Ribociclib Contraindications/ Ribociclib is an orally available cyclin-dependent kinase (CDK) inhibitor targets at cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. Ribociclib specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.
Ribociclib is a unique cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Ribociclib is associated with a moderate rate of serum aminotransferase elevations during therapy, and to clinically apparent liver injury in a proportion of these.
Mechanism of Action of Ribociclib
Inhibition of cyclin-dependent kinase 4 and 6 (CDK4/6) may provide protection against oncogenic processes in specific tissue types. For example, CDK4 is not required for normal mammary tissue development based on knockout mouse studies, but it is needed for growth of Ras-induced mammary tumors, suggesting a potential therapeutic window for treatment with lower toxicity. Ribociclib was reported to be a most selective CDK4/6 inhibitor and to have dose-dependent antitumor activity in a number of preclinical models. It inhibited the growth of tumor cells by arresting the cells at the G1 checkpoint, which prevents the tumor cells from proliferating.
Indications of Ribociclib
- Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.
- 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, endocrine therapy should be combined with a luteinizing hormone-releasing hormone (LHRH) agonist.
- Ribociclib is a unique cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Ribociclib is associated with a moderate rate of serum aminotransferase elevations during therapy, and to clinically apparent liver injury in a proportion of these.
- Ribociclib is a unique cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Ribociclib is associated with a moderate rate of serum aminotransferase elevations during therapy, and to clinically apparent liver injury in a proportion of these.
Contraindications of Ribociclib
- Severe infection
- Diabetes
- Anemia
- Decreased Blood Platelets
- Severely Decreased Platelets
- Decreased Neutrophils a Type of White Blood Cell
- Peripheral neuropathy
- Disease of Inadequate Blood Flow to the Heart Muscle
- Abnormal heart rhythm
- Heart Disease
- Liver problems
- Severe liver disease
- High Amount of Bilirubin in the Blood
- Abnormal liver function tests
- Pregnancy
- A mother who is producing milk and breastfeeding
- Severely Decreased Levels of Neutrophils in the Blood
Dosage of Ribociclib
Strengths: 200 mg
Breast Cancer
- 600 mg orally once a day for 21 consecutive days followed by 7 days off for a complete cycle of 28 days; continue until disease progression or unacceptable toxicity
Side Effects of Ribociclib
The Most Common
- abdominal pain
- bone fractures
- increased blood pressure
- increased cholesterol levels
- signs of infection (e.g., severe fever, chills, mouth ulcers, shortness of breath, sudden lack of energy)
- signs of depression (such as feeling sad, losing interest in things you used to enjoy, weight changes, changes in sleep habits, feelings of guilt or worthlessness, thoughts of suicide)
- signs of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odor)
- signs of liver problems (e.g., yellow skin and eyes, nausea, loss of appetite, dark-colored urine)
More Common
- Black, tarry stools
- body aches or pain
- burning, numbness, tingling, or painful sensations
- burning pain on urination
- chest pain
- chills
- cough
- difficult or labored breathing
- ear congestion
- fever
- headache
- loss of voice
- lower back or side pain
- nasal congestion
- painful or difficult urination
- pale skin
- red, swelling, or painful skin
Rare
- Bad, unusual, or unpleasant (after) taste
- change in taste
- cracked lips
- diarrhea
- difficulty having a bowel movement (stool)
- discoloration of the fingernails or toenails
- feeling of warmth
- hair loss or thinning of the hair
- heartburn
- lack or loss of strength
- loss of appetite
- nausea
- redness of the face, neck, arms, and occasionally, upper chest
- stomach pain
- sudden sweating
- swelling or inflammation of the mouth
Drug Interactions of Ribociclib
Ribociclib may interact with following drugs, supplements & may change the efficacy of drugs
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- BCG vaccine
- calcium channel blockers (e.g., diltiazem, nicardipine, verapamil)
- carbamazepine
- carvedilol
- cimetidine
- clozapine
- cyclosporine
- desipramine
- dexamethasone
- diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, rosiglitazone)
- hepatitis protease inhibitors (e.g., boceprevir, simeprevir)
- fosphenytoin
- grapefruit juice
- haloperidol
- HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., delavirdine, efavirenz, etravirine, nevirapine)
- HIV protease inhibitors (atazanavir, darunavir, lopinavir, ritonavir)
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- metronidazole
- mifepristone
- mirabegron
- modafinil
- norfloxacin
- oxcarbazepine
- pentobarbital
- phenobarbital
- phenytoin
- prazosin
- progesterone
- propranolol
- protein kinase inhibitors (e.g., crizotinib, dabrafenib, imatinib, lapatinib, nilotinib)
- St. John’s Wort
- tacrolimus
- tamoxifen
- tocilizumab
- trastuzumab
Pregnancy Category
FDA Pregnancy Category – D
Pregnancy
It is suspected that the use of ribociclib during pregnancy could cause miscarriages and other serious problems. It is not intended to be taken by women who have not reached menopause. This medication should not be taken during pregnancy unless the benefits outweigh the risks. Any woman taking this medication who may become pregnant should practice effective birth control and contact her doctor immediately if pregnancy is suspected while taking this medication.
Lactation
It is not known if ribociclib passes into breast milk. If you breastfeeding feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of this medication have not been established for children. Children under 18 years of age should not use this medication.
References
