Kryxana

Ribocillin (kryxana) instruction manual
Common name: Ribocillin
Trade name: Kisqali
Full names: ribociclib, ribociclib, kryxana, Kisqali, ribociclib

Indications:
Ribociclib (ribociclib) is used in combination with aromatase inhibitors (fulvestrant, letrozole) as initial endocrine therapy for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in postmenopausal women.

Usage and Dosage:
The recommended dose of ribociclib is 600mg (three 200mg film-coated tablets), taken once a day for 21 consecutive days, and then stopped for 7 days to form a complete cycle of 28 days. Ribociclib is combined with letrozole, 2.5 mg taken once daily for a complete 28-day cycle.
Patients should take KISQALI (ribociclib) ribocicillin and letrozole at approximately the same time each day, preferably in the morning.
If a patient vomits after taking a dose or misses a dose, no additional doses should be taken that day. The next prescribed dose should be taken at your usual time. KISQALI (ribociclib) ribocicillin tablets should be swallowed whole (the tablets should not be chewed, crushed, or split before swallowing). You should not ingest any tablets if the pieces are cracked, cracked, or incomplete.

Adverse reactions:
Adverse effects associated with the use of Kisqali may include, but are not limited to, the following:
Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, back pain.
In terms of serious side effects, the main ones are bone marrow suppression: 59.3% decrease in neutrophils and 21% decrease in white blood cells, which can be improved with active treatment.

Contraindications:
Not clear

Notes:
1. Kisqali (ribocillin tablets) cannot be taken alone. The dosage of each tablet is 200mg. It must be taken orally with letrozole, with food or on an empty stomach.

2. Recommended starting dose: 3 tablets/day, taken orally. Take it continuously for 21 days, then stop taking it for 7 days.

3. Before taking Kisqali (Ribociclib):
A. Do appropriate examinations. Electrolytes and electrocardiograms (ECGs) and pregnancy should be monitored, and liver function tests (LFTs) and complete blood counts (CBC) should be performed.
B. Make a list of all the medications you are taking and show it to your attending physician and pharmacist. Because Kisqali (Ribociclib) cannot be combined with drugs such as CYP3A4 inhibitors, CYP3A4 inducers, CYP3A substrates, drugs that prolong the QT interval, and antiarrhythmic drugs.
C. If you have other physical diseases or conditions, please inform your attending physician and pharmacist. The toxic side effects of Kisqali (Ribociclib) can aggravate your existing diseases, such as liver disease, heart disease, etc.

4. While taking Kisqali (ribociclib):
A. Continue to perform electrocardiogram (ECGs) examinations. Electrocardiograms (ECGs) should be repeated on day 14 of the first course of treatment, at the beginning of the second course of treatment, and when clinically indicated.
B. Continue to monitor electrolytes. Electrolytes should be monitored before each cycle during the first six cycles of treatment or as clinically directed.
C. Implement effective contraception during treatment.
D. Continue to perform liver function tests (LFTs) and complete blood counts (CBC). During the first two courses of treatment, perform liver function tests (LFTs) and complete blood counts (CBC) every two weeks. Liver function tests (LFTs) and a complete blood count (CBC) should also be performed before each of the subsequent four courses of treatment, or as clinically indicated.
E. Breastfeeding is prohibited.
F. Avoid eating pomegranate or grapefruit and foods and beverages containing pomegranate or grapefruit juice.
G. If any serious side effects occur, please inform your attending doctor immediately and follow the doctor's instructions to reduce the dose, temporarily stop taking the medicine, or stop taking it completely.
H. Please strictly follow the doctor's instructions to take the medicine, and do not stop the medicine or change the dosage without authorization.
I. Fix the daily medication time, and it is recommended to take it in the morning. If you miss the fixed medication time, do not take the medication that day and just take the next dose at the next fixed time.
J. Swallow the tablet whole. Do not chew, crush or break the tablet. If the medicine is damaged, do not take it. If you spit out the tablet after taking the medicine, do not take the medicine again on the same day.
K. If you add other medicines, please inform your attending physician and pharmacist immediately.
C. Breastfeeding is not allowed within 3 weeks after the end of treatment.
D. Use effective contraception for at least 3 weeks after the end of treatment.
E. It is prohibited to give medicines to others, even if they have the same symptoms as you.

Storage:
Keep medicines away from children. Store in original packaging, below 20-25℃.

Mechanism of Action:
Drugs that May Increase Ribociclib Plasma Concentrations of KISQALI (ribociclib)
CYP3A4 Inhibitors
Coadministration of a strong CYP3A4 inhibitor (ritonavir) increased ribociclib exposure in healthy subjects by 3.2-fold. Avoid concomitant use of strong CYP3A inhibitors (such as boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole) and consider alternative concomitant medications with less potential for CYP3A inhibition.
Instruct patients to avoid use of pomegranate or pomegranate juice, grapefruit, all of which can inhibit cytochrome CYP3A enzymes and may increase exposure to ribociclib.

Drugs that May Decrease Ribociclib Plasma Concentrations of KISQALI (ribociclib)
CYP3A4 Inducers
Coadministration of a strong CYP3A4 inducer (rifampicin) reduced the plasma exposure of ribociclib by 89% in healthy subjects. Avoid concomitant use of strong CYP3A inducers and consider an alternative concomitant drug that has little or no potential to induce CYP3A (e.g., phenytoin, rifampin, carbamazepine, and St. John's wort ( Hypericum perforatum / Hypericum perforatum)).

KISQALI (ribociclib) Effects of ribocicillin on other drugs.
CYP3A substrates have a narrow therapeutic index
Coadministration of midazolam, a sensitive CYP3A4 substrate, with multiple doses of ribociclib (400 mg) increased midazolam exposure in healthy subjects by 3.8-fold compared to midazolam alone. KISQALI at a clinically relevant dose of 600 mg is expected to increase midazolam AUC by 5.2-fold. Therefore, caution is recommended when using ribociclib with CYP3A substrates that have a narrow therapeutic index. Doses of sensitive CYP3A substrates with narrow therapeutic indexes, including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus, may need to be reduced because ribociclib can increase their exposure.

Efficacy and Safety:
Because clinical trials are conducted under a variety of conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect actual observed rates.
Reported safety data are based on Study 1 (MONALEESA-2), a clinical study of 668 postmenopausal women who received KISQALI (ribociclib) ribocicillin plus letrozole or placebo plus letrozole. The median duration of exposure to KISQALI plus letrozole was 13 months, with 58% of patients exposed for ≥12 months.