ribociclib

High Alert

Adjuvant treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer in patients at high risk of recurrence.
Advanced or metastatic HR-positive, HER2-negative breast cancer (as initial endocrine-based therapy) (in combination with an aromatase inhibitor).
Advanced or metastatic HR-positive, HER2-negative breast cancer (as initial endocrine-based therapy or following disease progression on endocrine therapy) (in combination with fulvestrant).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Congenital long QT syndrome;
Uncorrected hypokalemia or hypomagnesemia;
Recent MI, HF, unstable angina, bradycardia, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment (↓ dose);
Moderate or severe hepatic impairment (↓ dose);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, QT interval prolongation, syncope

Derm: alopecia, pruritus, rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

F and E: hypokalemia, hypophosphatemia

GI: ↑liver enzymes, abdominal pain, constipation, diarrhea, nausea, stomatitis, vomiting, HEPATOTOXICITY, hyperbilirubinemia

GU: ↑serum creatinine, ↓fertility (men)

Hemat: anemia, neutropenia, thrombocytopenia

Metab: ↓appetite

MS: back pain

Neuro: fatigue, headache, insomnia

Resp: dyspnea, INTERSTITIAL LUNG DISEASE (ILD)

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, or voriconazole, may ↑ levels and the risk of toxicity; avoid concurrent use, if possible; if unavoidable, ↓ dose of ribociclib.
Strong CYP3A4 inducers, including carbamazepine, phenytoin, or rifampin, can ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, and tacrolimus; if concurrent use is required, dose ↓ may be necessary.
QT-interval-prolonging medications, including amiodarone, chloroquine, clarithromycin, disopyramide, haloperidol, methadone, moxifloxacin, ondansetron, pimozide, procainamide, quinidine, sotalol, and tamoxifen, may ↑ risk of QT interval prolongation; avoid concurrent use.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit/grapefruit juice or pomegranate/pomegranate juice may ↑ levels and risk of toxicity; avoid ingestion.

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

Early Breast Cancer

PO (Adults ): 400 mg once daily for 21 days, followed by 7 days off to complete a 28-day treatment cycle; continue treatment cycles for 3 yr or until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor: 200 mg once daily for 21 days, followed by 7 days off to complete a 28-day treatment cycle; continue treatment cycles for 3 yr or until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults ): Severe renal impairment: 200 mg once daily for 21 days, followed by 7 days off to complete a 28-day treatment cycle; continue treatment cycles for 3 yr or until disease progression or unacceptable toxicity.

Advanced or Metastatic Breast Cancer

PO (Adults ): 600 mg once daily for 21 days, followed by 7 days off to complete a 28-day treatment cycle; continue treatment cycles until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor: 400 mg once daily for 21 days, followed by 7 days off to complete a 28-day treatment cycle; continue treatment cycles until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults ): Severe renal impairment: 200 mg once daily for 21 days, followed by 7 days off to complete a 28-day treatment cycle; continue treatment cycles until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Moderate or severe hepatic impairment: 400 mg once daily for 21 days, followed by 7 days off to complete a 28-day treatment cycle; continue treatment cycles until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits kinases (cyclin-dependent kinases 4 and 6) that are part of the signaling pathway for cell proliferation.

Therapeutic effects:

Improved survival and decreased spread of breast cancer.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 66% absorbed following oral administration.

Distribution: Extensively distributed to the tissues.

Metabolism/Excretion: Mostly metabolized in the liver by the CYP3A4 isoenzyme; 17% excreted unchanged in feces, 12% in urine.

Half-Life: 32 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–4 hr	unknown

Patient/Family Teaching ⬆ ⬇

Instruct patient to take ribociclib as directed. If patient vomits after taking dose or misses dose, omit for that day. Take next dose at usual time the next day. Advise patient to read Patient Information prior to starting and with each Rx refill in case of changes.
Advise patient to avoid eating pomegranate or grapefruit and to avoid drinking pomegranate or grapefruit juice during therapy.
Advise patient to notify health care professional if signs and symptoms of heart rhythm problems (fast or irregular heart rate, dizziness, feeling faint), low white blood cell counts (fever and chills), liver problems (yellowing of skin or whites of eyes, jaundice, dark or brown tea-colored urine, feeling very tired, loss of appetite, pain on upper right side of abdomen, unusual bleeding or bruising), or skin reactions occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception and to avoid breastfeeding during and for ≥3 wk after last dose of therapy. Inform male patients that ribociclib may impair fertility.

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Indications ⬇