Letrozole and ribociclib

Applies to letrozole / ribociclib: oral tablet therapy pack

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Dizziness or passing out.
• A fast heartbeat.
• A heartbeat that does not feel normal.
• Feeling very tired or weak.
• Shortness of breath.
• Swelling in the arms or legs.
• Any unexplained bruising or bleeding.

Data not available.

-MILD HEPATIC IMPAIRMENT (Child-Pugh A): No adjustment recommended for both ribociclib and letrozole.
-MODERATE HEPATIC IMPAIRMENT (Child-Pugh B): Reduce the initial dose of ribociclib to 400 mg once a day; no adjustment recommended for letrozole.
-SEVERE HEPATIC IMPAIRMENT (Child-Pugh C) and/or CIRRHOSIS: Reduce the initial dose of ribociclib to 400 mg once a day; reduce the dose of letrozole by 50% to 2.5 mg every other day.

IF HEPATOBILIARY TOXICITY DEVELOPS DURING THERAPY:
AST AND/OR ALT ELEVATIONS FROM BASELINE (WITHOUT total bilirubin increase above 2 times upper limit of normal [ULN]):
-GRADE 1 (Greater than ULN to 3 x ULN): No adjustment recommended for both ribociclib and letrozole.
-GRADE 2 (Greater than 3 to 5 x ULN):
*Baseline at Grade 2: No dose interruption for both ribociclib and letrozole.
*Baseline Less than Grade 2: Interrupt ribociclib dose until recovery to baseline or less, then resume at the same dose; no dose adjustment recommended for letrozole.
-GRADE 2 RECURRENCE OR GRADE 3 (Greater than 5 to 20 x ULN): Interrupt ribociclib dose until recovery to baseline or less, then resume at the next lower dose; no dose adjustment recommended for letrozole.
-GRADE 3 RECURRENCE OR GRADE 4 (Greater than 20 x ULN): Discontinue treatment.

COMBINED ELEVATIONS IN AST AND/OR ALT GREATER THAN 3 x ULN (WITH total bilirubin greater than 2 x ULN irrespective of baseline grade, in the absence of cholestasis): Discontinue treatment.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.