KISQALI® NSS - Oman
KISQALI® NSS - Oman
Regulatory Affairs
KISQALI® (ribociclib) 200 mg Film-coated tablets
National Succinct Statement (NSS)
Version 3.2
Effective date: 22-Jan-2024
Safety Label 2023-PSB/GLC-1436-l
Change (SLC)
Tracking number:
Document status: Final
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without the consent of Novartis
KISQALI®
Important note: For Full prescribing information, please refer to www.swissmedicinfo.ch
This link will contain the most updated product information approved by the reference country.
Presentation: Film-coated tablets containing 200 mg of ribociclib.
Indications/Potential uses
Kisqali is indicated for the treatment of adults 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 as initial endocrine therapy or
• fulvestrant as initial endocrine therapy or following prior endocrine therapy in postmenopausal women or in men.
In pre- or perimenopausal women or in men the endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.
Dosage/Administration
Treatment with Kisqali should be initiated by a physician experienced in the use of cancer therapies.
1.1 Usual dosage
The recommended dose of Kisqali is 600 mg (3 x 200 mg film-coated tablets) taken orally once daily for 21 consecutive days followed by 7 days off treatment, resulting in a complete cycle of 28 days. Kisqali can be taken with or without food.
When Kisqali is administered in combination with letrozole, the recommended dose of letrozole is 2.5 mg, taken once daily throughout the 28-day cycle. Please read the prescribing information for letrozole. For information on dosage and administration with another aromatase inhibitor read the relevant prescribing information.
Patients should take their dose of Kisqali and letrozole/aromatase inhibitor at the same time each day, preferably in the morning.
When Kisqali is administered in combination with fulvestrant, the recommended dose of fulvestrant is 500 mg administered intramuscularly on days 1, 15 and 29 and once monthly thereafter. Please read the prescribing information for fulvestrant.
In pre- or perimenopausal women or in men an LHRH agonist should also be administered in accordance with local clinical practice when Kisqali is combined with an endocrine therapy.
When selecting therapy for men, it should be borne in mind that the evidence for ribociclib-based therapy of (locally) advanced or metastatic HR-positive, HER2-negative breast cancer in men is limited. For example, no data are available for comparison with palliative tamoxifen therapy. Furthermore, no clinical study data are available on treatment with ribociclib in combination with fulvestrant. Instead, an extrapolation from female to male HR-positive, HER2-negative breast cancer was undertaken based on results from the male population of the CLEE011A2404 study (combination with an aromatase inhibitor) and the pivotal studies in female patients (see “Clinical efficacy”).
Dose modification due to adverse effects
Management of severe or intolerable adverse drug reactions (ADRs) may require temporary dose interruption or reduction or discontinuation of Kisqali. If dose reduction is required, please see the dose reduction guidelines for adverse drug reactions in Table 1.
Table 1 Recommended dose modification guidelines for adverse drug reactions
| Kisqali | |
Dose | Number of tablets | |
Starting dose | 600 mg/day | 3 × 200 mg tablets |
First dose reduction | 400 mg/day | 2 × 200 mg tablets |
Second dose reduction | 200 mg/day* | 1 × 200 mg tablet |
*If further dose reduction to below 200 mg/day is required, discontinue treatment. | ||
Tables 2, 3, 4, 5 and 6 summarise the recommendations for dose interruption and reduction or discontinuation of Kisqali in response to specific adverse drug reactions. The clinical judgement of the treating physician should guide the treatment plan of each patient based on an individual benefit-risk assessment (see “Warnings and precautions” and “Adverse drug reactions”).
Table 2 Dose modification and treatment for neutropenia
Neutropenia | Grade 1 or 2 (ANC 1,000/mm3 to <LLN) | Grade 3 (ANC 500 to <1,000/mm3) | Grade 3 febrile* neutropenia | Grade 4 (ANC <500/mm3) |
No dose adjustment is required. | Interrupt Kisqali until recovery to grade ≤2. Resume Kisqali at the same dose. If toxicity recurs at grade 3, interrupt Kisqali dose until recovery to grade ≤2, then resume Kisqali at the next lower dose. | Interrupt Kisqali until recovery of neutropenia to grade ≤2. Resume Kisqali at the next lower dose. | Interrupt Kisqali until recovery to grade ≤2. Resume Kisqali at the next lower dose.
| |
| Perform a complete blood count (CBC) before initiating treatment with Kisqali. After initiating treatment with Kisqali, monitor the blood count every 2 weeks in the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. | |||
*Grade 3 neutropenia with a single episode of fever >38.3ᵒC or above 38°C for more than one hour and/or concurrent infection Grading according to CTCAE Version 4.03. CTCAE = Common Terminology Criteria for Adverse Events. | ||||
Table 3 Dose modification and treatment for hepatobiliary toxicity
AST and/or ALT elevation from baseline* without increase in total bilirubin above 2 x ULN | Grade 1 (>ULN to 3 x ULN) | Grade 2 (>3 to 5 x ULN) | Grade 3 (>5 to 20 x ULN) | Grade 4 (>20 x ULN) |
No dose adjustment is required. | Baseline at <grade 2: Interrupt Kisqali until recovery to ≤baseline grade, then resume Kisqali at the same dose. If grade 2 recurs, resume Kisqali at the next lower dose. Baseline at grade 2: No dose interruption.
| Interrupt Kisqali until recovery to ≤baseline grade, then resume Kisqali at the next lower dose. If grade 3 recurs, discontinue Kisqali. | Discontinue Kisqali. | |
Combined elevation in AST and/or ALT together with total bilirubin increase, in the absence of cholestasis | If patients develop ALT and/or AST >3 x ULN along with total bilirubin >2 x ULN, irrespective of baseline grade, discontinue Kisqali.
| |||
Perform liver function tests (LFTs) before initiating treatment with Kisqali. After initiating treatment with Kisqali, perform LFTs every 2 weeks in the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. If grade ≥2 abnormalities are observed, more frequent monitoring is recommended. | ||||
*Baseline = prior to treatment initiation. Grading according to CTCAE Version 4.03. CTCAE = Common Terminology Criteria for Adverse Events. | ||||
Table 4 Dose modification and treatment for QT interval prolongation
ECG with QTcF >480 ms |
|
ECG with QTcF >500 ms | If QTcF is greater than 500 ms: interrupt Kisqali until QTcF reaches <481 ms, then resume Kisqali at next lower dose. If QTcF prolongation to greater than 500 ms occurs or QTcF prolongation occurs in combination with torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia or there is a change of more than 60 ms from baseline, permanently discontinue Kisqali. |
Assess ECG prior to initiation of treatment. After initiating treatment with Kisqali, repeat ECG at approximately day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated. In case of QTcF prolongation during treatment more frequent ECG monitoring is recommended. | |
Table 5 Dose modification and treatment for ILD/pneumonitis
ILD/pneumonitis | Grade 1 (asymptomatic) | Grade 2 (symptomatic) | Grade 3 or 4 (severe) |
| No dose adjustment is required. Initiation of appropriate medical therapy and monitoring as clinically indicated. | Interrupt Kisqali until recovery to grade ≤1, then resume Kisqali treatment at the next lower dose*. | Discontinue Kisqali. |
Grading according to Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
*If continuation of Kisqali therapy is considered, an individual benefit-risk assessment should be performed.
ILD = interstitial lung disease
Table 6 Dose modification and treatment for other toxicities*
Other toxicities | Grade 1 or 2 | Grade 3 | Grade 4 |
No dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Interrupt Kisqali dose until recovery to grade ≤1, then resume Kisqali at the same dose level. If grade 3 recurs, resume Kisqali at the next lower dose. | Discontinue Kisqali. | |
*Excluding neutropenia, hepatobiliary toxicity, QT interval prolongation and ILD/pneumonitis. | |||
Other toxicities | Grade 1 or 2 | Grade 3 | Grade 4 |
No dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Interrupt Kisqali dose until recovery to grade ≤1, then resume Kisqali at the same dose level. If grade 3 recurs, resume Kisqali at the next lower dose. | Discontinue Kisqali. | |
Grading according to CTCAE Version 4.03. CTCAE = Common Terminology Criteria for Adverse Events. | |||
Refer to the prescribing information for the co-administered aromatase inhibitor, fulvestrant or LHRH agonist for guidelines on dose modification in the event of toxicity and other relevant safety information.
Dose modification for use of Kisqali with strong CYP3A inhibitors
Concomitant use of Kisqali with strong CYP3A inhibitors should be avoided and an alternative concomitant medication with a low potential for CYP3A inhibition should be considered. If a strong CYP3A inhibitor must be used concomitantly with Kisqali, the Kisqali dose should be reduced to 400 mg once daily. If the strong inhibitor is discontinued, the Kisqali dose should be changed (after at least 5 elimination half-lives of the strong CYP3A inhibitor) to the dose administered prior to the initiation of treatment with the strong CYP3A inhibitor (see “Warnings and precautions”, “Interactions” and “Properties/Actions”).
Patients with hepatic impairment
Based on a hepatic impairment study in healthy subjects and non-cancer subjects with hepatic impairment no dose adjustment is necessary in patients with mild hepatic impairment (Child- Pugh class A). Ribociclib exposure may be higher (less than twofold) in patients with moderate (Child-Pugh class B) and severe hepatic impairment (Child-Pugh class C). Kisqali has not yet been studied in breast cancer patients with moderate and severe hepatic impairment (see “Clinical efficacy”).
Refer to the prescribing information for the aromatase inhibitor, fulvestrant or LHRH agonist for information on dose modifications related to hepatic impairment.
Patients with renal impairment
Based on population pharmacokinetic analyses and data from cancer patients in clinical studies no dose adjustment is required in patients with mild or moderate renal impairment (see “Clinical efficacy”).
Based on a renal function study in healthy subjects and non-cancer subjects with severe renal impairment a starting dose of 200 mg is recommended. Kisqali has not been studied in breast cancer patients with severe renal impairment.
Elderly patients
No dose adjustment is required in patients over 65 years of age (see “Clinical efficacy”).
Children and adolescents
There are limited data in paediatric patients and the safety and efficacy of Kisqali in this patient population have not been sufficiently established.
Late administration
If the patient vomits after taking the dose or forgets a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time.
Method of administration
Kisqali should be taken orally, once daily at the same time every day (preferably in the morning), with or without food. Kisqali tablets should be swallowed whole (the tablets should not be chewed, crushed or divided before swallowing). Tablets that are broken, cracked or otherwise not intact should not be taken.
Contraindications: ♦Hypersensitivity to ribociclib or to any excipient.
Warnings and precautions:
Neutropenia was the most frequently reported ADR with Kisqali. Febrile neutropenia reported in 1.7% patients with a/mBC on Kisqali in phase III clinical studies. Based on the severity, of neutropenia, Kisqali may require dose interruption, reduction, or discontinuation. A complete blood count should be performed before initiating therapy and should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles and then as clinically indicated.
Increases in ALT and AST have been reported, the majority of without concurrent elevations of bilirubin. Liver function tests 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 and then as clinically indicated. Based on the severity of transaminase elevations, Kisqali may require dose interruption, reduction, or discontinuation.
QT interval prolongation has been reported with Kisqali. Kisqali should not be used in patients with a significant risk of QTc interval prolongation. The ECG should be assessed prior treatment. Treatment with Kisqali should be initiated only in patients with QTcF values <450 ms. ECG should be repeated at approximately Day 14 of the first cycle, and then as clinically indicated. Monitoring of serum electrolytes including potassium, calcium, phosphorous, and magnesium should be performed prior to treatment initiation, at the beginning of the first 6 cycles and then as clinically indicated. Abnormalities should be corrected before the start of Kisqali therapy. Based on observed QT prolongation during treatment, Kisqali may require dose interruption, reduction, or discontinuation. Kisqali is not recommended in combination with tamoxifen.
Severe cutaneous reactions: toxic epidermal necrolysis (TEN) has been reported with Kisqali. If signs and symptoms suggestive of severe cutaneous reactions appear, Kisqali should be immediately and permanently discontinued.
Interstitial lung disease (ILD) / Pneumonitis: ILD/pneumonitis has been reported with CDK4/6 inhibitors including Kisqali. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Based on the severity, patients may require treatment interruption, dose reduction, or permanent discontinuation.
Pregnancy, lactation, females and males of reproductive potential:
Pregnancy: Kisqali may cause fetal harm when administered to a pregnant woman. Patient should be advised of the risk to a fetus if Kisqali is used during pregnancy or if patient becomes pregnant while taking Kisqali.
Lactation: A decision to discontinue either Kisqali or nursing should be made taking into account the importance of Kisqali to the mother. Do not breastfeed while taking Kisqali and for at least 21 days after the last dose of Kisqali.
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 (methods that result in < 1 % pregnancy rates) when using Kisqali during treatment and for 21 days after discontinuation. ♦Infertility: Impairment of fertility in males of reproductive potential indicated in animal studies.
Adverse drug reactions:
Very common (≥10%): Neutropenia, infections, nausea, fatigue, diarrhoea, leukopenia, vomiting, headache, constipation, alopecia, cough, back pain, rash, anaemia, abnormal liver function tests, abdominal pain, pruritus, decreased appetite, peripheral oedema, pyrexia, asthenia, dyspnoea, dizziness, stomatitis, lymphopenia, dyspepsia.
Common (≥1 to <10%): Thrombocytopenia, dry skin, oropharyngeal pain, blood creatinine increased, dry mouth, lacrimation increased, dysgeusia, electrocardiogram QT prolonged, dry eye, vertigo, erythema, hypocalcaemia, hypokalaemia, hypophosphataemia, vitiligo, syncope, hepatotoxicity, febrile neutropenia.
Adverse drug reactions from post-marketing experience (frequency not known): Toxic epidermal necrolysis (TEN).
Interactions: ♦Concomitant use of strong CYP3A inhibitors should be avoided. Alternative medications with less potential to inhibit CYP3A should be considered. Patients should be monitored for ADRs. If concomitant use of a strong CYP3A inhibitor cannot be avoided, the Kisqali dose should be reduced to 400 mg. Grapefruit or grapefruit juice should be avoided.
Concomitant use of strong CYP3A inducers should be avoided. Alternative medications with no or minimal potential to induce CYP3A should be considered. ♦Caution is advised when Kisqali is co-administered with CYP3A substrates with narrow therapeutic index; their dose may need to be reduced. ♦Co-administration of Kisqali with medications with known potential to prolong the QT interval should be avoided. Kisqali is not recommended for use in combination with tamoxifen.