Version July 2025
Dosage guidance:
Safety: Correct electrolyte abnormalities prior to ribociclib treatment initiation. Initiate treatment only in patients with QTcF <450 msec. Avoid ribociclib use in patients who have or are at significant risk for developing QTc prolongation, including patients with long QT syndrome, uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, uncontrolled hypothyroidism, or with electrolyte abnormalities.
Clinical considerations: Ribociclib is associated with a moderate or high emetic potential; consider the addition of antiemetics as needed to prevent nausea and vomiting (Ref).
Breast cancer, early, high risk, hormone receptor positive, HER2 negative, adjuvant treatment:
In combination with an aromatase inhibitor: Oral: 400 mg once daily for 21 days, followed by a 7-day rest period to complete a 28-day treatment cycle; continue for a total of 3 years or until disease recurrence or unacceptable toxicity occurs (Ref). A luteinizing hormone-releasing hormone (LHRH) agonist should be administered to males and pre-/perimenopausal females receiving ribociclib in combination with an aromatase inhibitor.
Breast cancer, advanced or metastatic, hormone receptor positive, HER2 negative:
In combination with an aromatase inhibitor: Oral: 600 mg once daily for 21 days, followed by a 7-day rest period to complete a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref). A luteinizing hormone-releasing hormone (LHRH) agonist should be administered to males and pre-/perimenopausal females receiving ribociclib in combination with an aromatase inhibitor.
In combination with fulvestrant: Oral: 600 mg once daily for 21 days, followed by a 7-day rest period to complete a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref). An LHRH agonist should be administered to males and pre/perimenopausal females receiving ribociclib in combination with fulvestrant.
Missed doses: If a ribociclib dose is missed or vomited, do not administer an additional dose that day. Resume ribociclib dosing with the next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR 30 to 89 mL/minute/1.73 m2: No dosage adjustment is necessary (Ref).
eGFR <30 mL/minute/1.73 m2: Reduce initial dose to 200 mg once daily (Ref).
Hepatic impairment prior to treatment initiation:
Early breast cancer:
Mild, moderate, or severe impairment (Child-Turcotte-Pugh class A, B, C): No dosage adjustment necessary.
Advanced or metastatic breast cancer:
Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Turcotte-Pugh class B, C): Reduce initial ribociclib dose to 400 mg once daily.
Acute hepatotoxicity during treatment:
Elevations from baseline without total bilirubin increase >2 times the ULN:
Grade 1 (ALT and/or AST elevated >1 to 3 times ULN): No ribociclib dosage adjustment necessary.
Grade 2 (ALT and/or AST elevated >3 to 5 times ULN): If baseline was below grade 2, interrupt ribociclib treatment until recovery to baseline or lower and then resume ribociclib at the same dose level. For recurrent grade 2 elevations, interrupt treatment until recovery and then resume ribociclib at the next lower dose level. If baseline was at grade 2, no dose interruption necessary.
Grade 3 (ALT and/or AST elevated >5 to 20 times ULN): Interrupt ribociclib treatment until recovery to baseline or lower and then resume ribociclib at the next lower dose level. For recurrent grade 3 elevations, discontinue ribociclib.
Grade 4 (ALT and/or AST elevated >20 times ULN): Discontinue ribociclib.
Combined ALT and/or AST elevations >3 times ULN with total bilirubin increase >2 times ULN (in the absence of cholestasis), regardless of baseline grade: Discontinue ribociclib.
|
Dosage reduction levels |
Recommended ribociclib dosage (advanced or metastatic breast cancer) |
Recommended ribociclib dosage (early breast cancer) |
|---|---|---|
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a If further dose reduction below 200 mg/day is required, discontinue ribociclib treatment. | ||
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Starting dose |
600 mg/day |
400 mg/day |
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First dose reduction |
400 mg/day |
200 mg/daya |
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Second dose reduction |
200 mg/daya |
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Note: For dosage adjustment of concomitant aromatase inhibitor or fulvestrant therapy, refer to aromatase inhibitor or fulvestrant monograph and/or prescribing information.
|
Toxicity |
Severity |
Management |
|---|---|---|
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a SCARs = severe cutaneous adverse reactions. b SJS = Stevens-Johnson syndrome. SJS (grade 3 and 4) defined as skin sloughing covering <10% BSA and 10% to 30% BSA, respectively, with associated signs (eg, erythema, purpura, epidermal detachment and mucous membrane detachment). c TEN = toxic epidermal necrolysis. TEN (grade 4) defined as skin sloughing covering ≥30% BSA with associated symptoms (eg, erythema, purpura, epidermal detachment, and mucous membrane detachment). d DiHS/DRESS = Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. | ||
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Hematologic toxicity: neutropenia |
Grade 1 or 2 (ANC 1,000/mm3 to below the lower limit of normal) |
No ribociclib dosage adjustment necessary. |
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Grade 3 (ANC 500 to <1,000/mm3) |
Interrupt ribociclib treatment until recovery to grade 2 or lower and then resume ribociclib at the same dose. For recurrent grade 3 neutropenia, interrupt treatment until recovery and then resume ribociclib at the next lower dose level. | |
|
Grade 3 neutropenic fever (a single episode of fever >38.3°C or fever ≥38°C for >1 hour and/or concurrent infection) |
Interrupt ribociclib treatment until recovery (of neutropenia) to grade 2 or lower and then resume ribociclib at the next lower dose level. | |
|
Grade 4 (ANC <500/mm3) |
Interrupt ribociclib treatment until recovery to grade 2 or lower and then resume ribociclib at the next lower dose level. | |
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Cardiovascular toxicity: QT prolongation |
QTcF >480 msec and ≤500 msec |
Early breast cancer: Interrupt ribociclib treatment until QTcF resolves to ≤480 msec; resume ribociclib at the same dose level. If QTcF ≥480 msec recurs, interrupt ribociclib treatment until QTcF resolves to ≤480 msec and resume ribociclib at the next lower dose level. Advanced or metastatic breast cancer: Interrupt ribociclib treatment until QTcF resolves to ≤480 msec; resume ribociclib at the next lower dose level. If QTcF ≥480 msec recurs, interrupt ribociclib treatment until QTcF resolves to ≤480 msec and resume ribociclib at the next lower dose level. |
|
QTcF >500 msec |
Interrupt ribociclib treatment until QTcF resolves to ≤480 msec; resume ribociclib at the next lower dose level. If QTcF >500 msec recurs, discontinue ribociclib. | |
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QTcF >500 msec or >60 msec change from baseline and associated with torsades de pointes, polymorphic ventricular tachycardia, syncope, or signs/symptoms of serious arrhythmia |
Permanently discontinue ribociclib. | |
|
Dermatologic toxicity (cutaneous adverse reactions, including SCARs)a |
Signs/Symptoms of severe cutaneous reactions |
Interrupt ribociclib treatment until the etiology of the reaction has been established. To ensure appropriate management, consult a dermatologist early to allow for increased diagnostic accuracy and appropriate management. |
|
Grade 1 (<10% of BSA with active skin toxicity, no signs of systemic involvement) |
No dosage adjustment required. Initiate appropriate medical management and monitor as clinically indicated. | |
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Grade 2 (10% to 30% of BSA with active skin toxicity, no signs of systemic involvement) |
No dosage adjustment required. Initiate appropriate medical management and monitor as clinically indicated. | |
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Grade 3 (severe rash, not responsive to medical management, >30% of BSA with active skin toxicity, signs of systemic involvement; SJSb) |
Interrupt ribociclib treatment until etiology of reaction has been determined. If etiology is a SCAR, permanently discontinue ribociclib. If etiology is not a SCAR, interrupt ribociclib until recovery to ≤ grade 1, then resume ribociclib at the same dose level. If the cutaneous adverse reaction still recurs at grade 3, resume ribociclib at the next lower dose level. | |
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Grade 4 (any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences, TENc) |
Permanently discontinue ribociclib. | |
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Confirmed SJS, TEN, or DiHS/DRESSd |
Permanently discontinue ribociclib. Do not reinitiate ribociclib treatment in patients who have experienced SCARs or other life-threatening cutaneous reactions during ribociclib treatment. | |
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Pulmonary toxicity: Interstitial lung disease/pneumonitis |
Grade 1 (asymptomatic) |
No ribociclib dose interruption or adjustment necessary. Initiate appropriate medical management and monitoring as clinically indicated. |
|
Grade 2 (symptomatic) |
Interrupt ribociclib treatment until recovery to grade 1 or lower and then consider resuming ribociclib at the next lower dose level, based on the risks versus benefits of resuming therapy. If grade 2 toxicity recurs, discontinue ribociclib. | |
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Grade 3 (severe symptomatic) or grade 4 (life-threatening) |
Discontinue ribociclib. | |
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Other nonhematologic toxicities (excluding neutropenia, hepatobiliary toxicity, QT interval prolongation, interstitial lung disease/pneumonitis, and cutaneous adverse reactions, including SCARs) |
Grade 1 or 2 |
No ribociclib dose adjustment necessary. Initiate appropriate medical management and monitoring as clinically indicated. |
|
Grade 3 |
Interrupt ribociclib treatment until recovery to grade 1 or lower and then resume ribociclib at the same dose level. If grade 3 toxicity recurs, interrupt treatment until recovery to grade 1 or lower and then resume ribociclib at the next lower dose level. | |
|
Grade 4 |
Discontinue ribociclib. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with combination therapy in adults.
>10%:
Cardiovascular: Peripheral edema (7% to 15%)
Dermatologic: Alopecia (15% to 33%), pruritus (7% to 20%), skin rash (9% to 23%)
Endocrine & metabolic: Decreased serum albumin (12%), decreased serum glucose (10% to 23%), decreased serum phosphate (13% to 18%)
Gastrointestinal: Abdominal pain (11% to 17%), constipation (13% to 25%), decreased appetite (5% to 19%), diarrhea (15% to 35%; grade 3: ≤1%), nausea (23% to 52%; grade 3: ≤2%), stomatitis (6% to 12%; grade 3: <1%), vomiting (8% to 29%; grade 3: 1% to 4%)
Hematologic & oncologic: Decreased hemoglobin (47% to 84%; grades 3/4: ≤4%), leukopenia (93% to 95%; grades 3/4: 26% to 36%), lymphocytopenia (51% to 97%; grades 3/4: 14% to 19%), neutropenia (63% to 75%)
Hepatic: Increased gamma-glutamyl transferase (42% to 52%), increased serum alanine aminotransferase (33% to 46%), increased serum aspartate aminotransferase (37% to 50%)
Infection: Infection (36% to 42%; including gastroenteritis, respiratory tract infection, sepsis [≤1%], urinary tract infection [11%])
Nervous system: Asthenia (17%), dizziness (9% to 13%), fatigue (22% to 37%), headache (22% to 23%), insomnia (12%)
Neuromuscular & skeletal: Arthralgia (34%), back pain (20%)
Renal: Increased serum creatinine (8% to 65%)
Respiratory: Cough (13% to 22%), dyspnea (7% to 15%)
Miscellaneous: Fever (11% to 17%)
1% to 10%:
Cardiovascular: Prolonged QT interval on ECG (≤6%), syncope (≤1%)
Dermatologic: Erythema of skin (4%), vitiligo (3%), xeroderma (8% to 9%)
Endocrine & metabolic: Hypocalcemia (2% to 5%), hypokalemia (5%)
Gastrointestinal: Dysgeusia (7%), dyspepsia (5%), xerostomia (5%)
Hematologic & oncologic: Febrile neutropenia (≤2%), thrombocytopenia (9%)
Hepatic: Hepatic injury (≤2%), increased serum bilirubin (1%)
Nervous system: Vertigo (5%)
Neuromuscular & skeletal: Limb pain (10%)
Ophthalmic: Dry eye syndrome (4% to 5%), increased lacrimation (4%)
Respiratory: Interstitial lung disease (≤2%), oropharyngeal pain (6% to 7%), pneumonia (≤2%), pneumonitis (≤2%)
<1%:
Cardiovascular: Pulmonary embolism
Respiratory: Acute respiratory distress syndrome, hypersensitivity pneumonitis, pulmonary fibrosis, pulmonary infiltrates
Frequency not defined: Endocrine & metabolic: Hypomagnesemia
Postmarketing:
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to ribociclib or any component of the formulation; untreated congenital long QT syndrome, Fridericia-corrected QT interval (QTcF) ≥450 msec at baseline and patients at significant risk of developing QTc prolongation.
Concerns related to adverse effects:
• Bone marrow suppression: Concentration-dependent neutropenia commonly occurs, including grades 3 and 4 neutropenia. In patients with early breast cancer, the median time to onset of grade 2 or higher neutropenia was 18 days and median time to resolution of grade 3 or higher neutropenia was 10 days (resolution to less than grade 3 toxicity). In patients with advanced or metastatic breast cancer, the median time to onset for grade 2 or higher neutropenia was 17 days. The median recovery for grade 3 or higher neutropenia was 12 days (resolution to less than grade 3 toxicity). Neutropenic fever has been observed.
• Dermatologic toxicity: 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), may occur with ribociclib.
• Hepatotoxicity: ALT and/or AST elevations have been observed, including grade 3 or 4 events. The median time to onset for grade 3 or higher transaminase elevations in patients with advanced or metastatic breast cancer treated with ribociclib in combination with either an aromatase inhibitor or fulvestrant was 92 days; the median time for grade 3 or higher elevations to resolve to grade 2 or lower was 21 days. Concurrent elevation of ALT or AST >3 times ULN and total bilirubin >2 times ULN (with normal alkaline phosphatase and in the absence of cholestasis) occurred rarely in patients with either early or advanced or metastatic breast cancer; all cases improved or resolved following ribociclib discontinuation.
• Pulmonary toxicity: Severe, life-threatening, and/or fatal interstitial lung disease (ILD) and/or pneumonitis may occur with ribociclib (and other cyclin-dependent kinase inhibitors). Symptoms indicative of ILD/pneumonitis may include hypoxia, cough, and dyspnea.
• QT prolongation: Ribociclib is associated with concentration-dependent QT prolongation, with an estimated mean increase in the QT interval exceeding 20 msec at the mean steady-state Cmax of a 600 mg once daily dose (in patients with advanced or metastatic breast cancer) and a change of 10 msec at the mean steady-state Cmax of a 400 mg once daily dose (in patients with early breast cancer). QTcF interval prolongation >500 msec has been observed, as well as QTcF prolongations >60 msec from baseline. QT interval changes occurred within the initial 4 weeks of ribociclib therapy and were reversible with treatment interruption. Torsades de pointes has not been reported, although syncope occurred in a small percentage of patients. One sudden death was reported in a patient with advanced or metastatic breast cancer and grade 3 hypokalemia and grade 2 QT prolongation. In a clinical trial of ribociclib plus either tamoxifen or a nonsteroidal aromatase inhibitor, an increase of >60 msec from baseline in the QTcF interval was observed at an increased incidence in the tamoxifen arm compared to the aromatase inhibitor arm (Im 2019). Ribociclib is not indicated for concomitant use with tamoxifen. Avoid using ribociclib in patients with congenital long QT syndrome, uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, uncontrolled hypothyroidism, electrolyte abnormalities, and with medications known to prolong the QTc interval and/or strong CYP3A inhibitors (may prolong the QTcF interval).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Therapy Pack, Oral:
Kisqali (200 MG Dose): 200 mg (21 ea) [contains soybean lecithin]
Kisqali (400 MG Dose): 200 mg (14 ea, 42 ea) [contains soybean lecithin]
Kisqali (600 MG Dose): 200 mg (21 ea, 63 ea) [contains soybean lecithin]
No
Tablet Therapy Pack (Kisqali (200 MG Dose) Oral)
200 mg (per each): $436.57
Tablet Therapy Pack (Kisqali (400 MG Dose) Oral)
200 mg (per each): $436.58
Tablet Therapy Pack (Kisqali (600 MG Dose) Oral)
200 mg (per each): $363.81
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Kisqali: 200 mg [contains soybean lecithin]
Oral: May be administered with or without food. Administer at approximately the same time each day, preferably in the morning. Swallow tablets whole; do not crush, chew, or split tablets (do not ingest broken, cracked, or otherwise not intact tablets).
Ribociclib is associated with a moderate or high emetic potential; consider the addition of antiemetics as needed to prevent nausea and vomiting (Ref).
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Ribociclib may cause teratogenicity and reproductive toxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Breast cancer, early, high risk, hormone receptor positive, HER2-negative, adjuvant treatment:
Adjuvant treatment (in combination with an aromatase inhibitor) of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer in adults at high risk of recurrence.
Breast cancer, advanced or metastatic:
Treatment (in combination with an aromatase inhibitor) of HR-positive, HER2-negative advanced or metastatic breast cancer in adults as initial endocrine-based therapy.
Treatment (in combination with fulvestrant) of HR-positive, HER2-negative advanced or metastatic breast cancer in adults as initial endocrine-based therapy or following disease progression on endocrine therapy.
Ribociclib may be confused with abemaciclib, palbociclib, ribavirin, riboflavin, trilaciclib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Moderate);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider Therapy Modification
Acrivastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acrivastine. Risk C: Monitor
ALfentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider Therapy Modification
Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alfuzosin. Risk C: Monitor
Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alitretinoin (Systemic). Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider Therapy Modification
Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of AmLODIPine. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Apixaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Apixaban. Risk C: Monitor
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Aprepitant. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor
Atogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atogepant. Risk C: Monitor
Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atorvastatin. Risk C: Monitor
Avacopan: Ribociclib may increase serum concentration of Avacopan. Avacopan may increase serum concentration of Ribociclib. Risk C: Monitor
Avanafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider Therapy Modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider Therapy Modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Axitinib. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Barnidipine. Risk C: Monitor
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Benidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benidipine. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bortezomib. Risk C: Monitor
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bosutinib. Risk X: Avoid
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider Therapy Modification
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider Therapy Modification
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider Therapy Modification
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Topical). Risk X: Avoid
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of BusPIRone. Risk C: Monitor
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cabozantinib. Risk C: Monitor
Cannabis: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider Therapy Modification
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Cariprazine. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a moderate CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Citalopram: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Citalopram. Risk C: Monitor
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider Therapy Modification
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Codeine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider Therapy Modification
Conivaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Conivaptan. Risk C: Monitor
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Copanlisib. Risk C: Monitor
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Crizotinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Crizotinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Crizotinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Ribociclib. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Ribociclib. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Ribociclib. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Ribociclib. Management: Avoid use of ribociclib with strong CYP3A4 inhibitors when possible; if combined use cannot be avoided, reduce ribociclib dose to 400 mg once daily in advanced or metastatic breast cancer; reduce ribociclib dose to 200 mg daily in early breast cancer. Risk D: Consider Therapy Modification
Dabrafenib: May increase QTc-prolonging effects of Ribociclib. Ribociclib may increase serum concentration of Dabrafenib. Dabrafenib may decrease serum concentration of Ribociclib. Ribociclib may increase active metabolite exposure of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Also monitor for decreased ribociclib efficacy and increased dabrafenib adverse effects. Risk C: Monitor
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider Therapy Modification
Daridorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Darifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Darifenacin. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
DiazePAM: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Dienogest: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dienogest. Risk C: Monitor
DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DilTIAZem. Risk C: Monitor
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOCEtaxel. Risk C: Monitor
Domperidone: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Domperidone. Risk X: Avoid
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DroNABinol. Risk C: Monitor
Ebastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ebastine. Risk C: Monitor
Elacestrant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elacestrant. Risk X: Avoid
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eletriptan. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider Therapy Modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider Therapy Modification
Encorafenib: Ribociclib may increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Ribociclib. Ribociclib may increase serum concentration of Encorafenib. Risk X: Avoid
Ensartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Entrectinib. Risk X: Avoid
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider Therapy Modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Erlotinib. Risk C: Monitor
Erythromycin (Systemic): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Erythromycin (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Escitalopram: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor
Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eszopiclone. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etravirine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Etravirine. Risk C: Monitor
Everolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Everolimus. Risk C: Monitor
Felodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Felodipine. Risk C: Monitor
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider Therapy Modification
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid
Fluconazole: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Fluorouracil Products: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Nasal). Risk C: Monitor
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosaprepitant. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Gepirone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider Therapy Modification
Gepotidacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepotidacin. Risk C: Monitor
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Glasdegib. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Ribociclib. Risk C: Monitor
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider Therapy Modification
Haloperidol: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of HYDROcodone. Risk C: Monitor
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider Therapy Modification
Ifosfamide: CYP3A4 Inhibitors (Moderate) may increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Iloperidone. Risk C: Monitor
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Irinotecan Products. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. Risk C: Monitor
Isavuconazonium Sulfate: May increase serum concentration of Ribociclib. Ribociclib may increase serum concentration of Isavuconazonium Sulfate. Risk C: Monitor
Isradipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Isradipine. Risk C: Monitor
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider Therapy Modification
Ixabepilone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lapatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: May increase QTc-prolonging effects of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lemborexant. Risk X: Avoid
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Leniolisib. Risk C: Monitor
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lercanidipine. Risk C: Monitor
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levamlodipine. Risk C: Monitor
Levoketoconazole: QT-prolonging CYP3A4 Substrates may increase QTc-prolonging effects of Levoketoconazole. Levoketoconazole may increase serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomethadone. Risk C: Monitor
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomilnacipran. Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lidocaine (Systemic). CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. Risk C: Monitor
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lomitapide. Risk X: Avoid
Lovastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lovastatin. Risk C: Monitor
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurasidone. Management: Reduce the lurasidone dose by half when initiating therapy with a moderate CYP3A4 inhibitor. If initiating lurasidone in a patient already receiving a moderate CYP3A4 inhibitor, start lurasidone at 20 mg/day with a max dose of 80 mg/day. Risk D: Consider Therapy Modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Macitentan. Risk C: Monitor
Manidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Manidipine. Risk C: Monitor
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Maraviroc. Risk C: Monitor
Mavacamten: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a moderate CYP3A4 inhibitor, and reduce the mavacamten dose by one dose level if initiating a moderate CYP3A4 inhibitor. Avoid initiating moderate CYP3A4 inhibitors in patients on mavacamten 2.5 mg/day. Risk D: Consider Therapy Modification
Mavorixafor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavorixafor. Risk C: Monitor
Meperidine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Meperidine. Risk C: Monitor
Methadone: May increase QTc-prolonging effects of Ribociclib. Ribociclib may increase serum concentration of Methadone. Risk X: Avoid
MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of MethylPREDNISolone. Risk C: Monitor
Methysergide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Methysergide. Risk X: Avoid
Midazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider Therapy Modification
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mirodenafil. Risk C: Monitor
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naldemedine. Risk C: Monitor
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nalfurafine. Risk C: Monitor
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider Therapy Modification
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Neratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Neratinib. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine. Risk C: Monitor
Nilotinib: May increase QTc-prolonging effects of Ribociclib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider Therapy Modification
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NiMODipine. Risk C: Monitor
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nisoldipine. Risk X: Avoid
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nitrendipine. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider Therapy Modification
Oliceridine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider Therapy Modification
Ondansetron: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: Ribociclib may increase serum concentration of Pacritinib. Pacritinib may decrease serum concentration of Ribociclib. Risk C: Monitor
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palbociclib. Risk C: Monitor
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider Therapy Modification
Panobinostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Panobinostat. Risk C: Monitor
PAZOPanib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of PAZOPanib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider Therapy Modification
Pentamidine (Systemic): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimavanserin. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pirtobrutinib. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
PONATinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of PONATinib. Risk C: Monitor
Posaconazole: May increase serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid
Pralsetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Prazepam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Prazepam. Risk C: Monitor
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Praziquantel. Risk C: Monitor
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
QT-prolonging Agents (Highest Risk): May increase QTc-prolonging effects of Ribociclib. Risk X: Avoid
QT-prolonging Antidepressants (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Risk C: Monitor
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May increase QTc-prolonging effects of Ribociclib. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase serum concentration of Ribociclib. Risk X: Avoid
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Ribociclib may increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Ribociclib. Management: Avoid use of ribociclib and strong CYP3A4 inhibitors that prolong the QTc interval when possible. If combined, decrease ribociclib to 400 mg daily in advanced or metastatic breast cancer; reduce ribociclib to 200 mg daily in early breast cancer. Risk D: Consider Therapy Modification
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider Therapy Modification
Red Yeast Rice: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Red Yeast Rice. Risk C: Monitor
Regorafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Regorafenib. Risk C: Monitor
Repotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Repotrectinib. Risk X: Avoid
Rifabutin: May decrease serum concentration of Ribociclib. Ribociclib may increase serum concentration of Rifabutin. Risk C: Monitor
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider Therapy Modification
RisperiDONE: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Risk C: Monitor
Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rupatadine. Risk C: Monitor
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Salmeterol. Risk C: Monitor
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SAXagliptin. Risk C: Monitor
Selumetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider Therapy Modification
Sertindole: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Sertindole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Sertindole. Risk X: Avoid
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sildenafil. Risk C: Monitor
Silodosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Silodosin. Risk C: Monitor
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Solifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider Therapy Modification
Sparsentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sparsentan. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
St John's Wort: May decrease serum concentration of Ribociclib. Risk X: Avoid
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUFentanil. Risk C: Monitor
SUNItinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of SUNItinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of SUNItinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider Therapy Modification
Suzetrigine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suzetrigine. Management: Reduce suzetrigine dose as follows: initiate with 100 mg for 1 dose; then 12 hours after first dose, give 50 mg every 12 hours for doses 2, 3, and 4; then 50 mg every 24 hours for dose 5 and thereafter. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Tadalafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tadalafil. Risk C: Monitor
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tamoxifen: Ribociclib may increase serum concentration of Tamoxifen. Management: Concurrent use of ribociclib with tamoxifen is not indicated. Use of this combination may increase the effects and toxicities of tamoxifen. Risk D: Consider Therapy Modification
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider Therapy Modification
Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider Therapy Modification
Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Thiotepa: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Thiotepa. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Thiotepa. Risk C: Monitor
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ticagrelor. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor
Tilidine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tilidine. Risk C: Monitor
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Tolterodine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolterodine. Risk C: Monitor
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider Therapy Modification
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Trabectedin. Risk C: Monitor
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraZODone. Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tretinoin (Systemic). Risk C: Monitor
Triamcinolone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Udenafil. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vamorolone. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider Therapy Modification
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Verapamil: Ribociclib may increase serum concentration of Verapamil. Verapamil may increase serum concentration of Ribociclib. Risk C: Monitor
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vilazodone. Risk C: Monitor
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinBLAStine. Risk C: Monitor
VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinCRIStine. Risk C: Monitor
Vindesine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vindesine. Risk C: Monitor
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Vinflunine. Risk C: Monitor
Voclosporin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vorapaxar. Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider Therapy Modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zopiclone. Risk C: Monitor
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zuranolone. Risk C: Monitor
Grapefruit may inhibit the metabolism of ribociclib and increase its systemic exposure. Management: Avoid grapefruit and grapefruit juice during therapy.
Verify pregnancy status prior to treatment in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for at least 3 weeks after the last ribociclib dose.
Based on the mechanism of action and data from animal reproduction studies, ribociclib may cause fetal harm if used during pregnancy.
It is not known if ribociclib is present in breast milk.
Due to the potential for adverse events in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy or for at least 3 weeks after the last ribociclib dose.
Avoid grapefruit and grapefruit juice.
CBC (baseline, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles and as clinically necessary); LFTs (baseline, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles and as clinically necessary; if grade 2 or higher abnormalities occur, monitor more frequently and as clinically indicated); serum electrolytes (including potassium, magnesium, calcium, and phosphorous) prior to treatment, at the beginning of each of the first 6 cycles, and as clinically indicated. Evaluate pregnancy status prior to treatment (in patients who could become pregnant). Monitor ECG (prior to treatment initiation; repeat on approximately day 14 of cycle 1, and as clinically indicated; if QTcF is prolonged at any time during treatment, monitor ECG more frequently and as clinically indicated). Monitor for signs/symptoms of dermatologic toxicity and interstitial lung disease/pneumonitis (hypoxia, cough, and dyspnea). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Monitor QTc in all patients at baseline and at 14 and 28 days, as well as with any dose increases (ESC [Lyon 2022]).
Ribociclib is a small molecule cyclin-dependent kinase (CDK) inhibitor which is selective for CDK 4 and 6; it blocks retinoblastoma protein phosphorylation and prevents progression through the cell cycle, resulting in arrest at the G1 phase (Hortobagyi 2016). The combination of ribociclib and an aromatase inhibitor causes increased inhibition of tumor growth compared with each agent alone. The combination of ribociclib and fulvestrant resulted in tumor growth inhibition in estrogen receptor-positive breast cancer models.
Distribution: Vss/F: 1,090 L.
Protein binding: ~70%.
Metabolism: Extensively hepatic, predominantly via CYP3A4; undergoes oxidation to circulating metabolites M13, M4, and M1, although clinical activity is primarily due to the parent drug.
Bioavailability: Mean absolute bioavailability: 65.8% (single oral dose of 600 mg).
Half-life elimination; Terminal: ~30 to 55 hours.
Time to peak: 1 to 4 hours.
Excretion: Feces (69%; 17% as parent drug, 14% as metabolite M1, ≤3% as other metabolites); Urine (23%; 12% as parent drug, 4% as M1, ≤3% as other metabolites).
Clearance: ~40 to 77.5 L/hour (600 mg in healthy subjects); ~38 L/hour (400 mg in patients with early breast cancer); 25.5 L/hour (600 mg in patients with advanced cancer).
Altered kidney function: AUCinf increased by 2.4-fold and 3.8-fold, and Cmax increased by 2.1-fold and 2.7-fold, respectively, in subjects with severe kidney impairment (eGFR 15 to <30 mL/minute/1.73 m2) and end-stage kidney disease compared to subjects with normal kidney function.
Hepatic function impairment: The mean ribociclib Cmax and AUCinf ratio was 1.44 and 1.28, respectively in patients with moderate hepatic impairment (Child-Pugh class B) and the mean ribociclib Cmax and AUCinf ratio was 1.32 and 1.29, respectively in patients with severe hepatic impairment (Child-Pugh class and C).
