Note: Abemaciclib is associated with a moderate or high emetic potential; antiemetics may be necessary to prevent nausea and vomiting (ASCO [Hesketh 2020]). Pre/perimenopausal females or males receiving an aromatase inhibitor should also receive a gonadotropin-releasing hormone agonist according to current clinical practice standards.
Breast cancer, advanced or metastatic, HR-positive, HER2-negative:
Initial endocrine-based therapy in postmenopausal females and in males: Oral: 150 mg twice daily (in combination with an aromatase inhibitor); continue until disease progression or unacceptable toxicity (Goetz 2017).
Progressive disease following endocrine therapy and prior chemotherapy: Oral: 200 mg twice daily (as a single-agent); continue until disease progression or unacceptable toxicity (Dickler 2017).
Progressive disease on prior endocrine therapy: Oral: 150 mg twice daily (in combination with fulvestrant [pre/perimenopausal females should also receive a gonadotropin-releasing hormone agonist]); continue until disease progression or unacceptable toxicity (Sledge 2017).
Breast cancer, early, high risk, HR-positive, HER2-negative, node-positive: Note: Select patients for adjuvant therapy in early breast cancer based on Ki-67 score (≥20%) in tumor specimen.
Oral: 150 mg twice daily (in combination with endocrine therapy [eg, an aromatase inhibitor, tamoxifen]); continue until completion of 2 years of treatment or until disease recurrence or unacceptable toxicity (Harbeck 2021; Johnston 2020).
Missed/vomited doses: If a dose is missed or vomited, take the next dose at the scheduled time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Kidney function estimated with Cockcroft-Gault equation.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
End-stage renal disease or patients on dialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Hepatic impairment at treatment initiation:
Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): Reduce the abemaciclib frequency to once daily.
Hepatotoxicity during treatment:
Grade 1 (ALT, AST >ULN to 3 times ULN): No abemaciclib dosage modification is required.
Grade 2 (ALT, AST >3 to 5 times ULN) without increase in total bilirubin >2 times ULN: No abemaciclib dosage modification required.
Persistent or recurrent grade 2, or grade 3 (ALT, AST >5 to 20 times ULN) without increase in total bilirubin >2 times ULN: Withhold abemaciclib until toxicity resolves to baseline or grade 1, then resume at the next lower dose.
AST and/or ALT >3 times ULN with total bilirubin >2 times ULN (in the absence of cholestasis): Discontinue abemaciclib.
Grade 4 (ALT, AST >20 times ULN): Discontinue abemaciclib.
Refer to adult dosing.
|
Dose level |
Abemaciclib dose in combination with fulvestrant, tamoxifen, or an aromatase inhibitor |
Abemaciclib dose for monotherapy |
|---|---|---|
|
Recommended starting dose |
150 mg twice daily |
200 mg twice daily |
|
First dose reduction |
100 mg twice daily |
150 mg twice daily |
|
Second dose reduction |
50 mg twice daily |
100 mg twice daily |
|
Third dose reduction |
Not applicable |
50 mg twice daily |
|
Discontinue abemaciclib if unable to tolerate 50 mg twice daily. | ||
|
Adverse reaction |
Severity |
Abemaciclib dose modification |
|---|---|---|
|
Hematologic toxicity |
Any fever |
Patients should promptly report any fever episodes to health care provider. |
|
Grade 1 or 2 |
No abemaciclib dosage modification is required. | |
|
Grade 3 |
Withhold abemaciclib until toxicity resolves to ≤ grade 2 (no abemaciclib dosage reduction is necessary). | |
|
Recurrent grade 3 or grade 4 |
Withhold abemaciclib until toxicity resolves to ≤ grade 2 and then resume abemaciclib at the next lower dose. | |
|
Requiring blood cell growth factors |
Withhold abemaciclib dose for at least 48 hours after the last growth factor dose and until toxicity resolves to ≤ grade 2; resume abemaciclib at the next lower dose (unless already reduced due to the toxicity that required the growth factor). | |
|
GI toxicity: Diarrhea |
First sign of loose stools |
At the first sign of loose stools, begin management with antidiarrheal agents, increase oral fluid intake, and notify health care provider. |
|
Grade 1 |
No abemaciclib dosage modification is required. | |
|
Grade 2 |
If toxicity does not resolve to ≤ grade 1 within 24 hours, withhold abemaciclib until resolution (no abemaciclib dosage reduction is necessary). | |
|
Grade 2 that persists or recurs after resuming the same dose (despite maximal supportive measures) |
Withhold abemaciclib until toxicity resolves to ≤ grade 1 and then resume abemaciclib at the next lower dose. | |
|
Grade 3 or 4 or requires hospitalization |
Withhold abemaciclib until toxicity resolves to ≤ grade 1 and then resume abemaciclib at the next lower dose. | |
|
Pulmonary toxicity: Interstitial lung disease/pneumonitis |
Grade 1 or 2 |
No abemaciclib dosage modification is required. |
|
Persistent or recurrent grade 2 toxicity that does not resolve to baseline or grade 1 within 7 days (despite maximal supportive measures) |
Withhold abemaciclib until toxicity resolves to baseline or to ≤ grade 1 and then resume abemaciclib at the next lower dose. | |
|
Grade 3 or 4 |
Discontinue abemaciclib. | |
|
Venous thromboembolic events |
Early breast cancer: Any grade |
Withhold abemaciclib and manage as clinically indicated. Resume abemaciclib when clinically stable. |
|
Advanced or metastatic breast cancer: Grade 1 or 2 |
No abemaciclib dosage modification is required. | |
|
Advanced or metastatic breast cancer: Grade 3 or 4 |
Withhold abemaciclib and manage as clinically indicated. Resume abemaciclib when clinically stable. | |
|
Other toxicities (excluding diarrhea, hematologic toxicity, hepatotoxicity, interstitial lung disease/pneumonitis, or venous thrombotic events) |
Grade 1 or 2 |
No abemaciclib dosage modification is required. |
|
Persistent or recurrent grade 2 toxicity that does not resolve to baseline or grade 1 within 7 days (despite maximal supportive measures) |
Withhold abemaciclib until toxicity resolves to baseline or to ≤ grade 1 and then resume abemaciclib at the next lower dose. | |
|
Grade 3 or 4 |
Withhold abemaciclib until toxicity resolves to baseline or to ≤ grade 1 and then resume abemaciclib at the next lower dose. |
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Verzenio: 50 mg, 100 mg, 150 mg, 200 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Verzenio: 50 mg, 100 mg, 150 mg, 200 mg
Available through a specialty pharmacy distributor. Information regarding distribution is available from the manufacturer at 800-545-5979 or https://www.verzenio.com/assets/pdf/specialty-pharmacy-list.pdf.
Oral: Administer at approximately the same times each day. May be administered with or without food. Swallow whole, do not crush, chew, or split tablets (do not ingest if tablets are broken, cracked, or not fully intact).
Abemaciclib is associated with a moderate or high emetic potential; antiemetics may be necessary to prevent nausea and vomiting (ASCO [Hesketh 2020]).
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Abemaciclib may cause teratogenicity or 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 2016; 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, advanced or metastatic:
As initial endocrine-based therapy (in combination with an aromatase inhibitor) for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in postmenopausal females and in males.
In combination with fulvestrant for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in adults with disease progression following endocrine therapy.
As monotherapy for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in adults with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
Breast cancer, early, high risk: Adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer (in combination with endocrine therapy [eg, an aromatase inhibitor or tamoxifen]) in adults at high risk of recurrence and a Ki-67 score of ≥20% (as determined by an approved test).
Abemaciclib may be confused with acalabrutinib, afatinib, alectinib, alpelisib, axitinib, palbociclib, ribociclib, trilaciclib.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for monotherapy treatment in adults.
>10%:
Dermatologic: Alopecia (12%)
Endocrine & metabolic: Weight loss (14%)
Gastrointestinal: Abdominal pain (39%), constipation (17%), decreased appetite (45%), diarrhea (90%; grade 3: 20%), dysgeusia (12%), nausea (64% grade 3: 5%), stomatitis (14%), vomiting (35%; grade 3: 2%), xerostomia (14%)
Hematologic & oncologic: Anemia (69%), decreased neutrophils (88%; grade 3: 22%; grade 4: 5%), decreased platelet count (41%; grade 3: 2%), decreased white blood cell count (91%; grade 3: 28%), lymphocytopenia (42%; grade 3: 13%; grade 4: <1%)
Hepatic: Increased serum alanine aminotransferase (31%), increased serum aspartate aminotransferase (30%)
Infection: Infection (31%)
Nervous system: Dizziness (11%), fatigue (65%), headache (20%)
Neuromuscular & skeletal: Arthralgia (15%)
Renal: Increased serum creatinine (99%)
Respiratory: Cough (19%)
Miscellaneous: Fever (11%)
1% to 10%: Endocrine & metabolic: Dehydration (10%)
Frequency not defined:
Cardiovascular: Arterial thrombosis
Respiratory: Interstitial pulmonary disease, pneumonitis
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to abemaciclib or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, has occurred in patients treated with abemaciclib. Grade 3 or higher neutropenia has been observed. The median time to first episode of ≥ grade 3 neutropenia was 29 to 33 days, and the median duration of ≥ grade 3 neutropenia was 11 to 16 days.
• GI toxicity: Severe diarrhea associated with dehydration and infection has occurred in a majority of patients treated with abemaciclib; grade 3 diarrhea has occurred. Most patients experienced diarrhea during the initial month of abemaciclib; the median time to onset of the first diarrhea event was 6 to 8 days and the median duration of grade 2 and 3 diarrhea was 6 to 11 days and 5 to 8 days, respectively. Patients should initiate antidiarrheal medications (eg, loperamide) and increase oral fluid intake at the first sign of loose stools.
• Hepatotoxicity: Grade 3 or higher increases in ALT and AST have been reported with abemaciclib. The median time to onset of ≥ grade 3 ALT elevation was 57 to 87 days and the median time to resolution (to < grade 3) was 13 to 14 days; the median time to onset of ≥ grade 3 AST elevation was 71 to 185 days and the median time to resolution was 11 to 15 days.
• Pulmonary toxicity: Severe, life-threatening, and/or fatal interstitial lung disease (ILD) or pneumonitis may occur with abemaciclib (and other cyclin-dependent kinase inhibitors). Symptoms of ILD or pneumonitis may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exam. Exclude infectious, neoplastic, and other causes for pulmonary toxicity.
• Thromboembolism: Venous thromboembolic events (VTEs) have been reported in patients treated with abemaciclib. VTEs reported included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. Some VTEs were fatal. VTE may require treatment interruption. Abemaciclib has not been studied in patients with early breast cancer who had a history of VTE.
Other warnings/precautions:
• Early breast cancer patient selection: Select patients for adjuvant therapy in early high-risk breast cancer based on Ki-67 score (≥20%) in tumor specimen. Information on approved tests to measure Ki-67 score is available at http://www.FDA.gov/CompanionDiagnostics.
Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Abemaciclib. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Abemaciclib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the 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 therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Abemaciclib. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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
Ketoconazole (Systemic): May increase the serum concentration of Abemaciclib. Risk X: Avoid combination
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect 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
MetFORMIN: Abemaciclib may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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
Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Food: The AUC (of abemaciclib and active metabolites) is increased by 9% and the Cmax is increased by 26% with a high-fat, high-calorie meal (800 to 1,000 calories with 500 to 600 calories from fat).
Grapefruit: Coadministration with grapefruit may increase abemaciclib plasma concentrations. Management: Avoid concomitant administration with grapefruit and grapefruit products.
Verify pregnancy status prior to treatment in patients who can become pregnant. Patients who can become pregnant should use effective contraception during therapy and for 3 weeks after the last abemaciclib dose.
Based on the mechanism of action and data from animal reproduction studies, use during pregnancy may cause fetal harm.
It is not known if abemaciclib is present in breast milk. Due to the potential for adverse events in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for 3 weeks after the last abemaciclib dose.
Avoid grapefruit and grapefruit products. A high-fat, high-calorie meal (800 to 1,000 calories with 500 to 600 calories from fat) increases exposure.
CBC with differential and platelets (at baseline, every 2 weeks for the first 2 months, monthly for the next 2 months, then as clinically indicated); ALT, AST, and serum bilirubin (at baseline, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated). Verify pregnancy status prior to treatment (in patients who can become pregnant). Monitor for signs/symptoms of diarrhea/dehydration, interstitial lung disease/pneumonitis, and venous thrombosis and pulmonary embolism. 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.
Abemaciclib is a potent small molecule cyclin-dependent kinase (CDK) inhibitor which is selective for CDK 4 and 6; it blocks retinoblastoma tumor suppressor protein phosphorylation and prevents progression through the cell cycle, resulting in arrest at the G1 phase (Sledge 2017). Abemaciclib either alone or in combination with endocrine therapy has resulted in decreased tumor size.
Distribution: ~690.3 L; concentrations of abemaciclib and active metabolites M2 and M20 in CSF are comparable to unbound plasma concentrations
Protein binding: Bound to plasma proteins, serum albumin, and alpha-1 acid glycoprotein: ~96% (abemaciclib); ~93% (M2 metabolite); ~97% (M18 metabolite); ~98% (M20 metabolite)
Metabolism: Primarily hepatic, via CYP3A4; forms primary metabolite N-desethylabemaciclib (M2; active), as well as additional metabolites including hydroxyabemaciclib (M20; active), hydroxy-N-desethylabemaciclib (M18; active), and an oxidative metabolite (M1).
Bioavailability: 45% (following a single 200 mg oral dose)
Half-life, elimination: 18.3 hours
Time to peak: 8 hours (range: 4.1 to 24 hours)
Excretion: Feces (~81%; primarily as metabolites); Urine (~3%)
Hepatic function impairment: Following a single 200 mg oral dose, the relative potency of abemaciclib (and active metabolites) in plasma increased 1.2-fold in subjects with mild impairment (Child-Pugh class A), 1.1-fold in subjects with moderate impairment (Child-Pugh class B), and 2.4-fold in subjects with severe impairment (Child-Pugh class C) compared to subjects with normal hepatic function. In subjects with severe impairment, the mean elimination half-life of abemaciclib increased to 55 hours compared to 24 hours in subjects with normal hepatic function.
Tablets (Verzenio Oral)
50 mg (per each): $295.20
100 mg (per each): $295.20
150 mg (per each): $295.20
200 mg (per each): $295.20
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