Kisqali Femara Co-Pack Disease Interactions

Letrozole is extensively metabolized by the liver. The pharmacokinetic disposition of letrozole has not been assessed in patients with severe hepatic impairment. No dosage modification is recommended for patients with mild to moderate hepatic impairment, however, therapy with letrozole should be administered cautiously to patients with severe hepatic impairment.

Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. It is recommended to assess ECG prior to initiation of treatment and to correct any electrolyte abnormality. Initiate treatment only in patients with QTcF values less than 450 ms. Repeat ECG at approximately two weeks of the first cycle and the beginning of the second cycle, and as clinically indicated. Monitor serum electrolytes (including potassium, calcium, phosphorous, and magnesium) before the initiation of treatment, at the beginning of the first 6 cycles, and as clinically indicated. Therapy may require dose interruption, reduction, or discontinuation according to observed QT prolongation. Avoid the use of this drug in patients with or at risk of developing QT prolongation, including those with uncontrolled long QT syndrome or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina, bradyarrhythmias, and electrolyte abnormalities.

In an adjuvant clinical trial hypercholesterolemia was reported in 52.3% of letrozole patients and 28.6% of tamoxifen patients. CTC grade 3-4 hypercholesterolemia was reported in 0.4% of letrozole patients and 0.1% of tamoxifen patients. Also in the adjuvant setting, an increase of >=1.5 X ULN in total cholesterol (generally non-fasting) was observed in patients on monotherapy who had baseline total serum cholesterol within the normal range (i.e., <=1.5 X ULN) in 151/1843 (8.2%) on letrozole vs 57/1840 (3.2%). Caution is recommended when prescribing letrozole to these patients. Consideration should be given to monitoring serum cholesterol.

Use of letrozole tablets may cause decreases in bone mineral density (BMD). Caution should exercise when prescribing this agent to patients with a risk of fractures, such as the elderly and patients with osteoporosis. Consider bone mineral density monitoring in patients treated with letrozole.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

Patients receiving ribociclib have developed severe cutaneous adverse reactions (SCARs), including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS). It is recommended to interrupt treatment if signs or symptoms of severe cutaneous reactions occur until a definitive etiology by a qualified health care professional has been determined. Permanently discontinue treatment if confirmed SJS, TEN, or DiHS/DRESS and do not reintroduce therapy in patients who have experienced SCARs or other life-threatening cutaneous reactions during treatment.

Ribociclib undergoes extensive hepatic metabolism mainly via CYP450 3A4 in humans. Increase transaminases have been observed in clinical studies. It is recommended to reduce the starting dose to 400 mg in patients with moderate (Child-Pugh class B) and severe hepatic impairment (Child-Pugh class C). Consider performing liver function tests (LFTs) before initiating therapy and monitoring LFTs every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. Dose interruption, reduction, or discontinuation may be necessary based on the severity of LFTs. No dose adjustment is necessary for patients with mild hepatic impairment (Child-Pugh class A).

The use of ribociclib may result in a decrease in neutrophil count. Care should be exercised when using this drug in neutropenic patients. It is recommended to perform a complete blood count (CBC) before initiating therapy and to monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. Ribociclib may require dose interruption, reduction or discontinuation of treatment based on the severity of the neutropenia.

It is recommended to reduce the starting dose to 200 mg in patients with severe renal impairment. Care is recommended as this drug has not been studied in breast cancer patients with severe renal impairment. Based on a population pharmacokinetic analysis, no dose adjustment is necessary in patients with mild or moderate renal impairment.