Important Safety Information for KISQALI®
Important note: Before prescribing, consult full prescribing information.
Presentation: Film-coated tablets (FCT) containing 200 mg of ribociclib.
Indications:
Kisqali is indicated for the treatment of women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy.
In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone-releasing hormone (LHRH) agonist.
Dosage and administration:
Adults: The recommended dose of Kisqali is 600 mg (3 x 200-mg FCT) taken orally, once daily, with or without food for 21 consecutive days, followed by 7 days off treatment resulting in a complete cycle of 28 days.
Special populations: ♦Renal impairment: Mild or moderate: No dose adjustment is necessary. Severe: Caution should be used with close monitoring of signs of toxicity. ♦Hepatic impairment: Mild: No dose adjustment is necessary. Moderate or severe: Dose adjustment is required, and a starting dose of 400 mg is recommended. ♦Geriatrics (≥65 years): No dose adjustment is required. ♦Pediatrics: Safety and efficacy have not been established.
Contraindications: Patients with hypersensitivity to the active substance or to peanut, soya, or any of the excipients.
Warnings and precautions: ♦Critical visceral disease: The efficacy and safety of ribociclib have not been studied in patients with critical visceral disease. ♦Neutropenia: Neutropenia was very commonly reported. A complete blood count (CBC) should be performed before initiating therapy. CBC should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. Febrile neutropenia was reported in 1.5% of patients exposed to Kisqali in the phase III clinical study. Based on the severity of the neutropenia, Kisqali may require dose interruption, reduction, or discontinuation. ♦Hepatobiliary toxicity: Increases in alanine transaminase (ALT) and aspartate transaminase (AST) have been reported, with the majority of them without concurrent elevations of bilirubin. Concurrent elevations of ALT or AST >3 x ULN and of total bilirubin >2 x ULN, with normal alkaline phosphatase levels and no cholestasis occurred in 6 patients; 5 patients returned to normal within 154 days after discontinuation of Kisqali, and one within 532 days. Liver function tests (LFTs) should be performed before initiating therapy with Kisqali. LFTs should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. Based on the severity of transaminase elevations, Kisqali may require dose interruption, reduction, or discontinuation. ♦QT interval prolongation: In study E2301 (MONALEESA-7) a QTcF interval increase >60 msec from baseline was observed in 16.1% patients receiving Kisqali plus tamoxifen and in 7.3% patients receiving Kisqali plus an NSAI. Kisqali is not recommended to be used in combination with tamoxifen. The ECG should be assessed prior to initiation of treatment. Treatment with Kisqali should be initiated only in patients with QTcF values <450 msec. The ECG should be repeated at approximately Day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated. The use of Kisqali should be avoided in patients who already have or who are at significant risk of developing QTc prolongation. This includes patients with long QT syndrome, with uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmias; and with electrolyte abnormalities. Appropriate monitoring of serum electrolytes (including potassium, calcium, phosphorus, and magnesium) should be performed prior to initiation of treatment, at the beginning of the first 6 cycles, and then as clinically indicated. Any abnormality should be corrected before the start of Kisqali therapy. Based on the observed QT prolongation during treatment, Kisqali may require dose interruption, reduction, or discontinuation. ♦CYP3A4 substrates: Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index and the prescribing information of the other product should be consulted for recommendations regarding co-administration with CYP3A4 inhibitors. ♦Women of childbearing potential: patients should be advised to use an effective method of contraception while taking Kisqali and for at least 21 days after the last dose. ♦Soya lecithin: Kisqali contains soya lecithin. Patients who are hypersensitive to peanut or soya should not take Kisqali.
Pregnancy, lactation, females and males of reproductive potential:
Pregnancy: It is possible that Kisqali can cause fetal harm when administered to a pregnant woman. The patient should be advised of the risk to a fetus if Kisqali is used during pregnancy or if the patient becomes pregnant while taking Kisqali. Kisqali is not recommended during pregnancy and in women of childbearing potential not using contraception.
Lactation: A decision should be made whether to discontinue nursing or to discontinue Kisqali, taking into account the importance of Kisqali to the mother. It is recommended that women taking Kisqali should not breastfeed for at least 21 days after the last dose.
Females and males of reproductive potential: ♦Pregnancy testing: For females of reproductive potential, pregnancy status should be verified prior to initiating treatment with Kisqali. ♦Contraception: Sexually active females of reproductive potential should use effective contraception (eg double-barrier contraception) when using Kisqali during treatment and for 21 days after stopping treatment with Kisqali. ♦Fertility: Based on animal studies, Kisqali may impair fertility in males of reproductive potential.
Adverse drug reactions:
Very common (≥10%): Infections, neutropenia, leukopenia, headache, cough, nausea, fatigue, diarrhea, vomiting, constipation, alopecia, rash, anemia, decreased appetite, dizziness, dyspnea, nausea, stomatitis, abdominal pain, pruritus, back pain, peripheral edema, asthenia, pyrexia, and abnormal liver function tests.
Common (1 to 10%): Lymphopenia, thrombocytopenia, febrile neutropenia, hypocalcemia, hypokalemia, hypophosphatemia, vertigo, lacrimation increased, dry eye, syncope, dysgeusia, dyspepsia, hepatotoxicity, erythema, dry skin, vitiligo, dry mouth, oropharyngeal pain, blood creatinine increased, and electrocardiogram QT prolonged.
Interactions: ♦Concomitant use of strong CYP3A inhibitors should be avoided, including but not limited to clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, and voriconazole. Alternative medications with less potential to inhibit CYP3A4 should be considered. Patients should be monitored for adverse drug reactions (ADRs). If concomitant use of a strong CYP3A4 inhibitor cannot be avoided, the Kisqali dose should be reduced to 400 mg. In patients who already had their Kisqali dose reduced to 400 mg and in whom initiation of co-administration of a strong CYP3A4 inhibitor cannot be avoided, the dose should be further reduced to 200 mg. In patients who already had their Kisqali dose reduced to 200 mg and in whom initiation of co-administration of a strong CYP3A4 inhibitor cannot be avoided, Kisqali treatment should be interrupted. No dose adjustments are required for mild and moderate CYP3A4 inhibitors. However, if treatment with a moderate CYP3A4 inhibitor is initiated, monitoring of Kisqali-related ADRs is recommended. Grapefruits or grapefruit juice should be avoided. ♦Concomitant use of strong CYP3A4 inducers should be avoided, including but not limited to phenytoin, rifampicin, carbamazepine, and St John’s Wort (Hypericum perforatum). An alternative medication with no or minimal potential to induce CYP3A4 should be considered. ♦Caution is advised when Kisqali is administered with CYP3A4 substrates with narrow therapeutic index (including but not limited to alfentanil, cyclosporine, everolimus, fentanyl, sirolimus, and tacrolimus), and their dose may need to be reduced. Concomitant administration of Kisqali at the 600-mg dose with the following CYP3A4 substrates should be avoided: alfuzosin, amiodarone, cisapride, pimozide, quinidine, ergotamine, dihydroergotamine, quetiapine, lovastatin, simvastatin, sildenafil, midazolam, and triazolam. ♦Co-administration of Kisqali with medications with known potential to prolong the QT interval should be avoided such as anti-arrhythmic medicines (including but not limited to amiodarone, disopyramide, procainamide, quinidine, and sotalol), other medicinal products known to prolong the QT interval including but not limited to chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil, pimozide, and intravenous ondansetron. ♦Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of: P-gp, BCRP, OATP1B1/B3, OCT1, OCT2, MATE1, and BSEP transporters with a narrow therapeutic index, including but not limited to digoxin, pitavastatin, pravastatin, rouvastatin, and metformin. ♦It is currently unknown whether Kisqali may reduce the effectiveness of systemically acting hormonal contraceptives.
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