with an absolute neutrophil count (ANC) <1000 cells/mm3 • Long QT syndrome: avoid use in long QT syndrome, uncontrolled or sig- nificant cardiac disease (cardiac ar- rhythmias, recent MI, heart failure, un- stable angina, bradycardia or bradyarrhythmias), electrolyte imbal- ance (hypomagnesemia, hypokalemia, hypocalcemia), with products causing prolonged QT interval or that strongly inhibit CYP3A4. Females, geriatric patients, and patients with diabetes, thyroid disease, malnutrition, alcohol- ism, or hepatic disease may also be at increased risk for QT prolongation. As- sess ECG before starting therapy; do not start product if QTcF >450 msec. Repeat R ECG at day 14 of first cycle, at the begin- ning of second cycle, and then as needed; prolongation of the QTcF inter- val may require interruption of therapy, dose reduction, or discontinuation of therapy. Monitor serum electrolytes (po- tassium, calcium, phosphorous, and magnesium) baseline, at the beginning of the first 6 cycles, and as needed; cor- rect electrolyte imbalances before start- ing product • Pregnancy/breastfeeding: avoid use by females of reproductive potential during treatment and for at least 3 wk after last dose; can cause fetal harm or death; discontinue breastfeeding during treatment and for 3 wk after final dose; presence in breast milk unknown. Ob- tain pregnancy test before starting treatment Evaluate • Therapeutic outcome: decrease in size of cancerous tumor
PDF pages 1151, 1152
CLINICAL CONSIDERATIONS
PDF page 1151
Patient and caregiver information: • Hepatotoxicity: patient should report immediately yellowing of skin or eyes, dark urine • QT prolongation: signs and symp- toms of QT prolongation (irregular or rapid heartbeat, fainting). To notify health care provider immediately if any of these occur • Neutropenia: to immediately notify health care provider if a fever occurs; usually may occur with an infection • Drug interactions: to avoid pome- granates, pomegranate juice, grapefruit, and grapefruit juice; that all OTC or prescription medications, herbals, and supplements should be approved by provider • Alopecia: that hair is often lost; make suggestions for wigs, scarves to make patient feel more comfortable about hair loss • Pregnancy/breastfeeding: not to use drug in pregnancy, breastfeeding; contra- ception should be used during treatment and for at least 3 wk after last dose
PDF page 1152
PHARMACOKINETICS Protein binding 70%; half-life 29.7-54.7 hr; fecal excretion 97.1%; extensively metabolized (CYP3A4); unchanged drug 17% and 12% in feces and urine, respec- tively; peak 1-4 hr
PDF page 1151
• Adult: 600 mg/day on days 1 to 21, followed by 7 days of rest, in combination with letrozole (2.5 mg daily) or another aromatase inhibitor on days 1 to 28; repeat cycle q28days Therapeutic drug monitoring Neutropenia
PDF pages 1150, 1151
• ANC ≥1000 cells/mm3 (grade ≤2): no change
PDF pages 1150, 1151
• ANC 500 cells/mm3 to 999 cells/mm3 (grade 3): hold. For the first occur- rence of grade 3 neutropenia, resume at original dose level when the ANC re- turns to ≥1000 cells/mm3 (grade ≤2); for recurrent grade 3 neutropenia, re- sume at next lower dose level (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg). If further dose reduction be- low 200 mg per day is required, dis- continue
PDF pages 1150, 1151
• ANC 500 cells/mm3 to 999 cells/mm3 (grade 3 neutropenia) with single epi- sode of fever >38.3°C or >38°C for >1 hr and/or concurrent infection: hold; re- sume at the next lower dose level when ANC returns to ≥1000 cells/mm3 (grade 2 or less) (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg). If further dose reduction below 200 mg per day is required, discontinue QT prolongation
PDF pages 1150, 1151
• QTcF 481-500 msec and no serious arrhythmia: hold; monitor ECG fre- quently. For the first occurrence, re- sume at the same dose when QTcF prolongation resolves to ≤480 msec; for a recurrence of QTcF >480 msec, resume at the next lower dose level (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg). If further dose reduction below 200 mg/day is re- quired, discontinue
PDF pages 1150, 1151
• QTcF >500 msec and no serious ar- rhythmia: repeat ECG. If the QTcF >500 msec on at least 2 separate ECGs at the same visit, hold; monitor ECG more fre- quently. Resume at the next lower dose level (reduce 600 mg to 400 mg; reduce 400 mg to 200 mg) when QTcF prolonga- tion resolves to ≤480 msec. If further dose reduction below 200 mg/day is re- quired, discontinue Hepatic dose
PDF pages 1150, 1151
• Adult: Mild hepatic impairment (Child-Pugh A): no change; moderate to severe hepatic impairment (Child-Pugh B or C): reduce starting dose to 400 mg/ day Renal Dose
PDF pages 1150, 1151
• Adult: CCr<30 mL/min: use only if ben- efits outweigh risk
PDF pages 1150, 1151